Ammirati Dott. Enrico

Pubblicazioni su PubMed

• Long-Term Survival Rate of ATOMS Implant for Male Stress Urinary Incontinence and Management of Late Complications.
  J Clin Med

  2023 Mar;12(6):. doi: 2296.
  
  Giammò Alessandro, Ammirati Enrico
  
  Abstract
  
  BACKGROUND:
  stress urinary incontinence (SUI) still represents a major drawback of prostate surgery. The aim of this study is to evaluate long term efficacy, safety and survival of ATOMS system implant in a single center.
  
  METHODS:
  we retrospectively included al consecutive patients treated with ATOMS implant for SUI from October 2014 to July 2019. Patients received anamnesis, urodynamic evaluation, pre- and postoperative 24 h pad test and count. Patients were considered "continent" when dry or when wearing a security pad (social continence).
  
  RESULTS:
  we treated99 patientswith median age 77.98 years (IQR 72.7-82.52). Most of the patients had undergone radical prostatectomy. Median follow-up was 62.9 months (IQR 47.5-75.9). At last follow-up 74 (74.7%) patients reported continence. We had 21 early (
  CONCLUSIONS:
  This study demonstrates the good safety and efficacy of ATOMS implant for the treatment of SUI.
  
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• Use of patient-reported outcomes in heart failure: from clinical trials to routine practice.
  Eur J Heart Fail

  2023 Feb;25(2):139-151. doi: 10.1002/ejhf.2778.
  
  Savarese Gianluigi, Lindenfeld Joann, Stolfo Davide, Adams Kirkwood, Ahmad Tariq, Desai Nihar R, Ammirati Enrico, Gottlieb Stephen S, Psotka Mitchell A, Rosano Giuseppe M C, Allen Larry A
  
  Abstract
  
  Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient-reported outcomes (PROs) aim to switch traditional care to a more patient-centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care.
  
  © 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• Innate Immunity in Cardiovascular Diseases-Identification of Novel Molecular Players and Targets.
  J Clin Med

  2023 Jan;12(1):. doi: 335.
  
  Poller Wolfgang, Heidecker Bettina, Ammirati Enrico, Kuss Andreas W, Tzvetkova Ana, Poller Wolfram C, Skurk Carsten, Haghikia Arash
  
  Abstract
  
  During the past few years, unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking advantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss the emerging clinical relevance of advanced diagnostics for cardiovascular diseases, including those associated with COVID-19-with a focus on the role of inflammation in cardiomyopathies and arrhythmias. Second, we consider newly identified immunological interactions at organ and system levels which affect cardiovascular pathogenesis. Thus, studies into immune influences arising from the intestinal system are moving towards therapeutic exploitation. Further, powerful new research tools have enabled novel insight into brain-immune system interactions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress-acting through defined brain regions-upon viral and cardiovascular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.
  
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• Acute myocarditis after a first dose of COVID-19 mRNA vaccination: an uncommon but potentially serious adverse effect.
  J Cardiovasc Med (Hagerstown)

  2023 Feb;24(2):154-158. doi: 10.2459/JCM.0000000000001419.
  
  Bellamoli Michele, Vanoost Julien, Gonçalves Mariana, Ammirati Enrico, Honton Benjamin
  
  
  
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• Recent highlights on acute myocardial infarction and takotsubo syndrome from the International Journal of Cardiology: Heart & Vasculature.
  Int J Cardiol Heart Vasc

  2022 Dec;43():101155. doi: 101155.
  
  Tedeschi Andrea, Ammirati Enrico, Contri Nicolina, Dobrev Dobromir
  
  
  
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• Recent highlights on myocarditis, cardiovascular complications of COVID-19, and cardiomyopathies from the International Journal of Cardiology: Heart & Vasculature.
  Int J Cardiol Heart Vasc

  2022 Dec;43():101154. doi: 101154.
  
  Conti Nicolina, Ammirati Enrico, Tedeschi Andrea, Dobrev Dobromir
  
  
  
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• Combined Neuro-Humoral Modulation and Outcomes in Patients with Chronic Heart Failure and Mildly Reduced or Preserved Ejection Fraction.
  J Clin Med

  2022 Nov;11(22):. doi: 6627.
  
  Gori Mauro, Marini Marco, Gonzini Lucio, Carigi Samuela, De Gennaro Luisa, Gentile Piero, Leonardi Giuseppe, Orso Francesco, Tinti Denitza, Lucci Donata, Iacoviello Massimo, Navazio Alessandro, Ammirati Enrico, Municinò Annamaria, Benvenuto Manuela, Cassaniti Leonarda, Tavazzi Luigi, Maggioni Aldo Pietro, De Maria Renata,
  
  Abstract
  
  Pharmacotherapy of chronic heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains challenging. We aimed to assess whether combined neuro-humoral modulation (NHM) (renin?angiotensin system inhibitors, betablockers, mineralocorticoid receptor antagonists) was differentially associated with outcome according to phenotype and age groups. Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n = 2298, HFpEF n = 2409) from three age groups: 40%, triple NHM treatment increased over time and was associated with better patient outcomes.
  
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• Fulminant Lymphocytic Myocarditis During Pregnancy Treated With Temporary Mechanical Circulatory Supports and Aggressive Immunosuppression.
  Circ Heart Fail

  2022 Dec;15(12):e009810. doi: 10.1161/CIRCHEARTFAILURE.122.009810.
  
  Veronese Giacomo, Nonini Sandra, Cannata Aldo, Aresta Francesca, Olivieri Guido, Montrasio Elisa, De Caria Daniele, Perna Enrico, Calini Angelo, Bottiroli Maurizio, Cislaghi Francesca, Pedrazzini Giovanna, Baltaro Federica, Quattrocchi Giuseppina, Pedrotti Patrizia, Russo Claudio F, Garascia Andrea, Mondino Michele, Ammirati Enrico
  
  
  
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• Acute Myocarditis Associated With Desmosomal Gene Variants.
  JACC Heart Fail

  2022 Oct;10(10):714-727. doi: 10.1016/j.jchf.2022.06.013.
  
  Ammirati Enrico, Raimondi Francesca, Piriou Nicolas, Sardo Infirri Loren, Mohiddin Saidi A, Mazzanti Andrea, Shenoy Chetan, Cavallari Ugo A, Imazio Massimo, Aquaro Giovanni Donato, Olivotto Iacopo, Pedrotti Patrizia, Sekhri Neha, Van de Heyning Caroline M, Broeckx Glenn, Peretto Giovanni, Guttmann Oliver, Dellegrottaglie Santo, Scatteia Alessandra, Gentile Piero, Merlo Marco, Goldberg Randal I, Reyentovich Alex, Sciamanna Christopher, Klaassen Sabine, Poller Wolfgang, Trankle Cory R, Abbate Antonio, Keren Andre, Horowitz-Cederboim Smadar, Cadrin-Tourigny Julia, Tadros Rafik, Annoni Giuseppe A, Bonoldi Emanuela, Toquet Claire, Marteau Lara, Probst Vincent, Trochu Jean Noël, Kissopoulou Antheia, Grosu Aurelia, Kukavica Deni, Trancuccio Alessandro, Gil Cristina, Tini Giacomo, Pedrazzini Matteo, Torchio Margherita, Sinagra Gianfranco, Gimeno Juan Ramón, Bernasconi Davide, Valsecchi Maria Grazia, Klingel Karin, Adler Eric D, Camici Paolo G, Cooper Leslie T
  
  Abstract
  
  BACKGROUND:
  The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown.
  
  OBJECTIVES:
  The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV.
  
  METHODS:
  In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up.
  
  RESULTS:
  In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM.
  
  CONCLUSIONS:
  Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.
  
  Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Recovery from mRNA COVID-19 vaccine-related myocarditis.
  Lancet Child Adolesc Health

  2022 Nov;6(11):749-751. doi: 10.1016/S2352-4642(22)00272-3.
  
  Ammirati Enrico, Cooper Leslie T
  
  
  
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• Cardiac magnetic resonance abnormalities in patients with acute myocarditis proven by septal endomyocardial biopsy.
  Clin Res Cardiol

  2023 Mar;112(3):392-400. doi: 10.1007/s00392-022-02103-1.
  
  Peretto Giovanni, Merlo Marco, Gentile Piero, Porcari Aldostefano, Palmisano Anna, Vignale Davide, Sormani Paola, Rizzo Stefania, De Gaspari Monica, Basso Cristina, Bella Paolo Della, Sala Simone, Ammirati Enrico, Sinagra Gianfranco, Esposito Antonio, Pedrotti Patrizia
  
  Abstract
  
  BACKGROUND:
  Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB).
  
  METHODS:
  From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM.
  
  RESULTS:
  Among 74 patients [mean age 38?±?15 years, 65% males, left ventricular ejection fraction (LVEF) 40?±?18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p?0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p?=?0.006).
  
  CONCLUSION:
  In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.
  
  © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
  
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• A case of parvovirus B19-associated fulminant myocarditis in an infant successfully treated with immunosuppressive therapy.
  J Cardiovasc Med (Hagerstown)

  2022 Oct;23(10):697-699. doi: 10.2459/JCM.0000000000001358.
  
  Veronese Giacomo, Nonini Sandra, Bottiroli Maurizio, Annoni Giuseppe, Izzo Francesca, Nespoli Luisa F, Corato Alessandra, Marianeschi Stefano M, Aresta Francesca, Bramerio Manuela A, Mondino Michele, Ammirati Enrico
  
  
  
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• A heart of iron: juvenile haemochromatosis presents with cardiac failure.
  Lancet

  2022 Aug;400(10352):616. doi: 10.1016/S0140-6736(22)01285-5.
  
  Cartella Iside, Tavecchia Giovanni A, Quattrocchi Giuseppina, Giannattasio Cristina, Volpato Elisabetta, Palazzini Matteo, Garascia Andrea, Cipriani Manlio, Frigerio Maria, Ammirati Enrico, Pedrotti Patrizia
  
  
  
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• Enterovirus fulminant myocarditis as cause of acute heart failure in a newborn.
  Int J Cardiol Heart Vasc

  2022 Oct;42():101093. doi: 101093.
  
  Annoni Giuseppe, De Rienzo Francesca, Nonini Sandra, Pugni Lorenza, Marianeschi Stefano M, Mauri Luigi, Gatelli Italo, Mauri Lucia, Aresta Francesca, Bramerio Manuela, Francescato Gaia, Carro Cristina, Picciolli Irene, Nava Alice, Fanti Diana, Galli Cristina, Mosca Fabio, Martinelli Stefano, Ammirati Enrico
  
  
  
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• Systemic leak capillary syndrome with myocardial involvement and cardiogenic shock: a case report.
  Eur Heart J Case Rep

  2022 Jul;6(7):ytac262. doi: ytac262.
  
  Garatti Laura, Wu Maddalena Alessandra, Ammirati Enrico, Sacco Alice
  
  Abstract
  
  BACKGROUND:
  Systemic capillary leak syndrome (SCLS) is a potentially fatal disorder characterized by relapses of hypovolemic shock episodes.
  
  CASE SUMMARY:
  We present a case of a 58-year-old man who presented to the Emergency Department with a history of recurrent episodes of syncope in the last hours. A few days before medical contact the patient complained of sore throat, fever, and flu-like symptoms. He was initially admitted with a diagnosis of suspected myopericarditis. Forty-eight hours later, the haemodynamic status suddenly deteriorated to a mixed cardiogenic and shock; an endomyocardial biopsy showed localized inflammatory infiltrates and areas of necrosis of cardiomyocytes with positive viral search for parvovirus B19 (PVB19), therefore the patient was treated with methylprednisolone pulses. Based on the concurrent presence of the typical triad of hypotension, hypoalbuminaemia, and haemoconcentration we suspected systemic leak capillary syndrome potentially triggered by the PVB19 infection with acute myocarditis. The clinical conditions further deteriorated with rhabdomyolysis and acute kidney injury: we started continuous veno-venous haemofiltration adding a cytokines adsorber. In the following hours, we observed a significant clinical improvement. The patient was discharged 1 month later and 5 months after discharge he experienced a new attack of SCLS, this time without myocardial involvement and with prompt symptoms resolution.
  
  CONCLUSION:
  Systemic capillary leak syndrome is a potentially fatal disorder: early recognition of this entity and prompt initiation of supportive therapy are warranted, therefore, it is paramount that an emergency physician thinks of SCLS in patients with signs of cardiogenic shock and the classical triad of hypotension, hypoalbuminia, and haemoconcentration.
  
  © The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.
  
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• [Attilio Maseri: a gentleman of the Italian cardiology. Maseri commemoration at the 53rd ANMCO National Congress].
  G Ital Cardiol (Rome)

  2022 May;23(5):396. doi: 10.1714/3796.37819.
  
  Gulizia Michele, Colivicchi Furio, Ammirati Enrico
  
  
  
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• [ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device].
  G Ital Cardiol (Rome)

  2022 May;23(5):340-378. doi: 10.1714/3796.37817.
  
  Iacoviello Massimo, Cipriani Manlio, Valente Serafina, Marini Marco, Ammirati Enrico, Benvenuto Manuela, Cassaniti Leonarda Rosaria, De Maria Renata, Gori Mauro, Municinò Annamaria, Navazio Alessandro, Amodeo Vincenzo, Aspromonte Nadia, Barili Fabio, Casolo Giancarlo, Clemenza Francesco, Di Eusanio Marco, Di Lenarda Andrea, Di Tano Giuseppe, Domenicucci Stefano, Faggian Giuseppe, Francese Giuseppina Maura, Frongillo Doriana, Gilardi Rossella, Iacovoni Attilio, Imazio Massimo, Livi Ugolino, Maiello Ciro, Milano Aldo, Mondino Michele, Moreo Antonella Maurizia, Mortara Andrea, Murrone Adriano, Palmieri Vittorio, Pelenghi Stefano, Pini Daniela, Pistono Massimo, Porcu Maurizio, Potena Luciano, Rinaldi Mauro, Romanò Massimo, Roncon Loris, Rossini Roberta, Russo Claudio Francesco, Scotto di Uccio Fortunato, Urbinati Stefano, Zecchin Massimo, Caldarola Pasquale, Oliveti Alessandra, Frigerio Maria, Musumeci Francesco, Gulizia Michele Massimo, Oliva Fabrizio, Gabrielli Domenico, Colivicchi Furio
  
  Abstract
  
  Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.
  
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• Temporal trends in characteristics, treatment, and outcomes of heart failure in octogenarians over two decades.
  Rev Esp Cardiol (Engl Ed)

  2022 May;():. doi: S1885-5857(22)00061-5.
  
  De Maria Renata, Gori Mauro, Marini Marco, Gonzini Lucio, Benvenuto Manuela, Cassaniti Leonarda, Municinò Annamaria, Navazio Alessandro, Ammirati Enrico, Leonardi Giuseppe, Pagnoni Nicoletta, Montagna Laura, Catalano Mariarosaria, Midi Paolo, Marina Floresta Agata, Pulignano Giovanni, Iacoviello Massimo,
  
  Abstract
  
  INTRODUCTION AND OBJECTIVES:
  Octogenarians represent the most rapidly expanding population segment in Europe. The prevalence of heart failure (HF) in this group exceeds 10%. We assessed changes in clinical characteristics, therapy, and 1-year outcomes over 2 decades in chronic HF outpatients aged ? 80 years enrolled in a nationwide cardiology registry.
  
  METHODS:
  We included 2520 octogenarians with baseline echocardiographic ejection fraction measurements and available 1-year follow-up, who were recruited at 138 HF outpatient clinics (21% of national hospitals with cardiology units), across 3 enrolment periods (1999-2005, 2006-2011, 2012-2018).
  
  RESULTS:
  At recruitment, over the 3 study periods, there was an increase in age, body mass index, ejection fraction, the prevalence of obesity, diabetes, dyslipidemia, pre-existing hypertension, and atrial fibrillation history. The proportion of patients with preserved ejection fraction rose from 19.4% to 32.7% (P for trend <.0001 markers of advanced disease became less prevalent. prescription beta-blockers and mineralocorticoid receptor antagonists increased over time. during the follow-up patients died were admitted for cardiovascular causes overall met combined primary endpoint all-cause mortality or hospitalization. on adjusted multivariable analysis enrolment in to p=".004)" carried a lower risk outcome than recruitment>
  CONCLUSIONS:
  Among octogenarians, over 2 decades, risk factor prevalence increased, management strategies improved, and survival remained stable, but the proportion hospitalized for cardiovascular causes declined. Despite increasing clinical complexity, in cardiology settings the burden of hospitalizations in the oldest old with chronic HF is declining.
  
  Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
  
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• Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.
  Circulation

  2022 Apr;145(15):1123-1139. doi: 10.1161/CIRCULATIONAHA.121.056817.
  
  Ammirati Enrico, Lupi Laura, Palazzini Matteo, Hendren Nicholas S, Grodin Justin L, Cannistraci Carlo V, Schmidt Matthieu, Hekimian Guillaume, Peretto Giovanni, Bochaton Thomas, Hayek Ahmad, Piriou Nicolas, Leonardi Sergio, Guida Stefania, Turco Annalisa, Sala Simone, Uribarri Aitor, Van de Heyning Caroline M, Mapelli Massimo, Campodonico Jeness, Pedrotti Patrizia, Barrionuevo Sánchez Maria Isabel, Ariza Sole Albert, Marini Marco, Matassini Maria Vittoria, Vourc'h Mickael, Cannatà Antonio, Bromage Daniel I, Briguglia Daniele, Salamanca Jorge, Diez-Villanueva Pablo, Lehtonen Jukka, Huang Florent, Russel Stéphanie, Soriano Francesco, Turrini Fabrizio, Cipriani Manlio, Bramerio Manuela, Di Pasquale Mattia, Grosu Aurelia, Senni Michele, Farina Davide, Agostoni Piergiuseppe, Rizzo Stefania, De Gaspari Monica, Marzo Francesca, Duran Jason M, Adler Eric D, Giannattasio Cristina, Basso Cristina, McDonagh Theresa, Kerneis Mathieu, Combes Alain, Camici Paolo G, de Lemos James A, Metra Marco
  
  Abstract
  
  BACKGROUND:
  Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe.
  
  METHODS:
  A total of 112 patients with suspected AM from 56?963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM.
  
  RESULTS:
  AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47;
  CONCLUSIONS:
  AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.
  
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• Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis.
  Front Med (Lausanne)

  2022 ;9():838564. doi: 838564.
  
  Ammirati Enrico, Bizzi Emanuele, Veronese Giacomo, Groh Matthieu, Van de Heyning Caroline M, Lehtonen Jukka, Pineton de Chambrun Marc, Cereda Alberto, Picchi Chiara, Trotta Lucia, Moslehi Javid J, Brucato Antonio
  
  Abstract
  
  The field of inflammatory disease of the heart or "cardio-immunology" is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.
  
  Copyright © 2022 Ammirati, Bizzi, Veronese, Groh, Van de Heyning, Lehtonen, Pineton de Chambrun, Cereda, Picchi, Trotta, Moslehi and Brucato.
  
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• Takotsubo syndrome after BNT162b2 mRNA Covid-19 vaccine: Emotional or causative relationship with vaccination?
  Int J Cardiol Heart Vasc

  2022 Jun;40():101002. doi: 101002.
  
  Tedeschi Andrea, Camilli Massimiliano, Ianni Umberto, Tavecchia Giovanni, Palazzini Matteo, Cartella Iside, Gentile Piero, Quattrocchi Giuseppina, Maria Spanò Francesca, Cipriani Manlio, Garascia Andrea, Ammirati Enrico
  
  
  
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• Urethral Bulking in the Treatment of Stress and Mixed Female Urinary Incontinence: Results from a Multicenter Cohort and Predictors of Clinical Outcomes.
  J Clin Med

  2022 Mar;11(6):. doi: 1569.
  
  Giammò Alessandro, Geretto Paolo, Ammirati Enrico, Manassero Alberto, Squintone Luisella, Falcone Marco, Costantini Elisabetta, Del Popolo Giulio, Finazzi Agrò Enrico, Giannantoni Antonella, Li Marzi Vincenzo, Mancini Vito, Musco Stefania, Pastorello Mauro, Pistolesi Donatella, Risi Oreste, Gontero Paolo
  
  Abstract
  
  The aim of the present study is to analyze the outcomes of urethral bulking in the treatment of non-neurogenic female stress and mixed urinary incontinence and to assess predictors of clinical outcomes. We retrospectively included all consecutive patients affected by stress or mixed urinary incontinence and treated with urethral bulking. Outcomes were evaluated via the PGI-I questionnaire and the 24-h pad test. Between January 2010 and January 2020, we treated 216 patients (Bulkamid n = 206; Macro-plastique n = 10). The median age at surgery was 66 years (IQR 55?73.75). The median follow-up was 12 months (IQR 12?24). In total, 23.8% of patients were subjected to prior incontinence surgery, 63.8% of patients were affected by genuine stress urinary incontinence, 36.2% reported mixed urinary incontinence, whereas detrusor overactivity was confirmed in only 24.9%. The dry rate was 32.9%; nevertheless, 69.9% of patients declared themselves ?very improved? or ?improved? (PGI-I1-2). Low complications were observed, mostly classified as Clavien I. After univariate and multivariate analyses, the only statistically significant independent predictor of ?dry? outcome was the 24 h pad test, p
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• Fulminant myocarditis in adults: a narrative review.
  J Geriatr Cardiol

  2022 Feb;19(2):137-151. doi: 10.11909/j.issn.1671-5411.2022.02.006.
  
  Montero Santiago, Abrams Darryl, Ammirati Enrico, Huang Florent, Donker Dirk W, Hekimian Guillaume, García-García Cosme, Bayes-Genis Antoni, Combes Alain, Schmidt Matthieu
  
  Abstract
  
  Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe hemodynamic compromise secondary to acute myocardial inflammation, often presenting as profound cardiogenic shock, life-threatening ventricular arrhythmias and/or electrical storm. FM may be refractory to conventional therapies and require mechanical circulatory support (MCS). The immune system has been recognized as playing a pivotal role in the pathophysiology of myocarditis, leading to an increased focus on immunosuppressive treatment strategies. Recent data have highlighted not only the fact that FM has significantly worse outcomes than non-FM, but that prognosis and management strategies of FM are heavily dependent on histological subtype, placing greater emphasis on the role of endomyocardial biopsy in diagnosis. The impact of subtype on severity and prognosis will likewise influence how aggressively the myocarditis is managed, including whether MCS is warranted. Many patients with refractory cardiogenic shock secondary to FM end up requiring MCS, with venoarterial extracorporeal membrane oxygenation demonstrating favorable survival rates, particularly when initiated prior to the development of multiorgan failure. Among the challenges facing the field are the need to more precisely identify immunopathophysiological pathways in order to develop targeted therapies, and the need to better optimize the timing and management of MCS to minimize complications and maximize outcomes.
  
  Copyright and License information: Journal of Geriatric Cardiology 2022.
  
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• 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee.
  J Am Coll Cardiol

  2022 May;79(17):1717-1756. doi: 10.1016/j.jacc.2022.02.003.
  
  , Gluckman Ty J, Bhave Nicole M, Allen Larry A, Chung Eugene H, Spatz Erica S, Ammirati Enrico, Baggish Aaron L, Bozkurt Biykem, Cornwell William K, Harmon Kimberly G, Kim Jonathan H, Lala Anuradha, Levine Benjamin D, Martinez Matthew W, Onuma Oyere, Phelan Dermot, Puntmann Valentina O, Rajpal Saurabh, Taub Pam R, Verma Amanda K
  
  
  
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• State-of-the-Art of Endomyocardial Biopsy on Acute Myocarditis and Chronic Inflammatory Cardiomyopathy.
  Curr Cardiol Rep

  2022 May;24(5):597-609. doi: 10.1007/s11886-022-01680-x.
  
  Ammirati Enrico, Buono Andrea, Moroni Francesco, Gigli Lorenzo, Power John R, Ciabatti Michele, Garascia Andrea, Adler Eric D, Pieroni Maurizio
  
  Abstract
  
  PURPOSE OF REVIEW:
  Histologic evidence of myocardial inflammatory infiltrate not secondary to an ischemic injury is required by current diagnostic criteria to reach a definite diagnosis of myocarditis. Endomyocardial biopsy (EMB) is therefore often indicated for the diagnosis of myocarditis, although it may lack sufficient sensitivity considering the limited possibility of myocardial sampling. Improving the diagnostic yield and utility of EMB is of high priority in the fields of heart failure cardiology and myocarditis in particular. The aim of the present review is to highlight indications, strengths, and shortcomings of current EMB techniques, and discuss innovations currently being tested in ongoing clinical studies, especially in the setting of acute myocarditis and chronic inflammatory cardiomyopathy.
  
  RECENT FINDINGS:
  EMB provides unique diagnostic elements and prognostic information which can effectively guide the treatment of myocarditis. Issues affecting the diagnostic performance in the setting of acute myocarditis and chronic inflammatory cardiomyopathies will be discussed in this review in the light of recent expert consensus documents on the management of these conditions and on indication to EMB. Recent innovations using electroanatomic mapping (EAM)-guided EMB and fluoroscopic-guided EMB during temporary mechanical circulatory support have improved the utility of the procedure. EMB remains an important diagnostic test whose results need to be interpreted in the context of (1) clinical pre-test probability, (2) timing of sampling, (3) quality of sampling (4) site of sampling, (5) histologic type of myocarditis, and (6) analytic methods that are applied. Herein we will review these caveats as well as perspectives and innovations related to the use of this diagnostic tool.
  
  © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
  
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• Haemodynamic effects of sacubitril/valsartan in advanced heart failure.
  ESC Heart Fail

  2022 Apr;9(2):894-904. doi: 10.1002/ehf2.13755.
  
  Gentile Piero, Cantone Rosaria, Perna Enrico, Ammirati Enrico, Varrenti Marisa, D'Angelo Luciana, Verde Alessandro, Foti Grazia, Masciocco Gabriella, Garascia Andrea, Frigerio Maria, Cipriani Manlio
  
  Abstract
  
  AIMS:
  The angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, has been shown to be effective in treatment of patients with heart failure (HF), but limited data are available in patients with advanced disease. This retrospective observational study assessed the effects of ARNI treatment in patients with advanced HF.
  
  METHODS AND RESULTS:
  We reviewed medical records of all advanced HF patients evaluated at our centre for unconventional therapies from September 2016 to January 2019. We studied 44 patients who started ARNI therapy and who had a haemodynamic assessment before beginning ARNI and after 6 ± 2 months. The primary endpoint was variation in pulmonary pressures and filling pressures at 6 months after starting ARNI therapy. Mean patient age was 51.6 ± 7.4 years; 84% were male. At 6 ± 2 months after starting ARNI, there was significant reduction of systolic pulmonary artery pressure [32 mmHg, interquartile range (IQR) 27-45 vs. 25 mmHg, IQR 22.3-36.5; P 
  CONCLUSIONS:
  Sacubitril/valsartan is effective in reducing filling pressures and pulmonary pressures in patients with advanced HF. The absence of adverse events during follow-up suggests that sacubitril/valsartan is safe and well-tolerated in this cohort of patients.
  
  © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database.
  Nat Commun

  2022 Jan;13(1):25. doi: 25.
  
  Nguyen Lee S, Cooper Leslie T, Kerneis Mathieu, Funck-Brentano Christian, Silvain Johanne, Brechot Nicolas, Hekimian Guillaume, Ammirati Enrico, Ben M'Barek Badr, Redheuil Alban, Gandjbakhch Estelle, Bihan Kevin, Lebrun-Vignes Bénédicte, Ederhy Stephane, Dolladille Charles, Moslehi Javid J, Salem Joe-Elie
  
  Abstract
  
  While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n?=?3108 reports), salicylates (n?=?340), antineoplastic-cytotoxics (n?=?190), antineoplastic-immunotherapies (n?=?538), and vaccines (n?=?790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n?=?3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.
  
  © 2022. The Author(s).
  
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• Management of complex ischial-urethral fistula in neurogenic patients performing clean intermittent self-catheterization.
  Urologia

  2021 Dec;():3915603211062414. doi: 10.1177/03915603211062414.
  
  Ammirati Enrico, Geretto Paolo, Giammò Alessandro, Falcone Marco, Gontero Paolo, Manassero Alberto
  
  Abstract
  
  INTRODUCTION:
  Neurogenic patients performing clean-intermittent self-catheterization (CIC) may develop an urethral erosion, resulting in ischial-urethral fistulas (I-UF). In this work we present our single-center experience in dealing with this peculiar complication.
  
  METHODS:
  In this work we included all neurogenic patients performing CIC treated at out Institution for I-UF. All patients had a spinal cord injury or myelomeningocele. We extracted from the patients' medical records the surgical management and postoperative clinical data. We defined failure the persistence of the fistula at X-ray contrast fistulography, retrograde urethrography, or uretrocystoscopy.
  
  RESULTS:
  We treated 11 patients (8 spinal cord injury, 3 myelomeningocele). Four patients have been treated with the placement of a new generation urethral stent (Uventa) after surgical toilette of the skin ulcer and placement of a temporary suprapubic catheter. All patients demonstrated a complete healing of the urethral lesion at stent removal and continued CIC without any difficulty. Four patients have been treated with perineal urethroplasty, requiring a buccal mucosal graft in two cases. In two patients a suprapubic permanent catheter was placed for a simpler bladder management due to the patients' comorbidities. In one case the incidental finding of an high grade muscle invasive urothelial bladder cancer, made it mandatory to perform an uretheroileocutaneostomy.
  
  CONCLUSIONS:
  This work represent a unique series of I-UF in neurogenic patients performing CIC. Surgical urethral reconstruction, often with the use of buccal mucosa in large lesions, may be a difficult solution in neurogenic patients, new generation stents (Uventa) represent a minimally invasive, effective, and safe alternative.
  
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• Age-related changes in clinical characteristics and outcomes of chronic heart failure outpatients in a cardiology setting. A report from the Italian Network on Heart Failure.
  Int J Cardiol

  2022 Jan;346():36-44. doi: 10.1016/j.ijcard.2021.11.014.
  
  Gori Mauro, Marini Marco, De Maria Renata, Gonzini Lucio, Gorini Marco, Cassaniti Leonarda, Benvenuto Manuela, Municinò Annamaria, Navazio Alessandro, Ammirati Enrico, Leonardi Giuseppe, Pagnoni Nicoletta, Montagna Laura, Catalano Mariarosaria, Midi Paolo, Floresta Agata Marina, Pulignano Giovanni, Maggioni Aldo P, Tavazzi Luigi, Iacoviello Massimo,
  
  Abstract
  
  AIMS:
  Ageing and comorbidities are increasing frailty/complexity of heart failure (HF) patients globally. We assessed evolving trends over two decades according to patients' age and time of recruitment in a nationwide cardiology setting in Italy.
  
  METHODS AND RESULTS:
  Chronic HF outpatients recruited between 1999 and 2018 (N = 14,823) were divided into 3 cohorts: 1999-2005 (N = 5404); 2006-2011 (N = 3971); 2012-2018 (N = 5448). We analyzed temporal changes in clinical characteristics, therapies, and outcome (1-year all-cause mortality/cardiovascular hospitalization), overall and by age group:
  CONCLUSIONS:
  Over two decades in a cardiology outpatient setting, the prevalence of comorbid HFpEF increased in all age categories. Mortality improved among patients
  Copyright © 2021 Elsevier B.V. All rights reserved.
  
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• Single-case metanalysis of fat embolism syndrome.
  Int J Cardiol

  2021 Dec;345():111-117. doi: 10.1016/j.ijcard.2021.10.151.
  
  He Zuowen, Shi Zeqi, Li Chenze, Ni Li, Sun Yang, Arioli Francesco, Wang Yan, Ammirati Enrico, Wang Dao Wen
  
  Abstract
  
  BACKGROUND:
  Only one large series has been reported on fat embolism syndrome (FES), a condition caused by fat globules release into the circulation, primarily as consequence of bone fracture. Thus, more data on clinical features, therapies, and prognosis are needed.
  
  METHODS AND RESULTS:
  The study screened 1090 manuscripts in PubMed and Web of Science on cases of FES published from June 2010 to June 2020. The authors identified 124 studies and included in the pooled-analysis 135 patients (>14 years), plus one additional unpublished case managed in Tongji hospital. All had confirmed diagnosis of FES with complete clinical data. The median age at presentation was 39 years, and 82 (61.8%) were men. FES was predominantly associated with bone fractures (78, 57.4%), particularly femur fracture (59, 43.4%). The most common clinical finding at the onset was respiratory abnormalities in 34.6% of all clinical presentations. Therapies included respiratory supportive care in 127 (93.4%) patients, application of corticosteroids in 22 (16.2%) and anticoagulant in 5 (3.7%) cases. Overall mortality was 30.2% (N = 41), and logistic regression analysis showed that corticosteroid therapy was significantly associated with reduced mortality with an OR of 0.143 (95%CI 0.029-0.711), while age ? 65 years and non-orthopedic conditions were significantly associated with increased mortality with an OR of 4.816 (95%CI 1.638-14.160) and 4.785 (95%CI 1.019-22.474).
  
  CONCLUSIONS:
  FES has been associated with a larger mortality rate than previously observed, although publication bias can have led to overestimation of mortality. Finally, a potential protective effect of corticosteroid therapy has been suggested by the current analysis.
  
  Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
  
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• Impact of mechanical circulatory support and immunomodulation therapy on outcome of patients with fulminant myocarditis: Chinese registry of fulminant myocarditis.
  Signal Transduct Target Ther

  2021 Oct;6(1):350. doi: 350.
  
  Zhou Ning, Zhao Yuhua, Jiang Jiangang, Shen Lan, Li Junming, Wan Jing, Ma Xueping, Zhang Jing, Ammirati Enrico, Wang Dao Wen
  
  
  
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• PD-L1 (Programmed Death Ligand 1) as a Marker of Acute Cellular Rejection After Heart Transplantation.
  Circ Heart Fail

  2021 Oct;14(10):e008563. doi: 10.1161/CIRCHEARTFAILURE.121.008563.
  
  Choudhary Arrush, Brinkley D Marshall, Besharati Sepideh, Meijers Wouter C, Atkinson James B, Amancherla Kaushik, Zhu Qingfeng, Huang Shi, Nguyen Lee S, Salem Joe-Elie, Ammirati Enrico, Lindenfeld JoAnn, Anders Robert A, Moslehi Javid
  
  
  
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• Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.
  Int J Cardiol

  2021 Oct;340():26-33. doi: 10.1016/j.ijcard.2021.08.033.
  
  Darden Douglas, Ammirati Enrico, Brambatti Michela, Lin Andrew, Hsu Jonathan C, Shah Palak, Perna Enrico, Cikes Maja, Gjesdal Grunde, Potena Luciano, Masetti Marco, Jakus Nina, Van De Heyning Caroline, De Bock Dina, Brugts Jasper J, Russo Claudio F, Veenis Jesse F, Rega Filip, Cipriani Manlio, Frigerio Maria, Liviu Klein, Hong Kimberly N, Adler Eric, Braun Oscar Ö
  
  Abstract
  
  BACKGROUND:
  There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs.
  
  METHODS:
  Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111).
  
  RESULTS:
  A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D.
  
  CONCLUSION:
  In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV?lead pacing post LVAD implantation.
  
  Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
  
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• Cardiovascular injuries and SARS-COV-2 infection: focus on elderly people.
  J Geriatr Cardiol

  2021 Jul;18(7):534-548. doi: 10.11909/j.issn.1671-5411.2021.07.001.
  
  Colombo Claudia, Garatti Laura, Ferrante Giulia, Casadei Francesca, Montalto Claudio, Crimi Gabriele, Cogliati Chiara, Ammirati Enrico, Savonitto Stefano, Morici Nuccia
  
  Abstract
  
  The novel coronavirus disease (COVID-19) has hit the healthcare system worldwide. The risk of severe infection and mortality increases with advancing age, especially in subjects with comorbidities such as cardiovascular disease, hypertension, diabetes, obesity and cancer. Moreover, cardiovascular complications such as myocardial injury, heart failure and thromboembolism are frequently observed in COVID-19 cases, and several biomarkers (troponin, NTproBNP and D-Dimer) have been identified as prognostic indicators of disease severity and worst outcome. Currently, there is no specific therapy against SARS-CoV-2, although many medications are under investigation. The aim of this review will be to explore the intertwined relationship between COVID-19 disease and the cardiovascular system, focusing on elderly population. The available supportive treatments along with the related concerns in elderly patients, due to their comorbidities and polypharmacotherapy, will be explored.
  
  Copyright and License information: Journal of Geriatric Cardiology 2021.
  
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• Biventricular Intravascular Microaxial Blood Pumps and Immunosuppression as a Bridge to Recovery in Giant Cell Myocarditis.
  JACC Case Rep

  2020 Aug;2(10):1484-1488. doi: 10.1016/j.jaccas.2020.05.107.
  
  Ma Janet I, Ammirati Enrico, Brambatti Michela, Adler Eric
  
  Abstract
  
  We report a case of giant cell myocarditis in a 76-year-old patient managed with combined immunosuppression and biventricular intravascular microaxial blood pumps. This case highlights a feasible approach for managing such patients who are not candidates for transplantation or durable ventricular assist devices. ().
  
  © 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.
  
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• Post-discharge arrhythmic risk stratification of patients with acute myocarditis and life-threatening ventricular tachyarrhythmias.
  Eur J Heart Fail

  2021 Dec;23(12):2045-2054. doi: 10.1002/ejhf.2288.
  
  Gentile Piero, Merlo Marco, Peretto Giovanni, Ammirati Enrico, Sala Simone, Della Bella Paolo, Aquaro Giovanni Donato, Imazio Massimo, Potena Luciano, Campodonico Jeness, Foà Alberto, Raafs Anne, Hazebroek Mark, Brambatti Michela, Cercek Andreja Cerne, Nucifora Gaetano, Shrivastava Sanskriti, Huang Florent, Schmidt Matthieu, Muser Daniele, Van de Heyning Caroline M, Van Craenenbroeck Emeline, Aoki Tatsuo, Sugimura Koichiro, Shimokawa Hiroaki, Cannatà Antonio, Artico Jessica, Porcari Aldostefano, Colopi Marzia, Perkan Andrea, Bussani Rossana, Barbati Giulia, Garascia Andrea, Cipriani Manlio, Agostoni Piergiuseppe, Pereira Naveen, Heymans Stephane, Adler Eric D, Camici Paolo Guido, Frigerio Maria, Sinagra Gianfranco
  
  Abstract
  
  AIMS:
  The outcomes of patients presenting with acute myocarditis and life-threatening ventricular arrhythmias (LT-VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population.
  
  METHODS AND RESULTS:
  We retrospectively analysed 156 patients (median age 44?years; 77% male) discharged with a diagnosis of acute myocarditis and LT-VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death or successfully defibrillated ventricular fibrillation, or sustained ventricular tachycardia (sVT) requiring implantable cardioverter-defibrillator therapy or synchronized external cardioversion. Median follow-up was 23?months [first to third quartile (Q1-Q3) 7-60]. Fifty-eight (37.2%) patients experienced MAEs after discharge, at a median of 8 months (Q1-Q3 2.5-24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated with MAEs were presentation with sVT [hazard ratio (HR) 2.90, 95% confidence interval (CI) 1.38-6.11]; late gadolinium enhancement involving ?2 myocardial segments (HR 4.51, 95% CI 2.39-8.53), and absence of positive short-tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40-4.79) at first CMR.
  
  CONCLUSIONS:
  Among patients discharged with a diagnosis of myocarditis and LT-VA, 37.2% had recurrences of MAEs during follow-up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmia recurrence.
  
  © 2021 European Society of Cardiology.
  
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• Long-term administration of intravenous inotropes in advanced heart failure.
  ESC Heart Fail

  2021 Oct;8(5):4322-4327. doi: 10.1002/ehf2.13394.
  
  Gentile Piero, Marini Claudia, Ammirati Enrico, Perna Enrico, Saponara Gianluigi, Garascia Andrea, D'Angelo Luciana, Verde Alessandro, Foti Grazia, Masciocco Gabriella, Frigerio Maria, Cipriani Manlio
  
  Abstract
  
  BACKGROUND:
  Patients in heart transplantation (HTx) waiting list for advanced heart failure (HF) are susceptible to acute deterioration refractory to standard HF medical therapies. Limited data are available on long-term in-hospital continuous intravenous (IV) inotropic therapy as bridge to definite therapies.
  
  METHODS AND RESULTS:
  We reviewed medical records of all heart transplant recipients treated in the pre-HTx phase with in-hospital continuous IV inotropes at our institution between 2012 and 2018. We analysed data before the beginning of continuous IV therapy and at the moment of HTx. We report data of 24 patients (mean age of 43.5 ± 15.7 years) treated with IV inotropes as bridge to HTx (median follow-up of 28 months after HTx). The main length of IV inotropic therapy was 84 ± 66 days (min 22; max 264 days). At the beginning, the most frequently used inotrope was dopamine (median dosage of 3 mcg/kg/min, interquartile range 2.5-3.75), alone (n = 11, 46%) or in combination with other inotropes (n = 13, 54%). In 18 patients, the class of inotropes was changed during the hospitalization. We registered a progressive improvement of perfusion markers and neuro-hormonal activation.
  
  CONCLUSION:
  In-hospital continuous parenteral inotropic therapy may serve as a temporary pharmacological bridge to HTx in patients with advanced HF that are actively listed to HTx with good reply in terms of prognosis and perfusion markers.
  
  © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• Myocarditis After BNT162b2 and mRNA-1273 Vaccination.
  Circulation

  2021 Aug;144(6):506-508. doi: 10.1161/CIRCULATIONAHA.121.055913.
  
  Larson Kathryn F, Ammirati Enrico, Adler Eric D, Cooper Leslie T, Hong Kimberly N, Saponara Gianluigi, Couri Daniel, Cereda Alberto, Procopio Antonio, Cavalotti Cristina, Oliva Fabrizio, Sanna Tommaso, Ciconte Vincenzo Antonio, Onyango George, Holmes David R, Borgeson Daniel D
  
  Abstract
  
  Supplemental Digital Content is available in the text.
  
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• Overcoming the low yield of histology for the diagnosis of cardiac sarcoidosis.
  Int J Cardiol

  2021 Aug;337():86-87. doi: 10.1016/j.ijcard.2021.06.004.
  
  Ammirati Enrico, Camici Paolo G, Lehtonen Jukka
  
  
  
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• Prevalence and outcome of patients with acute myocarditis and positive viral search on nasopharyngeal swab.
  Eur J Heart Fail

  2021 Jul;23(7):1242-1245. doi: 10.1002/ejhf.2247.
  
  Ammirati Enrico, Varrenti Marisa, Veronese Giacomo, Fanti Diana, Nava Alice, Cipriani Manlio, Pedrotti Patrizia, Garascia Andrea, Bottiroli Maurizio, Oliva Fabrizio, Bramerio Manuela, Veronese Silvio, Giannattasio Cristina, Bonoldi Emanuela, Perno Carlo F, Camici Paolo G, Frigerio Maria
  
  
  
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• Temporal Relation Between Second Dose BNT162b2 mRNA Covid-19 Vaccine and Cardiac involvement in a Patient with Previous SARS-COV-2 Infection.
  Int J Cardiol Heart Vasc

  2021 Apr;():100778. doi: 100778.
  
  Ammirati Enrico, Cavalotti Cristina, Milazzo Angela, Pedrotti Patrizia, Soriano Francesco, Schroeder Jan W, Morici Nuccia, Giannattasio Cristina, Frigerio Maria, Metra Marco, Camici Paolo G, Oliva Fabrizio
  
  Abstract
  
  The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.ijcha.2021.100774. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at
  
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• Temporal relation between second dose BNT162b2 mRNA Covid-19 vaccine and cardiac involvement in a patient with previous SARS-COV-2 infection.
  Int J Cardiol Heart Vasc

  2021 Jun;34():100774. doi: 100774.
  
  Ammirati Enrico, Cavalotti Cristina, Milazzo Angela, Pedrotti Patrizia, Soriano Francesco, Schroeder Jan W, Morici Nuccia, Giannattasio Cristina, Frigerio Maria, Metra Marco, Camici Paolo G, Oliva Fabrizio
  
  
  
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• miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.
  Am J Transplant

  2021 Oct;21(10):3280-3295. doi: 10.1111/ajt.16581.
  
  Usuelli Vera, Ben Nasr Moufida, D'Addio Francesca, Liu Kaifeng, Vergani Andrea, El Essawy Basset, Yang Jun, Assi Emma, Uehara Mayuko, Rossi Chiara, Solini Anna, Capobianco Annalisa, Rigamonti Elena, Potena Luciano, Venturini Massimo, Sabatino Mario, Bottarelli Lorena, Ammirati Enrico, Frigerio Maria, Castillo-Leon Eduardo, Maestroni Anna, Azzoni Cinzia, Loretelli Cristian, Joe Seelam Andy, Tai Albert K, Pastore Ida, Becchi Gabriella, Corradi Domenico, Visner Gary A, Zuccotti Gian V, Chau Nelson B, Abdi Reza, Pezzolesi Marcus G, Fiorina Paolo
  
  Abstract
  
  Despite much progress in improving graft outcome during cardiac transplantation, chronic allograft vasculopathy (CAV) remains an impediment to long-term graft survival. MicroRNAs (miRNAs) emerged as regulators of the immune response. Here, we aimed to examine the miRNA network involved in CAV. miRNA profiling of heart samples obtained from a murine model of CAV and from cardiac-transplanted patients with CAV demonstrated that miR-21 was most significantly expressed and was primarily localized to macrophages. Interestingly, macrophage depletion with clodronate did not significantly prolong allograft survival in mice, while conditional deletion of miR-21 in macrophages or the use of a specific miR-21 antagomir resulted in indefinite cardiac allograft survival and abrogated CAV. The immunophenotype, secretome, ability to phagocytose, migration, and antigen presentation of macrophages were unaffected by miR-21 targeting, while macrophage metabolism was reprogrammed, with a shift toward oxidative phosphorylation in naïve macrophages and with an inhibition of glycolysis in pro-inflammatory macrophages. The aforementioned effects resulted in an increase in M2-like macrophages, which could be reverted by the addition of L-arginine. RNA-seq analysis confirmed alterations in arginase-associated pathways associated with miR-21 antagonism. In conclusion, miR-21 is overexpressed in murine and human CAV, and its targeting delays CAV onset by reprogramming macrophages metabolism.
  
  © 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
  
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• A Novel Artificial Urinary Sphincter (VICTO®) for the Management of Postprostatectomy Urinary Incontinence: Description of the Surgical Technique and Preliminary Results from a Multicenter Series.
  Urol Int

  2021 ;105(5-6):414-420. doi: 10.1159/000512722.
  
  Giammò Alessandro, Falcone Marco, Blecher Gideon, Ammirati Enrico, Geretto Paolo, Manassero Alberto, Bottero Danilo, Lorusso Vito, Signorello Diego, Gontero Paolo, Carone Roberto
  
  Abstract
  
  AIMS:
  The objective of the study was to analyze short-term outcomes and safety profile of the newly designed artificial urinary sphincters (AUSs) VICTO® and VICTOplus®.
  
  METHODS:
  Data from the implant of VICTO® or VICTOplus® AUSs on a series of consecutive male patients with stress urinary incontinence (SUI) following radical prostatectomy (RP) were retrospectively collected in 3 tertiary referral centers between May 2017 and December 2019. Patients were affected by moderate-severe genuine SUI (200-400 or >400 g urine leakage in 24-h pad test) refractory to conservative treatment. Outcomes were evaluated through the 24-h pad test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Follow-up was scheduled after 3, 6, and 12 months and then when clinically needed. Nonparametric tests were applied in subgroup analyses.
  
  RESULTS:
  Seventeen patients were enrolled: 8 were implanted with the VICTO® device and 9 with VICTOplus®. The median age at surgery was 69 (interquartile range (IQR) 60-75) years. The median follow-up was 15 (IQR 12-18) months. At 12 months, the dry rate was 76.4% and the social continence rate was 94%. The postoperative complication rate was 17.6%. All complications were classified as Clavien-Dindo I. No difference in terms of outcomes was observed between the VICTO® and the VICTOplus® subgroups.
  
  CONCLUSIONS:
  Preliminary outcomes of the VICTO® and VICTOplus® implantation are satisfactory. These devices may represent a safe and realistic solution for patients with moderate-severe SUI following RP.
  
  © 2021 S. Karger AG, Basel.
  
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• Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.
  J Am Coll Cardiol

  2020 Dec;76(25):2982-3021. doi: 10.1016/j.jacc.2020.11.010.
  
  Roth Gregory A, Mensah George A, Johnson Catherine O, Addolorato Giovanni, Ammirati Enrico, Baddour Larry M, Barengo Noël C, Beaton Andrea Z, Benjamin Emelia J, Benziger Catherine P, Bonny Aimé, Brauer Michael, Brodmann Marianne, Cahill Thomas J, Carapetis Jonathan, Catapano Alberico L, Chugh Sumeet S, Cooper Leslie T, Coresh Josef, Criqui Michael, DeCleene Nicole, Eagle Kim A, Emmons-Bell Sophia, Feigin Valery L, Fernández-Solà Joaquim, Fowkes Gerry, Gakidou Emmanuela, Grundy Scott M, He Feng J, Howard George, Hu Frank, Inker Lesley, Karthikeyan Ganesan, Kassebaum Nicholas, Koroshetz Walter, Lavie Carl, Lloyd-Jones Donald, Lu Hong S, Mirijello Antonio, Temesgen Awoke Misganaw, Mokdad Ali, Moran Andrew E, Muntner Paul, Narula Jagat, Neal Bruce, Ntsekhe Mpiko, Moraes de Oliveira Glaucia, Otto Catherine, Owolabi Mayowa, Pratt Michael, Rajagopalan Sanjay, Reitsma Marissa, Ribeiro Antonio Luiz P, Rigotti Nancy, Rodgers Anthony, Sable Craig, Shakil Saate, Sliwa-Hahnle Karen, Stark Benjamin, Sundström Johan, Timpel Patrick, Tleyjeh Imad M, Valgimigli Marco, Vos Theo, Whelton Paul K, Yacoub Magdi, Zuhlke Liesl, Murray Christopher, Fuster Valentin,
  
  Abstract
  
  Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
  
  Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
  
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• Association of White Matter Hyperintensities and Cardiovascular Disease: The Importance of Microcirculatory Disease.
  Circ Cardiovasc Imaging

  2020 Aug;13(8):e010460. doi: 10.1161/CIRCIMAGING.120.010460.
  
  Moroni Francesco, Ammirati Enrico, Hainsworth Atticus H, Camici Paolo G
  
  Abstract
  
  Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue perfusion through an intricate network of penetrating small vessels. Both organs rely on fine tuning of local blood flow to match metabolic demand. Blood flow regulation requires adequate functioning of the microcirculation in both organs, with loss of microvascular function, termed small vessel disease (SVD) underlying different potential clinical manifestations. SVD in the heart, known as coronary microvascular dysfunction, can cause chronic or acute myocardial ischemia and may lead to development of heart failure. In the brain, cerebral SVD can cause an acute stroke syndrome known as lacunar stroke or more subtle pathological alterations of the brain parenchyma, which may eventually lead to neurological deficits or cognitive decline in the long term. Coronary microcirculation cannot be visualized in vivo in humans, and functional information can be deduced by measuring the coronary flow reserve. The diagnosis of cerebral SVD is largely based on brain magnetic resonance imaging, with white matter hyperintensities, microbleeds, and brain atrophy reflecting key structural changes. There is evidence that such structural changes reflect underlying cerebral SVD. Here, we review interactions between SVD and cardiovascular risk factors, and we discuss the evidence linking cerebral SVD with large vessel atheroma, atrial fibrillation, heart failure, and heart valve disease.
  
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• [ANMCO/SIC Consensus document on the management of myocarditis].
  G Ital Cardiol (Rome)

  2020 Dec;21(12):969-989. doi: 10.1714/3472.34551.
  
  Cipriani Manlio, Merlo Marco, Gabrielli Domenico, Ammirati Enrico, Autore Camillo, Basso Cristina, Caforio Alida, Caldarola Pasquale, Camici Paolo, Di Lenarda Andrea, Frustaci Andrea, Imazio Massimo, Oliva Fabrizio, Pedrotti Patrizia, Perazzolo Marra Martina, Rapezzi Claudio, Urbinati Stefano, Zecchin Massimo, Filardi Pasquale Perrone, Colivicchi Furio, Indolfi Ciro, Frigerio Maria, Sinagra Gianfranco
  
  Abstract
  
  Myocarditis is an inflammatory heart disease that can occur acutely, as in acute myocarditis, or persistently, as in chronic myocarditis or chronic inflammatory cardiomyopathy. Different agents can induce myocarditis, with viruses being the most common triggers. Generally, acute myocarditis affects relatively young people and men more than women. Myocarditis has a broad spectrum of clinical presentations and evolution trajectories, although most cases resolve spontaneously. Patients with reduced left ventricular ejection fraction, heart failure symptoms, advanced atrioventricular block, sustained ventricular arrhythmias or cardiogenic shock (the latter known as fulminant myocarditis) are at increased risk for death and heart transplantation. The presentation of chronic inflammatory cardiomyopathy may be more subtle, with progressive symptoms of heart failure or appearance of rhythm disturbance, not rarely preceded by an infective episode. Autoimmune disorder or systemic inflammatory conditions can be another significant predisposing substrate of myocarditis, especially in women. Emerging causes of myocarditis are drug-related like the new anticancer therapies, the immune checkpoint inhibitors. In this Italian Association of Hospital Cardiologists (ANMCO) and Italian Society of Cardiology (SIC) expert consensus document on myocarditis, we propose diagnostic strategies for identifying possible causes of the disease and factors associated with increased risk. Finally, we propose potential treatments and when referring patients to tertiary centers, especially for high-risk patients. Even if endomyocardial biopsy is the invasive diagnostic tool for making definitive diagnosis and differentiation of histological subtypes (i.e., lymphocytic vs eosinophilic vs giant cell myocarditis), it is not always readily available in all centers. Thus, we propose when this exam is mandatory or when it can be postponed or substituted by cardiac magnetic resonance imaging. This document reflects the Italian perspective on managing patients with myocarditis and their follow-up, considering also current US and European scientific position statements.
  
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• Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document.
  Circ Heart Fail

  2020 Nov;13(11):e007405. doi: 10.1161/CIRCHEARTFAILURE.120.007405.
  
  Ammirati Enrico, Frigerio Maria, Adler Eric D, Basso Cristina, Birnie David H, Brambatti Michela, Friedrich Matthias G, Klingel Karin, Lehtonen Jukka, Moslehi Javid J, Pedrotti Patrizia, Rimoldi Ornella E, Schultheiss Heinz-Peter, Tschöpe Carsten, Cooper Leslie T, Camici Paolo G
  
  Abstract
  
  Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally
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• Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis.
  Int J Cardiol

  2021 Feb;324():131-138. doi: 10.1016/j.ijcard.2020.10.063.
  
  Veronese Giacomo, Ammirati Enrico, Chen Chen, Klingel Karin, Suzuki Makoto, Okumura Takahiro, Maisch Bernhard, Zuo Houjuan, Ni Li, Jiang Jiangang, Zhang Jing, Wang Hong, Zhou Ning, Tschope Carsten, Cooper Leslie T, Wang Dao Wen
  
  Abstract
  
  Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Myocardial injury in COVID-19: When observations become reality.
  Int J Cardiol

  2021 Jan;323():295-296. doi: 10.1016/j.ijcard.2020.10.061.
  
  Veronese Giacomo, Winterton Dario, Ammirati Enrico
  
  
  
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• Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.
  Nat Rev Cardiol

  2021 Mar;18(3):169-193. doi: 10.1038/s41569-020-00435-x.
  
  Tschöpe Carsten, Ammirati Enrico, Bozkurt Biykem, Caforio Alida L P, Cooper Leslie T, Felix Stephan B, Hare Joshua M, Heidecker Bettina, Heymans Stephane, Hübner Norbert, Kelle Sebastian, Klingel Karin, Maatz Henrike, Parwani Abdul S, Spillmann Frank, Starling Randall C, Tsutsui Hiroyuki, Seferovic Petar, Van Linthout Sophie
  
  Abstract
  
  Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.
  
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• Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).
  Int J Cardiol

  2021 Feb;324():122-130. doi: 10.1016/j.ijcard.2020.09.026.
  
  Ammirati Enrico, Brambatti Michela, Braun Oscar Ö, Shah Palak, Cipriani Manlio, Bui Quan M, Veenis Jesse, Lee Euyhyun, Xu Ronghui, Hong Kimberly N, Van de Heyning Caroline M, Perna Enrico, Timmermans Philippe, Cikes Maja, Brugts Jasper J, Veronese Giacomo, Minto Jonathan, Smith Saige, Gjesdal Grunde, Gernhofer Yan K, Partida Cynthia, Potena Luciano, Masetti Marco, Boschi Silvia, Loforte Antonio, Jakus Nina, Milicic Davor, Nilsson Johan, De Bock Dina, Sterken Caroline, Van den Bossche Klaartje, Rega Filip, Tran Hao, Singh Ramesh, Montomoli Jonathan, Mondino Michele, Greenberg Barry, Russo Claudio F, Pretorius Victor, Liviu Klein, Frigerio Maria, Adler Eric D
  
  Abstract
  
  BACKGROUND:
  Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown.
  
  METHODS:
  We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months.
  
  RESULTS:
  The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU.
  
  CONCLUSIONS:
  Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• A novel tool to predict functional outcomes after robot-assisted radical prostatectomy and the value of additional surgery for incontinence.
  BJU Int

  2021 May;127(5):575-584. doi: 10.1111/bju.15242.
  
  Tutolo Manuela, Bruyneel Luk, Van der Aa Frank, Van Damme Nancy, Van Cleynenbreugel Ben, Joniau Steven, Ammirati Enrico, Vos Gigi, Briganti Alberto, De Ridder Dirk, Everaerts Wouter,
  
  Abstract
  
  OBJECTIVES:
  To develop and validate a model to predict 12-month continence status after robot-assisted radical prostatectomy (RARP) from preoperative and 3-month postoperative data; this model could help in informing patients on their individualised risk of urinary incontinence (UI) after RP in order to choose the best treatment option.
  
  PATIENTS AND METHODS:
  Data on 9421 patients in 25 Belgian centres were prospectively collected (2009-2016) in a compulsory regional database. The primary outcome was the prediction of continence status, using the International Consultation on Incontinence Urinary Incontinence Short Form (ICIQ-UI-SF) at 12-months after RARP. Linear regression shrinkage was used to assess the association between preoperative 3-month postoperative characteristics and 12-month continence status. This association was visualised using nomograms and an online tool.
  
  RESULTS:
  At 12 months, the mean (sd) score of the ICIQ-UI-SF questionnaire was 4.3 (4.7), threefold higher than the mean preoperative score of 1.4. For the preoperative model, high European Association of Urology risk classification for biochemical recurrence (estimate [Est.] 0.606, se 0.165), postoperative radiotherapy (Est. 1.563, se 0.641), lower preoperative European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core (EORCT QLQ-C30)/quality of life (QoL) score (Est. -0.011, se 0.003), higher preoperative ICIQ-UI-SF score (Est 0.214, se 0.018), and older age (Est. 0.058, se 0.009), were associated with a higher 12-month ICIQ-UI-SF score. For the 3-month model, higher preoperative ICIQ-UI-SF score (Est. 0.083, se 0.014), older age (Est. 0.024, se 0.007), lower 3-month EORCT QLQ-C30/QoL score (Est. -0.010, se 0.002) and higher 3-month ICIQ-UI-SF score (Est. 0.562, se 0.009) were associated with a higher 12-month ICIQ-UI-SF score.
  
  CONCLUSIONS:
  Our models set the stage for a more accurate counselling of patients. In particular, our preoperative model assesses the risk of UI according to preoperative and early postoperative variables. Our postoperative model can identify patients who most likely would not benefit from conservative treatment and should be counselled on continence surgery.
  
  © 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.
  
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• Extent and characteristics of carotid plaques and brain parenchymal loss in asymptomatic patients with no indication for revascularization.
  Int J Cardiol Heart Vasc

  2020 Oct;30():100619. doi: 100619.
  
  Ammirati Enrico, Moroni Francesco, Magnoni Marco, Rocca Maria A, Messina Roberta, Anzalone Nicoletta, De Filippis Costantino, Scotti Isabella, Besana Francesca, Spagnolo Pietro, Rimoldi Ornella E, Chiesa Roberto, Falini Andrea, Filippi Massimo, Camici Paolo G
  
  Abstract
  
  BACKGROUND AND AIMS:
  Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization.
  
  METHODS AND RESULTS:
  Sixty-four patients (aged 69 ± 8 years, 45% females) with carotid stenosis
  CONCLUSIONS:
  WM and GM have different susceptibility to processes involved in parenchymal loss. Contrary to common belief, our results show that presence of fibrocalcific plaques is associated with brain atrophy.
  
  © 2020 The Authors. Published by Elsevier B.V.
  
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• Takotsubo syndrome as a complication in a critically ill COVID-19 patient.
  ESC Heart Fail

  2020 Dec;7(6):4297-4300. doi: 10.1002/ehf2.12912.
  
  Bottiroli Maurizio, De Caria Daniele, Belli Oriana, Calini Angelo, Andreoni Patrizia, Siragusa Antonio, Moreo Antonella, Ammirati Enrico, Mondino Michele, Fumagalli Roberto
  
  Abstract
  
  Coronavirus disease 2019 (COVID-19) patients with cardiac injury have an increased risk of mortality. It remains to be determined the mechanism of cardiac injury and the identification of specific conditions that affect the heart during COVID-19. We present the case of a 76-year-old woman with COVID-19 pneumonia that developed a takotsubo syndrome (TTS). Although the patient presented normal left ventricular ejection fraction and normal levels of troponin on admission, after 16 days in intensive care unit due to respiratory distress, she suddenly developed cardiogenic shock. Shock occurred few hours after a spontaneous breathing trial through her tracheostomy. Bed-side echocardiographic revealed apical ballooning promptly supporting the diagnosis of TTS. She was successfully treated with deep sedation and low dosage of epinephrine. The relevance of this case is that TTS can occur in the late phase of COVID-19. Awareness of late TTS and bed-side echocardiographic evaluation can lead to prompt identification and treatment.
  
  © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
  
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• Late-sequalae of Kawasaki disease characterized by optical coherence tomography.
  J Cardiovasc Med (Hagerstown)

  2021 Jul;22(7):597-599. doi: 10.2459/JCM.0000000000001083.
  
  Soriano Francesco, Veas Nicolas, Nava Stefano, Piccinelli Enrico, Pedrotti Patrizia, Oreglia Jacopo, Vignati Gabriele, Winter José, Ammirati Enrico, Burns Jane C, Gordon John B
  
  
  
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• Longitudinal correlation of biomarkers of cardiac injury, inflammation, and coagulation to outcome in hospitalized COVID-19 patients.
  J Mol Cell Cardiol

  2020 Oct;147():74-87. doi: 10.1016/j.yjmcc.2020.08.008.
  
  Li Chenze, Jiang Jiangang, Wang Feng, Zhou Ning, Veronese Giacomo, Moslehi Javid J, Ammirati Enrico, Wang Dao Wen
  
  Abstract
  
  BACKGROUND:
  Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome.
  
  METHODS:
  We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-?, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors.
  
  RESULTS:
  Median age was 63 years (first to third quartile 51-70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p 
  CONCLUSIONS:
  Cardiac injury commonly occurs in critically ill COVID-19 patients, with increased levels of hs-cTnI beyond day 3 since admission portending a poor prognosis. A consistent positive correlation of hs-cTnI with IL-6 and d-dimer at several timepoints along hospitalization could suggest nonspecific cytokine-mediated cardiotoxicity.
  
  Copyright © 2020. Published by Elsevier Ltd.
  
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• Mortality and Pre-Hospitalization use of Renin-Angiotensin System Inhibitors in Hypertensive COVID-19 Patients.
  J Am Heart Assoc

  2020 Nov;9(21):e017736. doi: e017736.
  
  Chen Chen, Wang Feng, Chen Peng, Jiang Jiangang, Cui Guanglin, Zhou Ning, Moroni Francesco, Moslehi Javid J, Ammirati Enrico, Wang Dao Wen
  
  Abstract
  
  Background There has been significant controversy regarding the effects of pre-hospitalization use of renin-angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID-19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID-19 patients at Tongji Hospital in Wuhan, China, from January 10 to March 30, 2020; and identified 1,182 patients with known hypertension on pre-hospitalization therapy. We compared the baseline characteristics and in-hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non-RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non-RAS inhibitors group (p
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• Heart-Kidney Transplanted patient affected by COVID-19 pneumonia treated with tocilizumab on top of immunosuppressive maintenance therapy.
  Int J Cardiol Heart Vasc

  2020 Aug;29():100596. doi: 100596.
  
  Ammirati Enrico, Travi Giovanna, Orcese Carloandrea, Sacco Alice, Auricchio Sara, Frigerio Maria, Puoti Massimo
  
  
  
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• ST-elevation acute myocardial infarction during COVID-19 pandemic: Are we missing the boat?
  Int J Cardiol Heart Vasc

  2020 Aug;29():100578. doi: 100578.
  
  Buono Andrea, Ammirati Enrico
  
  
  
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• First experience with ATOMS system implant in neurogenic stress urinary incontinence.
  Neurourol Urodyn

  2020 Aug;39(6):1837-1841. doi: 10.1002/nau.24433.
  
  Ammirati Enrico, Manassero Alberto, Mosiello Giovanni, Falcone Marco, Geretto Paolo, Giammò Alessandro
  
  Abstract
  
  AIM:
  To evaluate efficacy and safety of ATOMS implant in neurogenic patients with stress incontinence performing clean intermittent catheterization (CIC).
  
  METHODS:
  We included all patients with neurogenic sacral/subsacral lesion and stress urinary incontinence, treated with ATOMS implant between January 2018 and March 2019. All patients received anamnesis, 24-hour pad test and pad count, physical examination, video urodynamic evaluation, Qualiveen questionnaire. All patients were followed up at 12 months after implantation. Patients were considered "continent" when dry or when wearing a security pad (social continence).
  
  RESULTS:
  We treated eight male patients with a median age of 25 years, four affected by myelomeningocele, and four by cauda equine syndrome. The median preoperative 24-hour pad test was 225?g (interquartile range [IQR]: 180-275). During the surgical procedure, we did not fill the cushion to prevent postoperative urethral injuries when performing CIC in the early postoperative time. At a 12-month follow-up, we had a significant reduction in postoperative 24-hour pad test (median value: 7.5?g; IQR: 0-16.25; P?.05). All patients reached continence. We had a significant reduction in the Qualiveen scores (P?.05). Patients demonstrated to be satisfied with the results of the intervention at the PGI-I questionnaire. The only complications were four cases of temporary scrotal edema (Clavien-Dindo 1) treated with conservative therapy. All patients resumed CIC without urethral traumatism nor catheter insertion difficulties. We had no cases of device infection nor device removal.
  
  CONCLUSIONS:
  Implantation of ATOMS device seems to be an effective and safe minimally invasive procedure also in neurological patients with a low rate of postoperative complications.
  
  © 2020 Wiley Periodicals LLC.
  
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• Dual implantation of penile prosthesis and ATOMS system for post-prostatectomy erectile dysfunction and urinary incontinence: a feasibility study.
  Int J Impot Res

  2021 Sep;33(6):577-582. doi: 10.1038/s41443-020-0320-y.
  
  Falcone Marco, Preto Mirko, Ammirati Enrico, Blecher Gideon, Carone Roberto, Gontero Paolo, Giammò Alessandro
  
  
  
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• Update on acute myocarditis.
  Trends Cardiovasc Med

  2021 Aug;31(6):370-379. doi: 10.1016/j.tcm.2020.05.008.
  
  Ammirati Enrico, Veronese Giacomo, Bottiroli Maurizio, Wang Dao Wen, Cipriani Manlio, Garascia Andrea, Pedrotti Patrizia, Adler Eric D, Frigerio Maria
  
  Abstract
  
  Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.
  
  Copyright © 2020. Published by Elsevier Inc.
  
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• Fulminant myocarditis triggered by OC43 subtype coronavirus: a disease deserving evidence-based care bundles.
  J Cardiovasc Med (Hagerstown)

  2020 Jul;21(7):529-531. doi: 10.2459/JCM.0000000000000989.
  
  Veronese Giacomo, Cipriani Manlio, Bottiroli Maurizio, Garascia Andrea, Mondino Michele, Pedrotti Patrizia, Pini Daniela, Cozzi Ottavia, Messina Antonio, Droandi Ginevra, Petrella Duccio, Frigerio Maria, Ammirati Enrico
  
  
  
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• Risk scores did not reliably predict individual risk of mortality for patients with decompensated heart failure.
  J Clin Epidemiol

  2020 Sep;125():38-46. doi: 10.1016/j.jclinepi.2020.05.020.
  
  Scrutinio Domenico, Guida Pietro, Ammirati Enrico, Oliva Fabrizio, Passantino Andrea
  
  Abstract
  
  OBJECTIVE:
  We investigated the performance of four prognostic tools in predicting 180-day mortality for patients admitted for acute decompensated heart failure (ADHF) by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) over a range of risk thresholds, in addition to discrimination and calibration.
  
  STUDY DESIGN AND SETTING:
  We studied 1,458 patients. The risk assessment was performed using the Acute Decompensated Heart Failure National Registry (ADHERE) model and the Get With The Guidelines (GWTG), ADHF/NT-proBNP, and Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND) risk scores.
  
  RESULTS:
  C-statistics ranged from 0.727 for the ADHERE model to 0.767 for the ADHF/NT-proBNP score. The ADHF/NT-proBNP risk score, the ADHERE model, and the ASCEND risk score, but not the GWTG risk score, were also well calibrated. Sensitivity and PPV were modest at the >30% risk threshold and ranged from 55% for the ADHF/NT-proBNP risk score to 38.8% for the ADHERE model and from 46.7% for the ADHF/NT-proBNP risk score to 42.1% for the ASCEND risk score, respectively. There was a modest agreement between the risk scores in classifying the patients across risk strata or in classifying those who died as being at >30% risk of death.
  
  CONCLUSION:
  Although risk assessment tools work well for stratifying patients, their use in estimating the risk of mortality for individuals has limited clinical utility.
  
  Copyright © 2020 Elsevier Inc. All rights reserved.
  
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• Urethral bulking with Bulkamid: An analysis of efficacy, safety profile, and predictors of functional outcomes in a single-center cohort.
  Neurourol Urodyn

  2020 Jun;39(5):1523-1528. doi: 10.1002/nau.24388.
  
  Giammò Alessandro, Geretto Paolo, Ammirati Enrico, Manassero Alberto, Squintone Luisella, Vercelli Dario, Carone Roberto
  
  Abstract
  
  AIMS:
  The aim of the present work is to analyze the safety profile, effectiveness, and favorable and unfavorable predictors of clinical outcome in urethral bulking with Bulkamid, and to better identify the ideal candidate for the procedure.
  
  METHODS:
  We included all consecutive female patients treated with urethral bulking with Bulkamid at our institution within 2 years. Patients were affected by stress urinary incontinence (SUI) or mixed incontinence. Incontinence severity was classified as "mild" (urinary leakage 200?g/die) at 24-hours pad test. Clinical success was defined as "dry" (no pads); clinical failure included "partial improvement" (>50% 24-hours pad test reduction) and "no benefit" (
  RESULTS:
  The success rate was 36.1% (n?=?35). Forty-three patients (44.3%) reported continence improvement. Complications included eight urinary retention cases (8.2%). Statistically significant correlation was observed between incontinence severity and clinical outcome in thee ? test (P?=?.008). No significant correlation was found between functional outcome and urodynamic incontinence features, postoperative urinary retention, previous pelvic surgery, age, and other physiological, pathological, and urodynamics characteristics. Urinary retention following the surgical procedure appeared to be related to clinical success with nonsignificant P value (P?=?.10).
  
  CONCLUSIONS:
  Bulkamid procedure could be proposed with good results in elderly patients or in patients requiring a low-invasive procedure with low risk of complications, affected either by SUI or mixed incontinence and with mild to moderate incontinence. Previous training to clean intermittent self-catheterization maneuver should be performed.
  
  © 2020 Wiley Periodicals LLC.
  
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• Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19).
  J Cardiovasc Pharmacol

  2020 May;75(5):359-367. doi: 10.1097/FJC.0000000000000836.
  
  Dixon Dave L, Van Tassell Benjamin W, Vecchié Alessandra, Bonaventura Aldo, Talasaz Azita H, Kakavand Hessam, D'Ascenzo Fabrizio, Perciaccante Antonio, Castagno Davide, Ammirati Enrico, Biondi-Zoccai Giuseppe, Stevens Michael P, Abbate Antonio
  
  Abstract
  
  A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.
  
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• SARS-CoV-2 inflames the heart. The importance of awareness of myocardial injury in COVID-19 patients.
  Int J Cardiol

  2020 Jul;311():122-123. doi: 10.1016/j.ijcard.2020.03.086.
  
  Ammirati Enrico, Wang Dao Wen
  
  
  
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• Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19).
  JAMA Cardiol

  2020 Jul;5(7):819-824. doi: 10.1001/jamacardio.2020.1096.
  
  Inciardi Riccardo M, Lupi Laura, Zaccone Gregorio, Italia Leonardo, Raffo Michela, Tomasoni Daniela, Cani Dario S, Cerini Manuel, Farina Davide, Gavazzi Emanuele, Maroldi Roberto, Adamo Marianna, Ammirati Enrico, Sinagra Gianfranco, Lombardi Carlo M, Metra Marco
  
  Abstract
  
  IMPORTANCE:
  Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
  
  OBJECTIVE:
  To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms.
  
  DESIGN, SETTING, AND PARTICIPANT:
  This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course.
  
  EXPOSURE:
  Cardiac involvement with COVID-19.
  
  MAIN OUTCOMES AND MEASURES:
  Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging.
  
  RESULTS:
  An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization.
  
  CONCLUSIONS AND RELEVANCE:
  This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.
  
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• Viral genome search in myocardium of patients with fulminant myocarditis.
  Eur J Heart Fail

  2020 Jul;22(7):1277-1280. doi: 10.1002/ejhf.1738.
  
  Veronese Giacomo, Ammirati Enrico, Brambatti Michela, Merlo Marco, Cipriani Manlio, Potena Luciano, Sormani Paola, Aoki Tatsuo, Sugimura Koichiro, Sawamura Akinori, Okumura Takahiro, Pinney Sean, Hong Kimberly, Shah Palak, Braun Oscar Ö, Van de Heyning Caroline M, Montero Santiago, Petrella Duccio, Huang Florent, Schmidt Matthieu, Raineri Claudia, Lala Anuradha, Varrenti Marisa, Foà Alberto, Leone Ornella, Gentile Piero, Artico Jessica, Agostini Valentina, Patel Rajiv, Garascia Andrea, Van Craenenbroeck Emeline M, Hirose Kaoru, Isotani Akihiro, Murohara Toyoaki, Arita Yoh, Sionis Alessandro, Fabris Enrico, Hashem Sherin, Garcia-Hernando Victor, Oliva Fabrizio, Greenberg Barry, Shimokawa Hiroaki, Sinagra Gianfranco, Adler Eric D, Frigerio Maria, Camici Paolo G
  
  
  
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• Assessment of right ventricular function in advanced heart failure with nonischemic dilated cardiomyopathy: insights of right ventricular elastance.
  J Cardiovasc Med (Hagerstown)

  2020 Feb;21(2):134-143. doi: 10.2459/JCM.0000000000000921.
  
  Bianco Francesco, Bucciarelli Valentina, Ammirati Enrico, Occhi Lucia, Musca Francesco, Tonti Giovanni, Frigerio Maria, Gallina Sabina
  
  Abstract
  
  BACKGROUND:
  The right ventriculoarterial coupling (R-V/A), a measure of right ventricular systolic dysfunction (RVSD) adaptation/maladaptation to chronic overload, and consequent pulmonary hypertension, has been little investigated in nonischemic dilated cardiomyopathy (NIDCM). We examined the correlates of R-V/A and traditional echocardiographic indices of RVSD, over the spectrum of pulmonary hypertension and tertiles of mean pulmonary artery pressures (PAPm).
  
  METHODS:
  In 2016-2017, we studied 81 consecutive patients for heart transplant/advanced heart failure. Inclusion criteria were NIDCM, reduced ejection fraction (?40%) and sinus rhythm. R-V/A was computed as the RV/pulmonary elastances ratio (R-Elv/P-Ea), derived from a combined right heart catheterization/transthoracic- echocardiographic assessment [right heart catheterization/transthoracic-echocardiographic (RHC/TTE)].
  
  RESULTS:
  A total of 68 patients (mean age 64?±?7 years, 82% men) were eligible. After adjustments, R-Elv and P-Ea were higher in isolated postcapillary-pulmonary hypertension (Ipc-PH) than combined-pulmonary hypertension (Cpc-PH) (P?=?0.004 and P?=?0.002, respectively), whereas R-V/A progressively decreased over Ipc-PH and Cpc-PH (P?=?0.006). According to PAPm increment, P-Ea congruently increased (P-Trend?=?0.028), R-Elv progressively decreased (P-Trend
  CONCLUSION:
  Among NIDCM HF patients, in a small cohort study, RHC/TTE-derived R-V/A assessment demonstrated good correlations with pulmonary hypertension types and RV functional status. These data suggest that R-V/A encloses comprehensive information of the whole cardiopulmonary efficiency, better clarifying the amount of RVSD, with good reliability.
  
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• Resident inflammatory cells in the myocardium of children: On the way to set histologic reference standards to differentiate normal myocardium from myocarditis.
  Int J Cardiol

  2020 Mar;303():64-65. doi: 10.1016/j.ijcard.2019.12.039.
  
  Ammirati Enrico, Kaski Juan Pablo
  
  
  
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• Highlights from the International Journal of Cardiology Heart & Vasculature: Heart failure, atrial fibrillation, coronary artery disease and myocardial infarction.
  Int J Cardiol Heart Vasc

  2019 Dec;25():100443. doi: 100443.
  
  Linz Dominik, Ammirati Enrico, Dan Gheorghe-Andrei, Heijman Jordi, Dobrev Dobromir
  
  
  
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• An odd couple: acalculous cholecystitis masking a fulminant myocarditis.
  J Cardiovasc Med (Hagerstown)

  2020 Apr;21(4):327-332. doi: 10.2459/JCM.0000000000000909.
  
  Bellamoli Michele, Pellegrini Paolo, de Manna Nunzio Davide, Genco Bruno, Prati Daniele, Carbonieri Emanuele, Faggian Giuseppe, Ammirati Enrico, Frigerio Maria, Ribichini Flavio Luciano
  
  
  
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• Implant of ATOMS® system for the treatment of postoperative male stress urinary incontinence: an Italian multicentric study.
  Minerva Urol Nefrol

  2020 Dec;72(6):770-777. doi: 10.23736/S0393-2249.19.03457-X.
  
  Giammò Alessandro, Ammirati Enrico, Tullio Annarita, Morgia Giuseppe, Sandri Sandro, Introini Carlo, Canepa Giorgio, Timossi Luca, Rossi Cristina, Mozzi Cristina, Carone Roberto
  
  Abstract
  
  BACKGROUND:
  The aim of this study was to evaluate efficacy and safety of the ATOMS system for the treatment of postoperative stress urinary incontinence (SUI).
  
  METHODS:
  We included all consecutive male patients referring for postoperative SUI and treated with ATOMS system from June 2013 to July 2017. Patients received anamnesis, 24 h Pad Test, Pad count, physical examination, urodynamic evaluation, ICIQ-UI SF questionnaire. We excluded patients with low bladder capacity and compliance, uncontrolled detrusor overactivity.
  
  RESULTS:
  We treated 98 patients with median age of 70.21±10.02 years. The most common cause of SUI was open radical prostatectomy in 79 patients. Ten patients had undergone urethrotomy, 7 bladder neck incision, 14 adjuvant radiotherapy. Thirty-nine patients suffered of mild incontinence (24 h Pad Test
  CONCLUSIONS:
  The ATOMS system seems to be an effective and safe surgical treatment for postoperative male SUI.
  
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• [Myocardial infarction with non-obstructive coronary arteries (MINOCA): diagnosis, pathogenesis, therapy and prognosis].
  G Ital Cardiol (Rome)

  2019 Sep;20(9):499-511. doi: 10.1714/3207.31839.
  
  Buono Andrea, Pedrotti Patrizia, Soriano Francesco, Veas Nicolas, Oliva Fabrizio, Oreglia Jacopo, Ammirati Enrico
  
  Abstract
  
  The term MINOCA (myocardial infarction with non-obstructive coronary arteries) defines acute myocardial infarction with angiographic evidence of no significant coronary artery stenosis. Heterogeneous diseases are labelled as MINOCA. Incidence and epidemiological aspects differ on the basis of etiological causes. MINOCA include plaque (causing
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• Differences in clinical presentation and outcome between immune checkpoint inhibitor-associated myocarditis and classical acute myocarditis: Same disease, distinct challenges to face.
  Int J Cardiol

  2019 Dec;296():124-126. doi: 10.1016/j.ijcard.2019.08.038.
  
  Veronese Giacomo, Ammirati Enrico
  
  
  
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• Getting to the heart of the matter in a multisystem disorder: Erdheim-Chester disease.
  Lancet

  2019 Aug;394(10198):e19. doi: 10.1016/S0140-6736(19)31787-8.
  
  Buono Andrea, Bassi Ilaria, Santolamazza Caterina, Moreo Antonella, Pedrotti Patrizia, Sacco Alice, Morici Nuccia, Giannattasio Cristina, Oliva Fabrizio, Ammirati Enrico
  
  
  
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• Neuromodulation in urology, state of the art.
  Urologia

  2019 Nov;86(4):177-182. doi: 10.1177/0391560319866075.
  
  Ammirati Enrico, Giammò Alessandro, Manassero Alberto, Carone Roberto
  
  Abstract
  
  Sacral neuromodulation is an approved and validated treatment for overactive bladder syndrome, chronic non-obstructive retention, and chronic pelvic pain. Percutaneous tibial nerve stimulation is a less invasive approach of neuromodulation. We performed a literature research to assess the current evidence available about neuromodulation. Both techniques appear to be effective and safe third-line treatments. The overall success rate ranges from 43% to 85% for sacral neuromodulation and from 40% to 79.5% for percutaneous tibial nerve stimulation. Sacral neuromodulation has a higher incidence of complications in comparison to percutaneous tibial nerve stimulation, due to the more invasive surgical technique and the presence of a permanent implant. The incidence of surgical revision ranges between 9% and 33%. The most frequent complication with sacral neuromodulation is pain at implant site (15%-42%), followed by lead migration (4%-21%), pain at lead site (5.4%-19.1%), leg pain (18%), and infection (5.7%-6.1%). The quality of the studies on sacral neuromodulation and percutaneous tibial nerve stimulation in literature is quite modest, because of the shortage of good randomized clinical trial; most of the studies are prospective observational studies with mid-term follow-up.
  
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• Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.
  J Am Coll Cardiol

  2019 Jul;74(3):299-311. doi: 10.1016/j.jacc.2019.04.063.
  
  Ammirati Enrico, Veronese Giacomo, Brambatti Michela, Merlo Marco, Cipriani Manlio, Potena Luciano, Sormani Paola, Aoki Tatsuo, Sugimura Koichiro, Sawamura Akinori, Okumura Takahiro, Pinney Sean, Hong Kimberly, Shah Palak, Braun Öscar, Van de Heyning Caroline M, Montero Santiago, Petrella Duccio, Huang Florent, Schmidt Matthieu, Raineri Claudia, Lala Anuradha, Varrenti Marisa, Foà Alberto, Leone Ornella, Gentile Piero, Artico Jessica, Agostini Valentina, Patel Rajiv, Garascia Andrea, Van Craenenbroeck Emeline M, Hirose Kaoru, Isotani Akihiro, Murohara Toyoaki, Arita Yoh, Sionis Alessandro, Fabris Enrico, Hashem Sherin, Garcia-Hernando Victor, Oliva Fabrizio, Greenberg Barry, Shimokawa Hiroaki, Sinagra Gianfranco, Adler Eric D, Frigerio Maria, Camici Paolo G
  
  Abstract
  
  BACKGROUND:
  Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists.
  
  OBJECTIVES:
  This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information.
  
  METHODS:
  A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms 
  RESULTS:
  Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p 
  CONCLUSIONS:
  This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.
  
  Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Efficacy and safety of adjustable balloons (Proact?) to treat male stress urinary incontinence after prostate surgery: Medium and long-term follow-up data of a national multicentric retrospective study.
  Neurourol Urodyn

  2019 Sep;38(7):1979-1984. doi: 10.1002/nau.24103.
  
  Finazzi Agrò Enrico, Gregori Andrea, Bianchi Daniele, Carone Roberto, Giammò Alessandro, Ammirati Enrico, Giovannelli Vanni, Romanò Ai Ling, Martino Pasquale, Saracino Alberto, Volpe Alessandro, Favro Michele, Canepa Giorgio, Varca Virginia, Pinto Anna, Farullo Giuseppe
  
  Abstract
  
  AIMS:
  Male stress urinary incontinence (SUI) represents a complication after radical prostatectomy or benign prostatic obstruction surgery. The artificial urinary sphincter is considered the standard treatment but interest on minimally invasive devices, such as adjustable balloons, has recently increased. Aim of this study is to evaluate the efficacy and safety of the ProACT system.
  
  METHODS:
  In this multicentric retrospective study, we reported the data from nine centers. Patients with SUI who underwent a ProACT device implantation for postoperative SUI and had a minimum follow-up of 24 months were included. Efficacy was evaluated at the maximum available follow-up and was assessed utilizing a 24-hour pad test. Patients were considered: "Dry" if presenting a urine leak weight lower than 8?g at the 24-hour pad test; "Improved" if presenting a reduction of urine leak higher than 50% (but >8?g/24?hours); "Failure" if presenting a reduction in urine leak lower than 50%. The evaluation included a record of intraoperative and long-term complications.
  
  RESULTS:
  Safety and efficacy results are reported on 240 patients. 29.6% of patients were dry at 24 months, 37.5% were improved and 32.9% of patients were considered failures. The baseline mean pad weight of 367?g was reduced to 123?g at 24 months. Five-year follow-up on 152 patients showed similar efficacy. The complication rate was 22.5%, with the top complication being long-term balloon failure.
  
  CONCLUSIONS:
  ProACT implantation represents a safe and efficacious treatment for male postoperative SUI at both medium and long-term follow up. 67.1% of patients were dry or improved at 24 months. The majority of complications are low grade.
  
  © 2019 Wiley Periodicals, Inc.
  
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• MitraClip system as bridge to left ventricular assist device in selected patients with advanced heart failure.
  Int J Cardiol

  2019 Oct;292():160. doi: 10.1016/j.ijcard.2019.04.096.
  
  Van De Heyning Caroline M, Ammirati Enrico
  
  
  
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• Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization.
  Atherosclerosis

  2019 Aug;287():171-178. doi: 10.1016/j.atherosclerosis.2019.04.230.
  
  Ammirati Enrico, Moroni Francesco, Magnoni Marco, Rocca Maria A, Anzalone Nicoletta, Cacciaguerra Laura, Di Terlizzi Simona, Villa Chiara, Sizzano Federico, Palini Alessio, Scotti Isabella, Besana Francesca, Spagnolo Pietro, Rimoldi Ornella E, Chiesa Roberto, Falini Andrea, Filippi Massimo, Camici Paolo G
  
  Abstract
  
  BACKGROUND AND AIMS:
  Brain white matter hyperintensities (WMHs) have been associated with an increased risk of ischemic stroke and considered as markers of brain ischemia. Progression of WMHs in asymptomatic patients with non-hemodynamically significant carotid plaque could represent a putative marker of plaque vulnerability. We prospectively evaluate progression and determinants of WMHs in this population.
  
  METHODS:
  This prospective study included 51 asymptomatic patients with carotid stenosis
  RESULTS:
  Seventeen subjects (33.3%) had carotid stenoses of 50-70% (Doppler flow velocity) while the rest had stenoses of
  CONCLUSIONS:
  Half of the patients with carotid plaques of intermediate severity had evidence of WMH progression at follow up. Female gender and systemic factors such as hypercholesterolemia, and lower GFR, but not plaque characteristics or circulating cellular biomarkers, are associated with WMH progression.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• The Role of Monocytes and Macrophages in Human Atherosclerosis, Plaque Neoangiogenesis, and Atherothrombosis.
  Mediators Inflamm

  2019 ;2019():7434376. doi: 7434376.
  
  Moroni Francesco, Ammirati Enrico, Norata Giuseppe Danilo, Magnoni Marco, Camici Paolo G
  
  Abstract
  
  Atherosclerosis is one of the leading causes of death and disability worldwide. It is a complex disease characterized by lipid accumulation within the arterial wall, inflammation, local neoangiogenesis, and apoptosis. Innate immune effectors, in particular monocytes and macrophages, play a pivotal role in atherosclerosis initiation and progression. Although most of available evidence on the role of monocytes and macrophages in atherosclerosis is derived from animal studies, a growing body of evidence elucidating the role of these mononuclear cell subtypes in human atherosclerosis is currently accumulating. A novel pathogenic role of monocytes and macrophages in terms of atherosclerosis initiation and progression, in particular concerning the role of these cell subsets in neovascularization, has been discovered. The aim of the present article is to review currently available evidence on the role of monocytes and macrophages in human atherosclerosis and in relation to plaque characteristics, such as plaque neoangiogenesis, and patients' prognosis and their potential role as biomarkers.
  
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• Recurrent cardiac sarcoidosis after heart transplantation.
  Clin Res Cardiol

  2019 Oct;108(10):1171-1173. doi: 10.1007/s00392-019-01485-z.
  
  Veronese Giacomo, Cipriani Manlio, Petrella Duccio, Geniere Nigra Stefano, Pedrotti Patrizia, Garascia Andrea, Masciocco Gabriella, Bramerio Manuela A, Klingel Karin, Frigerio Maria, Ammirati Enrico
  
  
  
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• Transthyretin amyloidosis in Western Europe: a snapshot from the THAOS registry and a call for further perspectives.
  Eur Heart J

  2019 Apr;():. doi: ehz205.
  
  Ammirati Enrico, AbouEzzeddine Omar F
  
  
  
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• Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors.
  PLoS One

  2019 ;14(3):e0214616. doi: e0214616.
  
  Merlo Marco, Ammirati Enrico, Gentile Piero, Artico Jessica, Cannatà Antonio, Finocchiaro Gherardo, Barbati Giulia, Sormani Paola, Varrenti Marisa, Perkan Andrea, Fabris Enrico, Aleksova Aneta, Bussani Rossana, Petrella Duccio, Cipriani Manlio, Raineri Claudia, Frigerio Maria, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  Persistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored.
  
  OBJECTIVES:
  To assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission.
  
  METHODS AND RESULTS:
  We retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6-18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF
  CONCLUSIONS:
  More than half of patients presenting with acute LM and LVEF
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• Response by Ammirati et al to Letter Regarding Article, "Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis".
  Circulation

  2019 Mar;139(10):1346-1347. doi: 10.1161/CIRCULATIONAHA.118.039063.
  
  Ammirati Enrico, Cipriani Manlio, Frigerio Maria, Oliva Fabrizio, Camici Paolo G
  
  
  
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• Safety of centrifugal left ventricular assist device in patients previously treated with MitraClip system.
  Int J Cardiol

  2019 May;283():131-133. doi: 10.1016/j.ijcard.2019.02.039.
  
  Ammirati Enrico, Van De Heyning Caroline M, Musca Francesco, Brambatti Michela, Perna Enrico, Cipriani Manlio, Cannata Aldo, Mondino Michele, Moreo Antonella, De Bock Dina, Pretorius Victor, Claeys Marc J, Adler Eric D, Russo Claudio F, Frigerio Maria
  
  Abstract
  
  INTRODUCTION:
  No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD.
  
  METHODS:
  We retrospectively identified 6 patients (median age of 62?years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018.
  
  RESULTS:
  Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282?days (interquartile range 67 to 493), and median time on CF-LVAD support was 401?days (interquartile range 105 to 492?days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications.
  
  CONCLUSIONS:
  Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• Efficacy and safety of artificial urinary sphincter (AUS): Results of a large multi-institutional cohort of patients with mid-term follow-up.
  Neurourol Urodyn

  2019 Feb;38(2):710-718. doi: 10.1002/nau.23901.
  
  Tutolo Manuela, Cornu Jean-Nicolas, Bauer Ricarda M, Ahyai Sascha, Bozzini Giorgio, Heesakkers John, Drake Marcus J, Tikkinen Kari A O, Launonen Ene, Larré Stéphane, Thiruchelvam Nikesh, Lee Richard, Li Philip, Favro Michele, Zaffuto Emanuele, Bachmann Alexander, Martinez-Salamanca Juan I, Pichon Thomas, De Nunzio Cosimo, Ammirati Enrico, Haab Francois, Van Der Aa Frank
  
  Abstract
  
  AIMS:
  To assess efficacy and safety as well as predictive factors of dry rate and freedom from surgical revision in patients underwent AUS placement. The artificial urinary sphincter (AUS) is still considered the standard for the treatment of moderate to severe post-prostatectomy stress urinary incontinence (SUI). However, data reporting efficacy and safety from large series are lacking.
  
  METHODS:
  A multicenter, retrospective study was conducted in 16 centers in Europe and USA. Only primary cases of AUS implantation in non-neurogenic SUI after prostate surgery, with a follow-up of at least 1 year were included. Efficacy data (continence rate, based on pad usage) and safety data (revision rate in case of infection and erosion, as well as atrophy or mechanical failure) were collected. Multivariable analyses were performed in order to investigate possible predictors of the aforementioned outcomes.
  
  RESULTS:
  Eight hundred ninety-two men had primary AUS implantation. At 32 months mean follow-up overall dry rate and surgical revision were 58% and 30.7%, respectively. Logistic regression analysis showed that patients without previous incontinence surgery had a higher probability to be dry after AUS implantation (OR: 0.51, P?=?0.03). Moreover institutional case-load was positively associated with dry rate (OR: 1.18; P?=?0.005) and freedom from revision (OR: 1.51; P?=?0.00).
  
  CONCLUSIONS:
  The results of this study showed that AUS is an effective option for the treatment of SUI after prostate surgery. Moreover previous incontinence surgery and low institutional case-load are negatively associated to efficacy and safety outcomes.
  
  © 2018 Wiley Periodicals, Inc.
  
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• Implant of ATOMS® system for the treatment of postoperative male stress urinary incontinence: results of a single centre.
  Int Braz J Urol

  2019 ;45(1):127-136. doi: 10.1590/S1677-5538.IBJU.2018.0171.
  
  Giammò Alessandro, Ammirati Enrico, Tullio Annarita, Bodo Gianni, Manassero Alberto, Gontero Paolo, Carone Roberto
  
  Abstract
  
  PURPOSE:
  The aim of our study is to evaluate the efficacy and safety of ATOMS® system for the treatment of postoperative male stress urinary incontinence (SUI).
  
  MATERIALS AND METHODS:
  We retrospectively evaluated all patients treated at our institution for postoperative male SUI with ATOMS® implant. We excluded patients with low bladder compliance (
  RESULTS:
  From October 2014 to July 2017 we treated 52 patients, mean age 73.6 years. Most of them (92.3%) had undergone radical prostatectomy, 3.85% simple open prostatectomy, 3.85% TURP; 28.8% of patients had undergone urethral surgery, 11.5% adjuvant radiotherapy; 57.7% had already undergone surgical treatment for urinary incontinence. The average24 hours pad test was 411.6 g (180 - 1100). The mean follow-up was 20.1 months (8.1 - 41.5) 30.8% of patients were dry, 59.6% improved ? 50%, 7.7% improved
  CONCLUSIONS:
  The ATOMS® system is an effective and safe surgical treatment of mild and moderate male postoperative SUI with durable results in the short term.
  
  Copyright® by the International Brazilian Journal of Urology.
  
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• Acutely decompensated heart failure with chronic obstructive pulmonary disease: Clinical characteristics and long-term survival.
  Eur J Intern Med

  2019 Feb;60():31-38. doi: 10.1016/j.ejim.2018.11.002.
  
  Scrutinio Domenico, Guida Pietro, Passantino Andrea, Ammirati Enrico, Oliva Fabrizio, Lagioia Rocco, Raimondo Rosa, Venezia Mario, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Chronic obstructive pulmonary disease (COPD) is among the most common comorbidities in patients hospitalized with heart failure and is generally associated with poor outcomes. However, the results of previous studies with regard to increased mortality and risk trajectories were not univocal. We sought to assess the prognostic impact of COPD in patients admitted for acutely decompensated heart failure (ADHF) and investigate the association between use of ?-blockers at discharge and mortality in patients with COPD.
  
  METHODS:
  We studied 1530 patients. The association of COPD with mortality was examined in adjusted Fine-Gray proportional hazard models where heart transplantation and ventricular assist device implantation were treated as competing risks. The primary outcome was 5-year all-cause mortality.
  
  RESULTS:
  After adjusting for establisked risk markers, the subdistribution hazard ratios (SHR) of 5-year mortality for COPD patients compared with non-COPD patients was 1.25 (95% confidence intervals [CIs] 1.06-1.47; p?=?.007). The relative risk of death for COPD patients increased steeply from 30 to 180?days, and remained noticeably high throughout the entire follow-up. Among patients with comorbid COPD, the use of ?-blockers at discharge was associated with a significantly reduced risk of 1-year post-discharge mortality (SHR 0.66, 95%CIs 0.53-0.83; p??.001).
  
  CONCLUSIONS:
  Our data indicate that ADHF patients with comorbid COPD have a worse long-term survival than those without comorbid COPD. Most of the excess mortality occurred in the first few months following hospitalization. Our data also suggest that the use of ?-blockers at discharge is independently associated with improved survival in ADHF patients with COPD.
  
  Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Impact of Cardiovascular Risk Factors and Pharmacologic Treatments on Carotid Intraplaque Neovascularization Detected by Contrast-Enhanced Ultrasound.
  J Am Soc Echocardiogr

  2019 Jan;32(1):113-120.e6. doi: 10.1016/j.echo.2018.09.001.
  
  Magnoni Marco, Ammirati Enrico, Moroni Francesco, Norata Giuseppe D, Camici Paolo G
  
  Abstract
  
  BACKGROUND:
  Neovascularization is a marker of plaque vulnerability that can be assessed noninvasively using contrast-enhanced ultrasound (CEUS). The presence and extent of plaque neovascularization and their relation to cardiovascular risk factors and treatments were assessed in asymptomatic patients with carotid stenosis of intermediate severity and no indication for revascularization.
  
  METHODS:
  Sixty-six patients aged 69 ± 8 years (59% men) were prospectively enrolled. Plaque neovascularization was assessed using CEUS with sulfur hexafluoride contrast in each of the four carotid segments bilaterally (a total of 528 segments). In each plaque, the presence or absence of contrast enhancement was assessed semiquantitatively as CEUS grade 1 (no signal or signal confined to the adventitia and/or shoulder of the plaque) or CEUS grade 2 (signal within the plaque).
  
  RESULTS:
  Plaques were detectable in 289 of 528 carotid segments (54.7%). CEUS grade 2 was present in at least one plaque in 48 of 66 patients (72.7%) and was not influenced by stenosis severity or morphology. The highest CEUS grade 2 prevalence was observed in patients with diabetes and the lowest in those treated with angiotensin-converting enzyme inhibitors and statins, especially when low-density lipoprotein cholesterol was
  CONCLUSION:
  Intraplaque neovascularization is frequent in asymptomatic patients with intermediate carotid stenosis and is more prevalent in those with diabetes. Low-density lipoprotein cholesterol
  Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
  
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• Carotid artery plaque uptake of C-PK11195 inversely correlates with circulating monocytes and classical CD14CD16 monocytes expressing HLA-DR.
  Int J Cardiol Heart Vasc

  2018 Dec;21():32-35. doi: 10.1016/j.ijcha.2018.09.005.
  
  Ammirati Enrico, Moroni Francesco, Magnoni Marco, Busnardo Elena, Di Terlizzi Simona, Villa Chiara, Sizzano Federico, Scotti Isabella, Palini Alessio, Presotto Luca, Bettinardi Valentino, Spagnolo Pietro, Besana Francesca, Gianolli Luigi, Rimoldi Ornella E, Camici Paolo G
  
  Abstract
  
  BACKGROUND:
  We explored the relation between blood concentrations of monocyte/lymphocyte subsets and carotid artery plaque macrophage content, measured by positron emission tomography (PET) with C-PK11195.
  
  METHODS AND RESULTS:
  In 9 patients with carotid plaques we performed C-PK11195-PET/computed tomography angiography imaging and measurement of absolute concentrations and frequencies of circulating monocytes and T-cell subsets. Plaque standardized uptake value (SUV) for C-PK11195 was negatively correlated with concentrations of total monocytes (r?=?-0.58, p?=?0.05) and CD14CD16HLA-DR classical subset (r?=?-0.82, p?=?0.005). These correlations hold true also in relation to plaque target to background ratio. No correlation was observed between plaque SUV and CD3T lymphocytes, CD4T lymphocytes nor with activated CD3CD4T cells expressing HLA-DR.
  
  CONCLUSIONS:
  We first demonstrated a reduction in the absolute concentration of monocytes and particularly in classical monocytes expressing HLA-DR in the presence of an increased uptake of C-PK11195 in carotid plaques. The present work, despite being a pilot study comprising only a small number of subjects provides new insights in the search for specific cellular biomarkers with potential diagnostic and prognostic value in patients with a known carotid plaque.
  
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• Acute and Fulminant Myocarditis: a Pragmatic Clinical Approach to Diagnosis and Treatment.
  Curr Cardiol Rep

  2018 Sep;20(11):114. doi: 10.1007/s11886-018-1054-z.
  
  Ammirati Enrico, Veronese Giacomo, Cipriani Manlio, Moroni Francesco, Garascia Andrea, Brambatti Michela, Adler Eric D, Frigerio Maria
  
  Abstract
  
  PURPOSE OF REVIEW:
  To review the clinical features of acute myocarditis, including its fulminant presentation, and present a pragmatic approach to the diagnosis and treatment, considering indications of American and European Scientific Statements and recent data derived by large contemporary registries.
  
  RECENT FINDINGS:
  Patients presenting with acute uncomplicated myocarditis (i.e., without left ventricular dysfunction, heart failure, or ventricular arrhythmias) have a favorable short- and long-term prognosis: these findings do not support the indication to endomyocardial biopsy in this clinical scenario. Conversely, patients with complicated presentations, especially those with fulminant myocarditis, require an aggressive and comprehensive management, including endomyocardial biopsy and availability of advanced therapies for circulatory support. Although several immunomodulatory or immunosuppressive therapies have been studied and are actually prescribed in the real-world practice, their effectiveness has not been clearly demonstrated. Patients with specific histological subtypes of acute myocarditis (i.e., giant cell and eosinophilic myocarditis) or those affected by sarcoidosis or systemic autoimmune disorders seem to benefit most from immunosuppression. On the other hand, no clear evidence supports the use of immunosuppressive agents in patients with lymphocytic acute myocarditis, even though small series suggest a potential benefit. Acute myocarditis is a heterogeneous condition with distinct pathophysiological pathways. Further research is mandatory to identify factors and mechanisms that may trigger/maintain or counteract/repair the myocardial damage, in order to provide a rational for future evidence-based treatment of patients affected by this condition.
  
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• Antithrombotic therapy in ventricular assist device (VAD) management: From ancient beliefs to updated evidence. A narrative review.
  Int J Cardiol Heart Vasc

  2018 Sep;20():20-26. doi: 10.1016/j.ijcha.2018.06.005.
  
  Morici Nuccia, Varrenti Marisa, Brunelli Dario, Perna Enrico, Cipriani Manlio, Ammirati Enrico, Frigerio Maria, Cattaneo Marco, Oliva Fabrizio
  
  Abstract
  
  Platelets play a key role in the pathogenesis of ventricular assist device (VAD) thrombosis; therefore, antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in VAD management. Aspirin is the most used agent and still remains the first-choice drug for lifelong administration after VAD implantation. Anticoagulant drugs are usually recommended, but with a wide range of efficacy targets. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has been used for patients developing a thrombotic event, despite an increased risk of bleeding complications. Although different strategies have been attempted, bleeding and thrombotic events remain frequent and there are no uniform strategies adopted for pharmacological management in the short and mid- or long-term follow up. The aim of this article is to provide an overview of the evidence from randomized clinical trials and observational studies with a focus on the pathophysiologic mechanisms underlying bleeding and thrombosis in VAD patients and the best antithrombotic regimens available.
  
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• Conventional Troponin-I versus high-sensitivity troponin-T: Performance and incremental prognostic value in non-ST-elevation acute myocardial infarction patients with negative CK-MB based on a real-world multicenter cohort.
  Int J Cardiol Heart Vasc

  2018 Sep;20():38-39. doi: 10.1016/j.ijcha.2018.07.002.
  
  Ammirati Enrico, Dobrev Dobromir
  
  
  
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• Application of competing risks analysis improved prognostic assessment of patients with decompensated chronic heart failure and reduced left ventricular ejection fraction.
  J Clin Epidemiol

  2018 Nov;103():31-39. doi: 10.1016/j.jclinepi.2018.07.006.
  
  Scrutinio Domenico, Guida Pietro, Passantino Andrea, Ammirati Enrico, Oliva Fabrizio, Lagioia Rocco, Frigerio Maria
  
  Abstract
  
  OBJECTIVE:
  The Kaplan-Meier method may overestimate absolute mortality risk (AMR) in the presence of competing risks. Urgent heart transplantation (UHT) and ventricular assist device implantation (VADi) are important competing events in heart failure. We sought to quantify the extent of bias of the Kaplan-Meier method in estimating AMR in the presence of competing events and to analyze the effect of covariates on the hazard for death and competing events in the clinical model of decompensated chronic heart failure with reduced ejection fraction (DCHFrEF).
  
  STUDY DESIGN AND SETTING:
  We studied 683 patients. We used the cumulative incidence function (CIF) to estimate the AMR at 1 year. CIF estimate was compared with the Kaplan-Meier estimate. The Fine-Gray subdistribution hazard analysis was used to assess the effect of covariates on the hazard for death and UHT/VADi.
  
  RESULTS:
  The Kaplan-Meier estimate of the AMR was 0.272, whereas the CIF estimate was 0.246. The difference was more pronounced in the patient subgroup with advanced DCHF (0.424 vs. 0.338). The Fine-Gray subdistribution hazard analysis revealed that established risk markers have qualitatively different effects on the incidence of death or UHT/VADi.
  
  CONCLUSION:
  Competing risks analysis allows more accurately estimating AMR and better understanding the association between covariates and major outcomes in DCHFrEF.
  
  Copyright © 2018 Elsevier Inc. All rights reserved.
  
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• Cardiovascular disease and brain health: Focus on white matter hyperintensities.
  Int J Cardiol Heart Vasc

  2018 Jun;19():63-69. doi: 10.1016/j.ijcha.2018.04.006.
  
  Moroni Francesco, Ammirati Enrico, Rocca Maria A, Filippi Massimo, Magnoni Marco, Camici Paolo G
  
  Abstract
  
  Diseases affecting the brain contribute to a substantial proportion of morbidity and mortality in the general population. Conditions such as stroke, dementia and cognitive impairment have a prominent impact on global public health. Despite the heterogeneous clinical manifestations of these conditions and their diverse prognostic implications, current evidence supports a role for cardiovascular disease as a common pathophysiological ground. Brain white matter hyperintensities (WMH) are patchy white matter signal hyperintensity on T2-weighted magnetic resonance imaging sequences commonly found in elderly individuals. WMH appear to have a vascular pathogenesis and have been shown to confer an increased risk of stroke and cognitive decline. Indeed, they were proposed as a marker for central nervous system frailty. Cardiovascular diseases seem to play a key role in the etiology of WMH. Carotid atherosclerosis and atrial fibrillation were shown to be associated with higher WMH burden, while adequate blood pressure control has been reported reducing WMH progression. Aim of the present work is to review the available evidence linking WMH to cardiovascular disease, highlighting the complex interplay between cerebral and cardiovascular health.
  
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• Not every fulminant lymphocytic myocarditis fully recovers.
  J Cardiovasc Med (Hagerstown)

  2018 Aug;19(8):453-454. doi: 10.2459/JCM.0000000000000664.
  
  Veronese Giacomo, Cipriani Manlio, Petrella Duccio, Pedrotti Patrizia, Giannattasio Cristina, Garascia Andrea, Oliva Fabrizio, Klingel Karin, Frigerio Maria, Ammirati Enrico
  
  
  
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• Reduction of heart rate in patients with heart failure aiming to improve ventricular-arterial coupling.
  Int J Cardiol

  2018 Aug;265():172. doi: 10.1016/j.ijcard.2018.04.106.
  
  Buono Andrea, Oliva Fabrizio, Ammirati Enrico
  
  
  
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• What Is New in Neuromodulation for Overactive Bladder?
  Eur Urol Focus

  2018 Jan;4(1):49-53. doi: 10.1016/j.euf.2018.04.019.
  
  Tutolo Manuela, Ammirati Enrico, Van der Aa Frank
  
  Abstract
  
  UNLABELLED:
  We reviewed the available studies on efficacy and safety of percutaneous tibial nerve stimulation (PTNS) and sacral nerve modulation (SNM) for overactive bladder (OAB) symptoms not responsive to conservative treatments. We limited our search to randomized trials, in English, with at least 20 adult patients, and 6 mo and 12 wk of follow-up for SNM and PTNS, respectively, published between January 1998 and December 2017. Therapeutic success ranges from 61% to 90% for SNM and from 54% to 79% for PTNS. Both techniques are effective and safe, with no life-threatening adverse effects. PTNS is a less invasive technique that gives good results in short time with fewer side effects.
  
  PATIENT SUMMARY:
  Sacral nerve modulation and percutaneous tibial nerve stimulation are effective and safe in patients with overactive bladder syndrome not responsive to standard medical therapy.
  
  Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  
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• Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry.
  Circulation

  2018 Sep;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319.
  
  Ammirati Enrico, Cipriani Manlio, Moro Claudio, Raineri Claudia, Pini Daniela, Sormani Paola, Mantovani Riccardo, Varrenti Marisa, Pedrotti Patrizia, Conca Cristina, Mafrici Antonio, Grosu Aurelia, Briguglia Daniele, Guglielmetto Silvia, Perego Giovanni B, Colombo Stefania, Caico Salvatore I, Giannattasio Cristina, Maestroni Alberto, Carubelli Valentina, Metra Marco, Lombardi Carlo, Campodonico Jeness, Agostoni Piergiuseppe, Peretto Giovanni, Scelsi Laura, Turco Annalisa, Di Tano Giuseppe, Campana Carlo, Belloni Armando, Morandi Fabrizio, Mortara Andrea, Cirò Antonio, Senni Michele, Gavazzi Antonello, Frigerio Maria, Oliva Fabrizio, Camici Paolo G,
  
  Abstract
  
  BACKGROUND:
  There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals.
  
  METHODS:
  A total of 684 patients with suspected AM and recent onset of symptoms (70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance.
  
  RESULTS:
  At presentation, 118 patients (26.6%) had left ventricular ejection fraction
  CONCLUSIONS:
  In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction
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• "Summer Shift": A Potential Effect of Sunshine on the Time Onset of ST-Elevation Acute Myocardial Infarction.
  J Am Heart Assoc

  2018 Apr;7(8):. doi: e006878.
  
  Cannistraci Carlo Vittorio, Nieminen Tuomo, Nishi Masahiro, Khachigian Levon M, Viikilä Juho, Laine Mika, Cianflone Domenico, Maseri Attilio, Yeo Khung Keong, Bhindi Ravinay, Ammirati Enrico
  
  Abstract
  
  BACKGROUND:
  ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence.
  
  METHODS AND RESULTS:
  Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent.
  
  CONCLUSIONS:
  The "summer shift" of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis.
  
  © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
  
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• Response by Ammirati et al to Letter Regarding Article, "Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis".
  Circulation

  2018 Mar;137(13):1427-1428. doi: 10.1161/CIRCULATIONAHA.117.032056.
  
  Ammirati Enrico, Cipriani Manlio, Camici Paolo G, Frigerio Maria
  
  
  
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• What is the Best Treatment Option for Coexisting Pelvic Floor Dysfunctions?
  Eur Urol Focus

  2017 Dec;3(6):532-534. doi: 10.1016/j.euf.2018.03.005.
  
  Tutolo Manuela, Ammirati Enrico, Van der Aa Frank
  
  Abstract
  
  Although both intravesical onabotulinumtoxinA injections and sacral neuromodulation could be offered in cases of bladder pain syndrome and overactive bladder syndrome, there is still no scientific agreement on the best option after failure of standard therapies.
  
  Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  
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• Fulminant myocarditis: Characteristics, treatment, and outcomes.
  Anatol J Cardiol

  2018 Apr;19(4):279-286. doi: 10.14744/AnatolJCardiol.2017.8170.
  
  Veronese Giacomo, Ammirati Enrico, Cipriani Manlio, Frigerio Maria
  
  Abstract
  
  Myocarditis is an inflammatory disease of the myocardium with a broad spectrum of clinical presentations, ranging from mild symptoms to severe heart failure. The course of patients with myocarditis is heterogeneous, varying from partial or full clinical recovery in few days to advanced low cardiac output syndrome requiring mechanical circulatory support or heart transplantation. Fulminant myocarditis (FM) is a peculiar clinical condition and is an acute form of myocarditis, whose main characteristic is a rapidly progressive clinical course with the need for hemodynamic support. Despite the common medical belief of the past decades, recent comprehensive data, including a recent registry that compared FM with acute non-FM, highlighted that FM has a poor inhospital outcome, often requires advanced hemodynamic support, and may result in residual left ventricular dysfunction in survivors. This review aimed to provide an updated practical definition of FM, including essentials in the diagnosis and management of the disease. Finally, the outcome of FM was critically revised according to the current published registries focusing on the topic.
  
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• Clinical and Molecular Aspects of Cardiomyopathies: Emerging Therapies and Clinical Trials.
  Heart Fail Clin

  2018 Apr;14(2):161-178. doi: 10.1016/j.hfc.2018.01.001.
  
  Maurizi Niccolò, Ammirati Enrico, Coppini Raffaele, Morrone Amelia, Olivotto Iacopo
  
  Abstract
  
  Cardiomyopathies are diseases of the myocardium, often genetically determined, associated with heterogeneous phenotypes and clinical manifestations. Despite significant progress in the understanding of these conditions, available treatments mostly target late complications, whereas approaches that promise to interfere with the primary mechanisms and natural history are just beginning to surface. The last decade has witnessed the establishment of large international cardiomyopathy registries, paralleled by advances in cardiac imaging and genetic testing, deeper understanding of the pathophysiology and growing involvement by the pharmaceutical industry. As a result, the number of molecular interventions under scrutiny is increasing sharply.
  
  Copyright © 2018 Elsevier Inc. All rights reserved.
  
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• Single-center outbreak of Pneumocystis jirovecii pneumonia in heart transplant recipients.
  Transpl Infect Dis

  2018 Jun;20(3):e12880. doi: 10.1111/tid.12880.
  
  Veronese Giacomo, Ammirati Enrico, Moioli Maria Cristina, Baldan Rossella, Orcese Carlo Andrea, De Rezende Gisele, Veronese Silvio, Masciocco Gabriella, Perna Enrico, Travi Giovanna, Puoti Massimo, Cipriani Manlio, Tiberi Simon, Cirillo Daniela, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Pneumocystis jirovecii pneumonia (PJP) outbreaks are described in solid organ transplant recipients. Few reports suggest interhuman transmission with important infection control implications. We described a large PJP outbreak in heart transplant (HTx) recipients.
  
  METHODS:
  Six cases of PJP occurred in HTx recipients within 10 months in our hospital. Demographics, clinical characteristics, treatment and outcomes were described. To identify contacts among individuals a review of all dates of out-patient visits and patient hospitalizations was performed. Cross exposure was also investigated using genotyping on PJ isolates.
  
  RESULTS:
  At the time of PJP-related hospitalization, patients' mean age was 49 ± standard deviation 4 years, median time from HTx was 8 (25%-75% interquartile range [Q1-Q3] 5-12) months and none of the cases were on prophylaxis. At PJP-related admission, 5 patients had CMV reactivation, of whom 4 were on antiviral preemptive treatment. Median in-hospital stay was 30 (Q1-Q3, 28-48) days; and 2 cases required intensive care unit admission. All patients survived beyond 2 years. Transmission map analysis suggested interhuman transmission in all cases (presumed incubation period, median 90 [Q1-Q3, 64-91] days). Genotyping was performed in 4 cases, demonstrating the same PJ strain in 3 cases.
  
  CONCLUSIONS:
  We described a large PJP cluster among HTx recipients, supporting the nosocomial acquisition of PJP through interhuman transmission. Based on this experience, extended prophylaxis for more than 6 months after HTx could be considered in specific settings. Further work is required to understand its optimal duration and timing based on individual risk factor profiles and to define standardized countermeasures to prevent and limit PJP outbreaks.
  
  © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
  
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• Changes of late gadolinium enhancement extension compared with native T1 mapping early after acute myocarditis.
  Int J Cardiol

  2018 Apr;257():227. doi: 10.1016/j.ijcard.2017.12.056.
  
  Ammirati Enrico, Sormani Paola, Moroni Francesco, Camici Paolo G, Pedrotti Patrizia
  
  
  
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• Fractal analysis of plaque border, a novel method for the quantification of atherosclerotic plaque contour irregularity, is associated with pro-atherogenic plasma lipid profile in subjects with non-obstructive carotid stenoses.
  PLoS One

  2018 ;13(2):e0192600. doi: e0192600.
  
  Moroni Francesco, Magnoni Marco, Vergani Vittoria, Ammirati Enrico, Camici Paolo G
  
  Abstract
  
  BACKGROUND AND AIMS:
  Plaque border irregularity is a known imaging characteristic of vulnerable plaques, but its evaluation heavily relies on subjective evaluation and operator expertise. Aim of the present work is to propose a novel fractal-analysis based method for the quantification of atherosclerotic plaque border irregularity and assess its relation with cardiovascular risk factors.
  
  METHODS AND RESULTS:
  Forty-two asymptomatic subjects with carotid stenosis underwent ultrasound evaluation and assessment of cardiovascular risk factors. Total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) plasma cholesterol and triglycerides concentrations were measured for each subject. Fractal analysis was performed in all the carotid segments affected by atherosclerosis, i.e. 147 segments. The resulting fractal dimension (FD) is a measure of irregularity of plaque profile on long axis view of the plaque. FD in the severest stenosis (main plaque FD,mFD) was 1.136±0.039. Average FD per patient (global FD,gFD) was 1.145±0.039. FD was independent of other plaque characteristics. mFD significantly correlated with plasma HDL (r = -0.367,p = 0.02) and triglycerides-to-HDL ratio (r = 0.480,p = 0.002).
  
  CONCLUSIONS:
  Fractal analysis is a novel, readily available, reproducible and inexpensive technique for the quantitative measurement of plaque irregularity. The correlation between low HDL levels and plaque FD suggests a role for HDL in the acquisition of morphologic features of plaque instability. Further studies are needed to validate the prognostic value of fractal analysis in carotid plaques evaluation.
  
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• Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in Non-neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic Review of the Literature.
  Eur Urol

  2018 Mar;73(3):406-418. doi: 10.1016/j.eururo.2017.11.002.
  
  Tutolo Manuela, Ammirati Enrico, Heesakkers John, Kessler Thomas M, Peters Kenneth M, Rashid Tina, Sievert Karl-Dietrich, Spinelli Michele, Novara Giacomo, Van der Aa Frank, De Ridder Dirk
  
  Abstract
  
  CONTEXT:
  Neuromodulation is considered in patients with non-neurogenic lower urinary tract dysfunction (LUTD) not responsive to conservative treatment.
  
  OBJECTIVE:
  To systematically review the available studies on efficacy and safety of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) in non-neurogenic LUTDs not responsive to conservative treatments.
  
  EVIDENCE ACQUISITION:
  A literature research was conducted in PubMed/Medline and Scopus, restricted to articles in English, published between January 1998 and June 2017, with at least 20 patients and 6 mo of follow-up.
  
  EVIDENCE SYNTHESIS:
  Twenty-one reports were identified. Concerning SNM, the improvement of ?50% in leakage episodes ranged widely between 29% and 76%. Overall dry rate ranged between 43% and 56%. Overall success/improvement rate in PTNS varied between 54% and 59%. Symptom improvement or efficacy in interstitial cystitis/bladder pain syndrome patients appeared to be lower compared with other indications in both techniques. Safety data showed fewer side effects in patients submitted to PTNS.
  
  CONCLUSIONS:
  Neuromodulation gives good results and is a safe therapy for patients with overactive bladder or chronic nonobstructive urinary retention with long-lasting efficacy. Moreover, PTNS has been shown to have good success rates and fewer side effects compared with SNM. These data have to be confirmed with long-term follow-up.
  
  PATIENT SUMMARY:
  Sacral neuromodulation can improve low urinary tract symptoms in selected patients; it appears to be a safe therapy for nonresponders to standard medical therapies. Percutaneous tibial nerve stimulation (PTNS) is a less invasive technique that gives good results in short time with fewer side effects. However, we must consider that PTNS has not been tested in the long term and results are lower if compared with SNM.
  
  Copyright © 2017 European Association of Urology. All rights reserved.
  
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• Female gender and mortality risk in decompensated heart failure.
  Eur J Intern Med

  2018 May;51():34-40. doi: 10.1016/j.ejim.2018.01.011.
  
  Scrutinio Domenico, Guida Pietro, Passantino Andrea, Lagioia Rocco, Raimondo Rosa, Venezia Mario, Ammirati Enrico, Oliva Fabrizio, Stucchi Miriam, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Still there is conflicting evidence about gender-related differences in prognosis among patients with heart failure. This prognostic uncertainty may have implications for risk stratification and planning management strategy. The aim of the present study was to explore the association between gender and one-year mortality in patients admitted with acute decompensated heart failure (ADHF).
  
  METHODS:
  We studied 1513 patients. The Cumulative Incidence Function (CIF) method was used to estimate the absolute rate of mortality, heart transplantation (HT)/ventricular assist device (VAD) implantation, and survival free of HT/VAD implantation at 1year. An interaction analysis was performed to assess the association between covariates, gender, and mortality risk. Propensity score matching and Cox regression were used to compare mortality rates in the gender subgroups.
  
  RESULTS:
  The CIF estimates of 1-year mortality, HT/VAD implantation, and survival free of HT/VAD implantation at 1year were 33.1%, 7.0%, and 59.9% for women and 30.2%, 10.2%, and 59.6% for men, respectively. Except for diabetes, there was no significant interaction between gender, covariates, and mortality risk. In the matched cohort, the hazard ratio of death for women was 1.19 (95% confidence intervals [CIs]: 0.90-1.59; p=.202). After adjusting for age and baseline risk, the hazard ratio of death for women was 1.18 (95% CIs: 0.95-1.43; p=.127). The use of gender-specific predictive models did not allow improving the accuracy of risk prediction.
  
  CONCLUSIONS:
  Our data strongly suggest that women and men have comparable outcome in the year following a hospitalization for ADHF.
  
  Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Still poor prognosis for patients with giant cell myocarditis in the era of temporary mechanical circulatory supports.
  Int J Cardiol

  2018 Feb;253():122-123. doi: 10.1016/j.ijcard.2017.10.124.
  
  Ammirati Enrico, Camici Paolo G
  
  
  
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• Heart rate as a prognostic marker and therapeutic target in acute and chronic heart failure.
  Int J Cardiol

  2018 Feb;253():97-104. doi: 10.1016/j.ijcard.2017.09.191.
  
  Oliva Fabrizio, Sormani Paola, Contri Rachele, Campana Carlo, Carubelli Valentina, Cirò Antonio, Morandi Fabrizio, Di Tano Giuseppe, Mortara Andrea, Senni Michele, Metra Marco, Ammirati Enrico
  
  Abstract
  
  Since increased heart rate (HR) is associated with higher mortality in several cardiac disorders, HR is considered not only a physiological indicator but also a prognostic and biological marker. In heart failure (HF), it represents a therapeutic target in chronic phase. The use or up-titration of beta-blockers, a milestone in HF with reduced left ventricular ejection fraction (LVEF) treatment, is at times limited by patients' hemodynamic profile or intolerance. Ivabradine, a HR-lowering drug inhibiting the f-current in pacemaker cells, has been shown to improve outcome in patients with chronic HF, in sinus rhythm with increased HR beyond beta-blocker therapy. The rationale for this review is to update the role of HR as a prognostic biomarker and a potential therapeutic target in other scenarios than chronic HF; namely, in patients with coexisting atrial fibrillation (AF), in HF with preserved LVEF (HFpEF), in acute HF, and in patients discharged after an episode of acute HF. Preliminary studies and case reports that evaluated the use of ivabradine in the setting of acute HF will be summarized. Recent results of HR reduction in the setting of HFpEF with ivabradine will be presented. Finally, data from large registries and trials that evaluated the prognostic impact of HR in patients with acute HF and sinus rhythm or AF will be reviewed, showing that only patients in sinus rhythm may benefit from HR reduction.
  
  Copyright © 2017. Published by Elsevier B.V.
  
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• New concepts in fulminant myocarditis and risk of cardiac mortality.
  Oncotarget

  2017 Oct;8(49):84624-84625. doi: 10.18632/oncotarget.21393.
  
  Ammirati Enrico, Cipriani Manlio, Camici Paolo G
  
  
  
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• Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes.
  J Am Coll Cardiol

  2017 Nov;70(19):2363-2375. doi: 10.1016/j.jacc.2017.09.023.
  
  Brambatti Michela, Matassini Maria Vittoria, Adler Eric D, Klingel Karin, Camici Paolo G, Ammirati Enrico
  
  Abstract
  
  BACKGROUND:
  Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.
  
  OBJECTIVES:
  Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.
  
  METHODS:
  The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.
  
  RESULTS:
  Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (?16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).
  
  CONCLUSIONS:
  EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.
  
  Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Relation between characteristics of carotid atherosclerotic plaques and brain white matter hyperintensities in asymptomatic patients.
  Sci Rep

  2017 Sep;7(1):10559. doi: 10559.
  
  Ammirati Enrico, Moroni Francesco, Magnoni Marco, Rocca Maria A, Messina Roberta, Anzalone Nicoletta, De Filippis Costantino, Scotti Isabella, Besana Francesca, Spagnolo Pietro, Rimoldi Ornella E, Chiesa Roberto, Falini Andrea, Filippi Massimo, Camici Paolo G
  
  Abstract
  
  White matter hyperintensities (WMH) can be incidentally found in patients with carotid atherosclerosis on brain magnetic resonance imaging (MRI). We investigated the relationship between WMH and characteristics of carotid plaques in asymptomatic patients without indication for carotid revascularization. We prospectively screened 235 consecutive patients with carotid stenosis
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• Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis.
  Circulation

  2017 Aug;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386.
  
  Ammirati Enrico, Cipriani Manlio, Lilliu Marzia, Sormani Paola, Varrenti Marisa, Raineri Claudia, Petrella Duccio, Garascia Andrea, Pedrotti Patrizia, Roghi Alberto, Bonacina Edgardo, Moreo Antonella, Bottiroli Maurizio, Gagliardone Maria P, Mondino Michele, Ghio Stefano, Totaro Rossana, Turazza Fabio M, Russo Claudio F, Oliva Fabrizio, Camici Paolo G, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM.
  
  METHODS:
  The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms
  RESULTS:
  In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (
  CONCLUSIONS:
  Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.
  
  © 2017 American Heart Association, Inc.
  
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• Management of male and female neurogenic stress urinary incontinence in spinal cord injured (SCI) patients using adjustable continence therapy.
  Urologia

  2017 Aug;84(3):165-168. doi: 10.5301/uj.5000242.
  
  Ammirati Enrico, Manassero Alberto, Giammò Alessandro, Carone Roberto
  
  Abstract
  
  INTRODUCTION:
  Artificial urinary sphincter (AUS) is an option for the treatment of neurogenic stress urinary incontinence (nSUI), but complications and re-operation rates are high, and there is no clear indication from guidelines (1). The aim of our study is to evaluate the effectiveness of a less invasive continence device in neurogenic population: Adjustable Continence Therapy ProACT/ACT®.
  
  METHODS:
  We retrospectively includedpatients with spinal cord injuries in this study, complaining of nSUI and treated at our Institution with Pro-ACT/ACT® implantation. Diagnosis of nSUI was achieved with clinical history data collection and video-urodynamic testing.
  
  RESULTS:
  We treated 13 males and 3 females by proACT/ACT device, mean age 47.5 years (range 27-71). Fifteen implantations were performed bilaterally under spinal anesthesia and under fluoroscopic control; in one male patient, only the right balloon was implanted. Mean refilling number was 2.8 (range 0-6), and mean final volume was 3.6 ml. No patient reported any perioperative complications according to Clavien-Dindo. Follow-up was 37 months (range 7-156). Five patients (31%) underwent device explantation for deflate in one case, erosion or migration in three cases (18%), and infection in one case. About 43.75% of patients were dry and 18.75% improved more than 50% their urine loss, 37.5% of patients improved less than 50%, and no one reported worsening of incontinence.
  
  CONCLUSIONS:
  Implantation of proACT/ACT® device is safe and a minimally invasive procedure also in neurological patients, with a relative low rate of intra and postoperative complications. Efficacy is good, although slightly lower than the results in non-neurological patients.
  
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• Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4 T Cell Differentiation via PI3K p110?-Akt-Mediated Signals.
  Cell Metab

  2017 Mar;25(3):593-609. doi: 10.1016/j.cmet.2017.01.008.
  
  Mauro Claudio, Smith Joanne, Cucchi Danilo, Coe David, Fu Hongmei, Bonacina Fabrizia, Baragetti Andrea, Cermenati Gaia, Caruso Donatella, Mitro Nico, Catapano Alberico L, Ammirati Enrico, Longhi Maria P, Okkenhaug Klaus, Norata Giuseppe D, Marelli-Berg Federica M
  
  Abstract
  
  Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4 T cells. Memory CD4 T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4 T cell differentiation into CD44-CCR7-CD62L-CXCR3-LFA1 effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4 T cells and dendritic cells and was mediated via direct exposure of CD4 T cells to palmitate, leading to increased activation of a PI3K p110?-Akt-dependent pathway upon priming.
  
  Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
  
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• Relationship among body mass index, NT-proBNP, and mortality in decompensated chronic heart failure.
  Heart Lung

  2017 ;46(3):172-177. doi: 10.1016/j.hrtlng.2017.01.005.
  
  Scrutinio Domenico, Passantino Andrea, Guida Pietro, Ammirati Enrico, Oliva Fabrizio, Sarzi Braga Simona, La Rovere Maria Teresa, Lagioia Rocco, Frigerio Maria, Di Somma Salvatore
  
  Abstract
  
  BACKGROUND:
  Obesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI).
  
  OBJECTIVES:
  To investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF).
  
  METHODS:
  This was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis.
  
  RESULTS:
  During the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79-1.33; p = 0.862) for patients with a BMI of 25.0-29.9 kg/m and 0.83 (95% CIs 0.61-1.12; p = 0.213) for patients with a BMI ? 30 kg/m. NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction.
  
  CONCLUSIONS:
  Obesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories.
  
  Copyright © 2017 Elsevier Inc. All rights reserved.
  
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• Clinical relevance of biomarkers for the identification of patients with carotid atherosclerotic plaque: Potential role and limitations of cysteine protease legumain.
  Atherosclerosis

  2017 Feb;257():248-249. doi: 10.1016/j.atherosclerosis.2017.01.003.
  
  Ammirati Enrico, Fogacci Federica
  
  
  
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• A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis.
  Int Braz J Urol

  2017 ;43(1):134-141. doi: 10.1590/S1677-5538.IBJU.2016.0302.
  
  Tutolo Manuela, Ammirati Enrico, Castagna Giulia, Klockaerts Katrien, Plancke Hendrik, Ost Dieter, Van der Aa Frank, De Ridder Dirk
  
  Abstract
  
  OBJECTIVE:
  To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC).
  
  MATERIALS AND METHODS:
  Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O'Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain.
  
  RESULTS:
  Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O'Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO.
  
  CONCLUSIONS:
  Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.
  
  Copyright® by the International Brazilian Journal of Urology.
  
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• The key clues to reach the diagnosis of Loeffler endomyocardial fibrosis associated with eosinophilic granulomatosis with polyangiitis.
  J Cardiovasc Med (Hagerstown)

  2017 Oct;18(10):831-832. doi: 10.2459/JCM.0000000000000496.
  
  Ammirati Enrico, Sirico Domenico, Brevetti Linda, Scudiero Laura, Artioli Diana, Pedrotti Patrizia, Frigerio Maria
  
  
  
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• Quantitative changes in late gadolinium enhancement at cardiac magnetic resonance in the early phase of acute myocarditis.
  Int J Cardiol

  2017 Mar;231():216-221. doi: 10.1016/j.ijcard.2016.11.282.
  
  Ammirati Enrico, Moroni Francesco, Sormani Paola, Peritore Angelica, Milazzo Angela, Quattrocchi Giuseppina, Cipriani Manlio, Oliva Fabrizio, Giannattasio Cristina, Frigerio Maria, Roghi Alberto, Camici Paolo G, Pedrotti Patrizia
  
  Abstract
  
  BACKGROUND:
  The presence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has diagnostic and prognostic value in patients with acute myocarditis (AM). Aim of our study was to quantify the changes in LGE extension (LGE%) early after AM and evaluate its relations with biventricular function and morphology.
  
  METHODS:
  We investigated 76 consecutive patients with AM (acute onset of chest pain/heart failure/ventricular arrhythmias not explained by other causes, and raised troponin) that met CMR criteria based on myocardial oedema at T2-weighted images and LGE on post-contrast images at median time of 6days from onset of symptoms. We quantified LGE% at baseline and after 148days in 49 patients.
  
  RESULTS:
  Median left ventricular (LV)-ejection fraction (EF) was 64% (interquartile range [Q1-Q3]: 56-67%), and LGE% 9.4% (Q1-Q3: 7.5-13.2%). LGE% was correlated with LV end-systolic volume index (LV-ESVi; r=+0.34; p=0.003). LGE% was inversely correlated with LV-EF (r=-0.31; p=0.009) and time to CMR scan (r=-0.25; p=0.028). In the 49 patients with a second CMR scan, despite no significant variations in LV-EF, a significant decrease of LGE% was observed (p
  CONCLUSIONS:
  In the acute phase of AM the LGE extension is a dynamic process that reflects impairment of LV function and is time dependent. LGE% appears one of the CMR parameters with the largest relative variations in the first months after AM.
  
  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
  
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• Predictors of Long-Term Mortality in Older Patients Hospitalized for Acutely Decompensated Heart Failure: Clinical Relevance of Natriuretic Peptides.
  J Am Geriatr Soc

  2017 Apr;65(4):822-826. doi: 10.1111/jgs.14561.
  
  Passantino Andrea, Guida Piero, Lagioia Rocco, Ammirati Enrico, Oliva Fabrizio, Frigerio Maria, Scrutinio Domenico
  
  Abstract
  
  BACKGROUND:
  Acute heart failure is a common cause of hospitalization among older patients. Optimized risk stratification might improve the outcome for this subgroup of patients. Natriuretic peptides have been used in the diagnosis of heart failure and in evaluating the prognosis of patients hospitalized for heart failure. However, their utility in the elderly is still controversial.
  
  OBJECTIVE:
  To evaluate long-term survival and prognostic factors for elderly patients hospitalized for acutely decompensated heart failure and evaluate the prognostic utility of NT-proBNP.
  
  DESIGN:
  Retrospective, multicenter cohort study.
  
  SETTING:
  Two Italian hospitals.
  
  PARTICIPANTS:
  Two hundred seventy-nine patients, aged >75 years; hospitalized for decompensation of chronic, established heart failure.
  
  METHODS:
  Baseline clinical data were recorded at admission. The primary outcome was long-term mortality.
  
  RESULTS:
  In-hospital, 12-month and 5-year mortality were, respectively, 10%, 36%, and 77%. NT-proBNP, eGFR, hemoglobin, diabetes, systolic blood pressure, and moderate to severe tricuspid regurgitation were independently associated with long-term prognosis and were entered into a multivariate model, with a C-index of 0.765 for the determination of high-risk patients. The C-index for NT-proBNP to predict mortality at 2 and 12 months was 0.740 and 0.756, respectively. The optimal cutoff point for predicting mortality at 2 and 12 months was 8,444 pg/mL (hazard ratio 5.33) and 8,275 pg/mL (hazard ratio 6.03), respectively.
  
  CONCLUSION:
  Elderly patients hospitalized for acutely decompensated heart failure had a poor long-term outcome, especially in the subgroup with reduced ejection fraction (EF). In addition to EF and comorbidities, NT-pro-BNP remained independently prognostic among elderly patients hospitalized with heart failure.
  
  © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.
  
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• Female primary bladder neck obstruction: role of videourodynamics and treatment options in a rare clinical entity.
  Urologia

  2017 Apr;84(2):109-112. doi: 10.5301/uro.5000203.
  
  Ammirati Enrico, Manassero Alberto, Giammò Alessandro, Marson Francesco, Gurioli Alberto, Carone Roberto
  
  Abstract
  
  INTRODUCTION:
  Primary female bladder neck obstruction is a rare clinical condition characterized by the absence/incomplete bladder neck opening during the voiding phase of micturition.
  
  METHODS:
  We present the cases of two women complaining dysuria, abdominal straining and sensation of incomplete bladder emptying. Videourodynamic evaluation was fundamental for a correct diagnosis.
  
  RESULTS:
  Videourodynamic evaluation showed a high detrusor pressure during emptying phase, partial use of abdominal strain, very low urine flow rate and significant postvoid residual; imaging showed a defect in the physiological funneling of the bladder neck, absent or incomplete. The first step therapy is represented by oral alpha-blockers and clean intermittent self-catheterization in case of high postvoid residual. Surgical operations, such as bladder neck incision and resection, represent the last option.
  
  CONCLUSIONS:
  In our experience, bladder neck obstruction is a rare condition in women and only a complete clinical evaluation associated with videourodynamic study can lead to an appropriate diagnosis and treatment.
  
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• Extreme giant aneurysms of three coronary arteries causing heart failure as late sequelae of Kawasaki disease.
  Eur Heart J

  2017 Mar;38(10):759-760. doi: 10.1093/eurheartj/ehw510.
  
  Ammirati Enrico, Burns Jane C, Moreo Antonella, Daniels Lori B, Oliva Fabrizio
  
  
  
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• Long-term prognostic implications of the ADHF/NT-proBNP risk score in patients admitted with advanced heart failure.
  J Heart Lung Transplant

  2016 Oct;35(10):1264-1267. doi: 10.1016/j.healun.2016.07.007.
  
  Scrutinio Domenico, Guida Pietro, Ammirati Enrico, Oliva Fabrizio, Frigerio Maria
  
  
  
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• Circulating CD14+ and CD14CD16- classical monocytes are reduced in patients with signs of plaque neovascularization in the carotid artery.
  Atherosclerosis

  2016 Dec;255():171-178. doi: 10.1016/j.atherosclerosis.2016.10.004.
  
  Ammirati Enrico, Moroni Francesco, Magnoni Marco, Di Terlizzi Simona, Villa Chiara, Sizzano Federico, Palini Alessio, Garlaschelli Katia, Tripiciano Fernanda, Scotti Isabella, Catapano Alberico Luigi, Manfredi Angelo A, Norata Giuseppe Danilo, Camici Paolo G
  
  Abstract
  
  BACKGROUND AND AIMS:
  Monocytes are known to play a key role in the initiation and progression of atherosclerosis and contribute to plaque destabilization through the generation of signals that promote inflammation and neoangiogenesis. In humans, studies investigating the features of circulating monocytes in advanced atherosclerotic lesions are lacking.
  
  METHODS:
  Patients (mean age 69 years, 56% males) with intermediate asymptomatic carotid stenosis (40-70% in diameter) were evaluated for maximal stenosis in common carotid artery, carotid bulb and internal carotid artery, overall disease burden as estimated with total plaque area (TPA), greyscale and neovascularization in 244 advanced carotid plaques. Absolute counts of circulating CD14+ monocytes, of classical (CD14CD16-), intermediate (CD14CD16+) and non-classical (CD14CD16+) monocytes and HLA-DR+ median fluorescence intensity for each subset were evaluated with flow cytometry.
  
  RESULTS:
  No correlation was found between monocytes and overall atherosclerotic burden, nor with high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). In contrast, plaque signs of neovascularization were associated with significantly lower counts of circulating CD14+ monocytes (297 versus 350 cells/mm, p = 0.039) and of classical monocytes (255 versus 310 cells/mm, p = 0.029).
  
  CONCLUSIONS:
  Neovascularized atherosclerotic lesions selectively associate with lower blood levels of CD14+ and CD14CD16- monocytes independently of systemic inflammatory activity, as indicated by normal hsCRP levels. Whether the reduction of circulating CD14+ and CD14CD16- monocytes is due to a potential redistribution of these cell types into active lesions remains to be explored.
  
  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
  
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• Nondilated Left Ventricle as an Adding Clue Helping Discrimination Between Acute Myocarditis From Other Cardiomyopathies.
  J Am Coll Cardiol

  2016 Oct;68(16):1817-1818. doi: 10.1016/j.jacc.2016.05.101.
  
  Ammirati Enrico, Pedrotti Patrizia, Roghi Alberto
  
  
  
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• Carotid atherosclerosis, silent ischemic brain damage and brain atrophy: A systematic review and meta-analysis.
  Int J Cardiol

  2016 Nov;223():681-687. doi: 10.1016/j.ijcard.2016.08.234.
  
  Moroni Francesco, Ammirati Enrico, Magnoni Marco, D'Ascenzo Fabrizio, Anselmino Matteo, Anzalone Nicoletta, Rocca Maria Assunta, Falini Andrea, Filippi Massimo, Camici Paolo G
  
  Abstract
  
  BACKGROUND:
  The widespread use of brain imaging has led to increased recognition of subclinical brain abnormalities, including white matter hyperintensities (WMH) and silent brain infarctions (SBI), which have a vascular origin, and have been associated to a high risk of stroke, disability and dementia. Carotid atherosclerosis (CA) may be causative in the development of WMH, SBI and eventually brain atrophy. Aim of the present systematic review and meta-analysis was to assess the existing evidence linking CA to WMH, SBI and brain atrophy.
  
  METHODS:
  The relation between CA and WMH, SBI and brain atrophy was investigated through the systematic search of online databases up to September 2015 and manual searching of references and related citations. Pooled estimates were calculated by random-effects model, using restricted maximum likelihood method with inverse variance weighting method.
  
  RESULTS:
  Of the 3536 records identified, fifteen were included in the systematic review and 9 were found to be eligible for the meta-analysis. CA was significantly associated with the presence of WMH (Odds Ratio, OR 1.42, confidence interval, CI 1.22-1.66, p
  CONCLUSIONS:
  CA was found to be associated to WMH and SBI. While no causative association can be inferred from the available data, the presence of carotid plaque may be considered a significant risk factor for subclinical cerebral damage.
  
  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
  
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• Prognostic impact of comorbidities in hospitalized patients with acute exacerbation of chronic heart failure.
  Eur J Intern Med

  2016 Oct;34():63-67. doi: 10.1016/j.ejim.2016.05.020.
  
  Scrutinio Domenico, Passantino Andrea, Guida Pietro, Ammirati Enrico, Oliva Fabrizio, Braga Simona Sarzi, La Rovere Maria Teresa, Lagioia Rocco, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF).
  
  METHODS:
  1119 patients admitted for AE-CHF and with NT-proBNP levels >900pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all-cause mortality.
  
  RESULTS:
  During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180days after admission. Increasing age (p=.012), obesity (p=.037), atrial fibrillation (p=.030), CHD (p=.015), CLD (p=.001), RI (p<.001 and anemia were independently associated with all-cause mortality. most of the prognostic impact chd took place within first after admission. male gender was mortality beyond compared normal weight obesity better overall survival. obese patients however had significantly lower nt-probnp concentrations less frequently presented hypotension hyponatremia severe left ventricular systolic dysfunction despite a similar prevalence dyspnea at>
  CONCLUSIONS:
  Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions.
  
  Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• A prospective comparison of mid-term outcomes in patients treated with heart transplantation with advanced age donors versus left ventricular assist device implantation.
  Interact Cardiovasc Thorac Surg

  2016 Oct;23(4):584-92. doi: 10.1093/icvts/ivw164.
  
  Ammirati Enrico, Cipriani Manlio G, Varrenti Marisa, Colombo Tiziano, Garascia Andrea, Cannata Aldo, Pedrazzini Giovanna, Benazzi Elena, Milazzo Filippo, Oliva Fabrizio, Gagliardone Maria P, Russo Claudio F, Frigerio Maria
  
  Abstract
  
  OBJECTIVES:
  In Europe, the age of heart donors is constantly increasing. Ageing of heart donors limits the probability of success of heart transplantation (HTx). The aim of this study is to compare the outcome of patients with advanced heart failure (HF) treated with a continuous-flow left ventricular assist device (CF-LVAD) with indication as bridge to transplantation (BTT) or bridge to candidacy (BTC) versus recipients of HTx with the donor's age above 55 years (HTx with donors >55 years).
  
  METHODS:
  we prospectively evaluated 301 consecutive patients with advanced HF treated with a CF-LVAD (n = 83) or HTx without prior bridging (n = 218) in our hospital from January 2006 to January 2015. We compared the outcome of CF-LVAD-BTT (n = 37) versus HTx with donors >55 years (n = 45) and the outcome of CF-LVAD-BTT plus BTC (n = 62) versus HTx with donors >55 years at the 1- and 2-year follow-up. Survival was evaluated according to the first operation.
  
  RESULTS:
  The perioperative (30-day) mortality rate was 0% in the LVAD-BTT group vs 20% (n = 9) in the HTx group with donors >55 years (P = 0.003). Perioperative mortality occurred in 5% of the LVAD-BTT/BTC patients (n = 3) and in 20% of the HTx with donors >55 year group (P = 0.026). Kaplan-Meier curves estimated a 2-year survival rate of 94.6% in CF-LVAD-BTT vs 68.9% in HTx with donors >55 years [age- and sex-adjusted hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.08-0.81; P = 0.02 in favour of CF-LVAD]. Considering the post-HTx outcome, a trend in favour of CF-LVAD-BTT was also observed (age- and sex-adjusted HR 0.45; 95% CI 0.17-1.16; P = 0.09 in favour of CF-LVAD), whereas CF-LVAD-BTT/BTC showed a similar survival at 2 years compared with HTx with donors >55 years, both censoring the follow-up at the time of HTx and considering the post-HTx outcome.
  
  CONCLUSIONS:
  Early and mid-term outcomes of patients treated with a CF-LVAD with BTT indication seem better than HTx with old donors. It must be emphasized that up to 19% of patients in the CF-LVAD/BTT group underwent transplantation in an urgent condition due to complications related to the LVAD. At the 2-year follow-up, CF-LVAD with BTT and BTC indications have similar outcome than HTx using old heart donors. These results must be confirmed in a larger and multicentre population and extending the follow-up.
  
  © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• A minimum of 1-year follow-up for MiniArc single incision slings compared to Monarc transobturator slings: An analysis to evaluate durability of continence and medium-term outcomes.
  Neurourol Urodyn

  2017 Mar;36(3):803-807. doi: 10.1002/nau.23036.
  
  Tutolo Manuela, De Ridder Dirk J M K, Montorsi Francesco, Castagna Giulia, Deprest Jan, Schellart Renè P, Ammirati Enrico, Van Der Aa Frank
  
  Abstract
  
  AIMS:
  To compare efficacy and safety of two commercially available single incision slings (SIS) and trans-obturator vaginal tapes (TOT), namely MiniArc? and Monarc? slings, and report the results at 5-year follow-up.
  
  METHODS:
  A retrospective-observational study of prospectively collected data was conducted on 381 women with primary stress urinary incontinence (SUI) in a single tertiary referral center. Patients treated with MiniArc? and Monarc? were compared. Data regarding intraoperative and post-operative outcomes were collected and compared. Kaplan-Meier analyses assessed continence rate (CR), objective cure (OC) rate, de novo overactive bladder symptoms (OAB), surgical failure (SF), and erosion free rates at 1-, 3-, and 5-year follow-up. The log-rank test was used to compare efficacy and complication between patients stratified according to the type of surgery.
  
  RESULTS:
  Median follow-up was 60 months. Of 381 patients, 215 (56%) were treated with Monarc? slings and 166 (44%) with MiniArc?. The two groups were homogeneous in terms of pre-operative characteristics. At 5-year follow-up, no difference was found in CR between Monarc? and Miniarc? patients (87% vs. 89%; P?=?0.41). Monarc? showed better OAB free rates (97% vs. 92%; P?=?0.012). No significant differences have been found in terms of SF, erosion, and OC rates. These results are limited by their retrospective nature.
  
  CONCLUSIONS:
  We demonstrated that the short-term results of MiniArc?, are maintained over time, defining the comparability of the two slings at 5 years in terms of subjective and objective outcomes and complications. Neurourol. Urodynam. 36:803-807, 2017. © 2016 Wiley Periodicals, Inc.
  
  © 2016 Wiley Periodicals, Inc.
  
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• Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives.
  Eur J Heart Fail

  2016 Sep;18(9):1106-18. doi: 10.1002/ejhf.541.
  
  Ammirati Enrico, Contri Rachele, Coppini Raffaele, Cecchi Franco, Frigerio Maria, Olivotto Iacopo
  
  Abstract
  
  Hypertrophic cardiomyopathy (HCM) is entering a phase of intense translational research that holds promise for major advances in disease-specific pharmacological therapy. For over 50?years, however, HCM has largely remained an orphan disease, and patients are still treated with old drugs developed for other conditions. While judicious use of the available armamentarium may control the clinical manifestations of HCM in most patients, specific experience is required in challenging situations, including deciding when not to treat. The present review revisits the time-honoured therapies available for HCM, in a practical perspective reflecting real-world scenarios. Specific agents are presented with doses, titration strategies, pros and cons. Peculiar HCM dilemmas such as treatment of dynamic outflow obstruction, heart failure caused by end-stage progression and prevention of atrial fibrillation and ventricular arrhythmias are assessed. In the near future, the field of HCM drug therapy will rapidly expand, based on ongoing efforts. Approaches such as myocardial metabolic modulation, late sodium current inhibition and allosteric myosin inhibition have moved from pre-clinical to clinical research, and reflect a surge of scientific as well as economic interest by academia and industry alike. These exciting developments, and their implications for future research, are discussed.
  
  © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.
  
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• Incremental utility of prognostic variables at discharge for risk prediction in hospitalized patients with acutely decompensated chronic heart failure.
  Heart Lung

  2016 ;45(3):212-9. doi: 10.1016/j.hrtlng.2016.03.004.
  
  Scrutinio Domenico, Passantino Andrea, Guida Pietro, Ammirati Enrico, Oliva Fabrizio, Lagioia Rocco, Sarzi Braga Simona, Agostoni Piergiuseppe, Frigerio Maria
  
  Abstract
  
  OBJECTIVES:
  To assess the incremental prognostic utility of discharge serum creatinine (SCr), systolic blood pressure (SBP), and NT-proBNP and sodium concentrations in hospitalized patients with acutely decompensated chronic heart failure.
  
  BACKGROUND:
  Whether key prognostic variables at discharge provide incremental prognostic information beyond that provided by a model based on admission variables (referent) remains incompletely defined.
  
  METHODS:
  The primary outcome was a composite of death, urgent heart transplantation, or ventricular assist device implantation at 1 year. The gain in predictive performance was assessed using C index, Bayesian Information Criterion, and Net Reclassification Improvement.
  
  RESULTS:
  The best fit was obtained when discharge NT-proBNP was added to the referent model. No interaction between admission and discharge NT-proBNP was found. Discharge SCr, SBP, and sodium did not improve goodness-of-fit.
  
  CONCLUSIONS:
  Admission and discharge NT-proBNP provide complementary and independent prognostic information; as such, they should be taken into account concurrently.
  
  Copyright © 2016 Elsevier Inc. All rights reserved.
  
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• [Heart rate and outcome in patients with acute and chronic heart failure].
  G Ital Cardiol (Rome)

  2016 Mar;17(3 Suppl 1):3S-16. doi: 10.1714/2192.23678.
  
  Oliva Fabrizio, Ammirati Enrico, Campana Carlo, Carubelli Valentina, Cirò Antonio, Di Tano Giuseppe, Mortara Andrea, Senni Michele, Morandi Fabrizio, Metra Marco
  
  Abstract
  
  Heart rate (HR) is not only a physical sign but also a biomarker. High HR in several cardiac disorders is associated with increased mortality. In heart failure (HF), HR represents an important therapeutic target, both in the acute and chronic phase. Beta-blockers are a milestone of recommended treatments in HF patients with reduced ejection fraction. However, hemodynamic profile or intolerance may limit the use or the optimization of beta-blocker treatment, both during hospitalization and outpatient follow-up. More recently, ivabradine has become available, a drug that lowers HR by blocking the I(f) current in the pacemaker cells at the sinoatrial node level. In the SHIFT trial, ivabradine was shown to improve the outcome of patients with chronic HF, in sinus rhythm, with HR >70 b/min while on beta-blockers. Preliminary data have shown that this drug has a good safety profile and lowers effectively HR even during hospitalization due to worsening HF. However, further studies are warranted to understand if an earlier administration of ivabradine can lead to a better prognosis beyond symptom control and improved hemodynamics. In patients with atrial fibrillation and HF, the target is the restoration of sinus rhythm, alternatively rate control should be pursued with beta-blockers, amiodarone or digitalis, even if there is no clear evidence of an association between ventricular rate response in patients with atrial fibrillation at discharge after an HF hospitalization and major cardiovascular events. In this review, the studies that point to a role of HR both as a biomarker and a therapeutic target in patients with acute and chronic HF are described. In addition, the proportions of patients who do not reach target HR values at discharge after an acute decompensated HF episode or in the chronic phase are evaluated based on the Italian registries.
  
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• Tricuspid Annular Plane Systolic Excursion in Acute Decompensated Heart Failure: Relevance for Risk Stratification.
  Can J Cardiol

  2016 Aug;32(8):963-9. doi: 10.1016/j.cjca.2015.09.019.
  
  Scrutinio Domenico, Catanzaro Raffaella, Santoro Daniela, Ammirati Enrico, Passantino Andrea, Oliva Fabrizio, La Rovere Maria Teresa, De Salvo Maria, Guzzetti Daniela, Vaninetti Raffaella, Venezia Mario, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Although the prognostic value of right ventricular dysfunction in chronic heart failure (HF) has been studied extensively, it remains insufficiently characterized in the setting of acute decompensated HF (ADHF). We sought to assess whether measurement of tricuspid annular plane systolic excursion (TAPSE) or TAPSE-to-estimated pulmonary arterial systolic pressure (ePASP) ratio allows improvement of risk prediction in ADHF.
  
  METHODS:
  Four hundred ninety-nine patients with ADHF were studied. Cox regression analyses were used to analyze the association of TAPSE and TAPSE-to-ePASP ratio with 1-year mortality and logistic regression analyses to analyze the association of the 2 variables of interest with adverse in-hospital outcome (AiHO) (in-hospital death plus worsening HF).
  
  RESULTS:
  During the 365-day follow-up, 143 patients (28.7%) died. At univariable analysis, both TAPSE (P = 0.026) and TAPSE-to-ePASP ratio (P
  CONCLUSIONS:
  Our data strongly suggest that early assessment of TAPSE or TAPSE-to-ePASP ratio does not improve prediction of 1-year mortality over other key risk markers in ADHF. Nonetheless, the TAPSE-to-ePASP ratio did appear to be independently associated with AiHO.
  
  Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
  
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• Reduction of Circulating HLA-DR T Cell Levels Correlates With Increased Carotid Intraplaque Neovascularization and Atherosclerotic Burden.
  JACC Cardiovasc Imaging

  2016 Oct;9(10):1231-1233. doi: 10.1016/j.jcmg.2015.10.010.
  
  Ammirati Enrico, Magnoni Marco, Moroni Francesco, Di Terlizzi Simona, Scotti Isabella, Villa Chiara, Sizzano Federico, Impellizzeri Matteo, Fanelli Giovanna, Esposito Gloria, Chiesa Roberto, Camici Paolo G
  
  
  
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• A life-threatening presentation of eosinophilic granulomatosis with polyangiitis.
  J Cardiovasc Med (Hagerstown)

  2016 Dec;17 Suppl 2():e109-e111. doi: 10.2459/JCM.0000000000000330.
  
  Ammirati Enrico, Cipriani Manlio, Musca Francesco, Bonacina Edgardo, Pedrotti Patrizia, Roghi Alberto, Astaneh Arash, Schroeder Jan W, Nonini Sandra, Russo Claudio F, Oliva Fabrizio, Frigerio Maria
  
  Abstract
  
  : Necrotizing eosinophilic myocarditis (NEM) is a life-threatening condition that needs rapid diagnosis by endomyocardial biopsy and hemodynamic support usually by mechanical circulatory systems. We present the case of a 25-year-old Caucasian man who developed a refractory cardiogenic shock due to a NEM that was supported with a peripheral veno-arterial extracorporeal membrane oxygenation associated with intravenous steroids and recovered after 2 weeks. Further instrumental investigations lead to the final diagnosis of NEM as first presentation of eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), remarking the importance of identifying the systemic disorder that usually triggers the eosinophilic damage of the myocardium.
  
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• Determinants of outcome in patients with chronic ischemic left ventricular dysfunction undergone percutaneous coronary interventions.
  BMC Cardiovasc Disord

  2015 Oct;15():137. doi: 137.
  
  Ammirati Enrico, Guida Valentina, Latib Azeem, Moroni Francesco, Arioli Francesco, Scotti Isabella, Rimoldi Ornella E, Colombo Antonio, Camici Paolo G
  
  Abstract
  
  BACKGROUND:
  Percutaneous coronary interventions (PCI) in patients with ischemic systolic left ventricular dysfunction (SLVD) are routinely performed although their impact on prognosis remains unclear.
  
  METHODS:
  We retrospectively evaluated 385 consecutive patients (76 % male, 66?±?9 years) with SLVD (left ventricular ejection fraction [LVEF] ?40 %) due to chronic coronary artery disease, who underwent PCI between 1999 and 2009, and explored clinical factors associated with higher risk of death or of a composite of death and hospitalization for acute decompensated heart failure (ADHF).
  
  RESULTS:
  The median follow-up was 28 months (inter-quartile range 14-46 months). Death and the composite outcome of death and hospitalization for ADHF occurred in 80 (21 %) and 109 (28 %) patients respectively (8.4 and 11.5 per 100 patient-years of follow-up). Insulin-dependent diabetes mellitus (IDDM), multivessel disease, LVEF?35 %, symptoms of heart failure (HF) emerged both as independent predictors of death (adjusted hazard ratios [HR] 2.64; 1.92, 1.88 and 1.67 respectively) and composite outcome of death and hospitalization for ADHF (adjusted HR 2.22, 1.92, 1.79 and 1.94 respectively). Furthermore advanced age (HR?=?1.03) emerged as independent predictors of death and having performed a stress test before PCI correlated with reduced number of deaths and ADHF hospitalizations (HR?=?0.60). Of note, PCI significantly reduced the symptom of angina from 63.2 % at baseline to 16.3 % at the last follow up (p?0.0001).
  
  CONCLUSIONS:
  IDDM, symptoms of HF, multivessel disease and LVEF?35 % appear to be associated with worse outcome patients with ischemic SLVD undergoing PCI, and may be taken into account for optimal risk stratification. On the other hand, performing a stress testing before PCI seems to be associated with a more favorable outcome.
  
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• [Endomyocardial biopsy should be performed in selected patients with suspected myocarditis].
  G Ital Cardiol (Rome)

  2015 Oct;16(10):539-43. doi: 10.1714/2028.22034.
  
  Ammirati Enrico, Cipriani Manlio, Bonacina Edgardo, Garascia Andrea, Oliva Fabrizio
  
  Abstract
  
  Endomyocardial biopsy (EMB) is the gold standard for the diagnosis of myocarditis. Patients with clinical presentation consistent with myocarditis and acute heart failure should undergo EMB, in particular to exclude giant-cell myocarditis or necrotizing eosinophilic myocarditis that are life-threatening conditions. The indication for EMB is debatable in case of suspected myocarditis with infarct-like presentation and preserved left ventricular ejection fraction. In fact, in this group of patients the prognosis is fairly good, and the clinical advantage to reach a histological diagnosis by means of an invasive procedure with potential complications such as EMB is limited. In this article we discuss the indication for EMB in the light of current guidelines based on existing consensus documents.
  
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• [Cardiac involvement in Churg-Strauss syndrome].
  G Ital Cardiol (Rome)

  2015 Sep;16(9):493-500. doi: 10.1714/1988.21524.
  
  Brucato Antonio, Maestroni Silvia, Masciocco Gabriella, Ammirati Enrico, Bonacina Edgardo, Pedrotti Patrizia
  
  Abstract
  
  Churg-Strauss syndrome, recently renamed eosinophilic granulomatosis with polyangiitis (EGPA), is a rare form of systemic vasculitis, characterized by disseminated necrotizing vasculitis with extravascular granulomas occurring among patients with asthma and tissue eosinophilia. EGPA is classified as a small and medium-sized vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) and the hypereosinophilic syndrome. Typical clinical features include asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Blood eosinophils are often >1500/µl or more than 10% on the differential leukocyte count. Blood eosinophils should always be tested in unexplained cardiac disorders, and may normalize even after low doses of corticosteroids. ANCA are positive in 40-60% of cases, mainly anti-myeloperoxidase. Heart involvement occurs in approximately 15-60% of EGPA patients, especially those who are ANCA negative. Any cardiac structure can be involved, and patients present with myocarditis, heart failure, pericarditis, arrhythmia, coronary arteritis, valvulopathy, intracavitary cardiac thrombosis. Although cardiovascular involvement is usually an early manifestation, it can also occur later in the course of the disease. A significant proportion of patients with cardiac involvement is asymptomatic. In the absence of symptoms and major ECG abnormalities, cardiac involvement may be detected in nearly 40% of the patients. All patients with EGPA should be studied not only with a detailed history of cardiac symptoms and ECG, but also with echocardiography; if abnormalities are detected, a cardiac magnetic resonance study should be performed. Coronary angiography and endomyocardial biopsy should be reserved to selected cases. Heart involvement carries a poor prognosis and causes 50% of the deaths of these patients. It is often insidious and underestimated. Optimal therapy is therefore important and based on high-dose corticosteroids plus immunosuppressive agents, particularly cyclophosphamide in case of myocardial inflammation. Thus, early diagnosis of cardiac involvement and subsequent therapy may prevent progression of cardiac disease. At present, the role of troponin and brain natriuretic peptide in monitoring and therapy remains unclear. Orthotopic heart transplantation is feasible in case of severe disease, even if the experience is limited in -EGPA, and optimal post-transplantation immunosuppressive strategy has yet to be defined.
  
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• [Ventricular aneurysm as a complication of giant cell myocarditis].
  G Ital Cardiol (Rome)

  2015 Jun;16(6):389-90. doi: 10.1714/1934.21040.
  
  Ammirati Enrico, Roghi Alberto, Oliva Fabrizio, Turazza Fabio M, Frigerio Maria, Pedrotti Patrizia
  
  Abstract
  
  Ventricular aneurysm as late complication has been described in cardiac sarcoidosis and occasionally in giant cell myocarditis. The images from the present case of ventricular aneurysm formation as a late complication of giant cell myocarditis underline a potential cause of sudden arrhythmic death in patients who survive this life-threatening condition in the absence of recurrent inflammation and with preserved left ventricular ejection fraction. Follow-up with cardiac magnetic resonance can detect small aneurysms, and an implantable cardioverter-defibrillator may be considered when this complication occurs.
  
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• Eosinophilic myocarditis: a paraneoplastic event.
  Lancet

  2015 Jun;385(9986):2546. doi: 10.1016/S0140-6736(15)60903-5.
  
  Ammirati Enrico, Stucchi Miriam, Brambatti Michela, Spanò Francesca, Bonacina Edgardo, Recalcati Fabio, Cerea Giulio, Vanzulli Angelo, Frigerio Maria, Oliva Fabrizio
  
  
  
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• Markers of inflammation associated with plaque progression and instability in patients with carotid atherosclerosis.
  Mediators Inflamm

  2015 ;2015():718329. doi: 718329.
  
  Ammirati Enrico, Moroni Francesco, Norata Giuseppe Danilo, Magnoni Marco, Camici Paolo G
  
  Abstract
  
  Atherosclerosis is the focal expression of a systemic disease affecting medium- and large-sized arteries, in which traditional cardiovascular risk factor and immune factors play a key role. It is well accepted that circulating biomarkers, including C-reactive protein and interleukin-6, reliably predict major cardiovascular events, including myocardial infarction or death. However, the relevance of biomarkers of systemic inflammation to atherosclerosis progression in the carotid artery is less established. The large majority of clinical studies focused on the association between biomarkers and subclinical atherosclerosis, that is, carotid intima-media thickening (cIMT), which represents an earlier stage of the disease. The aim of this work is to review inflammatory biomarkers that were associated with a higher atherosclerotic burden, a faster disease progression, and features of plaque instability, such as inflammation or neovascularization, in patients with carotid atherosclerotic plaque, which represents an advanced stage of disease compared with cIMT. The association of biomarkers with the occurrence of cerebrovascular events, secondary to carotid plaque rupture, will also be presented. Currently, the degree of carotid artery stenosis is used to predict the risk of future cerebrovascular events in patients affected by carotid atherosclerosis. However, this strategy appears suboptimal. The identification of suitable biomarkers could provide a useful adjunctive criterion to ensure better risk stratification and optimize management.
  
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• Ventricular aneurysms in cardiac sarcoidosis: From physiopathology to surgical treatment through a clinical case presenting with ventricular arrhythmias.
  Int J Cardiol

  2015 ;186():294-6. doi: 10.1016/j.ijcard.2015.03.256.
  
  Pedrotti Patrizia, Ammirati Enrico, Bonacina Edgardo, Roghi Alberto
  
  
  
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• Predicting short-term mortality in advanced decompensated heart failure - role of the updated acute decompensated heart failure/N-terminal pro-B-type natriuretic Peptide risk score.
  Circ J

  2015 ;79(5):1076-83. doi: 10.1253/circj.CJ-14-1219.
  
  Scrutinio Domenico, Ammirati Enrico, Passantino Andrea, Guida Pietro, D'Angelo Luciana, Oliva Fabrizio, Ciccone Marco Matteo, Iacoviello Massimo, Dentamaro Ilaria, Santoro Daniela, Lagioia Rocco, Sarzi Braga Simona, Guzzetti Daniela, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF).
  
  METHODS AND RESULTS:
  We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow ?(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models.
  
  CONCLUSIONS:
  Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.
  
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• Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation.
  Heart Vessels

  2016 May;31(5):722-33. doi: 10.1007/s00380-015-0654-4.
  
  Ammirati Enrico, Oliva Fabrizio G, Colombo Tiziano, Russo Claudio F, Cipriani Manlio G, Garascia Andrea, Guida Valentina, Colombo Giulia, Verde Alessandro, Perna Enrico, Cannata Aldo, Paino Roberto, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.
  
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• Non-invasive molecular imaging of vulnerable atherosclerotic plaques.
  J Cardiol

  2015 Apr;65(4):261-9. doi: 10.1016/j.jjcc.2015.01.004.
  
  Magnoni Marco, Ammirati Enrico, Camici Paolo G
  
  Abstract
  
  The growing discoveries coming from clinical and basic research during the past decades have revolutionized our knowledge regarding pathophysiologic mechanisms underlying the atherosclerotic process and its thrombotic complications. The traditional view focusing on the severity of stenosis of atherosclerotic plaque has given way to the evidence that the clinical complications of atherosclerotic vascular disease, particularly the propensity to develop thrombotic complications, are determined mainly by the biological composition of the plaque. This paradigm shift has reinforced the need to move from the sole anatomical assessment toward combined anatomic and functional imaging modalities enabling the molecular and cellular characterization of the disease on top of its structural properties. Together, the progress to identify molecular targets related to plaque vulnerability and the improvement of imaging techniques for the detection of such molecular targets have allowed us to obtain new important pathophysiological information. This might allow better patient stratification for the identification of subjects at high risk to develop premature atherosclerosis who might need an aggressive therapeutic approach. Nuclear techniques, magnetic resonance imaging, computed tomography angiography, and contrast-enhanced ultrasound represent the currently available non-invasive imaging modalities for molecular imaging which can provide different and complementary insights into the biological features of the atherosclerotic process. This clinical review will discuss the evidence and potential translational applications of the individual imaging techniques particularly concerning their ability to detect the main atherosclerotic features related to plaque vulnerability, such as plaque inflammation and intertwined neovascularization.
  
  Copyright © 2015. Published by Elsevier Ltd.
  
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• Giant cell myocarditis successfully treated with antithymocyte globuline and extracorporeal membrane oxygenation for 21 days.
  J Cardiovasc Med (Hagerstown)

  2016 Dec;17 Suppl 2():e151-e153. doi: 10.2459/JCM.0000000000000250.
  
  Ammirati Enrico, Oliva Fabrizio, Belli Oriana, Bonacina Edgardo, Pedrotti Patrizia, Turazza Fabio Maria, Roghi Alberto, Paino Roberto, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  : A 31-year-old man presenting with cardiogenic shock and left ventricular ejection fraction of 10% received the diagnosis of giant cell myocarditis by endomyocardial biopsy. The patient was successfully treated with high-dose inotropes, intra-aortic balloon pump and venoarterial extracorporeal membrane oxygenation for 21 days associated with combined immunosuppression (thymoglobulin, steroids, cyclosporine). Immunosuppression including thymoglobulin is the regimen associated with the highest probability of recovery in case of giant cell myocarditis. Immunosuppression needs time to be effective; thus, hemodynamic support must be guaranteed. In the present case, we observed that full recovery can be obtained up to 21 days of support with extracorporeal membrane oxygenation and adequate immunosuppression.
  
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• Cumulative analysis on 4802 patients confirming that women benefit more than men from cardiac resynchronization therapy.
  Int J Cardiol

  2015 Mar;182():454-6. doi: 10.1016/j.ijcard.2015.01.028.
  
  Cipriani Manlio, Ammirati Enrico, Landolina Maurizio, Oliva Fabrizio, Ghio Stefano, Rordorf Roberto, Lunati Maurizio
  
  
  
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• [Female incontinence surgery: state of the art].
  Urologia

  2015 ;82(1):1-9. doi: 10.5301/uro.5000093.
  
  Marson Francesco, Ammirati Enrico, Gurioli Alberto, Destefanis Paolo, Gontero Paolo, Frea Bruno
  
  Abstract
  
  Female urinary incontinence represents a medical and social problem with huge impact regarding both patient's quality of life and social costs. The diagnosis is important for therapeutic choice and should consider some factors: the degree of urethral mobility, urodynamics parameters, patient's will and expectations, information about surgical complications and risks. Nowadays suburethral sling evolution and bulking therapy for selected cases consent to perform miniinvasive surgery; the most relevant problem concerns the management of postoperative complications: in this sense autologous slings are used after urethrolisis. In most difficult cases, it is possible to consider artificial sphincter as the best option.
  
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• Mitral prosthetic valve thrombosis and cardiogenic shock in a limited resource setting in sub-Saharan Africa: a tailored treatment approach.
  Int J Cardiol

  2015 Jan;178():65-6. doi: 10.1016/j.ijcard.2014.10.105.
  
  Arioli Francesco, Ammirati Enrico
  
  
  
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• Women with nonischemic cardiomyopathy have a favorable prognosis and a better left ventricular remodeling than men after cardiac resynchronization therapy.
  J Cardiovasc Med (Hagerstown)

  2016 Apr;17(4):291-8. doi: 10.2459/JCM.0000000000000187.
  
  Cipriani Manlio, Landolina Maurizio, Oliva Fabrizio, Ghio Stefano, Vargiu Sara, Rordorf Roberto, Raineri Claudia, Ammirati Enrico, Petracci Barbara, Campo Claudia, Bisetti Silvia, Lunati Maurizio
  
  Abstract
  
  AIMS:
  Cardiac resynchronization therapy (CRT) is a well established therapy in heart failure patients who are on optimal medical therapy and have reduced left ventricular ejection fraction (LVEF) and wide QRS complexes. Although women and patients with nonischemic cardiomyopathy are under-represented in CRT trials and registries, there is evidence that these two groups of patients can benefit more from CRT. The aim of our analysis was to investigate the impact of female sex on mortality in a population that included a high percentage of patients (61%) with nonischemic cardiomyopathy.
  
  METHODS:
  We analyzed data on 507 consecutive patients (20% women) who received CRT at two Italian Heart Transplant centers and were followed up for a maximum of 48 months.
  
  RESULTS:
  After multivariate adjustment, women showed a trend toward better survival with regard to all-cause mortality [hazard ratio (HR) 0.32, confidence interval (CI) 0.10-1.04; P = 0.059]. However, this benefit was limited to nonischemic patients with regard to all-cause mortality (HR 0.20, CI 0.05-0.87, P = 0.032) and cardiovascular mortality (HR 0.14, CI 0.02-1.05, P = 0.056).
  
  CONCLUSION:
  Female CRT recipients, at mid-term, have a favorable prognosis than male patients and this benefit appears to be more evident in nonischemic patients. Thus, we strongly believe that the apparent under-utilization of CRT in females is an anomaly that should be corrected.
  
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• Non-invasive imaging of vascular inflammation.
  Front Immunol

  2014 ;5():399. doi: 399.
  
  Ammirati Enrico, Moroni Francesco, Pedrotti Patrizia, Scotti Isabella, Magnoni Marco, Bozzolo Enrica P, Rimoldi Ornella E, Camici Paolo G
  
  Abstract
  
  In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular (CV) risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization, or increased cellular metabolic activity can represent effective means of non-invasive detection of vascular inflammation. In the present review, novel non-invasive imaging tools that have been successfully tested in humans will be presented. These include contrast-enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast-enhanced CV magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences, respectively; and positron emission tomography associated with radio-tracers such as [(18)F]-fluorodeoxyglucose and the new [(11)C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels.
  
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• [Right ventricular dysfunction in advanced heart failure].
  G Ital Cardiol (Rome)

  2014 ;15(7-8):430-40. doi: 10.1714/1596.17420.
  
  Cipriani Manlio, De Chiara Benedetta, Ammirati Enrico, Roghi Alberto, D'Angelo Luciana, Oliva Fabrizio, Moreo Antonella, Bonacina Edgardo, Martinelli Luigi
  
  Abstract
  
  The role of the right ventricle has often been underestimated in heart failure. It has been thought that the right cavity has a less prominent impact on symptoms, therapeutic approach, and prognosis. Right ventricular dysfunction is a complex issue and its diagnosis has acquired a relevant role, in particular with the improvement of new therapeutic options such as ventricular assist devices. The complex geometry of the right ventricle and its interaction with the left ventricle are still a matter of debate, leaving several open questions about the best therapeutic approach to manage right ventricular dysfunction. Echocardiography remains the first-line imaging technique, but an integrated multimodality evaluation with clinical, biochemical and hemodynamic parameters, and cardiovascular magnetic resonance imaging can provide a more comprehensive way to choose the most appropriate treatment for patients with heart failure associated with right ventricular dysfunction.
  
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• Renal dysfunction and accuracy of N-terminal pro-B-type natriuretic peptide in predicting mortality for hospitalized patients with heart failure.
  Circ J

  2014 ;78(10):2439-46.
  
  Scrutinio Domenico, Mastropasqua Filippo, Guida Pietro, Ammirati Enrico, Ricci Vitoantonio, Raimondo Rosa, Frigerio Maria, Lagioia Rocco, Oliva Fabrizio
  
  Abstract
  
  BACKGROUND:
  Renal dysfunction may confound the clinical interpretation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. This study investigated whether renal dysfunction influences the prognostic accuracy of NT-proBNP in acute decompensated heart failure (ADHF).
  
  METHODS AND RESULTS:
  We studied 908 ADHF patients. The primary outcome was 12-month mortality. Interaction between estimated glomerular filtration rate (eGFR) and NT-proBNP in predicting mortality was tested with the likelihood ratio test. The patients were classified into 3 eGFR strata: ?60, 30-59, and 5,180 pg/ml was 2.09 (P
  CONCLUSIONS:
  There was no evidence of interaction between eGFR and NT-proBNP in predicting mortality. The NT-proBNP cut-off of 5,180 ng/L provided independent prognostic information, irrespective of the level of residual renal function.
  
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• Giant single atrium.
  Int J Cardiol

  2014 Nov;177(1):e37-8. doi: 10.1016/j.ijcard.2014.07.276.
  
  Grimaldi Antonio, Figini Filippo, Ammirati Enrico, Arioli Francesco, Vermi Anna Chiara, De Concilio Annalisa, Trucco Giorgio, D'Arbela Paul G
  
  
  
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• Prosthetic thrombosis and pregnancy on warfarin: debate on mechanical mitral valve replacement in sub-Saharan Africa based on a case report.
  Int J Cardiol

  2014 Oct;176(3):e86-8. doi: 10.1016/j.ijcard.2014.07.162.
  
  Arioli Francesco, D'Arbela Paul G, Aloi Francesco, Nsubuga Martin M, Grimaldi Antonio, Ammirati Enrico
  
  
  
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• Left ventricular or Bi-ventricular assist device? How dobutamine stress echocardiography can untie the dilemma of right ventricular dysfunction.
  Int J Cardiol

  2014 Nov;177(1):e6-8. doi: 10.1016/j.ijcard.2014.07.194.
  
  Ammirati Enrico, Cipriani Manlio, De Chiara Benedetta, D'Angelo Luciana, Belli Oriana, Moreo Antonella, Oliva Fabrizio, Martinelli Luigi, Frigerio Maria
  
  
  
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• Cardiac surgery for patients with heart failure due to structural heart disease in Uganda: access to surgery and outcomes.
  Cardiovasc J Afr

  2014 ;25(5):204-11. doi: 10.5830/CVJA-2014-034.
  
  Grimaldi Antonio, Ammirati Enrico, Karam Nicole, Vermi Anna Chiara, de Concilio Annalisa, Trucco Giorgio, Aloi Francesco, Arioli Francesco, Figini Filippo, Ferrarello Santo, Sacco Francesco Maria, Grottola Renato, D'Arbela Paul G, Alfieri Ottavio, Marijon Eloi, Freers Juergen, Mirabel Mariana
  
  Abstract
  
  OBJECTIVE:
  Few data are available on heart failure (HF) in sub-Saharan Africa. We aimed to provide a current picture of HF aetiologies in urban Uganda, access to heart surgery, and outcomes.
  
  METHODS:
  We prospectively collected clinical and echocardiographic data from 272 consecutive patients referred for suspected heart disease to a tertiary hospital in Kampala during seven non-governmental organisation (NGO) missions from 2009 to 2013. We focused the analysis on 140 patients who fulfilled standardised criteria of HF by echocardiography.
  
  RESULTS:
  Rheumatic heart disease (RHD) was the leading cause of HF in 44 (31%) patients. Among the 50 children included (age ? 16 years), congenital heart disease (CHD) was the first cause of HF (30 patients, 60%), followed by RHD (16 patients, 32%). RHD was the main cause of HF (30%) among the 90 adults. All 85 patients with RHD and CHD presented with an indication for heart surgery, of which 74 patients were deemed fit for intervention. Surgery was scheduled in 38 patients with RHD [86%, median age 19 years (IQR: 12-31)] and in 36 patients with CHD [88%, median age 4 years (IQR 1-5)]. Twenty-seven candidates (32%) were operated on after a median waiting time of 10 months (IQR 6-21). Sixteen (19%) had died after a median of 38 months (IQR 5-52); 19 (22%) were lost to follow up.
  
  CONCLUSION:
  RHD still represents the leading cause of HF in Uganda, in spite of cost-efficient prevention strategies. The majority of surgical candidates, albeit young, do not have access to treatment and present high mortality rates.
  
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• [The IABP-SHOCK II study].
  G Ital Cardiol (Rome)

  2014 Mar;15(3):133-7. doi: 10.1714/1463.16157.
  
  Pappalardo Federico, Ammirati Enrico, Ferrari Stefano
  
  
  
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• The missing link between high-density lipoprotein cholesterol and inflammatory response in cardiovascular disease.
  J Am Coll Cardiol

  2014 Jun;63(24):2747-8. doi: 10.1016/j.jacc.2013.12.057.
  
  Ammirati Enrico, Scotti Isabella, Norata Giuseppe D
  
  
  
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• Current indications for heart transplantation and left ventricular assist device: a practical point of view.
  Eur J Intern Med

  2014 Jun;25(5):422-9. doi: 10.1016/j.ejim.2014.02.006.
  
  Ammirati Enrico, Oliva Fabrizio, Cannata Aldo, Contri Rachele, Colombo Tiziano, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  Heart transplantation (HTx) is considered the "gold standard" therapy of refractory heart failure (HF), but it is accessible only to few patients because of the paucity of suitable heart donors. On the other hand, left ventricular assist devices (LVADs) have proven to be effective in improving survival and quality of life in patients with refractory HF. The challenge encountered by multidisciplinary teams in dealing with advanced HF lies in identifying patients who could benefit more from HTx as compared to LVAD implantation and the appropriate timing. The decision-making is based on clinical parameters, imaging-based data and risk scores. Current outcome of HF patients supported by LVAD (2-year survival around 70%) is rapidly improving and leads the way to a new therapeutic strategy. Patients who have a low likelihood to gain access to the heart graft pool could benefit more from LVAD implantation (defined as bridge to transplantation indication) than from remaining on HTx waiting list with the likely risk of clinical deterioration or removal from the list because patients are no longer suitable for transplantation. LVAD has also demonstrated to be effective in patients who are not considered eligible candidates for HTx with a destination therapy indication. HTx should be reserved to those patients for whom the maximum clinical benefit can be expected, such as young patients with no comorbidities. Here we discuss the current listing criteria for HTx and indications to implant of LVAD for patients with refractory acute and chronic HF based on the guidelines and the practical experience of our center.
  
  Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Can silent brain lesions be a target to guide anticoagulation treatment in patients with low-risk atrial fibrillation to reduce cognitive impairment?
  J Am Coll Cardiol

  2014 May;63(20):2174-2175. doi: 10.1016/j.jacc.2013.12.044.
  
  Ammirati Enrico, Scotti Isabella, Camici Paolo G
  
  
  
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• Circulatory shock.
  N Engl J Med

  2014 Feb;370(6):582. doi: 10.1056/NEJMc1314999.
  
  Ammirati Enrico, Oliva Fabrizio, Frigerio Maria
  
  
  
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• The ADHF/NT-proBNP risk score to predict 1-year mortality in hospitalized patients with advanced decompensated heart failure.
  J Heart Lung Transplant

  2014 Apr;33(4):404-11. doi: 10.1016/j.healun.2013.12.005.
  
  Scrutinio Domenico, Ammirati Enrico, Guida Pietro, Passantino Andrea, Raimondo Rosa, Guida Valentina, Sarzi Braga Simona, Canova Paolo, Mastropasqua Filippo, Frigerio Maria, Lagioia Rocco, Oliva Fabrizio
  
  Abstract
  
  BACKGROUND:
  The acute decompensated heart failure/N-terminal pro-B-type natriuretic peptide (ADHF/NT-proBNP) score is a validated risk scoring system that predicts mortality in hospitalized heart failure patients with a wide range of left ventricular ejection fractions (LVEFs). We sought to assess discrimination and calibration of the score when applied to patients with advanced decompensated heart failure (AHF).
  
  METHODS:
  We studied 445 patients hospitalized for AHF, defined by the presence of severe symptoms of worsening HF at admission, severely depressed LVEF, and the need for intravenous diuretic and/or inotropic drugs. The primary outcome was cumulative (in-hospital and post-discharge) mortality and post-discharge 1-year mortality. Separate analyses were performed for patients aged ? 70 years. A Seattle Heart Failure Score (SHFS) was calculated for each patient discharged alive.
  
  RESULTS:
  During follow-up, 144 patients (32.4%) died, and 69 (15.5%) underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. After accounting for the competing events (VAD/HT), the ADHF/NT-proBNP score's C-statistic for cumulative mortality was 0.738 in the overall cohort and 0.771 in patients aged ? 70 years. The C-statistic for post-discharge mortality was 0.741 and 0.751, respectively. Adding prior (?6 months) hospitalizations for HF to the score increased the C-statistic for post-discharge mortality to 0.759 in the overall cohort and to 0.774 in patients aged ? 70 years. Predicted and observed mortality rates by quartiles of score were highly correlated. The SHFS demonstrated adequate discrimination but underestimated the risk. The ADHF/NT-proBNP risk calculator is available at http://www.fsm.it/fsm/file/NTproBNPscore.zip.
  
  CONCLUSIONS:
  Our data suggest that the ADHF/NT-proBNP score may efficiently predict mortality in patients hospitalized with AHF.
  
  Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
  
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• Beyond age, the need for useful parameters to identify heart failure patients in sinus rhythm that can benefit from oral anticoagulation.
  Int J Cardiol

  2014 ;172(1):e243-4. doi: 10.1016/j.ijcard.2013.12.146.
  
  Ammirati Enrico, Dalla Libera Dacia, Frigerio Maria
  
  
  
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• Letter by Ammirati and Maseri regarding article, "Bacterial signatures in thrombus aspirates of patients with myocardial infarction".
  Circulation

  2013 Oct;128(15):e235. doi: 10.1161/CIRCULATIONAHA.113.002860.
  
  Ammirati Enrico, Maseri Attilio
  
  
  
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• Still need for compelling evidence to support the circadian dependence of infarct size after ST-elevation myocardial infarction.
  Circ Res

  2013 Aug;113(4):e43-4. doi: 10.1161/CIRCRESAHA.113.301908.
  
  Ammirati Enrico, Maseri Attilio, Cannistraci Carlo V
  
  
  
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• Patent foramen ovale closure and brain ischaemic lesions.
  Heart

  2013 Oct;99(20):1543. doi: 10.1136/heartjnl-2013-304508.
  
  Ammirati Enrico, Comi Giancarlo, Camici Paolo G
  
  
  
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• Levosimendan reverted severe pulmonary hypertension in one patient on waiting list for heart transplantation.
  Int J Cardiol

  2013 Oct;168(4):4518-9. doi: 10.1016/j.ijcard.2013.06.106.
  
  Ammirati Enrico, Musca Francesco, Oliva Fabrizio, Garascia Andrea, Pacher Valentina, Verde Alessandro, Cipriani Manlio, Moreo Antonella, Martinelli Luigi, Frigerio Maria
  
  
  
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• Need for new non-invasive imaging strategies to identify high-risk asymptomatic patients with carotid stenosis.
  Int J Cardiol

  2013 Oct;168(4):4342-3. doi: 10.1016/j.ijcard.2013.05.079.
  
  Ammirati Enrico, Magnoni Marco, Camici Paolo G
  
  
  
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• Questing for circadian dependence in ST-segment-elevation acute myocardial infarction: a multicentric and multiethnic study.
  Circ Res

  2013 May;112(10):e110-4. doi: 10.1161/CIRCRESAHA.112.300778.
  
  Ammirati Enrico, Cristell Nicole, Cianflone Domenico, Vermi Anna-Chiara, Marenzi Giancarlo, De Metrio Monica, Uren Neal G, Hu Dayi, Ravasi Timothy, Maseri Attilio, Cannistraci Carlo V
  
  Abstract
  
  RATIONALE:
  Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI).
  
  OBJECTIVE:
  To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population.
  
  METHODS AND RESULTS:
  We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time
  CONCLUSIONS:
  Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time-dynamic mechanisms underlying such a relation.
  
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• Limited changes in severe functional mitral regurgitation and pulmonary hypertension after left ventricular assist device implantation: a clue to consider concurrent mitral correction?
  Int J Cardiol

  2013 Jul;167(2):e35-7. doi: 10.1016/j.ijcard.2013.03.098.
  
  Ammirati Enrico, Musca Francesco, Cannata Aldo, Garascia Andrea, Verde Alessandro, Pacher Valentina, Moreo Antonella, Oliva Fabrizio, Martinelli Luigi, Frigerio Maria
  
  
  
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• Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score.
  Int J Cardiol

  2013 Oct;168(3):2120-6. doi: 10.1016/j.ijcard.2013.01.005.
  
  Scrutinio Domenico, Ammirati Enrico, Guida Pietro, Passantino Andrea, Raimondo Rosa, Guida Valentina, Sarzi Braga Simona, Pedretti Roberto F E, Lagioia Rocco, Frigerio Maria, Catanzaro Raffaella, Oliva Fabrizio
  
  Abstract
  
  BACKGROUND:
  NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score.
  
  METHODS:
  This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score.
  
  RESULTS:
  One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798-0.880) and the Hosmer-Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711-0.817); the Hosmer-Lemeshow statistic was 2.76 (p=0.251), after recalibration.
  
  CONCLUSIONS:
  The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.
  
  Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
  
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• [Proposal for updated listing criteria for heart transplantation and indications to implant of left ventricular assist devices].
  G Ital Cardiol (Rome)

  2013 Feb;14(2):110-9. doi: 10.1714/1218.13523.
  
  Ammirati Enrico, Oliva Fabrizio, Colombo Tiziano, Botta Luca, Cipriani Manlio, Cannata Aldo, Verde Alessandro, Turazza Fabio M, Russo Claudio F, Paino Roberto, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  Heart transplantation (HTx) is considered to be the gold standard treatment for advanced heart failure (HF) but it is available only for a minority of patients, due to paucity of donor hearts (278 HTx were performed in 2011 in Italy). Patients listed for HTx have a prolonged waiting time (that is about 2.3 years in the 2006-2010 time period in Italy) that is superior compared with patients who receive HTx (median time around 6 months), to underline the presence of an allocation system that prioritizes candidates in critical conditions. Patients listed for HTx have a poor quality of life and their annual mortality is around 8-10%. Another 10-15% of HTx candidates are removed from the waiting list each year because they are no longer suitable for transplantation. On the other hand, continuous-flow left ventricular assist devices (LVADs) have been demonstrated to improve survival and quality of life of patients with advanced/refractory HF. LVAD therapy can represent a valid alternative to HTx, and it is recommended for patients with advanced HF in the recent edition of the European Society of Cardiology guidelines on HF management. In the United States, a larger number of centers compared with European ones started to apply a strategy of LVAD implant for many patients who meet clinical criteria for listing for HTx. Data from our center concerning the last 6 years of LVAD implant (51 implants since 2006) reported a 75.5% survival rate at 1 year. In Italian series, as in our center, current HTx survival is only slightly superior (83% survival rate at 1 year), based on data from the Italian National Transplant Center. We report a proposal for updated listing criteria for HTx and indications for LVAD implant in patients with advanced acute and chronic HF. Criteria for identifying suitable patients for HTx and/or LVAD considering the shortage of donors are discussed.
  
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• C-reactive protein, fibrinogen, and cardiovascular risk.
  N Engl J Med

  2013 Jan;368(1):85. doi: 10.1056/NEJMc1213688.
  
  Ammirati Enrico, Maseri Attilio
  
  
  
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• Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7.
  Circulation

  2013 Jan;127(4):463-75. doi: 10.1161/CIRCULATIONAHA.112.123653.
  
  Vergani Andrea, Tezza Sara, D'Addio Francesca, Fotino Carmen, Liu Kaifeng, Niewczas Monika, Bassi Roberto, Molano R Damaris, Kleffel Sonja, Petrelli Alessandra, Soleti Antonio, Ammirati Enrico, Frigerio Maria, Visner Gary, Grassi Fabio, Ferrero Maria E, Corradi Domenico, Abdi Reza, Ricordi Camillo, Sayegh Mohamed H, Pileggi Antonello, Fiorina Paolo
  
  Abstract
  
  BACKGROUND:
  Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation.
  
  METHODS AND RESULTS:
  We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well.
  
  CONCLUSIONS:
  P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival.
  
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• Challenges of using ultrasounds for subclinical rheumatic heart disease screening.
  Int J Cardiol

  2013 Sep;167(6):3061. doi: 10.1016/j.ijcard.2012.11.083.
  
  Grimaldi Antonio, Ammirati Enrico, Mirabel Mariana, Marijon Eloi
  
  
  
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• Clinical outcome and quality of life in octogenarians following transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis.
  Int J Cardiol

  2013 Sep;168(1):281-6. doi: 10.1016/j.ijcard.2012.09.079.
  
  Grimaldi Antonio, Figini Filippo, Maisano Francesco, Montorfano Matteo, Chieffo Alaide, Latib Azeem, Pappalardo Federico, Spagnolo Pietro, Cioni Micaela, Vermi Anna Chiara, Ferrarello Santo, Piraino Daniela, Cammalleri Valeria, Ammirati Enrico, Sacco Francesco Maria, Arendar Iryna, Collu Egidio, La Canna Giovanni, Alfieri Ottavio, Colombo Antonio
  
  Abstract
  
  OBJECTIVE:
  TAVI is the alternative option in pts with AS deemed ineligible for surgery. Although mortality and morbidity are measures to assess the effectiveness of treatments, quality of life (QOL) should be an additional target. We assessed clinical outcome and QOL in octogenarians following TAVI.
  
  DESIGN:
  All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this registry. QOL was assessed by questionnaires concerning physical and psychic performance.
  
  PATIENTS:
  A hundred forty-five octogenarians (age: 84.7 ± 3.4 years; male: 48.3%) underwent TAVI for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 ± 0.6; Logistic EuroScore: 26.1 ± 16.7; STS score: 9.2 ± 7.7.Echocardiographic assessments included AVA (0.77 ± 0.21 cm2), mean/peak gradients (54.5 ± 12.2/88 ± 19.5 mm Hg), LVEF (21%=EF ? 40%), sPAP (43.1 ± 11.6 mmHg).
  
  INTERVENTIONS:
  All pts underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic CoreValve (28.8%).
  
  MAIN OUTCOME MEASURES:
  Rates of mortality at 30 days, 6 months and 1 year were 2.8%, 11.2% and 17.5%.
  
  RESULTS:
  At 16-month follow up, 85.5% survived showing improved NYHA class (2.8 ± 0.6 vs 1.5 ± 0.7; p
  CONCLUSION:
  TAVI procedures improve clinical outcome and subjective health-related QOL in very elderly patients with symptomatic AS.
  
  Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
  
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• Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models.
  J Am Heart Assoc

  2012 Feb;1(1):27-41. doi: 10.1161/JAHA.111.000125.
  
  Ammirati Enrico, Cianflone Domenico, Vecchio Viviana, Banfi Michela, Vermi Anna C, De Metrio Monica, Grigore Liliana, Pellegatta Fabio, Pirillo Angela, Garlaschelli Katia, Manfredi Angelo A, Catapano Alberico L, Maseri Attilio, Palini Alessio G, Norata Giuseppe D
  
  Abstract
  
  BACKGROUND#ENTITYSTARTX02014;: Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naïve CD4(+)T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4(+)T-cell subsets and atherosclerosis. METHODS AND RESULTS#ENTITYSTARTX02014;: We analyzed 57 subsets of circulating CD4(+)T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (T(EM): CD3(+)CD4(+)CD45RA(-)CD45RO(+)CCR7(-) cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P
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• Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6- interleukin-10+ cytokine patterns in ST-elevation acute myocardial infarction.
  Circ Res

  2012 Oct;111(10):1336-48. doi: 10.1161/CIRCRESAHA.111.262477.
  
  Ammirati Enrico, Cannistraci Carlo V, Cristell Nicole A, Vecchio Viviana, Palini Alessio G, Tornvall Per, Paganoni Anna M, Miendlarzewska Ewa A, Sangalli Laura M, Monello Alberto, Pernow John, Björnstedt Bennermo Marie, Marenzi Giancarlo, Hu Dayi, Uren Neal G, Cianflone Domenico, Ravasi Timothy, Manfredi Angelo A, Maseri Attilio
  
  Abstract
  
  RATIONALE:
  At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6(+)) levels or very low-IL-6(-) levels.
  
  OBJECTIVE:
  We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response.
  
  METHODS AND RESULTS:
  We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6(+) STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6(-) STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6(+) STEMI and IL-6(-) STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6(+) STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1?, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1?, and monokine induced by interferon-?. IL-10 was increased both in IL-6(+) STEMI and IL-6(-) STEMI patients compared with controls. IL-6(+)IL-10(+) STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6(-)IL-10(+) STEMI patients. We combined IL-10 and monokine induced by interferon-? (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death.
  
  CONCLUSIONS:
  We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.
  
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• Antigen-dependent and antigen-independent pathways modulate CD4+CD28null T-cells during atherosclerosis.
  Circ Res

  2012 Jul;111(2):e48-9; author reply e50-1. doi: 10.1161/CIRCRESAHA.112.271627.
  
  Ammirati Enrico, Monaco Claudia, Norata Giuseppe Danilo
  
  
  
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• [Cavernous hemangioma of the spongious body of the urethra: a case report].
  Urologia

  2012 Jul;79(3):211-3. doi: 10.5301/RU.2012.9371.
  
  Abbinante Maria, Crivellaro Simone, Guaitoli Paolo, Mastrocinque Giuseppe, Ammirati Enrico, Frea Bruno
  
  Abstract
  
  Urethral hemangiomas are rare and benign tumors, probably originating from a unipotent angioblastic stem cell. They can vary in size and the clinical appearance can range from asymptomatic lesions to urethral bleeding or gross hematuria. We present the case of an 18-year-old male, with a history of urethral bleeding. Cystourethoscopy revealed a solitary bulging mass into the lumen, about 6 cm far from the external meatus. Doppler study confirmed that the lesion was in communication with the vessels of the left spongious body. The patient underwent surgical removal of the lesion. The post-procedure Doppler study revealed an inflammation-based remodeling of the spongoius urethra and the absence of the previous vascular connection. At the time of publication the patient is still symptom-free. The surgical removal of urethral hemangiomas is by far the technique of choice for treating such lesions in young patients, thus avoiding side effects of LASER treatments.
  
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• The first Caucasian patient with p.Val122Ile mutated-transthyretin cardiac amyloidosis treated with isolated heart transplantation.
  Amyloid

  2012 Jun;19(2):113-7. doi: 10.3109/13506129.2012.666509.
  
  Ammirati Enrico, Marziliano Nicola, Vittori Claudia, Pedrotti Patrizia, Bramerio Manuela A, Motta Valentina, Orsini Francesco, Veronese Silvio, Merlini Piera A, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  Effective treatments for mutated transthyretin (TTR)-related cardiac amyloidosis are limited. Heart transplantation or combined liver-heart transplantation are the most successful options, although results rely on underline mechanism and systemic nature of the disease. In this report, we present the first case of a Caucasian patient with the p.Val122Ile mutated TTR-related cardiac amyloidosis treated with heart transplantation due to this gene mutation frequent in Afro-Americans with a prevalent isolated heart involvement. The choice of isolated heart transplantation instead of combined heart and liver transplantations was based on (1) severe and progressive cardiac disease, (2) evidence of a gene mutation generally associated with isolated cardiac disease and (3) absence of relevant extra-cardiac involvement (with the possible exception of mild peripheral neuropathy). In any case, the very short post-transplant observation period of 10 months does not allow any conclusions on the long-term course of the presented strategy. Finally, it is the first European Caucasian family with the p.Val122Ile TTR mutation that has been described. Till now, very few Caucasian cases of p.Val122Ile mutated TTR-related cardiac amyloidosis have been reported. The patient and some members of his family also had mild peripheral neuropathy suggesting a regional phenotypic heterogeneity of European Caucasian TTR p.Val122Ile.
  
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• [The PROSPECT study].
  G Ital Cardiol (Rome)

  2012 Mar;13(3):143-6. doi: 10.1714/1038.11318.
  
  Maseri Attilio, Prati Francesco, Ammirati Enrico
  
  
  
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• [Revascularization of the hibernated myocardium: a clinical problem still unsolved].
  G Ital Cardiol (Rome)

  2012 Feb;13(2):102-9. doi: 10.1714/1021.11143.
  
  Ammirati Enrico, Guida Valentina, Rimoldi Ornella E, Camici Paolo G
  
  Abstract
  
  The mid- and long-term outcome of revascularization procedures is still uncertain in patients with chronic left ventricular systolic dysfunction due to coronary artery disease. The identification of dysfunctional myocardial segments with residual viability that can improve after revascularization is pivotal for further patient management. Hibernating myocardium (chronically dysfunctional but still viable tissue) can be identified by positron emission tomography and cardiac magnetic resonance and its presence and extent can predict functional recovery after revascularization. Before beta-blockers were introduced as routine care for heart failure, surgical revascularization appeared to improve survival in these patients. Nowadays, novel medical treatments and devices such as cardiac resynchronization therapy and implantable cardioverter-defibrillators have improved prognosis of these patients and their use is supported by a number of clinical trials. A recently concluded randomized trial, the STICH (Surgical Treatment for Ischemic Heart Failure) trial, has assessed the prognostic benefit derived from revascularization added to optimal medical therapy in patients with ischemic left ventricular dysfunction. This is an overview of the pathophysiological mechanisms as well as the main clinical studies and meta-analyses that have addressed this issue in the past four decades. Furthermore, a brief proposal for a randomized trial to assess effect on prognosis of revascularization of hibernating myocardium will be presented.
  
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• High-sensitivity C-reactive protein is within normal levels at the very onset of first ST-segment elevation acute myocardial infarction in 41% of cases: a multiethnic case-control study.
  J Am Coll Cardiol

  2011 Dec;58(25):2654-61. doi: 10.1016/j.jacc.2011.08.055.
  
  Cristell Nicole, Cianflone Domenico, Durante Alessandro, Ammirati Enrico, Vanuzzo Diego, Banfi Michela, Calori Giliola, Latib Azeem, Crea Filippo, Marenzi Giancarlo, De Metrio Monica, Moretti Luciano, Li Hui, Uren Neal G, Hu Dayi, Maseri Attilio,
  
  Abstract
  
  OBJECTIVES:
  This study sought to assess the prevalence of normal levels of high sensitivity C-reactive protein (hsCRP) at the very onset of ST-segment elevation myocardial infarction (STEMI).
  
  BACKGROUND:
  Levels of hsCRP ?2 mg/l identify individuals who benefit from lipid lowering and possibly anti-inflammatory agents, but how many patients develop infarction in spite of hsCRP levels
  METHODS:
  We studied 887 patients with unequivocally documented STEMI as the first manifestation of coronary disease and 887 matched control subjects from urban areas of Italy, Scotland, and China. Blood samples were obtained before reperfusion strategies
  RESULTS:
  hsCRP values were similar in samples obtained
  CONCLUSIONS:
  The measurement of hsCRP, with a 2 mg/l cutoff, would not have predicted 41% of unequivocally documented STEMIs in 3 ethnic groups without evidence of previous coronary disease, thus indicating both its limitations as an individual prognostic marker and as an indicator of a generalized inflammatory pathogenetic component of STEMI. New specific prognostic and therapeutic approaches should be found for such a large fraction of patients at risk.
  
  Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Dynamic assessment of 'valvular reserve capacity' in patients with rheumatic mitral stenosis.
  Eur Heart J Cardiovasc Imaging

  2012 Jun;13(6):476-82. doi: 10.1093/ejechocard/jer269.
  
  Grimaldi Antonio, Olivotto Iacopo, Figini Filippo, Pappalardo Federico, Capritti Elvia, Ammirati Enrico, Maisano Francesco, Benussi Stefano, Fumero Andrea, Castiglioni Alessandro, De Bonis Michele, Vermi Anna Chiara, Colombo Antonio, Zangrillo Alberto, Alfieri Ottavio
  
  Abstract
  
  AIMS:
  Mitral stenosis (MS) may exhibit a dynamic valvular reserve. When resting gradients and systolic pulmonary pressure (sPAP) do not reflect the real severity of the disease, a dynamic evaluation becomes necessary. The aim of the study was to assess the clinical utility of exercise echocardiography in symptomatic patients with apparently subcritical MS.
  
  METHODS AND RESULTS:
  One hundred and thirty consecutive patients were referred for symptomatic MS. Patients with unimpressive resting MVA (>1-1.5 cm(2)) and mean PG (?5-9 mmHg) underwent exercise echocardiography. Cardiac performance and mitral indices (MVA, peak/mean PG, sPAP) were measured. Exhaustion of valvular reserve capacity under exercise was defined as appearance of symptoms and sPAP > 60 mmHg. Forty-six patients (35%) (age: 53 ± 10 years; 74%, female) with resting MVA (1.2 ± 0.36 cm(2)), mean PG (6.8 ± 2.7 mmHg), and sPAP (38 ± 7 mmHg) inconsistent with symptoms underwent stress echocardiography. Exercise was stopped for dyspnoea (76%) or fatigue (24%). At peak workloads (57.2 ± 21.8 Watts), increased mean PG (17.2 ± 4.8 mmHg, P
  CONCLUSION:
  In MS with limiting symptoms despite unimpressive findings at rest, valvular capacity exhaustion should be tested on a dynamic background, as no single resting index can predict potential haemodynamic adaptation to exercise. In such context, the contribution of exercise echocardiography remains extremely valuable.
  
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• Blood cyst of the mitral valve.
  J Cardiovasc Med (Hagerstown)

  2012 Jan;13(1):46. doi: 10.2459/JCM.0b013e32834d21b4.
  
  Grimaldi Antonio, Capritti Elvia, Pappalardo Federico, Radinovic Andrea, Ferrarello Santo, Cammalleri Valeria, Collu Egidio, Ammirati Enrico, Fumero Andrea, Benussi Stefano, De Bonis Michele, Zangrillo Alberto, Alfieri Ottavio
  
  Abstract
  
  Blood cysts of the mitral valve are mostly benign diverticuli lined by endothelium and filled with blood and can be safely monitored with echocardiographic follow-up. We report a case of asymptomatic blood cyst of the mitral valve in a 63-year-old woman referred for a systolic murmur. At 3-year echo follow-up, the patient is free from notable clinical events.
  
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• Polypoid atrial myxoma.
  J Cardiovasc Med (Hagerstown)

  2012 Aug;13(8):529-30. doi: 10.2459/JCM.0b013e32834ae647.
  
  Grimaldi Antonio, Fumero Andrea, Taramasso Maurizio, Pappalardo Federico, Sanvito Francesca, Ammirati Enrico, Capritti Elvia, Castiglioni Alessandro, Collu Egidio, Pala Maria Grazia, Zangrillo Alberto, Alfieri Ottavio
  
  Abstract
  
  Myxomas are by far the most common tumours of the heart. A 75-year-old man with no notable medical history presented with a 2-month progressive weight loss and dyspnoea on exertion. Physical examination revealed an opening snap and a diastolic decrescendo murmur at the apex. Transthoracic echocardiography showed a large, 85?×?30? mm, mobile, polypoid mass arising from the atrial fossa ovalis and protruding into the left ventricle during diastole. Irregular shape, multilobated surface and soft-tissue echogenicity were consistent with emboligenic myxoma. Surgical inspection confirmed a reddish gelatinous myxoma with villous, friable, thrombus-like surface prone to embolize. The mass was successfully removed and the histologic report confirmed the diagnosis.At 3-year follow-up, the patient is asymptomatic and no further mass has been detected. The case confirms that echocardiography remains a primary tool for the assessment of cardiac masses, providing morphological clues to define the potential risk of complications such as valve obstruction and systemic embolization.
  
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• Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: relevance for recent optic nerve ischemia.
  Arthritis Rheum

  2012 Mar;64(3):854-65. doi: 10.1002/art.33411.
  
  Baldini Mattia, Maugeri Norma, Ramirez Giuseppe A, Giacomassi Chiara, Castiglioni Alessandra, Prieto-González Sergio, Corbera-Bellalta Marc, Di Comite Gabriele, Papa Ilenia, Dell'antonio Giacomo, Ammirati Enrico, Cuccovillo Ivan, Vecchio Viviana, Mantovani Alberto, Rovere-Querini Patrizia, Sabbadini Maria Grazia, Cid Maria C, Manfredi Angelo A
  
  Abstract
  
  OBJECTIVE:
  To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA).
  
  METHODS:
  Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age-matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin-1? (IL-1?), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1? (MIP-1?), CCL4/MIP-1?, CCL11/eotaxin, CXCL9/monokine induced by interferon-?, CXCL10/interferon-?-inducible 10-kd protein, tumor necrosis factor ? (TNF?), interferon-?, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor, and FasL were measured via a multiplexed cytometric assay. PTX3 and VEGF concentrations were assessed by enzyme-linked immunosorbent assay. PTX3 and CD68 expression were determined by immunohistochemistry and immunofluorescence on temporal artery samples.
  
  RESULTS:
  GCA patients with very recent optic nerve ischemia had significantly higher PTX3 and VEGF levels compared to other GCA patients and controls. GCA patients with a disease duration of
  CONCLUSION:
  Our findings indicate that local expression of PTX3 is a feature of vascular inflammation in GCA; elevated circulating levels of PTX3 identify patients with very recent optic nerve ischemia or a recent diagnosis. Optic nerve ischemia is also associated with increased circulating VEGF levels.
  
  Copyright © 2012 by the American College of Rheumatology.
  
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• Myocardial viability in ischemic left ventricular dysfunction.
  N Engl J Med

  2011 Aug;365(5):471; author reply 472-3. doi: 10.1056/NEJMc1106545.
  
  Ammirati Enrico, Rimoldi Ornella E, Camici Paolo G
  
  
  
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• Emerging role of high density lipoproteins as a player in the immune system.
  Atherosclerosis

  2012 Jan;220(1):11-21. doi: 10.1016/j.atherosclerosis.2011.06.045.
  
  Norata Giuseppe Danilo, Pirillo Angela, Ammirati Enrico, Catapano Alberico Luigi
  
  Abstract
  
  High density lipoproteins (HDL) possess a number of physiological activities. The most studied and, perhaps, better understood is the ability of HDL to promote excess cholesterol efflux from peripheral tissues and transport to the liver for excretion, a mechanism believed to confer protection against atherosclerotic cardiovascular disease. The ability of HDL to modulate cholesterol bioavailability in the lipid rafts, membrane microdomains enriched in glycosphingolipids and cholesterol, is evolutionary conserved and affects the properties of cells involved in the innate and adaptive immune response, tuning inflammatory response and antigen presentation functions in macrophages as well as B and T cell activation. Also sphingosine-1 phosphate (S1P), a major active sphingolipid carried by HDL, is of relevance in the pathogenesis of several immuno-inflammatory disorders through the modulation of macrophage and lymphocyte functions. Furthermore, HDL influence the humoral innate immunity by modulating the activation of the complement system and the expression of pentraxin 3 (PTX3). Finally, in humans, HDL levels and functions are altered in several immune-mediated disorders, such as rheumatoid arthritis, systemic lupus eritematosus, Crohn's disease and multiple sclerosis as well as during inflammatory responses. Altogether these observations suggest that the effects of HDL in immunity could be related, to either the ability of HDL to modulate cholesterol content in immune cell lipid rafts and to their role as reservoir for several biologically active substances that may impact the immune system.
  
  Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
  
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• A natural-history study of coronary disease.
  N Engl J Med

  2011 Apr;364(15):1469; author reply 1471-2. doi: 10.1056/NEJMc1101916.
  
  Maseri Attilio, Ammirati Enrico, Prati Francesco
  
  
  
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• Echocardiographic 'brainstorm' to detect anomalous origin of the left coronary artery from the pulmonary artery.
  J Cardiovasc Med (Hagerstown)

  2012 Feb;13(2):152-5. doi: 10.2459/JCM.0b013e328343cc47.
  
  Grimaldi Antonio, Ammirati Enrico, La Canna Giovanni, Sora Nicoleta, Faletra Francesco, De Bonis Michele, Maisano Francesco, Castiglioni Alessandro, Colombo Antonio, Alfieri Ottavio
  
  
  
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• Downgrading mitral regurgitation in the echo laboratory: a case of rheumatic mitral restricted motion unmasked by emotional stress.
  J Cardiovasc Med (Hagerstown)

  2015 Jan;16 Suppl 1():S55-7. doi: 10.2459/JCM.0b013e3283435936.
  
  Grimaldi Antonio, De Gennaro Luisa, Brunetti Natale Daniele, Ammirati Enrico, Arioli Francesco, Arendar Iryna, De Concilio Annalisa, Alfieri Ottavio, La Canna Giovanni
  
  Abstract
  
  We report the case of a 76-year-old woman with mild-to-moderate mitral regurgitation due to rheumatic disease, severe dyspnoea, pulmonary hypertension and a recent episode of heart failure with paroxysmal atrial fibrillation. Transthoracic echocardiography at rest showed a mild-to-moderate mitral regurgitation, which was unable to justify the acute worsening of heart failure symptoms. During transesophageal echocardiography (TEE), deep anxiety induced sinus tachycardia and high SBP followed by pulmonary subedema. The TEE study ascertained a new-onset transient severe mitral regurgitation induced by stress and tachycardia. We speculate that the mechanism underlying the increasing of mitral regurgitation was related to the restricted motion of the posterior leaflet worsened by tachycardia. A further TEE, performed in the operating room under general anesthesia, thus without the emotional involvement of the patient, was not able to provoke a heart failure, even after dobutamine infusion, thus, downgrading the anatomical and functional mitral regurgitation severity.
  
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• Is there evidence supporting coronary revascularization in patients with left ventricular systolic dysfunction?
  Circ J

  2011 ;75(1):3-10.
  
  Ammirati Enrico, Rimoldi Ornella E, Camici Paolo G
  
  Abstract
  
  The mid- and long-term outcomes of revascularization procedures in patients with chronic left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) in the presence or absence of heart failure (HF) symptoms are still uncertain. The identification of dysfunctional myocardial segments with residual viability that can improve after revascularization is pivotal for further patient management. Hibernating myocardium (ie, chronically dysfunctional but still viable tissue) can be identified by positron emission tomography (PET) and cardiac magnetic resonance (CMR) and its presence and extent can predict functional recovery after revascularization. Before ?-blockers were introduced as routine care for HF, surgical revascularization appeared to improve survival in these patients. Nowadays, novel medical treatments and devices, such as cardiac-resynchronization therapy and implantable cardioverter-defibrillators, have improved the prognosis of HF patients and their use is supported by a number of clinical trials. To adequately address the unresolved issue of the prognostic benefits of coronary revascularization in CAD patients with chronic LV dysfunction on optimal medical therapy with/without devices a randomized trial is warranted. In such a trial the presence of viability will be assessed by either PET or CMR. This is an overview of the pathophysiological mechanisms, as well as of the main clinical studies and meta-analyses that have addressed this issue in the past 4 decades.
  
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• Circulating CD4+CD25hiCD127lo regulatory T-Cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis.
  Arterioscler Thromb Vasc Biol

  2010 Sep;30(9):1832-41. doi: 10.1161/ATVBAHA.110.206813.
  
  Ammirati Enrico, Cianflone Domenico, Banfi Michela, Vecchio Viviana, Palini Alessio, De Metrio Monica, Marenzi Giancarlo, Panciroli Claudio, Tumminello Gabriele, Anzuini Angelo, Palloshi Altin, Grigore Liliana, Garlaschelli Katia, Tramontana Simona, Tavano Davide, Airoldi Flavio, Manfredi Angelo A, Catapano Alberico Luigi, Norata Giuseppe Danilo
  
  Abstract
  
  OBJECTIVE:
  Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries.
  
  METHODS AND RESULTS:
  We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3(+)CD4(+)CD25(high)CD127(low)) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (n=65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients).
  
  CONCLUSIONS:
  The results suggest that determination of circulating Treg-cell levels based on flow cytometry or mRNA assessment is not a useful indicator of the extent or severity of atherosclerosis.
  
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• Anti-inflammatory action of apoptotic cells in patients with acute coronary syndromes.
  Atherosclerosis

  2009 Aug;205(2):391-5. doi: 10.1016/j.atherosclerosis.2008.12.042.
  
  Ferri Luca A, Maugeri Norma, Rovere-Querini Patrizia, Calabrese Alice, Ammirati Enrico, Cianflone Domenico, Maseri Attilio, Manfredi Angelo A
  
  Abstract
  
  OBJECTIVES:
  Atherosclerotic plaques contain both apoptotic cells and phagocytes. Apoptotic cells are known to exert an anti-inflammatory effect. Little is known on their action in patients with acute coronary syndromes.
  
  METHODS AND RESULTS:
  We challenged mononuclear phagocytes from the peripheral blood of patients with acute coronary syndromes (n=20) and healthy controls (n=30) with lipopolysaccharide (LPS, 100ng/ml) or peptidoglycan (PGN, 20microg/ml) in the presence or in the absence of apoptotic cells. After 24h, mononuclear phagocytes from patients with acute coronary syndromes produced more TNFalpha and IL-10 than controls; moreover, they were significantly more susceptible to the anti-inflammatory action of apoptotic cells. Apoptotic cells were more effective in ACS patients with C-reactive protein levels 3mg/l.
  
  CONCLUSIONS:
  Patients with acute coronary syndromes and low circulating C-reactive protein levels are more sensitive to the anti-inflammatory action of apoptotic cells: this suggests the existence of an enhanced anti-inflammatory feedback circuit, which could contribute to protect from plaque instability.
  
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• Expansion of T-cell receptor zeta dim effector T cells in acute coronary syndromes.
  Arterioscler Thromb Vasc Biol

  2008 Dec;28(12):2305-11. doi: 10.1161/ATVBAHA.108.174144.
  
  Ammirati Enrico, Vermi Anna-Chiara, Cianflone Domenico, Banfi Michela, Foglieni Chiara, Godino Cosmo, Airoldi Flavio, Ferri Luca A, Gorman Claire L, Manfredi Angelo A, Maseri Attilio, Cope Andrew P, Monaco Claudia
  
  Abstract
  
  OBJECTIVE:
  The T-cell receptor zeta (TCR zeta)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR zeta-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR zeta(dim) T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR zeta(dim) T cells in coronary artery disease.
  
  METHODS AND RESULTS:
  We examined the expression of TCR zeta-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4(+) TCR zeta(dim) T cells were found in patients with acute coronary syndromes (ACS, n=66; median 5.3%, interquartile 2.6 to 9.1% of total CD4(+) T cells; P
  CONCLUSIONS:
  TCR zeta(dim) T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.
  
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