Pubblicazioni - Dott. Oliva Fabrizio

• [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 <50% stenosis) rupture or erosion, coronary embolism and dissection, and coronary artery spasm. Diagnosis may require multiple diagnostic tools, including cardiac imaging or provocative tests, in addition to standard coronary angiography, according to clinical suspicion. Cardiac magnetic resonance plays a key role in confirming the diagnosis and excluding other diseases with similar clinical presentation. Prognosis is not as benign as previously thought, on the opposite it is characterized by morbidity and mortality rates similar to other forms of myocardial infarction. Once the causative mechanism has been identified, appropriate therapy can be delivered.
  
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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: 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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• Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.
  J Am Coll Cardiol

  2019 Jul;74(3):299-311. doi: S0735-1097(19)35290-8.
  
  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 <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up.
  
  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 < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004).
  
  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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• Treating Patients Following Hospitalisation for Acute Decompensated Heart Failure: An Insight into Reducing Early Rehospitalisations.
  Card Fail Rev

  2019 May;5(2):78-82. doi: 10.15420/cfr.2018.46.2.
  
  Iacovoni Attilio, D'Elia Emilia, Gori Mauro, Oliva Fabrizio, Lorini Ferdinando Luca, Senni Michele
  
  Abstract
  
  Heart failure (HF) is a pandemic syndrome characterised by raised morbidity and mortality. An acute HF event requiring hospitalisation is associated with a poor prognosis, in both the short and the long term. Moreover, early rehospitalisation after discharge negatively affects HF management and survival rates. Cardiovascular and non-cardiovascular conditions combine to increase rates of HF hospital readmission at 30 days. A tailored approach for HF pharmacotherapy while the patient is in hospital and immediately after discharge could be useful in reducing early adverse events that cause rehospitalisation and, consequently, prevent worsening HF and readmission during the vulnerable phase after discharge.
  
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• Use of PRECISE-DAPT Score and Admission Platelet Count to Predict Mortality Risk in Patients With Acute Coronary Syndrome.
  Angiology

  2019 Oct;70(9):867-877. doi: 10.1177/0003319719848547.
  
  Morici Nuccia, Tavecchia Giovanni A, Antolini Laura, Caporale Maria R, Cantoni Silvia, Bertuccio Paola, Sacco Alice, Meani Paolo, Viola Giovanna, Brunelli Dario, Oliva Fabrizio, Lombardi Federico, Segreto Antonio, Oreglia Jacopo A, La Vecchia Carlo, Cattaneo Marco, Valgimigli Marco, Savonitto Stefano
  
  Abstract
  
  The PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Antiplatelet Therapy (PRECISE-DAPT) score has been validated to predict bleeding complications in patients undergoing stent implantation and dual antiplatelet therapy. This score does not include the platelet count (PC), which has been shown to be an independent marker of mortality in patients with acute coronary syndrome (ACS). We assessed the role of the PRECISE-DAPT score calculated on admission for mortality risk prediction and evaluated whether the predictive accuracy of this score improved by adding the PC. In a retrospective cohort study of 1000 patients with ACS, after adjustment for relevant covariates, a PRECISE-DAPT score ?25 was independently associated with mortality (hazard ratio [HR]: 7.91; 95% confidence interval [CI]: 4.37-14.30). When this score was combined with PC, compared to patients with PRECISE-DAPT <25 and PC ?150 × 10/L, the adjusted HR was 7.2 (95% CI 2.4-21.6) for those with PRECISE-DAPT <25 and PC <150 × 10/L; 10.7 (95% CI: 5.2-21.9) for those with PRECISE-DAPT ?25 and PC ?150 × 10/L; and 17.9 (95% CI 7.0-45.4) for those with PRECISE-DAPT ?25 and PC <150 × 10/L. Selecting thresholds for high-risk designation, the PRECISE-DAPT score integrated with PC had a higher prediction value, compared to the PRECISE-DAPT and Global Registry of Acute Coronary Events scores.
  
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• [ANMCO/FADOI/SIAARTI/SIC/SIMG/SIMI/SIMEU consensus document: The clinical care pathway of acute heart failure patients from symptom onset to discharge from the emergency department].
  G Ital Cardiol (Rome)

  2019 May;20(5):289-334. doi: 10.1714/3151.31321.
  
  Mortara Andrea, Gabrielli Domenico, Pugliese Francesco Rocco, Corcione Antonio, Perticone Francesco, Fontanella Andrea, Mercuro Giuseppe, Cricelli Claudio, Iacoviello Massimo, D'Ambrosio Gaetano, Guarracino Fabio, Modesti Pietro Amedeo, Vescovo Giorgio, De Maria Renata, Iacovoni Attilio, Macera Francesca, Palmieri Vittorio, Pasqualucci Daniele, Battistoni Ilaria, Alunni Gianfranco, Aspromonte Nadia, Caldarola Pasquale, Campanini Mauro, Caporale Roberto, Casolo Giancarlo, Cipriani Manlio, Di Tano Giuseppe, Domenicucci Stefano, Murrone Adriano, Nardi Federico, Navazio Alessandro, Oliva Fabrizio, Parretti Damiano, Urbinati Stefano, Valente Serafina, Valeriano Valentina, Zuin Guerrino, Metra Marco, Sinagra Gianfranco, Gulizia Michele Massimo, Di Lenarda Andrea
  
  Abstract
  
  Acute heart failure (AHF) represents a relevant burden for emergency departments worldwide. AHF patients have markedly worse long-term outcomes than patients with other acute cardiac diseases (e.g. acute coronary syndromes); mortality or readmissions rates at 3 months approximate 33%, whereas 1-year mortality from index discharge ranges from 25% to 50%.The multiplicity of healthcare professionals acting across the care pathway of AHF patients represents a critical factor, which generates the need for integrating the different expertise and competence of general practitioners, emergency physicians, cardiologists, internists, and intensive care physicians to focus on care goals able to improve clinical outcomes.This consensus document results from the cooperation of the scientific societies representing the different healthcare professionals involved in the care of AHF patients and describes shared strategies and pathways aimed at ensuring both high quality care and better outcomes. The document describes the patient journey from symptom onset to the clinical suspicion of AHF and home management or referral to emergency care and transportation to the hospital, through the clinical diagnostic pathway in the emergency department, acute treatment, risk stratification and discharge from the emergency department to ordinary wards or home. The document analyzes the potential role of a cardiology fast-track and Observation Units and the transition to outpatient care by general practitioners and specialist heart failure clinics.The increasing care burden and complex problems generated by AHF are unlikely to be solved without an integrated multidisciplinary approach. Efficient networking among emergency departments, intensive care units, ordinary wards and primary care settings is crucial to achieve better outcomes. Thanks to the joint effort of qualified scientific societies, this document aims to achieve this goal through an integrated, shared and applicable pathway that will contribute to a homogeneous care management of AHF patients across the country.
  
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• Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?
  Platelets

  2019 May;():1-4. doi: 10.1080/09537104.2019.1609663.
  
  Morici Nuccia, Nava Stefano, Sacco Alice, Viola Giovanna, Oreglia Jacopo, Meani Paolo, Oliva Fabrizio, Ranucci Marco, Leonardi Sergio, Rossini Roberta
  
  Abstract
  
  Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.
  
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• Letter to the editor regarding the results of the retrospective study "Predictors of intra-aortic balloon pump hemodynamic failure in non-acute myocardial infarction cardiogenic shock" published in the American Heart Journal.
  Am Heart J

  2019 Jul;213():123. doi: S0002-8703(19)30056-0.
  
  Sacco Alice, Morici Nuccia, Oliva Fabrizio
  
  
  
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• Cardiogenic shock: old and new circulatory assist devices: the role of counter-pulsation.
  Eur Heart J Suppl

  2019 Mar;21(Suppl B):B59-B60. doi: 10.1093/eurheartj/suz020.
  
  Viola Giovanna, Morici Nuccia, Sacco Alice, Stucchi Miriam, Brunelli Dario, Cipriani Manlio, Garascia Andrea, Bottiroli Maurizio, Frigerio Maria, Oliva Fabrizio
  
  
  
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• Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) Rescues Defective HDL (High-Density Lipoprotein)-Mediated Endothelial Protection in Acute Coronary Syndrome.
  Arterioscler Thromb Vasc Biol

  2019 May;39(5):915-924. doi: 10.1161/ATVBAHA.118.311987.
  
  Ossoli Alice, Simonelli Sara, Varrenti Marisa, Morici Nuccia, Oliva Fabrizio, Stucchi Miriam, Gomaraschi Monica, Strazzella Arianna, Arnaboldi Lorenzo, Thomas Michael J, Sorci-Thomas Mary G, Corsini Alberto, Veglia Fabrizio, Franceschini Guido, Karathanasis Sotirios K, Calabresi Laura
  
  Abstract
  
  Objective- Aim of this study was to evaluate changes in LCAT (lecithin:cholesterol acyltransferase) concentration and activity in patients with an acute coronary syndrome, to investigate if these changes are related to the compromised capacity of HDL (high-density lipoprotein) to promote endothelial nitric oxide (NO) production, and to assess if rhLCAT (recombinant human LCAT) can rescue the defective vasoprotective HDL function. Approach and Results- Thirty ST-segment-elevation myocardial infarction (STEMI) patients were enrolled, and plasma was collected at hospital admission, 48 and 72 hours thereafter, at hospital discharge, and at 30-day follow-up. Plasma LCAT concentration and activity were measured and related to the capacity of HDL to promote NO production in cultured endothelial cells. In vitro studies were performed in which STEMI patients' plasma was added with rhLCAT and HDL vasoprotective activity assessed by measuring NO production in endothelial cells. The plasma concentration of the LCAT enzyme significantly decreases during STEMI with a parallel significant reduction in LCAT activity. HDL isolated from STEMI patients progressively lose the capacity to promote NO production by endothelial cells, and the reduction is related to decreased LCAT concentration. In vitro incubation of STEMI patients' plasma with rhLCAT restores HDL ability to promote endothelial NO production, possibly related to significant modification in HDL phospholipid classes. Conclusions- Impairment of cholesterol esterification may be a major factor in the HDL dysfunction observed during acute coronary syndrome. rhLCAT is able to restore HDL-mediated NO production in vitro, suggesting LCAT as potential therapeutic target for restoring HDL functionality in acute coronary syndrome.
  
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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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• Long-term survival and major outcomes in post-cardiotomy extracorporeal membrane oxygenation for adult patients in cardiogenic shock.
  Ann Cardiothorac Surg

  2019 Jan;8(1):116-122. doi: 10.21037/acs.2018.12.04.
  
  Meani Paolo, Matteucci Matteo, Jiritano Federica, Fina Dario, Panzeri Francesco, Raffa Giuseppe M, Kowalewski Mariusz, Morici Nuccia, Viola Giovanna, Sacco Alice, Oliva Fabrizio, Alyousif Amal, Heuts Sam, Gilbers Martijn, Schreurs Rick, Maessen Jos, Lorusso Roberto
  
  Abstract
  
  Extracorporeal membrane oxygenation (ECMO) in the veno-arterial (VA) configuration is an established method for the treatment of refractory cardiogenic shock. Such a condition characterizes the postoperative course of approximatively 1% of cardiac surgery patients. Although some studies have reported ECMO-related short-term results, little is known about the long-term outcomes of VA-ECMO therapy in the post-cardiotomy setting. Therefore, an extensive literature search was conducted regarding articles published after 1990 reporting postoperative ECMO use. PubMed, EMBASE and Web of Science were searched for sources. In-hospital mortality was high in post-cardiotomy VA-ECMO patients, ranging from 24.8% to 52%. Long-term results were poorly reported. However, based on the limited information available, hospital survivors showed a favorable outcome, with improvement in overall clinical condition, quality of life and limited hospital readmission for cardiac-related events. To conclude, in-hospital outcome in post-cardiotomy ECMO is often unfavorable, post-discharge results show satisfactory condition, with stable improvement of overall patient clinical status and low rate of hospital readmission and cardiac-related adverse events. Data reporting is, however, scarce and hence new and detailed studies are still warranted to investigate such aspects.
  
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• Repetitive levosimendan treatment in the management of advanced heart failure.
  Eur Heart J Suppl

  2018 Dec;20(Suppl I):I11-I20. doi: 10.1093/eurheartj/suy040.
  
  Oliva Fabrizio, Comin-Colet Josep, Fedele Francesco, Fruhwald Friedrich, Gustafsson Finn, Kivikko Matti, Borbély Attila, Pölzl Gerhard, Tschöpe Carsten
  
  Abstract
  
  Inotropes may be an appropriate treatment for patients with advanced heart failure (AdHF) who remain highly symptomatic despite optimized standard therapies. Objectives for inotrope use in these situations include relief of symptoms and improvement of quality of life, and reduction in unplanned hospitalizations and the costs associated with such episodes. All of these goals must be attained without compromising survival. Encouraging findings with intermittent cycles of intravenous levosimendan have emerged from a range of exploratory studies and from three larger controlled trials (LevoRep, LION-HEART, and LAICA) which offered some evidence of clinical advantage. In these settings, however, obtaining statistically robust data may prove elusive due to the difficulties of endpoint assessment in a complex medical condition with varying presentation and trajectory. Adoption of a composite clinical endpoint evaluated in a hierarchical manner may offer a workable solution to this problem. Such an instrument can explore the proposition that repetitive administration of levosimendan early in the period after discharge from an acute episode of worsening heart failure may be associated with greater subsequent clinical stability vis-à-vis standard therapy. The use of this methodology to develop a 'stability score' for each patient means that all participants in such a trial contribute to the overall outcome analysis through one or more of the hierarchical endpoints; this has helpful practical implications for the number of patients needed and the length of follow-up required to generate endpoint data. The LeoDOR study (NCT03437226), outlined in this review, has been designed to explore this new approach to outcome assessment in AdHF.
  
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• Acutely decompensated heart failure with chronic obstructive pulmonary disease: Clinical characteristics and long-term survival.
  Eur J Intern Med

  2019 02;60():31-38. doi: S0953-6205(18)30447-3.
  
  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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• Mycotic coronary aneurysms.
  J Cardiovasc Med (Hagerstown)

  2019 Jan;20(1):10-15. doi: 10.2459/JCM.0000000000000734.
  
  Buono Andrea, Maloberti Alessandro, Bossi Irene M, Piccaluga Emanuela, Piccalò Giacomo, Oreglia Jacopo A, Moreo Antonella, Russo Claudio F, Oliva Fabrizio, Giannattasio Cristina
  
  Abstract
  
  : Mycotic coronary aneurysm is a rare infective disease of arterial vessel walls. Their development could be linked to the presence of an infective endocarditis or could represent a primary infection at the site of an implanted intracoronary stent. Bacterial agents, particularly Staphylococcus aureus, are the most common etiological agents. Due to an aspecific clinical presentation and examination, diagnosis could be challenging. Multiple imaging techniques (both invasive and noninvasive) are often required to reach the final diagnosis. Prognosis is characterized by high morbidity and mortality rates and, in fact, a tempestive treatment is required, although, to date, scanty data concerning the optimal treatment choice are present in literature.
  
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• [ANMCO position paper on sacubitril/valsartan in the management of patients with heart failure].
  G Ital Cardiol (Rome)

  2018 Oct;19(10):568-590. doi: 10.1714/2978.29843.
  
  Di Tano Giuseppe, Di Lenarda Andrea, Gabrielli Domenico, Aspromonte Nadia, De Maria Renata, Frigerio Maria, Iacoviello Massimo, Mortara Andrea, Murrone Adriano, Nardi Federico, Oliva Fabrizio, Pontremoli Roberto, Scherillo Marino, Senni Michele, Urbinati Stefano, Gulizia Michele Massimo
  
  Abstract
  
  Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction (HFrEF) since the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin-aldosterone system activation through blockade of angiotensin II type 1 receptors and enhances the activity of vasoactive peptides including natriuretic peptides, through inhibition of neprilysin, the enzyme responsible for their degradation. In the landmark PARADIGM-HF trial, patients with HFrEF treated with sacubitril/valsartan had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, a 20% lower risk of cardiovascular death, a 21% to 20% lower risk of a first heart failure hospitalization, and a 16% to 20% lower risk of death from any cause, compared with subjects allocated to enalapril (all p<0.001).Following the trial, new international guidelines endorsed sacubitril/valsartan as a class I recommendation for the management of patients with HFrEF who remain symptomatic despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed by the National Health Service since March 2017 within criteria set by the Italian Medicines Agency subject to patient inclusion in a dedicated monitoring registry. Although numerous post-hoc analyses of the original trial suggested that the benefits of this innovative medication may extend across a variety of subgroups, many questions do not yet have an evidence-based answer.In this position paper, we discuss the current role of sacubitril/valsartan in the management of chronic HFrEF, treatment eligibility and the modulating role of patients' characteristics. Moreover, we address concerns elicited by the PARADIGM-HF study and shortcomings of this novel drug, to clarify the place of this new therapy in the context of global care of heart failure in Italy. Our aim is to provide clinical cardiologists with a concise and practical guidance on when and how to use sacubitril/valsartan, to assist clinicians in closing the gap between scientific innovation and real-world experience.
  
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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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• Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration.
  Int J Cardiol

  2018 Dec;272():255-259. doi: S0167-5273(18)34420-6.
  
  Oliva Fabrizio, Perna Enrico, Marini Marco, Nassiacos Daniele, Cirò Antonio, Malfatto Gabriella, Morandi Fabrizio, Caico Ivan, Perna Gianpiero, Meloni Sabina, Vincenzi Antonella, Villani Alessandra, Vecchi Andrea Lorenzo, Minoia Chiara, Verde Alessandro, De Maria Renata,
  
  Abstract
  
  BACKGROUND:
  Ambulatory Advanced Heart Failure (AAHF) is characterized by recurrent HF hospitalizations, escalating diuretic requirements, intolerance to neurohormonal antagonists, end-organ dysfunction, short-term reduced life expectancy despite optimal medical management (OMM). The role of intermittent inotropes in AAHF is unclear. The RELEVANT-HF registry was designed to obtain insight on the effectiveness and safety of compassionate scheduled repetitive 24-hour levosimendan infusions (LEVO) in AAHF patients.
  
  METHODS:
  185 AAHF NYHA class III-IV patients, with ?2 HF hospitalizations/emergency visits in the previous 6?months and systolic dysfunction, were treated with LEVO at tailored doses (0.05-0.2??g/kg/min) without prior bolus every 3-4?weeks. We compared data on HF hospitalizations (percent days spent in hospital, DIH) in the 6?months before and after treatment start.
  
  RESULTS:
  Infusion-related adverse events occurred in 23 (12.4%) patients the commonest being ventricular arrhythmias (16, 8.6%). During follow-up, 37 patients (20%) required for clinical instability treatment adjustments (decreases in infusion dose, rate of infusion or interval). From the 6?months before to the 6?months after treatment start we found lower DIH (9.4 (8.2) % vs 2.8 (6.6) %, p?
  CONCLUSIONS:
  In AAHF patients, who remain symptomatic despite OMM, LEVO is well tolerated and associated with lower overall length of hospital stay during six months. This multicentre clinical experience underscores the need for a randomized controlled trial of LEVO impact on outcomes in AAHF patients.
  
  Copyright © 2018 Elsevier B.V. All rights reserved.
  
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• Management of cardiogenic shock in acute decompensated chronic heart failure: The ALTSHOCK phase II clinical trial.
  Am Heart J

  2018 10;204():196-201. doi: S0002-8703(18)30217-5.
  
  Morici Nuccia, Oliva Fabrizio, Ajello Silvia, Stucchi Miriam, Sacco Alice, Cipriani Manlio Gianni, De Bonis Michele, Garascia Andrea, Gagliardone Maria Pia, Melisurgo Giulio, Russo Claudio Francesco, La Vecchia Carlo, Frigerio Maria, Pappalardo Federico
  
  Abstract
  
  Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7?days (interquartile range 6-15), and the median dose was 0.08 ?g/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60?days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.
  
  Copyright © 2018 Elsevier Inc. All rights reserved.
  
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• Protracted aortic valve closure during peripheral veno-arterial extracorporeal life support: is intra-aortic balloon pump an effective solution?
  Perfusion

  2019 01;34(1):35-41. doi: 10.1177/0267659118787426.
  
  Meani Paolo, Delnoij Thijs, Raffa Giuseppe M, Morici Nuccia, Viola Giovanna, Sacco Alice, Oliva Fabrizio, Heuts Sam, Sels Jan-Willem, Driessen Rob, Roekaerts Paul, Gilbers Martijn, Bidar Elham, Schreurs Rick, Natour Ehsan, Veenstra Leo, Kats Suzanne, Maessen Jos, Lorusso Roberto
  
  Abstract
  
  BACKGROUND:
  Left ventricular (LV) afterload increase with protracted aortic valve (AV) closure may represent a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). The aim of the present study was to assess the effects of an intra-aortic balloon pump (IABP) to overcome such a hemodynamic shortcoming in patients submitted to peripheral V-A ECMO.
  
  METHODS:
  Among 184 adult patients who were treated with peripheral V-A ECMO support at Medical University Center Maastricht Hospital between 2007 and 2018, patients submitted to IABP implant for protracted AV closure after V-A ECMO implant were retrospectively identified. All clinical and hemodynamic data, including echocardiographic monitoring, were collected and analyzed.
  
  RESULTS:
  During the study period, 10 subjects (mean age 60 years old, 80% males) underwent IABP implant after peripheral V-A ECMO positioning due to the diagnosis of protracted AV closure and inefficient LV unloading as assessed by echocardiography and an absence of pulsation in the arterial pressure wave. Recovery of blood pressure pulsatility and enhanced LV unloading were observed in 8 patients after IABP placement, with no significant differences in the main hemodynamic parameters, inotropic therapy or in the ECMO flow (p=0.48). The weaning rate in this patient subgroup (mean ECMO duration 8 days), however, was only 10%, with another patient finally transplanted, leading to a 20% survival-to-hospital discharge.
  
  CONCLUSION:
  IABP placement was an effective solution in order to reverse the protracted AV closure and impaired LV unloading observed during peripheral V-A ECMO support. However, the impact on the weaning rate and survival needs further investigations.
  
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• Differences in biochemical markers between Heart-transplanted and Left Ventricular Assist Device implanted patients, during cardiac rehabilitation.
  Sci Rep

  2018 Jul;8(1):10816. doi: 10.1038/s41598-018-29193-0.
  
  Racca Vittorio, Castiglioni Paolo, Panzarino Claudia, Saresella Marina, Marventano Ivana, Verde Alessandro, Oliva Fabrizio, Ferratini Maurizio
  
  Abstract
  
  Heart transplant (HTx) and left ventricular assist device (LVAD) implant are the best options for symptomatic end stage heart failure, but LVAD patients show lower rehabilitative outcome than HTx patients. To investigate the causes, we compared biomarkers levels and their association with rehabilitative outcome in 51 HTx and in 46 LVAD patients entering the same cardiac rehabilitation program. In both groups, routine biomarkers were measured at start (T1) and end (T2) of cardiac rehabilitation while homocysteine, leptine and IGF-1 were measured at T1 only. HTx patients had lower lymphocyte, platelets, glucose, total proteins and albumin at T1; differences with LVAD patients vanished during rehabilitation when new cases of diabetes were observed in HTx. By contrast, total cholesterol, LDL and HDL fractions, leptin and IGF-1 were higher in HTx patients. The increase from T1 to T2 in six-minute walking test distance, measure of functional rehabilitation outcome, was positively associated with homocysteine and IGF-1 levels in HTx patients. In conclusion, during rehabilitation care should be paid to the early occurrence of dyslipidemia and hyperglycemia in HTx patients, which also require a proper protein dietary support. IGF-1, dangerously low in LVAD patients, might contribute to their lower rehabilitative outcome.
  
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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 11;103():31-39. doi: S0895-4356(18)30188-4.
  
  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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• [Paclitaxel-coated balloons for in-stent restenosis treatment: long-term clinical results and predictors of recurrent target lesion revascularization].
  G Ital Cardiol (Rome)

  2018 Apr;19(4):232-238. doi: 10.1714/2898.29217.
  
  Bossi Irene, D'Anna Margherita, Vaccaro Valentina, Caria Maria Paola, Colombo Paola, De Marco Federico, Oreglia Jacopo, Piccalò Giacomo, Piccaluga Emanuela, Soriano Francesco, Oliva Fabrizio, Klugmann Silvio
  
  Abstract
  
  BACKGROUND:
  The aim of this study was to report clinical outcomes in patients treated with paclitaxel-coated balloons (PCB) for in-stent restenosis (ISR) in both bare metal (BMS) and drug-eluting stent (DES).
  
  METHODS:
  Between May 2009 and December 2015, we treated 155 ISR in 140 patients. At recruitment, 35% of patients had diabetes. Among the lesions, 125 were first occurrence (55 within BMS and 70 within DES) and 30 recurrent; 24 ISR were multi-metal layered. Mean reference diameter was 2.79 ± 0.52 mm and mean lesion length 13.2 ± 7.1 mm. PCB use included 32 Dior I, 97 InPact Falcon, 18 Panthera Lux, and 8 Restore DEB.
  
  RESULTS:
  At a median follow-up of 442 days, we observed 18 target lesion revascularizations (TLR), one myocardial infarction, 3 cardiac deaths, and 5 non-cardiac deaths. TLR occurrence differed according to type of ISR (4% within BMS, 14% within DES, 28% within recurrent ISR; p<0.05). TLR was associated with PCB type (35% Dior I, 9% InPact Falcon, 0% Panthera Lux and Restore DEB; p<0.05). Multivariable analysis revealed that first-generation PCB without a carrier (hazard ratio [HR] 2.50, 95% confidence interval [CI] 0.96-6.50; p=0.06) and recurrent ISR (HR 7.76, 95% CI 1.56-38.66; p=0.01) correlated with subsequent TLR.
  
  CONCLUSIONS:
  Our results confirm the safety and efficacy of PCB for ISR treatment both within BMS and DES. PCB type and recurrent ISR correlate with subsequent TLR.
  
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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 08;265():172. doi: S0167-5273(18)31725-X.
  
  Buono Andrea, Oliva Fabrizio, Ammirati Enrico
  
  
  
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• Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis.
  Circulation

  2018 09;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 (<30 days) were screened between May 2001 and February 2017. Patients >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 <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). ?-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation.
  
  CONCLUSIONS:
  In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.
  
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• Real-world application of currently available decision models for dual antiplatelet therapy duration in acute coronary syndrome.
  J Cardiovasc Med (Hagerstown)

  2018 06;19(6):310-313. doi: 10.2459/JCM.0000000000000655.
  
  Morici Nuccia, Piccinelli Enrico, Brunelli Dario, Sacco Alice, Viola Giovanna, Oreglia Jacopo A, Oliva Fabrizio, Valgimigli Marco
  
  
  
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• Mineralocorticoid receptor antagonists for heart failure: a real-life observational study.
  ESC Heart Fail

  2018 06;5(3):267-274. doi: 10.1002/ehf2.12244.
  
  Bruno Noemi, Sinagra Gianfranco, Paolillo Stefania, Bonomi Alice, Corrà Ugo, Piepoli Massimo, Veglia Fabrizio, Salvioni Elisabetta, Lagioia Rocco, Metra Marco, Limongelli Giuseppe, Cattadori Gaia, Scardovi Angela B, Carubelli Valentina, Scrutino Domenico, Badagliacca Roberto, Guazzi Marco, Raimondo Rosa, Gentile Piero, Magrì Damiano, Correale Michele, Parati Gianfranco, Re Federica, Cicoira Mariantonietta, Frigerio Maria, Bussotti Maurizio, Vignati Carlo, Oliva Fabrizio, Mezzani Alessandro, Vergaro Giuseppe, Di Lenarda Andrea, Passino Claudio, Sciomer Susanna, Pacileo Giuseppe, Ricci Roberto, Contini Mauro, Apostolo Anna, Palermo Pietro, Mapelli Massimo, Carriere Cosimo, Clemenza Francesco, Binno Simone, Belardinelli Romualdo, Lombardi Carlo, Perrone Filardi Pasquale, Emdin Michele, Agostoni Piergiuseppe
  
  Abstract
  
  AIMS:
  Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients.
  
  METHODS AND RESULTS:
  We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P < 0.001). MRA-treated patients had more severe heart failure (higher New York Heart Association class and lower left ventricular ejection fraction, kidney function, and peak VO ). At a propensity-score-matching analysis performed on 1587 patients, MRA-treated and MRA-untreated patients showed similar study endpoint values.
  
  CONCLUSIONS:
  In conclusion, MRA treatment does not affect the composite of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation in a real-life setting. A meticulous patient follow-up, as performed in trials, is likely needed to match the positive MRA-related benefits observed in clinical trials.
  
  © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
  
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• Female gender and mortality risk in decompensated heart failure.
  Eur J Intern Med

  2018 05;51():34-40. doi: S0953-6205(18)30011-6.
  
  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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• The inodilator levosimendan in repetitive doses in the treatment of advanced heart failure.
  Eur Heart J Suppl

  2017 Mar;19(Suppl C):C8-C14. doi: 10.1093/eurheartj/sux004.
  
  Delgado Juan F, Oliva Fabrizio, Reinecke Alexander
  
  Abstract
  
  Inotropes may be an appropriate response for some patients with advanced heart failure who remain highly symptomatic despite optimization of evidence-based therapy. These patients need to be supported waiting for a heart transplant or ventricular assist device, or may be candidates for inotropy as an intervention in its own right to maintain a patient in the best achievable circumstances. Objectives in such a situation include relieving symptoms, improving quality of life and reducing unplanned hospitalizations and the costs associated with such admissions. Levosimendan, a calcium sensitizer and potassium channel opener with inotrope and vasodilator actions, has emerged as a potentially valuable addition to the armamentarium in this context, used in repeated or intermittent cycles of therapy. Detailed proposals and guidance are offered for the identification of candidate patients with good prospects of a beneficial response to levosimendan, and for the safe and effective implementation of a course of therapy.
  
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• Heart rate as a prognostic marker and therapeutic target in acute and chronic heart failure.
  Int J Cardiol

  2018 02;253():97-104. doi: S0167-5273(17)30300-5.
  
  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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• End-stage heart failure: Two surgical approaches with different rehabilitative outcomes.
  PLoS One

  2017 ;12(10):e0185717. doi: 10.1371/journal.pone.0185717.
  
  Racca Vittorio, Castiglioni Paolo, Panzarino Claudia, Oliva Fabrizio, Perna Enrico, Ferratini Maurizio
  
  Abstract
  
  BACKGROUND:
  A rising number of patients are surgically treated for heart failure at the more advanced stage, thanks to the increasing use of left ventricular assist device (LVAD) as a reliable alternative to heart transplantation (HTx). However, it is still unknown whether differences exist between the two surgical approaches in the efficacy of rehabilitation programmes. Therefore, aim of this study was to evaluate whether functional capacity and rehabilitative outcomes differ between HTx and implantation of LVAD.
  
  METHODS AND RESULTS:
  We enrolled 51 patients with HTx and 46 with LVAD upon admission to our rehabilitation-unit. We evaluated six-minute walking test (6MWT), resting oxygen saturation (SaO2) and nutritional assessment before and after a standardised cardiovascular rehabilitation programme. HTx and LVAD groups differed in age, anthropometric variables, gender distribution. Upon enrolment, 6MWT distance was similar in the two groups, whereas malnutrition was less frequent and the waist circumference/height ratio (WHtR) was greater in LVAD patients. SaO2 was greater in HTx patients. Rehabilitation improved SaO2, 6MWT distance and nutritional status. The difference in malnutrition disappeared, but WHtR remained higher in the LVAD and SaO2 higher in the HTx patients; the 6MWT distance improved more in the HTx patients. Multivariate linear regression analysis confirmed that the type of intervention was independent predictor of 6MWT distance after rehabilitation.
  
  CONCLUSIONS:
  HTx patients improve more rapidly and perform better after rehabilitation, suggesting the need for more tailored rehabilitation training for LVAD patients.
  
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• Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison.
  Eur J Heart Fail

  2018 04;20(4):700-710. doi: 10.1002/ejhf.989.
  
  Agostoni Piergiuseppe, Paolillo Stefania, Mapelli Massimo, Gentile Piero, Salvioni Elisabetta, Veglia Fabrizio, Bonomi Alice, Corrà Ugo, Lagioia Rocco, Limongelli Giuseppe, Sinagra Gianfranco, Cattadori Gaia, Scardovi Angela B, Metra Marco, Carubelli Valentina, Scrutinio Domenico, Raimondo Rosa, Emdin Michele, Piepoli Massimo, Magrì Damiano, Parati Gianfranco, Caravita Sergio, Re Federica, Cicoira Mariantonietta, Minà Chiara, Correale Michele, Frigerio Maria, Bussotti Maurizio, Oliva Fabrizio, Battaia Elisa, Belardinelli Romualdo, Mezzani Alessandro, Pastormerlo Luigi, Guazzi Marco, Badagliacca Roberto, Di Lenarda Andrea, Passino Claudio, Sciomer Susanna, Zambon Elena, Pacileo Giuseppe, Ricci Roberto, Apostolo Anna, Palermo Pietro, Contini Mauro, Clemenza Francesco, Marchese Giovanni, Gargiulo Paola, Binno Simone, Lombardi Carlo, Passantino Andrea, Filardi Pasquale Perrone
  
  Abstract
  
  AIMS:
  Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction.
  
  METHODS AND RESULTS:
  We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67?years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4?years (AUC 0.764, 0.725, and 0.720, respectively).
  
  CONCLUSION:
  In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.
  
  © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.
  
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• [Management of outpatients with cardiac disease: follow-up timing and modalities].
  G Ital Cardiol (Rome)

  2017 Jun;18(6):467-484. doi: 10.1714/2700.27608.
  
  Rossini Roberta, Lina Daniela, Ferlini Marco, Belotti Giuseppina, Caico Salvatore Ivan, Caravati Fabrizio, Faggiano Pompilio, Iorio Annamaria, Lauri Davide, Lettieri Corrado, Locati Emanuela Teresa, Maggi Antonio, Massari Ferdinando, Mortara Andrea, Moschini Luigi, Musumeci Giuseppe, Nassiacos Daniele, Negri Fabrizio, Pecora Domenico, Pierini Simona, Pedretti Roberto, Ravizza Pierfranco, Romano Michele, Oliva Fabrizio
  
  Abstract
  
  The increasing rate of cardiovascular diseases, the improved survival after the acute phase, the aging of the population and the implementation of primary prevention caused an exponential increase in outpatient cardiac performance, thereby making it difficult to maintain a balance between the citizen-patient request and the economic sustainability of the healthcare system. On the other side, the prescription of many diagnostic tests with a view to defensive medicine and the related growth of patients' expectations, has led several scientific societies to educational campaigns highlighting the concept that "less is more".The present document is aimed at providing the general practitioner with practical information about a prompt diagnosis of signs/symptoms (angina, dyspnea, palpitations, syncope) of the major cardiovascular diseases. It will also provide an overview about appropriate use of diagnostic exams (echocardiogram, stress test), about the appropriate timing of their execution, in order to ensure effectiveness, efficiency, and equity of the health system.
  
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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 <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis.
  
  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 (<0.0001). Long-term heart transplantation-free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank <0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%-40%] versus 3% [0%-10%], respectively; <0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45-7.64, =0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ?55% at discharge had a significant decrease in LVEF at follow-up.
  
  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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• Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.
  Int J Cardiol

  2017 Sep;243():389-395. doi: S0167-5273(17)31017-3.
  
  Pölzl Gerhard, Altenberger Johann, Baholli Loant, Beltrán Paola, Borbély Attila, Comin-Colet Josep, Delgado Juan F, Fedele Francesco, Fontana Antonella, Fruhwald Friedrich, Giamouzis Gregory, Giannakoulas George, Garcia-González Martín J, Gustafsson Finn, Kaikkonen Kari, Kivikko Matti, Kubica Jacek, von Lewinski Dirk, Löfman Ida, Malfatto Gabriella, Manito Nicolás, Martínez-Sellés Martin, Masip Josep, Merkely Bela, Morandi Fabrizio, Mølgaard Henning, Oliva Fabrizio, Pantev Emil, Papp Zoltán, Perna Gian Piero, Pfister Roman, Piazza Vito, Bover Ramón, Rangel-Sousa Diego, Recio-Mayoral Alejandro, Reinecke Alexander, Rieth Andreas, Sarapohja Toni, Schmidt Gunter, Seidel Mirko, Störk Stefan, Vrtovec Bojan, Wikström Gerhard, Yerly Patrik, Pollesello Piero
  
  Abstract
  
  Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.
  
  Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
  
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• von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.
  Thromb Res

  2017 Jul;155():78-85. doi: S0049-3848(17)30326-2.
  
  Morici Nuccia, Cantoni Silvia, Panzeri Francesco, Sacco Alice, Rusconi Chiara, Stucchi Miriam, Oliva Fabrizio, Cattaneo Marco
  
  Abstract
  
  BACKGROUND:
  Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS.
  
  METHODS AND RESULTS:
  Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS.
  
  CONCLUSIONS:
  The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist.
  
  Copyright © 2017 Elsevier Ltd. All rights reserved.
  
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• [Follow-up strategies after percutaneous coronary intervention: prognostic stratification and multidisciplinary management based on patient risk profile].
  G Ital Cardiol (Rome)

  2017 Jan;18(1):3-12. doi: 10.1714/2655.27229.
  
  Musumeci Giuseppe, Faggiano Pompilio, Ferlini Marco, Lettieri Corrado, Castiglioni Battistina, Maggi Antonio, Negri Fabrizio, Colombo Paola, Oliva Fabrizio, Pedretti Roberto F E, Centola Marco, Rossini Roberta
  
  Abstract
  
  The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. In the present paper, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners equally contributed to the creation of the present document and defined three follow-up strategies and types and timing of clinical and instrumental evaluations in post-PCI patients.
  
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• [The slow acceptance of new oral anticoagulants in Italy: a critical analysis of a problem].
  G Ital Cardiol (Rome)

  2017 Mar;18(3):208-218. doi: 10.1714/2674.27398.
  
  Botto Giovanni Luca, Cuccia Claudio, Gronda Edoardo, Lombardi Federico, Lunati Maurizio, Maggi Antonio, Massari Ferdinando Maria, Musumeci Giuseppe, Oliva Fabrizio, Visconti Luigi Oltrona, Proto Cesare, Pusineri Enrico, Ageno Walter
  
  Abstract
  
  The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice has revolutionized the prevention and the therapeutic approaches to thromboembolic events in patients with nonvalvular atrial fibrillation and represents with no doubts one of the most remarkable advances in the history of cardiovascular medicine over the last years. NOACs beyond a comparable efficacy with vitamin K antagonists allow to overcome the limitations of this last category of drugs owing to their less drug to drug interactions and a predictable anticoagulant effect that allows a fixed dose administration without the need for continuous monitoring. However, the penetration of NOACs into the Italian market is still lower than predicted with respect to their use in other European countries.The aim of this review is to critically analyze the reasons behind this attitude through the adoption of the nominal group technique, a methodology that permits to reach an official consensus.
  
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• Prognostic role of ?-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database.
  Eur J Heart Fail

  2017 07;19(7):904-914. doi: 10.1002/ejhf.775.
  
  Paolillo Stefania, Mapelli Massimo, Bonomi Alice, Corrà Ugo, Piepoli Massimo, Veglia Fabrizio, Salvioni Elisabetta, Gentile Piero, Lagioia Rocco, Metra Marco, Limongelli Giuseppe, Sinagra Gianfranco, Cattadori Gaia, Scardovi Angela B, Carubelli Valentina, Scrutino Domenico, Badagliacca Roberto, Raimondo Rosa, Emdin Michele, Magrì Damiano, Correale Michele, Parati Gianfranco, Caravita Sergio, Spadafora Emanuele, Re Federica, Cicoira Mariantonietta, Frigerio Maria, Bussotti Maurizio, Minà Chiara, Oliva Fabrizio, Battaia Elisa, Belardinelli Romualdo, Mezzani Alessandro, Pastormerlo Luigi, Di Lenarda Andrea, Passino Claudio, Sciomer Susanna, Iorio Annamaria, Zambon Elena, Guazzi Marco, Pacileo Giuseppe, Ricci Roberto, Contini Mauro, Apostolo Anna, Palermo Pietro, Clemenza Francesco, Marchese Giovanni, Binno Simone, Lombardi Carlo, Passantino Andrea, Perrone Filardi Pasquale, Agostoni Piergiuseppe
  
  Abstract
  
  AIMS:
  The use of ?-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared ?-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of ?-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of ?-selectivity and dosage regimens.
  
  METHODS AND RESULTS:
  In 5242 HFrEF patients, we investigated the role of: (i) ?-blocker treatment vs. non-?-blocker treatment, (ii) ?1-/?2-receptor-blockers vs. ?1-selective blockers, and (iii) daily ?-blocker dose. Patients were followed for 3.58?years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on ?-blockers, while 807 (13.2%) were not. At 5?years, ?-blocker-patients showed a better outcome than non-?-blocker-subjects [hazard ratio (HR) 0.48, P?2?5?mg carvedilol equivalent daily dose, n?=?1005) patients than in both medium dose (12.5-25?mg, n?=?1431) and low dose (<12.5?mg, n?=?1960) (HR 1.97, P?
  CONCLUSION:
  In a large population of chronic HFrEF patients, ?-blockers were associated with a more favourable prognosis without any difference between ?1- and ?2-receptor-blockers vs. ?1-selective blockers. A better outcome was observed in subjects receiving a high daily dose.
  
  © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.
  
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• Relationship among body mass index, NT-proBNP, and mortality in decompensated chronic heart failure.
  Heart Lung

  ;46(3):172-177. doi: S0147-9563(17)30017-1.
  
  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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• Portico Sheathless Transcatheter Aortic Valve Implantation via Distal Axillary Artery.
  Ann Thorac Surg

  2017 Feb;103(2):e175-e177. doi: S0003-4975(16)30974-2.
  
  Bruschi Giuseppe, Colombo Paola, Botta Luca, Nava Stefano, Merlanti Bruno, Belli Oriana, Musca Francesco, Soriano Francesco, Russo Claudio F, Oliva Fabrizio
  
  Abstract
  
  Transcatheter aortic valve implantation has been designed to treat older patients affected by severe aortic stenosis who are considered high-risk surgical candidates because of multiple comorbidities. The least invasive approach for transcatheter aortic valves implantation should be considered the transfemoral retrograde route, because it is minimally invasive and is feasible with local anesthesia and mild sedation. Despite significant technical improvements in recent years, the transfemoral approach is contraindicated in cases of severe peripheral artery disease. We describe the first case of a Portico transcatheter aortic valve implantation system (St. Jude Medical, Minneapolis, MN) made through the distal axillary artery in a 90-year-old patient affected by severe aortic stenosis.
  
  Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
  High Blood Press Cardiovasc Prev

  2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
  
  Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
  
  AIM:
  We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
  
  METHODS:
  30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
  
  RESULTS:
  On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
  
  CONCLUSIONS:
  In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
  
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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: S0167-5273(16)32250-1.
  
  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<0.0001) with a relative reduction of 42% compared with baseline. Patients showing increased LV-ESVi at follow up had a lower decrease of LGE% (p=0.038).
  
  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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• Extreme giant aneurysms of three coronary arteries causing heart failure as late sequelae of Kawasaki disease.
  Eur Heart J

  2017 03;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 10;35(10):1264-1267. doi: S1053-2498(16)30247-9.
  
  Scrutinio Domenico, Guida Pietro, Ammirati Enrico, Oliva Fabrizio, Frigerio Maria
  
  
  
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• Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease.
  Open Heart

  2016 ;3(2):e000472.
  
  Morici Nuccia, Farioli Laura, Losappio Laura Michelina, Colombo Giulia, Nichelatti Michele, Preziosi Donatella, Micarelli Gianluigi, Oliva Fabrizio, Giannattasio Cristina, Klugmann Silvio, Pastorello Elide Anna
  
  Abstract
  
  OBJECTIVE:
  To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).
  
  METHODS:
  We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2?years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.
  
  RESULTS:
  Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7?ng/mL (sensitivity 46%, specificity 84%).
  
  CONCLUSIONS:
  In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2?years, demonstrating a possible long-term prognostic role of this biomarker.
  
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• Heart failure and anemia: Effects on prognostic variables.
  Eur J Intern Med

  2017 Jan;37():56-63. doi: S0953-6205(16)30312-0.
  
  Cattadori Gaia, Agostoni Piergiuseppe, Corrà Ugo, Sinagra Gianfranco, Veglia Fabrizio, Salvioni Elisabetta, Bonomi Alice, La Gioia Rocco, Scardovi Angela B, Ferraironi Alessandro, Emdin Michele, Metra Marco, Di Lenarda Andrea, Limongelli Giuseppe, Raimondo Rosa, Re Federica, Guazzi Marco, Belardinelli Romualdo, Parati Gianfranco, Caravita Sergio, Magrì Damiano, Lombardi Carlo, Frigerio Maria, Oliva Fabrizio, Girola Davide, Mezzani Alessandro, Farina Stefania, Mapelli Massimo, Scrutinio Domenico, Pacileo Giuseppe, Apostolo Anna, Iorio AnnaMaria, Paolillo Stefania, Filardi Pasquale Perrone, Gargiulo Paola, Bussotti Maurizio, Marchese Giovanni, Correale Michele, Badagliacca Roberto, Sciomer Susanna, Palermo Pietro, Contini Mauro, Giannuzzi Pantaleo, Battaia Elisa, Cicoira Mariantonietta, Clemenza Francesco, Minà Chiara, Binno Simone, Passino Claudio, Piepoli Massimo F,
  
  Abstract
  
  BACKGROUND:
  Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown.
  
  METHODS:
  Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively.
  
  RESULTS:
  Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO), ventilatory efficiency (VE/VCO slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO slope was associated with poor prognosis only in patients with low and normal Hb.
  
  CONCLUSIONS:
  Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO and LVEF, but not VE/VCO slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.
  
  Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Vasopressors and inotropes in cardiogenic shock: is there room for "adrenaline resuscitation"?
  Crit Care

  2016 Sep;20(1):302.
  
  Morici Nuccia, Stucchi Miriam, Sacco Alice, Bottiroli Maurizio A, Oliva Fabrizio,
  
  
  
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• A new access for transcatheter aortic valve implantation: Distal axillary artery.
  Int J Cardiol

  2016 Nov;223():810-812. doi: S0167-5273(16)32008-3.
  
  Bruschi Giuseppe, Colombo Paola, Merlanti Bruno, Nava Stefano, Belli Oriana, Musca Francesco, Soriano Francesco, Botta Luca, Calini Angelo, De Caria Daniele F, Oliva Fabrizio, Russo Claudio F
  
  
  
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• Ticagrelor for left ventricular assist device thrombosis: A new therapeutic option to be evaluated with caution.
  Int J Cardiol

  2016 Oct;221():58-9. doi: 10.1016/j.ijcard.2016.06.304.
  
  Morici Nuccia, Perna Enrico, Cipriani Manlio, Femia Eti Alessandra, Oliva Fabrizio, Frigerio Maria, Cattaneo Marco
  
  
  
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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: S0953-6205(16)30136-4.
  
  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 (p<.001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180days after admission. Male gender was associated with mortality beyond 180days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission.
  
  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 10;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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• The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion.
  Int J Cardiol

  2016 Sep;218():150-157. doi: S0167-5273(16)30911-1.
  
  Nieminen Markku S, Buerke Michael, Cohen-Solál Alain, Costa Susana, Édes István, Erlikh Alexey, Franco Fatima, Gibson Charles, Gorjup Vojka, Guarracino Fabio, Gustafsson Finn, Harjola Veli-Pekka, Husebye Trygve, Karason Kristjan, Katsytadze Igor, Kaul Sundeep, Kivikko Matti, Marenzi Giancarlo, Masip Josep, Matskeplishvili Simon, Mebazaa Alexandre, Møller Jacob E, Nessler Jadwiga, Nessler Bohdan, Ntalianis Argyrios, Oliva Fabrizio, Pichler-Cetin Emel, Põder Pentti, Recio-Mayoral Alejandro, Rex Steffen, Rokyta Richard, Strasser Ruth H, Zima Endre, Pollesello Piero
  
  Abstract
  
  Acute heart failure and/or cardiogenic shock are frequently triggered by ischemic coronary events. Yet, there is a paucity of randomized data on the management of patients with heart failure complicating acute coronary syndrome, as acute coronary syndrome and cardiogenic shock have frequently been defined as exclusion criteria in trials and registries. As a consequence, guideline recommendations are mostly driven by observational studies, even though these patients have a particularly poor prognosis compared to heart failure patients without signs of coronary artery disease. In acute heart failure, and especially in cardiogenic shock related to ischemic conditions, vasopressors and inotropes are used. However, both pathophysiological considerations and available clinical data suggest that these treatments may have disadvantageous effects. The inodilator levosimendan offers potential benefits due to a range of distinct effects including positive inotropy, restoration of ventriculo-arterial coupling, increases in tissue perfusion, and anti-stunning and anti-inflammatory effects. In clinical trials levosimendan improves symptoms, cardiac function, hemodynamics, and end-organ function. Adverse effects are generally less common than with other inotropic and vasoactive therapies, with the notable exception of hypotension. The decision to use levosimendan, in terms of timing and dosing, is influenced by the presence of pulmonary congestion, and blood pressure measurements. Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics. Levosimendan can be used alone or in combination with other inotropic or vasopressor agents, but requires monitoring due to the risk of hypotension.
  
  Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
  
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• Allogeneic peripheral blood stem cell transplantation and accelerated atherosclerosis: An intriguing association needing targeted surveillance. Lessons from a rare case of acute anterior myocardial infarction.
  Eur Heart J Acute Cardiovasc Care

  2016 May;():. doi: 2048872616652311.
  
  Scudiero Laura, Soriano Francesco, Morici Nuccia, Grillo Giovanni, Belli Oriana, Sacco Alice, Cipriani Manlio, Pedrotti Patrizia, Quattrocchi Giuseppina, Klugmann Silvio, Oliva Fabrizio
  
  Abstract
  
  We report the case of a 23-year-old man who developed an acute ST-elevation myocardial infarction secondary to acute thrombotic occlusion of the proximal left anterior descending coronary artery five years after undergoing chemotherapy, radiotherapy, haematopoietic stem cell transplantation for acute lymphoblastic leukaemia and bulky mediastinal mass involving the pleura and pericardium. His medical history also included Graft versus Host Disease developed 13 months after transplantation and acute myocarditis three months before the actual hospital admission. To the best of our knowledge, coronary artery disease as a complication of haematopoietic stem cell transplantation and low-dose mediastinal radiation therapy in young patients has been rarely reported in the medical literature. Clinicians should have a high degree of suspicion of coronary artery disease in patients treated with allogeneic haematopoietic stem cell transplantation, especially in patients previously treated with target mediastinal radiotherapy, as a group at risk of premature and significantly accelerated atherosclerosis, in order to make a timely and correct diagnosis.
  
  © The European Society of Cardiology 2016.
  
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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

  ;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 08;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 < 0.0001) were significantly associated with 1-year mortality. At multivariable Cox analysis, age (P = 0.0270), ischemic heart disease (P = 0.020), systolic blood pressure (P = 0.006), log N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < 0.0001), serum sodium levels (P = 0.001), and hemoglobin levels (P = 0.001) at admission were independently associated with 1-year mortality. Adjusting for these covariates, neither TAPSE (P = 0.314) nor TAPSE-to-ePASP ratio (P = 0.237) remained independently associated with 1-year mortality. Eighty-three patients (16.6%) had an AiHO. At multivariable logistic regression analysis, the TAPSE-to-ePASP ratio was independently associated with an AiHO (P = 0.024). The association of TAPSE alone or ePASP alone was not statistically significant.
  
  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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• Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel.
  Interact Cardiovasc Thorac Surg

  2016 Mar;22(3):371-3. doi: 10.1093/icvts/ivv349.
  
  Maloberti Alessandro, Oliva Fabrizio, De Chiara Benedetta, Giannattasio Cristina
  
  Abstract
  
  Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, ?-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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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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• [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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• [Primary prevention of sudden cardiac death through a wearable cardioverter-defibrillator].
  G Ital Cardiol (Rome)

  ;16(7-8):418-25. doi: 10.1714/1954.21242.
  
  Gabrielli Domenico, Benvenuto Manuela, Baroni Matteo, Oliva Fabrizio, Capucci Alessandro
  
  Abstract
  
  Nowadays, the implantable cardioverter-defibrillator is the gold standard for the prevention of sudden cardiac death due to tachyarrhythmias. However, its use is not free from short and long-term risks. In the last years, the wearable cardioverter-defibrillator (WCD) has become a widespread option for patients who need a safe and reversible protection against ventricular tachyarrhythmias. Notwithstanding this, its everyday application is restricted by several limitations, including the risk of inappropriate shocks, the device size and the need for strict compliance of both patients and caregivers. In this review, we report the most relevant literature data on WCD usage along with the main fields of applications and future perspectives.
  
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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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• The 30-day metric in acute heart failure revisited: data from IN-HF Outcome, an Italian nationwide cardiology registry.
  Eur J Heart Fail

  2015 Oct;17(10):1032-41. doi: 10.1002/ejhf.290.
  
  Di Tano Giuseppe, De Maria Renata, Gonzini Lucio, Aspromonte Nadia, Di Lenarda Andrea, Feola Mauro, Marini Marco, Milli Massimo, Misuraca Gianfranco, Mortara Andrea, Oliva Fabrizio, Pulignano Giovanni, Russo Giulia, Senni Michele, Tavazzi Luigi,
  
  Abstract
  
  AIMS:
  Unplanned readmissions early after a discharge from acute heart failure hospitalization are common and have become a reimbursement benchmark and marker of hospital quality. However, the competing risk of short-term post-discharge mortality is substantial.
  
  METHODS AND RESULTS:
  Using data from the prospective, nationwide Registry IN-HF Outcome, we analysed the incidence and predictors of 30-day mortality or readmissions and associated days-alive-out-of-hospital (DAOH) in 1520 patients discharged alive after admission for acute heart failure. Within 30 days after discharge, 94 patients (6.2%) were readmitted (91% for cardiovascular causes; 60% recurrent heart failure) and 42 (2.8%) died, 10 of which occurred during readmission. Overall, 126 patients (8.3%) met the combined endpoint. By multivariable logistic regression, worsening chronic heart failure as clinical presentation [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.21-2.77, P = 0.005), inotropes during admission (OR 2.19, 95% CI 1.40-3.43, P = 0.0006), length of stay (OR 1.02, 95% CI 1.01-1.04, P = 0.002) and renin-angiotensin system inhibitors at discharge (OR 0.52, 95%CI 0.35-0.77, P = 0.001) independently predicted 30-day all-cause mortality and/or readmission (c-statistic = 0.695). Per cent 30-day DAOH was lower in patients with in-hospital inotrope use, no renin-angiotensin system inhibitors prescription at discharge, New York Heart Association III-IV class at discharge, and correlated inversely with length of stay and age.
  
  CONCLUSION:
  A clinical and biohumoral profile consistent with chronic advanced heart failure and end-organ damage identifies acute heart failure patients discharged home from cardiology units, who are at highest risk of early death and/or readmission. These findings have practical implications for tailoring specific follow-up.
  
  © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.
  
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• The patient perspective: Quality of life in advanced heart failure with frequent hospitalisations.
  Int J Cardiol

  2015 Jul;191():256-64. doi: 10.1016/j.ijcard.2015.04.235.
  
  Nieminen Markku S, Dickstein Kenneth, Fonseca Cândida, Serrano Jose Magaña, Parissis John, Fedele Francesco, Wikström Gerhard, Agostoni Piergiuseppe, Atar Shaul, Baholli Loant, Brito Dulce, Colet Josep Comín, Édes István, Gómez Mesa Juan E, Gorjup Vojka, Garza Eduardo Herrera, González Juanatey José R, Karanovic Nenad, Karavidas Apostolos, Katsytadze Igor, Kivikko Matti, Matskeplishvili Simon, Merkely Béla, Morandi Fabrizio, Novoa Angel, Oliva Fabrizio, Ostadal Petr, Pereira-Barretto Antonio, Pollesello Piero, Rudiger Alain, Schwinger Robert H G, Wieser Manfred, Yavelov Igor, Zymli?ski Robert
  
  Abstract
  
  End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.
  
  Copyright © 2015. Published by Elsevier Ireland Ltd.
  
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• [Why NAO: Know How. Why and how to choose the new oral anticoagulant in cardiological clinical practice].
  G Ital Cardiol (Rome)

  2015 Mar;16(3):161-74. doi: 10.1714/1820.19826.
  
  Rossini Roberta, Pecora Domenico, Ferlini Marco, Gentile Francesco, Moschini Luigi, Pedrinazzi Claudio, Ravizza Pierfranco, Romano Michele, Canova Paolo, Oliva Fabrizio
  
  Abstract
  
  Although it is well recognized that warfarin dramatically reduces the risk for ischemic stroke, its use for stroke prevention in patients with atrial fibrillation is often inadequate. Even among patients with other known risk factors for stroke (e.g., high blood pressure) and no contraindications to warfarin, warfarin therapy is prescribed in less than 60% of cases. In addition, safety and efficacy of warfarin therapy depend on adequate anticoagulation effect, but time in therapeutic range is 63%. Notably, major bleeding and intracranial hemorrhage represent a feared, though infrequent, complication. Aspirin monotherapy for stroke prevention in patients with atrial fibrillation should be discouraged, as it does not provide adequate protection against stroke and is associated with a significant increase in bleeding complications. New oral anticoagulants have a favorable risk-benefit profile, resulting in significant reductions in stroke, intracranial hemorrhage and mortality, with similar rates of major bleeding compared to warfarin but increased risk for gastrointestinal bleeding. The present review describes the new oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban with a focus on the results from major randomized clinical trials and meta-analyses. It also provides practical suggestions for their use in daily clinical practice, introducing a dedicated, novel application for smartphones and tablets.
  
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• Cardiogenic shock: How to overcome a clinical dilemma. Unmet needs in Emergency medicine.
  Int J Cardiol

  2015 ;186():19-21. doi: 10.1016/j.ijcard.2015.02.111.
  
  Morici Nuccia, Sacco Alice, Paino Roberto, Oreglia Jacopo Andrea, Bottiroli Maurizio, Senni Michele, Nichelatti Michele, Canova Paolo, Russo Claudio, Garascia Andrea, Kulgmann Silvio, Frigerio Maria, Oliva Fabrizio
  
  
  
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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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• [The serotonin syndrome: why should cardiologists be aware and scared of it].
  G Ital Cardiol (Rome)

  2015 Jan;16(1):34-43. doi: 10.1714/1776.19248.
  
  Temporelli Pier Luigi, Boccanelli Alessandro, Desideri Giovambattista, Faggiano Pompilio, Mora Gabriele, Oliva Fabrizio, Terrosu Pierfranco
  
  Abstract
  
  The serotonin syndrome (SS) represents a life-threatening adverse drug reaction, caused by serotonin overload in the central and peripheral nervous system, producing autonomic instability, neuromuscular and cardiovascular abnormalities, and cognitive alterations. The incidence of SS has been growing over the last few years, as a consequence of population aging and the steadily increasing use of pro-serotoninergic agents in clinical practice, in the presence of various comorbidities, mainly cardiovascular. Cardiologists often use combination therapies including serotoninergic agents, and should therefore consider the risk of serotoninergic adverse events caused by inappropriate drug interactions. SS is often difficult to diagnose and may be life-threatening if not adequately managed. Considering the several published case reports of overdose or not recommended associations, a greater awareness by clinicians about the potential risks associated with inappropriate use of these drugs is needed, as well as better information on the clinical features and therapeutic approaches to SS.
  
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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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• [Cost-effectiveness and budget impact of ivabradine in heart failure therapy].
  G Ital Cardiol (Rome)

  2014 Nov;15(11):626-33. doi: 10.1714/1694.18508.
  
  Polistena Barbara, Maggioni Aldo Pietro, Oliva Fabrizio, Spandonaro Federico
  
  Abstract
  
  BACKGROUND:
  Cost-effectiveness of ivabradine was assessed by the National Institute for Health and Clinical Excellence (NICE) in 2012, based on the data derived from the SHIFT trial: NICE considered ivabradine cost-effective for treating chronic heart failure, supporting drug reimbursement by the national healthcare system (NHS). The aim of this study was to assess the cost-effectiveness of ivabradine on top of standard care in heart failure therapy, by adapting a Markovian model to the Italian population and organization, previously developed for submission to national regulatory bodies.
  
  METHODS:
  The demographic and clinical characteristics of the Italian population were derived from both the SHIFT trial and the IN-HF Outcome registry (Italian real practice data). Costs were drawn from the Italian NHS information system. All analyses adopted the Italian NHS perspective.
  
  RESULTS:
  In a lifetime horizon, in the base case, our assessment confirms that adoption of ivabradine seems socially acceptable with a cost per quality-adjusted life year (QALY) of ?17,434.86 (incremental cost of ?2,952.85 and QALYs gained 0.21). The incremental cost/life-year gained (LYG) is ?15,557.24 (LYG gained 0.24) and hospitalization costs avoided are ?3,420.77 (avoided hospitalizations 0.76). A probabilistic sensitivity analysis showed that ivabradine on top of standard treatment is cost-effective in more than 87% of cases accepting a threshold of ?30,000, and in more than 93% of cases with a threshold of ?40,000.
  
  CONCLUSIONS:
  The results obtained for the Italian population and in the organizational context of the Italian NHS show social acceptability (cost per QALY) of ivabradine therapy in the treatment of heart failure.
  
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• Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation.
  Eur J Prev Cardiol

  2015 08;22(8):1046-55. doi: 10.1177/2047487314551546.
  
  Magrì Damiano, Agostoni Piergiuseppe, Corrà Ugo, Passino Claudio, Scrutinio Domenico, Perrone-Filardi Pasquale, Correale Michele, Cattadori Gaia, Metra Marco, Girola Davide, Piepoli Massimo F, Iorio AnnaMaria, Emdin Michele, Raimondo Rosa, Re Federica, Cicoira Mariantonietta, Belardinelli Romualdo, Guazzi Marco, Limongelli Giuseppe, Clemenza Francesco, Parati Gianfranco, Frigerio Maria, Casenghi Matteo, Scardovi Angela B, Ferraironi Alessandro, Di Lenarda Andrea, Bussotti Maurizio, Apostolo Anna, Paolillo Stefania, La Gioia Rocco, Gargiulo Paola, Palermo Pietro, Minà Chiara, Farina Stefania, Battaia Elisa, Maruotti Antonello, Pacileo Giuseppe, Contini Mauro, Oliva Fabrizio, Ricci Roberto, Sinagra Gianfranco,
  
  Abstract
  
  BACKGROUND:
  Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties.
  
  DESIGN:
  We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF.
  
  METHODS:
  Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET).
  
  RESULTS:
  The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p?=?0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, ?-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7?ml/kg/min, while it was 12.8?ml/kg/min for the AF group.
  
  CONCLUSIONS:
  VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted.
  
  © The European Society of Cardiology 2014.
  
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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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• Quality of life and emotional distress early after left ventricular assist device implant: a mixed-method study.
  Artif Organs

  2015 Mar;39(3):220-7. doi: 10.1111/aor.12362.
  
  Modica Maddalena, Ferratini Maurizio, Torri Anna, Oliva Fabrizio, Martinelli Luigi, De Maria Renata, Frigerio Maria
  
  Abstract
  
  Patients who temporarily or permanently rely on left ventricular assist devices (LVADs) for end-stage heart failure face complex psychological, emotional, and relational problems. We conducted a mixed-method study to investigate quality of life, psychological symptoms, and emotional and cognitive reactions after LVAD implant. Twenty-six patients admitted to cardiac rehabilitation were administered quality of life questionnaires (Short Form 36 of the Medical Outcomes Study and Minnesota Living with Heart Failure Questionnaire), the Hospital Anxiety and Depression Scale, and the Coping Orientation for Problem Experiences inventory, and underwent three in-depth unstructured interviews within 2 months after LVAD implant. Quality of life assessment (Short Form 36) documented persistently low physical scores whereas mental component scores almost achieved normative values. Clinically relevant depression and anxiety were observed in 18 and 18% of patients, respectively; avoidant coping scores correlated significantly with both depression and anxiety (Pearson correlation coefficients 0.732, P?
  Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
  
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• [Right ventricular dysfunction in advanced heart failure].
  G Ital Cardiol (Rome)

  ;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 <30 ml·min(-1)·1.73 m(-2). Cox models were used to calculate the adjusted hazard ratios (HR) for NT-proBNP, modeled as a dichotomous or categorized variable, within each level of eGFR. NT-proBNP was categorized using optimal cut-offs defined in ROC analysis for each eGFR level. A total of 234 patients (25.8%) died. Testing for interaction was not significant (?(2)=0.29; P=0.5928). The adjusted HR for NT-proBNP >5,180 pg/ml was 2.09 (P<0.001) in the highest, 1.7 (P<0.001) in the intermediate, and 3.33 (P=0.010) in the lowest eGFR level. The adjusted HR for NT-proBNP above the optimal cut-offs defined on ROC analysis were 1.5 (P=0.239), 2.2 (P<0.001), and 3.24 (P=0.002), respectively. The models incorporating NT-proBNP as a dichotomous or categorized variable had equivalent C-statistics.
  
  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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• 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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• Treatment with inotropes and related prognosis in acute heart failure: contemporary data from the Italian Network on Heart Failure (IN-HF) Outcome registry.
  J Heart Lung Transplant

  2014 Oct;33(10):1056-65. doi: 10.1016/j.healun.2014.05.015.
  
  Mortara Andrea, Oliva Fabrizio, Metra Marco, Carbonieri Emanuele, Di Lenarda Andrea, Gorini Marco, Midi Paolo, Senni Michele, Urso Renato, Lucci Donata, Maggioni Aldo P, Tavazzi Luigi,
  
  Abstract
  
  BACKGROUND:
  In the recent Italian Network on Heart Failure (IN-HF) Outcome registry, including 1,855 patients with acute heart failure (AHF), we reviewed the use of inotropes and their prognostic implication on in-hospital and 12-month mortality.
  
  METHODS:
  IN-HF Outcome is a prospective, multicenter, observational, study involving 61 Italian cardiology centers. AHF patients have been enrolled over a 2-year period and followed-up for 1 year. Inotropes were used in 360 patients (19.4%).
  
  RESULTS:
  Patients who received inotropes had a more severe clinical and hemodynamic profile than those who did not and exhibited a significantly higher rate of in-hospital (21.4% vs 2.7%, p < 0.01) and 1-year (50.6% vs 17.7%, p < 0.01) mortality. At entry, systolic blood pressure (SBP) was ? 110 mm Hg in 58%, 111 to 130 mm Hg in 24.5%, and > 130 mm Hg in 17.5%. Multivariable analyses showed use of inotropes was the strongest predictor of all-cause death. These data were confirmed by propensity score analyses. According to SBP at entry, the 2 groups with SBP > 110 mm Hg who took inotropes, despite a more favorable clinical profile, exhibited a similar worse prognosis, particularly at 1 year: 56.3% (? 110 mm Hg), 43.7% (111-130 mm Hg), and 40.3% (>130 mm Hg) vs 17.7%.
  
  CONCLUSIONS:
  Inotropes were used in nearly 20% of the patient admitted for AHF, and this treatment was associated with a short-term to medium-term poor prognosis. An inappropriate use of inotropes in patients with normal to high SBP, and presumably preserved cardiac output, may have significantly contributed to affect the all-group outcome.
  
  Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
  
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• Transcatheter treatment of chronic mitral regurgitation with the MitraClip system: an Italian consensus statement.
  J Cardiovasc Med (Hagerstown)

  2014 Mar;15(3):173-88. doi: 10.2459/JCM.0000000000000004.
  
  Maisano Francesco, Alamanni Francesco, Alfieri Ottavio, Bartorelli Antonio, Bedogni Francesco, Bovenzi Francesco M, Bruschi Giuseppe, Colombo Antonio, Cremonesi Alberto, Denti Paolo, Ettori Federica, Klugmann Silvio, La Canna Giovanni, Martinelli Luigi, Menicanti Lorenzo, Metra Marco, Oliva Fabrizio, Padeletti Luigi, Parolari Alessandro, Santini Francesco, Senni Michele, Tamburino Corrado, Ussia Gian P, Romeo Francesco
  
  Abstract
  
  New percutaneous technologies are rapidly emerging for the treatment of structural heart disease including mitral valve disease. Preliminary data suggest a potential clinical benefit of percutaneous treatment of mitral regurgitation by the MitraClip procedure in selected patients. Until final data are available from randomized, controlled, multicenter clinical trials, there is an urgent need for a consensus among all the operators involved in the treatment of patients with mitral regurgitation, including clinical cardiologists, heart failure specialists, surgeons, interventional cardiologists, and imaging experts. In the absence of evidence-based guidelines, the heart-team approach is the most reliable method of making proper decisions. This study is the result of multidisciplinary consensus activity, and has the aim of helping physicians in the difficult task of making decisions for the treatment of patients with mitral regurgitation. It is the result of a joint effort of the major Italian Cardiology and Cardiac Surgery Societies, working together to find a proper balance between the points of view of the clinical cardiologist, the interventional cardiologist, and the cardiac surgeon.
  
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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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• In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo vs. worsening) and ejection fraction. Results from IN-HF Outcome Registry.
  Int J Cardiol

  2014 May;173(2):163-9. doi: 10.1016/j.ijcard.2014.02.018.
  
  Senni Michele, Gavazzi Antonello, Oliva Fabrizio, Mortara Andrea, Urso Renato, Pozzoli Massimo, Metra Marco, Lucci Donata, Gonzini Lucio, Cirrincione Vincenzo, Montagna Laura, Di Lenarda Andrea, Maggioni Aldo P, Tavazzi Luigi,
  
  Abstract
  
  BACKGROUND:
  To investigate the outcomes of hospitalized patients with both de-novo and worsening heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF) (LVEF ? 50%), compared to those with reduced LVEF (HFrEF).
  
  METHODS AND RESULTS:
  We studied 1669 patients (22.6% HFpEF) hospitalized for acute HF in the prospective multi-center nationwide Italian Network on Heart Failure (IN-HF) Outcome Registry. In all patients LVEF was assessed during hospitalization. De-novo HF presentations constituted 49.6% of HFpEF and 43.1% of HFrEF hospitalizations. All-cause mortality during hospitalization was lower in HFpEF than HFrEF (2.9% vs 6.5%, p=0.01), but this mortality difference was not significant at 1 year (19.6% vs 24.4%, p=0.06), even after adjusting for clinical covariates. Similarly, there were no differences in 1-year mortality between HFpEF and HFrEF when compared by cause of death (cardiovascular vs non-cardiovascular) or mode of presentation (worsening HF vs de novo). Rehospitalization rates (all-cause, non-cardiovascular, cardiovascular, HF-related) at 90 days and 1 year were also similar. Mode of presentation influenced rehospitalizations in HFpEF, where those presenting with worsening HFpEF had higher all-cause (36.8% vs 21.6%, p=0.001), cardiovascular (28.1% vs 14.9%, p=0.002), and HF-related (21.1% vs 7.7%, p=0.0003) rehospitalization rates at 1 year compared to those with de novo presentations.
  
  CONCLUSIONS:
  Outcomes at 1 year following hospitalization for HFpEF are as poor as that of HFrEF. A prior history of HF decompensation or hospitalization identifies patients with HFpEF at particularly high risk of recurrent events. These findings may have implications for clinical practice, quality and process improvements and trial design.
  
  Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
  
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• [The ROSE study].
  G Ital Cardiol (Rome)

  2014 Jan;15(1):9-12. doi: 10.1714/1394.15512.
  
  Campana Carlo, Oliva Fabrizio
  
  
  
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• Circulatory shock.
  N Engl J Med

  2014 02;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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• [What cardiologists should know to manage acute complications in mechanical circulatory support recipients].
  G Ital Cardiol (Rome)

  2013 Oct;14(10):659-68. doi: 10.1714/1335.14832.
  
  Marini Marco, Raineri Claudia, Di Tano Giuseppe, Cipriani Manlio, Oliva Fabrizio, De Maria Renata,
  
  Abstract
  
  Patients with advanced heart failure refractory to optimal medical treatment have a high mortality and a poor quality of life with frequent hospital admissions. The lack of alternative treatment options has prompted the development of mechanical circulatory support (MCS) devices, first as bridge to heart transplant and subsequently as destination therapy as a valid alternative to transplant. Last generation MCS devices are mechanically reliable and their management has become increasingly less complex. Nowadays, medium-term survival does not significantly differ between MCS and heart transplant recipients. MCS management programs require a multidisciplinary team to optimize the pathway leading to rehabilitation and improved quality of life and decrease the frequent occurrence of complications. However, in the near future with the growing number of implants, the chances for clinical cardiologists to come across a MCS recipient will increase. The management of general or acute problems will no longer be limited to tertiary implanting centers. A key issue to improve patient outcomes is the provision of a smooth and careful transition from the hospital environment to home care. The aim of this review is to start this process by providing basic notions and general indications through several scenarios of MCS recipients presenting to the emergency room for acute clinical problems.
  
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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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• Clinical features, and in-hospital and 1-year mortalities of patients with acute heart failure and severe renal dysfunction. Data from the Italian Registry IN-HF Outcome.
  Int J Cardiol

  2013 Oct;168(4):3691-7. doi: 10.1016/j.ijcard.2013.06.020.
  
  Cioffi Giovanni, Mortara Andrea, Di Lenarda Andrea, Oliva Fabrizio, Lucci Donata, Senni Michele, Cacciatore Giuseppe, Chinaglia Alessandra, Tarantini Luigi, Metra Marco, Maggioni Aldo Pietro, Tavazzi Luigi,
  
  Abstract
  
  BACKGROUND:
  Chronic renal dysfunction (RD) frequently coexists with heart failure (HF) and influences outcome. Patients with acute HF (AHF) and severe RD are frequently excluded in the trials. We characterized these subjects and assessed incidence and predictors of in-hospital and one-year mortalities.
  
  METHODS:
  We selected the 455 patients included in the "IN-HF Outcome" Italian registry belonging to the lowest quartile of estimated glomerular filtration rate (eGFR<40 ml/min/1.73 m(2)).
  
  RESULTS:
  Mean eGFR at entry in severe RD patients was 28±9 ml/min/1.73 m(2). Compared to 1368 patients with more preserved eGFR, they were older, with more co-morbidities and more frequently ischemic etiology of HF. In-hospital and one-year all-cause mortality rates were 14% and 44% respectively, twice higher than the entire population. Predictors of in-hospital mortality were an abnormal status of consciousness, older age, hyponatremia, lower systolic blood pressure and eGFR. The same conditions (except eGFR) predicted one-year mortality together with the absence of diabetes and no treatment with beta-blockers or diuretics.
  
  CONCLUSIONS:
  In patients with AHF and severe RD, in-hospital and one-year all-cause mortality rates are very high. Independent predictors such as older age, and signs of hypoperfusion and hyponatremia may be identified but preventing and reversing RD remain the key targets for the clinical management of these patients.
  
  © 2013.
  
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• [Treatment of advanced heart failure in women: heart transplantation and ventricular assist devices].
  G Ital Cardiol (Rome)

  2012 May;13(5 Suppl 1):35S-41S.
  
  Cipriani Manlio, Macera Francesca, Verde Alessandro, Bruschi Giuseppe, del Medico Marta, Oliva Fabrizio, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  Women candidates for heart transplantation are definitely less than men, just 20% of all patients transplanted; even in the INTERMACS registry they represent only 21% of all ventricular assist devices (VAD) implanted. The reasons for this big difference are discussed in this article. Why women are less frequently assessed for unconventional therapies? Are they sicker or just less regarded? Our experience and the literature show us clear epidemiological, clinical and treatment differences that could lead to a lower prevalence of end-stage disease in women of an age suitable for unconventional therapies. Once on the transplant list, women wait less than men for a heart transplant, because they present with more severe disease, have a lower body mass index and undergo less VAD implants. After transplantation women's survival is comparable to men's, although they usually complain of a lower quality of life. Females receive less often a VAD than men. The main reasons for this include presentation with advanced heart failure at an older age than men, worse outcomes related to small body surface area, and lower survival rates on VAD when implanted as bridge to heart transplantation.
  
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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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• [ANMCO statement on prevention of thromboembolism in atrial fibrillation and role of the new oral anticoagulants].
  G Ital Cardiol (Rome)

  2013 Apr;14(4):295-322. doi: 10.1714/1257.13889.
  
  Colonna Paolo, Abrignani Maurizio G, Colivicchi Furio, Verdecchia Paolo, Alunni Gianfranco, Bongo Angelo S, Ceravolo Roberto, Oliva Fabrizio, Rakar Serena, Riccio Carmine, Scherillo Marino, Valle Roberto, Bovenzi Francesco,
  
  Abstract
  
  The introduction in the therapeutic armamentarium of three new oral anticoagulants for the prevention of thromboembolism in atrial fibrillation (AF) has stimulated the development of this position paper from the Italian Association of Hospital Cardiologists (ANMCO). First, the pathophysiology of arterial thromboembolism in AF is reviewed, describing the mechanisms of action of the new oral anticoagulants, their pharmacology and pharmacokinetics, and highlighting differences and similarities observed in preclinical studies and trials. Stratification of thromboembolic and bleeding risk is made using different risk scores; a comprehensive analysis of the various international guidelines should emphasize convergences or divergences. An in-depth examination of the limitations of current therapeutic strategies for the prevention of stroke in non-valvular AF provides insight into the difficulty in maintaining adequate adherence to therapy with warfarin and a constant and effective anticoagulation, without wide fluctuations in prothrombin time international normalized ratio (INR) values. Clinical trials of new oral anticoagulants for AF are discussed in detail in the present document, with a focus on similarities and differences, efficacy and safety data, and the net clinical benefit of each new oral anticoagulant. Results obtained in elderly patients, or in patients with renal, liver and ischemic heart disease or previous stroke are reported separately, as well as those regarding combination therapy with antiplatelet agents. Finally, this document provides indications, practical applications and cost-effectiveness analysis of each new oral anticoagulant. It is of utmost importance to know how treatment should be started, how you should switch from warfarin, which patients should be maintained on warfarin, how and when cardioversion, catheter ablation or appendage closure should be performed, what drug and food interactions may affect these medications, and how treatment adherence may be improved to avoid therapy discontinuation. An accurate examination of the risk of bleeding is also provided, with special reference to laboratory monitoring of renal and hepatic function, timing for discontinuing these medications prior to surgery, and treatment of patients with major and minor bleeding.
  
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• Multicenter prospective observational study on acute and chronic heart failure: one-year follow-up results of IN-HF (Italian Network on Heart Failure) outcome registry.
  Circ Heart Fail

  2013 May;6(3):473-81. doi: 10.1161/CIRCHEARTFAILURE.112.000161.
  
  Tavazzi Luigi, Senni Michele, Metra Marco, Gorini Marco, Cacciatore Giuseppe, Chinaglia Alessandra, Di Lenarda Andrea, Mortara Andrea, Oliva Fabrizio, Maggioni Aldo P,
  
  Abstract
  
  BACKGROUND:
  Clinical observational studies on heart failure (HF) deal mostly with hospitalized patients, few with chronic outpatients, all with no or limited longitudinal observation.
  
  METHODS AND RESULTS:
  This is a multicenter, nationwide, prospective observational trial on a population of 5610 patients, 1855 hospitalized for acute HF (AHF) and 3755 outpatients with chronic HF (CHF), followed up for 1 year. The cumulative total mortality rate at 1 year was 24% in AHF (19.2% in 797 patients with de novo HF and 27.7% in 1058 with worsening HF) and 5.9% in CHF. Cardiovascular deaths accounted for 73.1% and 65.3% and HF deaths for 42.4% and 40.5% of total deaths in AHF and CHF patients, respectively. One-year hospitalization rates were 30.7% in AHF and 22.7% in CHF patients. Among the independent predictors of 1-year all-cause death, age, low systolic blood pressure, anemia, and renal dysfunction were identified in both acute and chronic patients. A few additional variables were significant only in AHF (signs of cerebral hypoperfusion, low serum sodium, chronic obstructive pulmonary disease, and acute pulmonary edema), whereas others were observed only in CHF patients (lower body mass index, higher heart rate, New York Heart Association class, large QRS, and severe mitral regurgitation).
  
  CONCLUSIONS:
  In this contemporary data set, patients with CHF had a relatively low mortality rate compared with those with AHF. Rates of adverse outcomes in patients admitted for AHF remain very high either in-hospital or after discharge. Most deaths were cardiovascular in origin and ?40% of deaths were directly related to HF.
  
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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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• Heart transplantation: 25 years' single-centre experience.
  J Cardiovasc Med (Hagerstown)

  2013 Sep;14(9):637-47. doi: 10.2459/JCM.0b013e32835dbd74.
  
  Bruschi Giuseppe, Colombo Tiziano, Oliva Fabrizio, Botta Luca, Morici Nuccia, Cannata Aldo, Vittori Claudia, Turazza Fabio, Garascia Andrea, Pedrazzini Giovanna, Frigerio Maria, Martinelli Luigi
  
  Abstract
  
  OBJECTIVES:
  Heart transplantation (HTx) is still one of the most effective therapies for end-stage heart disease for patients with no other medical or surgical therapy. We report the results of our 25-year orthotropic HTx single-centre experience.
  
  METHODS:
  From November 1985, 905 orthotopic heart transplants have been performed at our centre. We exclude from the present analysis 13 patients who underwent re-transplantation and 14 pediatric cases (age at HTx <15 years).
  
  RESULTS:
  The present study collected the data of 878 primary adult orthotopic HTx performed at our centre. Mean age at HTx was of 49.6?±?11.6 years. Mean donor age was 36.9?±?14.8 years. Hospital mortality was 11.6% (102 patients), early graft failure was the principal cause of death (58 patients) followed by infections (18 cases) and acute rejection (7 patients). Overall actuarial survival was 78.1% at 5 years and 63.8% and 47.5%, respectively, at 10 and 15 years from HTx. Mean survival was 10.74 years; 257 late deaths were reported (33.1%); main causes were neoplasm in 83 patients, and cardiac causes included coronary allograft vasculopathy in 78 patients. Freedom from any infection at 5, 10 and 15 years was 52.2, 44.1 and 40.1%, respectively. Freedom from rejection at 5 years was 36.2%, with 493 patients experiencing at last one episode of rejection, the majority occurring during the first 2 months after transplantation. The long-term survival of HTx recipients is limited in large part by the development of coronary artery vasculopathy and malignancies. In our experience freedom from coronary allograft vasculopathy at 10 years was 66.9%, and 85 patients underwent percutaneous coronary revascularization. In our study population, 44 patients experienced posttransplant lymphoproliferative disorder and 91 patients experienced a solid neoplasm, mean survival free from neoplasm was 12.23 years.
  
  CONCLUSION:
  Over the past four decades the field of HTx has evolved considerably, with improvements in surgical techniques and postoperative patients' care. A careful patient selection and treatment of candidates for transplantation as well as accurate clinical follow-up combined with real multidisciplinary teamwork that involved different heart failure specialists, allowed us to obtain our excellent long-term results.
  
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• Acute heart failure patient profiles, management and in-hospital outcome: results of the Italian Registry on Heart Failure Outcome.
  Eur J Heart Fail

  2012 Nov;14(11):1208-17. doi: 10.1093/eurjhf/hfs117.
  
  Oliva Fabrizio, Mortara Andrea, Cacciatore Giuseppe, Chinaglia Alessandra, Di Lenarda Andrea, Gorini Marco, Metra Marco, Senni Michele, Maggioni Aldo P, Tavazzi Luigi,
  
  Abstract
  
  AIMS:
  Registries and surveys improve knowledge of the 'real world'. This paper aims to describe baseline clinical profiles, management strategies, and the in-hospital outcome of patients admitted to hospital for an acute heart failure (AHF) episode.
  
  METHODS AND RESULTS:
  IN-HF Outcome is a nationwide, prospective, multicentre, observational study conducted in 61 Cardiology Centres in Italy. Up to December 2009, 5610 patients had been enrolled, 1855 (33%) with AHF and 3755 (67%) with chronic heart failure (CHF). Baseline and in-hospital outcome data of AHF patients are presented. Mean age was 72 ± 12 years, and 39.8% were female. Hospital admission was due to new-onset heart failure (HF) in 43% of cases. Co-morbid conditions were observed more frequently in the worsening HF group, while those with de novo HF showed a higher heart rate, blood pressure, and more preserved left ventricular ejection fraction (LVEF). Electrical devices were previously implanted in 13.3% of the entire group. Inotropes were administered in 19.4% of the patients. The median duration of hospital stay was 10 days (interquartile range 7-15). All-cause in-hospital death was 6.4%, similar in worsening and de novo HF. Older age, hypotension, cardiogenic shock, pulmonary oedema, symptoms of hypoperfusion, hyponatraemia, and elevated creatinine were independent predictors of all-cause death.
  
  CONCLUSION:
  Our registry confirms that in-hospital mortality in AHF is still high, with a long length of stay. Pharmacological treatment seems to be practically unchanged in the last decades, and the adherence to HF guidelines concerning implantable cardioverter defibrillators/cardiac resynchronization therapy is still very low. Some AHF phenotypes are characterized by worst prognosis and need specific research projects.
  
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• Predicting heart failure outcome from cardiac and comorbid conditions: the 3C-HF score.
  Int J Cardiol

  2013 Feb;163(2):206-11. doi: 10.1016/j.ijcard.2011.10.071.
  
  Senni Michele, Parrella Piervirgilio, De Maria Renata, Cottini Ciro, Böhm Michael, Ponikowski Piotr, Filippatos Gerasimos, Tribouilloy Christophe, Di Lenarda Andrea, Oliva Fabrizio, Pulignano Giovanni, Cicoira Mariantonietta, Nodari Savina, Porcu Maurizio, Cioffi Gianni, Gabrielli Domenico, Parodi Oberdan, Ferrazzi Paolo, Gavazzi Antonello
  
  Abstract
  
  BACKGROUND:
  Prognostic stratification in heart failure (HF) is crucial to guide clinical management and treatment decision-making. Currently available models to predict HF outcome have multiple limitations. We developed a simple risk stratification model, based on routinely available clinical information including comorbidities, the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause 1-year mortality in HF patients.
  
  METHODS:
  We recruited in a cohort study 6274 consecutive HF patients at 24 Cardiology and Internal Medicine Units in Europe. 2016 subjects formed the derivation cohort and 4258 the validation cohort. We entered information on cardiac and comorbid candidate prognostic predictors in a multivariable model to predict 1-year outcome.
  
  RESULTS:
  Median age was 69 years, 35.8% were female, 20.6% had a normal ejection fraction, and 65% had at least one comorbidity. During 5861 person-years follow-up, 12.1% of the patients met the study end-point of all-cause death (n=750) or urgent transplantation (n=9). The variables that contributed to outcome prediction, listed in decreasing discriminating ability, were: New York Heart Association class III-IV, left ventricular ejection fraction <20%, no beta-blocker, no renin-angiotensin system inhibitor, severe valve heart disease, atrial fibrillation, diabetes with micro or macroangiopathy, renal dysfunction, anemia, hypertension and older age. The C statistic for 1-year all-cause mortality was 0.87 for the derivation and 0.82 for the validation cohort.
  
  CONCLUSIONS:
  The 3C-HF score, based on easy-to-obtain cardiac and comorbid conditions and applicable to the 1-year time span, represents a simple and valuable tool to improve the prognostic stratification of HF patients in daily practice.
  
  Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
  
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• Use of implantable cardioverter defibrillator and cardiac resynchronization therapy: an Italian survey study on 220 cardiology departments.
  J Cardiovasc Med (Hagerstown)

  2012 Nov;13(11):675-83. doi: 10.2459/JCM.0b013e32834bd918.
  
  Inama Giuseppe, Pedrinazzi Claudio, Landolina Maurizio, Oliva Fabrizio, Senni Michele, Proclemer Alessandro, Berisso Massimo Zoni, Pirelli Salvatore,
  
  Abstract
  
  OBJECTIVES:
  To evaluate the criteria for the use of implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy (CRT) and other strategies in order to reduce the incidence of sudden death among adults at high risk and to identify the major barriers for the implementation of quality of care involving Italian cardiology departments in the context of 'Progetto Aritmie Area Scompenso Cardiaco ANMCO'. An additional aim was to evaluate how European Guidelines are applied in 'real-life' scenarios.
  
  METHODS:
  The clinical survey involved 220 centres. An 11-item questionnaire with prespecified multiple choice answers was used. In the specific clinical section, three clinical scenarios were described: the first concerning a patient with non-ischaemic dilated cardiomyopathy and left ventricular ejection fraction (LVEF) 35%; the second, a patient with ischaemic dilated cardiomyopathy and LVEF 30%; and the third, a patient with ischaemic dilated cardiomyopathy and LVEF between 30 and 40%. For each clinical scenario, the centres were asked to indicate whether ICD implantation should be indicated and which diagnostic tests or clinical predictors should be used to stratify the risk.
  
  RESULTS:
  The mean number of procedures (ICD and CRT, ICD alone, CRT alone) performed in each centre was 59 per year with a total number of 11 ?229 procedures per year. ICD, alone or with CRT, was the most common procedure performed with a mean number of 52 implants per centre per year. Concomitant diseases represented the most frequent (>94% of the cases) contraindication. Arrhythmic risk stratification was tested in 76.4% of the centres. Most of the centres (76.4%) stated that they routinely performed adjunctive tests, in addition to LVEF, to identify individuals at higher risk prior to ICD implantation, whereas 23.6% reported that they did not perform any risk stratification. The tools most frequently used for risk stratification (alone or in combination) were as follows: QRS duration on 12-lead ECG (71% of centres), presence of non-sustained ventricular tachycardia on 24-h recording (90%) and programmed ventricular stimulation (65%).
  
  CONCLUSION:
  This survey reveals a fairly good correspondence between the therapeutic choices made by the Italian centres involved in the study and the recommendations set out in the guidelines of the Italian, European and American scientific societies.
  
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• [Selection criteria for referral to cardiac rehabilitation centers].
  Monaldi Arch Chest Dis

  2011 Mar;76(1):1-12.
  
  Greco Cesare, Cacciatore Giuseppe, Gulizia Michele, Martinelli Luigi, Oliva Fabrizio, Olivari Zoran, Seccareccia Fulvia, Temporelli Pier Luigi, Urbinati Stefano, , ,
  
  Abstract
  
  Current guidelines state that cardiac rehabilitation is indicated after the acute phase of major cardiovascular diseases and interventions; on the other hand implementation of these indications is difficult because of several barriers, i.e. the number of patients per year with an indication exceeds by far the accommodation offer of cardiac rehabilitation centers; the demand for access to cardiac rehabilitation from acute cardiac care hospitals is low because the attention is focused on the acute phase of cardiac diseases. The present Consensus Document describes the changes in clinical epidemiology of the main cardiovascular diseases, showing that complications are increasingly more frequent in the postacute phase, especially in the setting of myocardial infarction. The Joint ANMCO/IACPR-GICR Committee defines priority criteria based on clinical risk for admission to cardiac rehabilitation centers as inpatients. This Consensus Document represents, therefore, an important step forward in the search for continuity of care in high-risk patients during the post-acute phase.
  
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• [Selection criteria for patient admission to cardiac rehabilitation centers].
  G Ital Cardiol (Rome)

  2011 Mar;12(3):219-29.
  
  Greco Cesare, Cacciatore Giuseppe, Gulizia Michele, Martinelli Luigi, Oliva Fabrizio, Olivari Zoran, Seccareccia Fulvia, Temporelli Pier Luigi, Urbinati Stefano, , ,
  
  Abstract
  
  Current guidelines state that cardiac rehabilitation is indicated after the acute phase of major cardiovascular diseases and interventions; on the other hand implementation of these indications is difficult because of several barriers, i.e. the number of patients per year with an indication exceeds by far the accommodation offer of cardiac rehabilitation centers; the demand for access to cardiac rehabilitation from acute cardiac care hospitals is low because the attention is focused on the acute phase of cardiac diseases. The present Consensus Document describes the changes in clinical epidemiology of the main cardiovascular diseases, showing that complications are increasingly more frequent in the post-acute phase, especially in the setting of myocardial infarction. The Joint ANMCO/IACPR-GICR Committee defines priority criteria based on clinical risk for admission to cardiac rehabilitation centers as inpatients. This Consensus Document represents, therefore, an important step forward in the search for continuity of care in high-risk patients during the post-acute phase.
  
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• Prevalence and prognostic role of anaemia in patients with acute heart failure and preserved or depressed ventricular function.
  Intern Emerg Med

  2013 Mar;8(2):147-55. doi: 10.1007/s11739-011-0601-z.
  
  Tarantini Luigi, Oliva Fabrizio, Cantoni Silvia, Cioffi Giovanni, Agnoletto Virginia, Alunni Gianfranco, De Cian Francesca, Di Lenarda Andrea, Lucci Donata, Pulignano Giovanni, Scelsi Laura, Maggioni Aldo Pietro, Tavazzi Luigi
  
  Abstract
  
  Observations available for patients with acute heart failure (HF) show conflicting results, and the prognostic role of anaemia ascertained on hospital admission is not well defined. We investigated the database of the Italian Survey on Acute Heart Failure (IS-AHF) to analyze prevalence, factors associated with and the prognostic role of anaemia (defined as haemoglobin < 12 g/dl) in patients hospitalized for acute HF with either depressed or preserved (>40%) ejection fraction (EF). The median haemoglobin level of the 2,318 patients considered in this analysis was 13 g/dl (inter-quartile range 11.5-14.3). The prevalence of anaemia was 31%. Patients who had anaemia were older, more frequently female gender, hospitalized for a chronic destabilized HF, had higher prevalence of preserved EF, hyponatremia, elevated troponin and other comorbidities (including diabetes, peripheral artery disease, chronic renal failure) than those who did not have anaemia. During the hospital stay, they were treated with higher doses of diuretics, and more frequently required mechanical ventilation and ultrafiltration, and less frequently received ACEi/ARB, aldosterone blockers and beta-blockers at hospital discharge. In-hospital mortality was 12.1 and 5.3% in patients with and without anaemia, respectively (p < 0.0001). In the multivariable analysis, anaemia was a significant independent predictor of in-hospital mortality apart from age, low systolic blood pressure, impaired renal function, elevated troponin assay, the non use of beta-blocker and the requirement of inotropic drug. In conclusion, anaemia diagnosed at hospital admission for acute HF is a frequent comorbidity with meaningful implications on the clinical management and prognosis both in patients with reduced and preserved EF.
  
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• Orthotopic heart transplantation with donors greater than or equal to 60 years of age: a single-center experience.
  Eur J Cardiothorac Surg

  2011 Jul;40(1):e55-61. doi: 10.1016/j.ejcts.2011.02.013.
  
  Bruschi Giuseppe, Colombo Tiziano, Oliva Fabrizio, Morici Nuccia, Botta Luca, Cannata Aldo, Frigerio Maria, Martinelli Luigi
  
  Abstract
  
  OBJECTIVES:
  Heart transplantation is the best therapeutic option for patients suffering from end-stage heart failure, but donor organ availability still represents a major problem. This had led to a shift toward extended donor criteria. The aim of the present study is to analyze the short- and long-term results of heart transplantation in patients with donor age ? 60 years.
  
  METHODS:
  Since November 1985, 890 patients have been transplanted at our center. We consider, for the present study, only primary adult heart transplantations performed after 1990, totaling 761 patients, mean age at transplantation 49.8 years, and 616 patients being male (81%). We compare the short- and long-term results of patients transplanted with donors younger than 60 years or ? 60 years.
  
  RESULTS:
  Since 1990, at our center, 711 patients have been heart transplanted with a donor younger than 60 years, while 50 patients received a heart from a donor older than 60 years. No differences have been reported in the etiology of cardiomyopathy, previous surgery, or mean ischemic time. Patients transplanted with donors ? 60 years of age were significantly older compared to the younger donors' group. Donor cause of death was a cerebrovascular accident in 82% of donors ? 60 years versus 41% in younger donors. Patients' heart transplanted with donors ? 60 years had a higher incidence of acute graft failure with a hospital mortality of 32% (16 patients) significantly higher compared with 10.2% for the other group. No differences were noticed in the incidence of renal failure, acute rejection treated, coronary allograft vasculopathy, and neoplasm during long-term follow-up.
  
  CONCLUSIONS:
  It was possible to expand the cardiac donor pool by accepting allografts from donors ? 60 years of age in selected cases by performing a coronary angiogram. A meticulous donor evaluation and a careful risk assessment between the risk of death on the waiting list and probable increased hospital mortality are needed.
  
  Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
  
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• Epinephrine for acute decompensated heart failure and low output state: friend or foe?
  Int J Cardiol

  2011 Jun;149(3):384-5. doi: 10.1016/j.ijcard.2011.03.006.
  
  Morici Nuccia, Sacco Alice, Oliva Fabrizio, Ferrari Stefano, Paino Roberto, Milazzo Filippo, Frigerio Maria, Pirola Roberto, Klugmann Silvio, Mafrici Antonio
  
  
  
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• Sensitivity and positive predictive value of implantable intrathoracic impedance monitoring as a predictor of heart failure hospitalizations: the SENSE-HF trial.
  Eur Heart J

  2011 Sep;32(18):2266-73. doi: 10.1093/eurheartj/ehr050.
  
  Conraads Viviane M, Tavazzi Luigi, Santini Massimo, Oliva Fabrizio, Gerritse Bart, Yu Cheuk-Man, Cowie Martin R
  
  Abstract
  
  AIMS:
  Early recognition of impending decompensation and timely intervention may prevent heart failure (HF) hospitalization. We investigated the performance of OptiVol® intrathoracic fluid monitoring for the prediction of HF events in chronic HF patients newly implanted with a device (implantable cardioverter-defibrillator with or without cardiac resynchronization therapy).
  
  METHODS AND RESULTS:
  SENSE-HF was a prospective, multi-centre study that enrolled 501 patients. Phase I (double blinded, 6 months) determined the sensitivity and positive predictive value (PPV) of the OptiVol data in predicting HF hospitalizations. Of 58 adjudicated HF hospitalizations that occurred during the first 6 months in Phase I, 12 were predicted by OptiVol (sensitivity = 20.7%). Sensitivity appeared to be dynamic in nature and at the end of Phase I, had increased to 42.1%. With 253 OptiVol detections, PPV for Phase I was 4.7%. Phase II/III (unblinded, 18 months) determined the PPV of the first OptiVol Patient Alert for detection of worsening HF status with signs and/or symptoms of pulmonary congestion. A total of 233 patients noted such an OptiVol alert and for 210, HF status was evaluated within 30 days. Heart failure status had worsened for 80 patients (PPV = 38.1%).
  
  CONCLUSIONS:
  An intrathoracic impedance-derived fluid index had low sensitivity and PPV in the early period after implantation of a device in chronic HF patients. Sensitivity improved within the first 6 months after implant. Further studies are needed to assess the place of this monitoring technology in the clinical management of patients with HF.
  
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• [Continuity of care in patients with cardiac failure after acute event].
  Monaldi Arch Chest Dis

  2010 Jun;74(2):58-63.
  
  Tridico Caterina, Fontana Giancarlo, Diaco Tommaso, Oliva Fabrizio, Giordano Amerigo, Senni Michele, Filippi Alessandro, Marzegalli Maurizio, Fiorini Gianfrancesco, Ambrosetti Marco, Febo Oreste, ,
  
  
  
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• [Current perspectives in telemonitoring and devices in chronic heart failure patients: lights and shadows].
  G Ital Cardiol (Rome)

  2010 May;11(5 Suppl 2):33S-37S.
  
  Mortara Andrea, Oliva Fabrizio, Di Lenarda Andrea
  
  Abstract
  
  The complexity of an integrated approach, mandatory for chronic diseases such as heart failure, might be simplified by the availability of new technologies for remote data transmission at relatively low costs. Home telemonitoring for complex patients opens new perspectives for the safe discharge of chronically severe patients and intensive surveillance for unstable subjects, and shows potential benefits on patients' quality of life and cost containment. Systematic reviews and meta-analyses document a 30-35% decrease in mortality and a 15-20% reduction in hospital admissions. Critical issues remain the presence of health facilities and professionals both in hospital and in the community adequately prepared for patient management through the telemonitoring tool, the selection of patients who may benefit most from it, and financial reimbursement of remote monitoring. The main indication to telemonitoring is the patient at high risk of short-term hemodynamic deterioration, but psychosocial issues should also be considered. New perspectives for tailored management of heart failure patients come from the recent availability of implantable devices able to record hemodynamic parameters. Current evidence is, however, insufficient to affirm their reliability, efficacy, cost-effectiveness, and management changes that may derive from their use.
  
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• [Consensus document on endomyocardial biopsy of the Associazione per la Patologia Cardiovascolare Italiana].
  G Ital Cardiol (Rome)

  2009 Sep;10(9 Suppl 1):3S-50S.
  
  Leone Ornella, Rapezzi Claudio, Sinagra Gianfranco, Angelini Annalisa, Arbustini Eloisa, Bartoloni Giovanni, Basso Cristina, Caforio Alida L P, Calabrese Fiorella, Coccolo Fabio, d'Amati Giulia, Mariesi Emiliano, Milanesi Ornella, Nodari Savina, Oliva Fabrizio, Perkan Andrea, Prandstraller Daniela, Pucci Angela, Ramondo Angelo, Silvestri Furio, Valente Marialuisa, Thiene Gaetano, ,
  
  Abstract
  
  The Italian Scientific Associations of Cardiologists and Cardiovascular Pathologists have produced this consensus document on the diagnostic role of endomyocardial biopsy (EMB) in terms of techniques, analysis and reporting. The document is intended for clinical cardiologists, hemodynamic experts, electrophysiologists, surgical pathologists, and cardiac surgeons. It has three main aims: a) to collocate EMB in the context of currently available tools for diagnosis of heart diseases; b) to provide recommendations for rational implementation; c) to outline key characteristics (standards) for Italian cardiology and surgical pathology centers that perform and analyze EMB. A general lack of prospective, controlled studies addressing EMB prohibited the use of traditional evidence-based recommendations that rely on classes of available evidence. Thus, it was agreed that three key points should be taken into account: a) the specific pathology to be diagnosed (or excluded); b) the existence of any alternative, non-invasive diagnostic techniques; c) the overall consequences of reaching a definite diagnosis on patients' clinical management. Accordingly, we propose recommendations for EMB based on the following levels of diagnostic value: level 1: no alternative method exists to reach a definite diagnosis that can have obvious consequences for clinical management; level 2a: no alternative method exists to reach a definite diagnosis; however, the implications for clinical management are uncertain; level 2b: no alternative method exists to reach a definite diagnosis; however, the diagnosis would not influence clinical management; level 3: an alternative method exists to reach a definite diagnosis. The second part of the document proposes current protocols for the preparation, analysis and reporting of EMB in the context of each main pathologic entity. Particular attention is given to tissue characterization and implementation of molecular tests.
  
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• Evolution of renal function during and after an episode of cardiac decompensation: results from the Italian survey on acute heart failure.
  J Cardiovasc Med (Hagerstown)

  2010 Apr;11(4):234-43. doi: 10.2459/JCM.0b013e3283334e12.
  
  Tarantini Luigi, Cioffi Giovanni, Gonzini Lucio, Oliva Fabrizio, Lucci Donata, Di Tano Giuseppe, Maggioni Aldo Pietro, Tavazzi Luigi,
  
  Abstract
  
  BACKGROUND:
  Renal dysfunction is frequently associated with heart failure and strongly influences the outcome of heart failure patients. Although recommended pharmacological interventions for heart failure may contribute to the development of, or worsen renal dysfunction, their relations with renal function have not been fully explored in an unselected community population. METHODS AND AIM: We studied 1008 patients recruited in the Italian survey on acute heart failure to assess the prevalence, the prognostic role of renal function and the relations between the changes in renal function and the pharmacological interventions during hospitalization and at 6-month follow-up. Patients were categorized using the National Kidney Foundation cut-offs for degree of renal function measured by the glomerular filtration rate.
  
  RESULTS:
  Moderate-to-severe renal dysfunction was diagnosed in 59% of patients at hospital admission and 61% at discharge. These patients were older and had a higher prevalence of diabetes, anemia, history of hypertension, myocardial infarction and hospitalization for heart failure than those with normal or mildy impaired renal function. At admission the former were treated more frequently with diuretics, angiotensin converting enzyme-inhibitor (ACEi) or angiotensin receptor blockers (ARBs) than the latter. Diuretics were given at higher dose and for a longer time during the hospital stay while beta-blockers, digoxin, antialdosterone agents, ACEi and ARBs were given less frequently in patients who had moderate-to-severe renal dysfunction than those who did not. High-dose diuretic treatment, inability to start or maintain beta-blockers during hospital stay and the nonprescription of ACEi/ARBs at discharge emerged, by multivariate analysis, as predictors of death at 6-month follow-up (mortality rate = 14%), independent of the persistence of moderate-to-severe renal dysfunction over time, anemia, male sex and history of heart failure.
  
  CONCLUSIONS:
  In acute heart failure, renal dysfunction is frequent and impacts prognosis. In this setting, the pharmacological interventions are significantly associated with changes in renal function and 6-month mortality.
  
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• [Inotrope therapy in acute heart failure: a critical review of clinical and scientific evidence for levosimendan in the context of traditional treatment].
  G Ital Cardiol (Rome)

  2009 Jul;10(7):422-33.
  
  Ambrosio Giuseppe, Di Lenarda Andrea, Fedele Francesco, Gabrielli Domenico, Metra Marco, Oliva Fabrizio, Perna Gianpiero, Senni Michele, De Maria Renata
  
  Abstract
  
  The clinical heterogeneity of acute heart failure and the low number of controlled trials, to date, are the main causes of the lack of agreement on therapeutic objectives, uncertainty on the most appropriate management, and difficulties to obtain robust evidence for the treatment of this syndrome. The inappropriate use of inotropic agents is one the most common pitfalls shown by registries. Two to 10% of patients admitted for acute heart failure present with a low output syndrome, a clinical profile associated with high mortality, where inotropes may be a rational therapeutic choice. Crucial points for an effective use of inotropes are an accurate evaluation and selection of patients, tailoring of therapeutic schemes and strict patient monitoring. Beta-adrenergic agonists and phosphodiesterase inhibitors increase myocardial oxygen demand, favor arrhythmias and may cause peripheral vasodilation with a secondary decrease in coronary perfusion pressure. These effects may translate in myocardial ischemia, loss of cardiomyocytes and accelerated ventricular remodeling with worse prognosis. Levosimendan, a novel inotropic agent studied according to the principles of evidence-based medicine, augments myocardial contractility without changes in intracellular calcium concentrations, and with minimal impact on myocardial oxygen consumption. This paper, based on an expert consensus, aims to suggest criteria for the appropriate use of inotropic agents in acute heart failure, based on a critical appraisal of the existing evidence and clinical experience.
  
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• Monitoring intrathoracic impedance with an implantable defibrillator reduces hospitalizations in patients with heart failure.
  Pacing Clin Electrophysiol

  2009 Mar;32(3):363-70. doi: 10.1111/j.1540-8159.2008.02245.x.
  
  Catanzariti Domenico, Lunati Maurizio, Landolina Maurizio, Zanotto Gabriele, Lonardi Gabriele, Iacopino Saverio, Oliva Fabrizio, Perego Giovanni B, Varbaro Annamaria, Denaro Alessandra, Valsecchi Sergio, Vergara Giuseppe,
  
  Abstract
  
  PURPOSE:
  Some implantable cardioverter-defibrillators (ICDs) are now able to monitor intrathoracic impedance. The aim of the study was to describe the use of such monitoring in clinical practice and to evaluate the clinical impact of the fluid accumulation alert feature of these ICDs.
  
  METHODS AND RESULTS:
  Five hundred thirty-two heart failure (HF) patients implanted with these ICDs were followed up for 11 +/- 7 months. A clinical event (CE) was deemed to have occurred if it resulted in hospitalization or milder manifestations of HF deterioration. Three hundred sixty-two acute decreases in intrathoracic impedance (Z events) occurred in 230 patients. Of these episodes, 171 (47%) were associated with a CE within 2 weeks of the Z event. In another 71 (20%) Z events, drug therapy was adjusted despite the absence of overt signs of clinical deterioration. The rate of unexplained Z events was 0.25 per patient-year and 25 hospitalizations were not associated with Z events. The audible alert was disabled in a group of 102 patients (OFF group). HF hospitalizations occurred in 29 (7%) patients in the ON group and 20 (20%, P < 0.001) patients in the OFF group. The rate of combined cardiac death and HF hospitalization was lower in patients with Alert ON (log-rank test, P = 0.007).
  
  CONCLUSIONS:
  The ICD reliably detected CE and yielded low rates of unexplained and undetected events. The alert capability seemed to reduce the number of HF hospitalizations by allowing timely detection and therapeutic intervention.
  
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• [Management of advanced chronic heart failure].
  G Ital Cardiol (Rome)

  2008 Oct;9(10 Suppl 1):112S-117S.
  
  Oliva Fabrizio, Macera Francesca, Verde Alessandro, Frigerio Maria
  
  Abstract
  
  Because of the progressive ageing of the population and the extensive use of recommended drugs, the number of patients with advanced chronic heart failure constantly increases. Several studies showed the efficacy of neurohormonal antagonists and electric devices in NYHA class III-IV patients; however, there is no agreement on the management of refractory heart failure, especially for patients who are not candidates for heart transplantation, because of age or comorbidity. The treatment with intravenous inotropic agents is considered a palliative care. The growing experience with implant of left ventricular assist devices, on the other hand, is encouraging and suggests more extensive use of these devices, both as bridge to transplant and as destination therapy.
  
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• [Changes in patient survival and quality of life after heart transplantation].
  G Ital Cardiol (Rome)

  2008 Jul;9(7):461-71.
  
  Frigerio Maria, Oliva Fabrizio, Turazza Fabio M, Macera Francesca, Galvanin Silvia, Verde Alessandro, Bruschi Giuseppe, Pedrazzini Giovanna
  
  Abstract
  
  Heart transplantation was performed firstly in 1967, but it became a valuable option in the 1980s, due to the availability of cyclosporine and of the technique for rejection monitoring by means of serial endomyocardial biopsies. Post-transplant survival improved over the years, mainly due to a reduction in early mortality for infection or acute rejection. Expected 1-year and 5-year survivals are around 85% and 70%, respectively. During the past 20-30 years, better therapies for heart failure have been developed, leading to restriction of heart transplant candidacy to truly refractory heart failure. On the contrary, the criteria for donor acceptance have been liberalized, due to the discrepancy between heart transplant candidates and available organs. It must be kept in mind that renal and/or hepatic insufficiency that may be a consequence of heart failure, pulmonary hypertension, and donor age, all remain risk factors for mortality after transplantation. In order to maintain and possibly improve the results of heart transplantation, effective strategies to increase safely the donor pool are of utmost importance. Moreover, long-term post-transplant recipients present new challenges to research and clinical practice. Mechanical circulatory support devices represent a surgical bridge or an alternative to transplantation; their expansion is limited by costs, organizational burden, and by patient difficulties in accepting this therapy.
  
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• Aminothiol redox alterations in patients with chronic heart failure of ischaemic or non-ischaemic origin.
  J Cardiovasc Med (Hagerstown)

  2007 Dec;8(12):1024-8.
  
  Campolo Jonica, Caruso Raffaele, De Maria Renata, Parolini Marina, Oliva Fabrizio, Roubina Elena, Cighetti Giuliana, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  Oxidative stress plays a role in the progression of chronic heart failure (CHF), but whether and how ischaemic heart disease (IHD) or non-IHD aetiology may account for differential redox alterations is currently unclear. We assessed the relation between thiol redox state and lipid peroxidation, as a marker of oxidative stress, in patients with CHF of ischaemic or non-ischaemic origin.
  
  METHODS:
  Blood reduced glutathione, plasma total and reduced cysteine, cysteinylglycine, homocysteine, glutathione, plasma alpha-tocopherol, ascorbic acid, and free malondialdehyde were assessed in 43 CHF heart transplant candidates (24 IHD and 19 non-IHD) and 30 controls matched for age, gender and number of atherosclerotic risk factors.
  
  RESULTS:
  Reduced cysteine was increased in CHF patients compared with controls. The highest levels were found in IHD versus non-IHD patients versus controls. Malondialdehyde levels were significantly higher in IHD patients than in controls, whereas antioxidant vitamins did not differ among the three groups.
  
  CONCLUSIONS:
  Specific abnormalities in the thiol pattern are associated with heart failure aetiology in CHF patients. Our findings point to the possible role of reduced cysteine in the progression of chronic IHD to heart failure status, as an additional pro-oxidant stimulus for worsening oxidative stress.
  
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• [Heart failure: critical patients].
  G Ital Cardiol (Rome)

  2007 Sep;8(9):568-73.
  
  Fabbri Gianna, Gorini Marco, Maggioni Aldo P, Oliva Fabrizio,
  
  Abstract
  
  Patients with heart failure in the "real world" are often elderly and with multiple comorbid diseases. These conditions create a dilemma for the physician responsible for the treatment of heart failure and are associated with a substantial underutilization of evidence-based treatments. Clarifying the prognostic impact of comorbidities in heart failure could provide more precise risk stratification and optimize the management of these patients. The negative prognostic impact of concomitant diseases has been shown in several studies: in the TEMISTOCLE study, carried out in Italy on patients hospitalized for heart failure in Internal Medicine and Cardiology wards, the presence of comorbidities was associated with higher in-hospital mortality and prolonged length of stay. In the IN-CHF registry, enrolling out patients with heart failure in a cardiological setting, the rate of coexisting diseases is not very high according to the epidemiological characteristics of this population. Renal impairment, particularly in patients >70 years old, and chronic obstructive pulmonary disease (COPD) are frequent comorbid diseases in heart failure. Renal impairment has been recognized as an independent risk factor for morbidity and mortality in heart failure while the role of COPD is controversial. Patients with renal dysfunction and COPD have largely been excluded from randomized controlled trials for safety reasons, so data are scarce. In the IN-CHF registry the prevalence of elderly patients with renal impairment (serum creatinine > or = 2 mg/dl and age > or = 70 years) is 5.1%; this subgroup of patients has an increased risk for both 1-year death (28.1 vs 11.2%) and hospital admission (34.9 vs 22.5%) compared with the remaining population. The prescription pattern has been evaluated in the last years (2003-2005) and shows that angiotensin system inhibitors (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) as well as beta-blockers are less prescribed in these patients (78.9 vs 86.1% and 42.2 vs 55.9%, respectively). The prevalence of patients with COPD in the registry was 13.2%: considerable differences in COPD prevalence estimates exist in the general population depending on many factors such as method for diagnosis or lack of agreement on diagnostic criteria. COPD patients were older and with more severe symptoms; with respect to the pharmacological treatment, beta-blockers are significantly less prescribed in COPD patients while a similar proportion of patients are receiving angiotensin system antagonists. The adjusted analysis shows that COPD in not an independent predictor of 1-year mortality in this population while it is independently associated with 1-year all-cause hospitalization. Non-cardiovascular hospital admissions seem to be more influenced by the presence of this comorbidity than cardiovascular admissions.
  
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• [Heart failure: the importance of a disease management program].
  G Ital Cardiol (Rome)

  2007 Jun;8(6):353-8.
  
  Fabbri Gianna, Gorini Marco, Maggioni Aldo P, Oliva Fabrizio,
  
  Abstract
  
  Heart failure remains a growing public health problem, hospitalizations represent the main cost component of heart failure care and the poor quality of life of patients is often worsened by frequent admissions. A multidisciplinary approach and specific disease management programs are a potentially useful instrument to reducing hospitalizations in heart failure patients. These concepts have recently been discussed in a consensus document by all the Scientific Societies involved in the care of heart failure patients. The effectiveness of intervention programs delivering continuity of care by a multidisciplinary team achieved a promising reduction in admissions, but the results of the studies have not been univocal for category of strategies and about the effect on survival. Telephone intervention significantly decreased heart failure admissions but not all-cause admissions and mortality. The multicenter randomized DIAL study, comparing a centralized telephone intervention program delivering continuity of care by a multidisciplinary team with usual care in patients with heart failure, confirms these findings. After a mean 16-month follow-up, there was a benefit mostly due to a significant reduction in admissions for heart failure, but mortality was similar in both groups. Data on 9000 patients from the IN-CHF registry show that hospitalizations are a serious problem in Italy: 44% of the patients had at least one hospitalization for heart failure in the year prior to the entry visit and this is the most powerful independent predictor of rehospitalization during the follow-up. Nearly a quarter of the population with follow-up data availability (92%) has been rehospitalized in the year after enrollment; patients in advanced functional class (32.1% hospitalization rate) and with ischemic etiology (25.0%) are more likely to be hospitalized than those in NYHA class I-II and without ischemic etiology. In a survey carried out recently in Italy, in 1152 patients admitted for decompensated heart failure, readmission rate was even higher: more than 40% of patients have been readmitted once in the 6 months after discharge and 7.2% had two or more admissions.
  
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• Hydrotherapy in advanced heart failure: the cardio-HKT pilot study.
  Monaldi Arch Chest Dis

  2006 Dec;66(4):247-54.
  
  Municinó Annamaria, Nicolino Annamaria, Milanese Manlio, Gronda Edoardo, Andreuzzi Bruno, Oliva Fabrizio, Chiarella Francesco,
  
  Abstract
  
  BACKGROUND:
  In-water exercise, hydrotherapy, may offer an attractive alternative to conventional training in markedly compromised patients with advanced HF. This Pilot Study evaluates the safety and efficacy of Cardio-Hydrokinesitherapy (Cardio-HKT) in patients with advanced HF on optimal medical therapy. Cardio-HKT is a novel rehabilitation program that includes training sessions in warm water (31 degrees C), integrated by educational and psycho-behavioural sessions to promote healthy life style modifications.
  
  METHODS:
  We studied 18 adult patients with advanced HF, LVEF < 35%, NYHA functional class > II and peak oxygen uptake (peak VO2) < 18 ml/kg/min. Cardio-HKT consisted of a 3 weeks daily in-water training, combined to educational and psycho-behavioural sessions. Patients underwent a six-minute-walking-test (6mWT), a cardiopulmonary exercise test at baseline and after 3 weeks of Cardio-HKT. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHF).
  
  RESULTS:
  All patients completed the Cardio-HKT rehabilitation program without complications. The 6mWT improved from 453 +/- 172 m to 571 +/- 120 m (p < 0.01), peak VO2 from 13.0 +/- 3.1 to 14.5 +/- 2.9 ml/kg/min (p = 0.03), whereas VE/ CO2 slope declined from 37 +/- 10 to 33 +/- 9 (p = 0.01). MLHF markedly improved from 56 (68-27) to 18 (40-7) (p < 0.01).
  
  CONCLUSIONS:
  Our results support the safety and efficacy of the innovative Cardio-HKT rehabilitation program in patients with advanced HF.
  
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• Bridge to transplantation with the MicroMed DeBakey ventricular assist device axial pump: a single centre report.
  J Cardiovasc Med (Hagerstown)

  2006 Feb;7(2):114-8.
  
  Bruschi Giuseppe, Ribera Elena, Lanfranconi Marco, Russo Claudio, Colombo Tiziano, Garatti Andrea, Oliva Fabrizio, Milazzo Filippo, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  OBJECTIVE:
  Left ventricular assist devices (VADs) are an accepted therapy to bridge patients with end-stage heart failure to heart transplantation. The DeBakey VAD, a continuous axial flow pump weighing 93 g, has been introduced into clinical practice as a bridge to transplant.
  
  METHODS:
  Starting from April 2000,17 patients (12 males, five females, mean age 44.3 +/- 12.8 years; 11 dilated idiopathic cardiomyopathy, five ischaemic cardiomyopathy, one pulsatile device failure) with end-stage heart failure were implanted with a DeBakey VAD as a bridge to transplantation at our institution. Before implant, all patients suffered from severe heart failure (New York Heart Association functional class IV) despite optimal medical therapy and were put on the waiting list for heart transplantation. Mean cardiac index was 1.59 +/- 0.51 l/min/m2.
  
  RESULTS:
  Fourteen patients were successfully transplanted after 99 +/- 117 days of assistance (range 11-443 days). Two patients died during assistance of multiorgan failure, one patient is still on VAD. No patient needed additional right ventricular mechanical support. Left ventricular/left VAD thrombosis occurred in one patient who was successfully treated conservatively. No clinical elevation of plasma free haemoglobin was detected. Neither device, driveline, abdominal pocket infection nor device failure occurred.
  
  CONCLUSIONS:
  In our experience with the continuous axial flow DeBakey VAD, a high success rate was obtained associated with a low risk of complications. All the patients tolerated continuous blood flow for extended periods that makes this device a valuable alternative to pulsatile VADs as a bridge to transplantation.
  
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• Nationwide survey on acute heart failure in cardiology ward services in Italy.
  Eur Heart J

  2006 May;27(10):1207-15.
  
  Tavazzi Luigi, Maggioni Aldo P, Lucci Donata, Cacciatore Giuseppe, Ansalone Gerardo, Oliva Fabrizio, Porcu Maurizio,
  
  Abstract
  
  AIMS:
  Chronic heart failure (HF) is recognized as an important public health problem but little attention has been focused on acute-stage HF.
  
  METHODS AND RESULTS:
  Nationwide, prospective, observational study setting 206 cardiology centres with intensive cardiac care units. During 3 months, 2807 patients diagnosed as having de novo acute HF (44%) or worsening chronic HF (56%) were enrolled. Acute pulmonary oedema was the presenting clinical feature in 49.6% of patients, cardiogenic shock in 7.7%, and worsened NYHA functional class in 42.7% of cases. Anaemia (Hb<12 g/dL) was present in 46% of patients, renal dysfunction (creatinine > or =1.5 mg%) in 47%, and hyponatraemia (< or =136 mEq/L) in 45%. An ejection fraction (EF)>40% was found in 34% of cases. Intravenous diuretics, nitrates, and inotropes were given to 95, 51, and 25% of patients, respectively. The median duration of hospital stay was 9 days. In-hospital mortality rate was 7.3%. Older age, use of inotropic drugs, elevated troponin, hyponatraemia, anaemia, and elevated blood urea nitrogen were independent predictors of all-cause death; prior revascularization procedures and elevated blood pressure were indicators of a better outcome. The rehospitalization rate within 6 months was 38.1%, all-cause mortality from discharge to 6 months was 12.8%.
  
  CONCLUSION:
  Acute HF is an ominous condition, needing more research activity and resources.
  
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• [Mechanical assist devices in advanced heart failure. Indications and perspectives].
  G Ital Cardiol (Rome)

  2006 Feb;7(2):91-108.
  
  Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Bruschi Giuseppe, Garatti Andrea, Milazzo Filippo, Catena Emanuele, Oliva Fabrizio, Turazza Fabio, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  Congestive heart failure is recognized as a major public health issue and is the leading cause of death in western countries. Heart transplantation currently remains the gold standard option for end-stage heart failure patients. Heart transplantation is also one of the most limited therapies, not only with regard to the lack of donor hearts but also because of the surgical limitations inherent to the clinical aspects of this severely ill patient population. Mechanical circulatory support systems have been developed as effective adjuvant therapeutic options in these terminally ill patients. Over the past two decades, mechanical circulatory support devices have steadily evolved in the clinical management of end-stage heart failure, and have emerged as a standard of care for the treatment of acute and chronic heart failure refractory to conventional medical therapy. Future blood pumps should be smaller and totally implantable, as well as more efficient, biocompatible, and reliable.
  
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• [Prevention, a primary objective according to the last revision of the European Society of Cardiology guidelines on chronic heart failure: is it possible to intervene early in high-risk patients?].
  Ital Heart J Suppl

  2005 Nov;6(11):716-9.
  
  Tarantini Luigi, Pulignano Giovanni, Oliva Fabrizio, Alunni Gianfranco, Di Lenarda Andrea
  
  
  
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• Fulminant myocarditis during HIV seroconversion: recovery with temporary left ventricular mechanical assistance.
  Ital Heart J

  2004 Mar;5(3):228-31.
  
  Brucato Antonio, Colombo Tiziano, Bonacina Edgardo, Orcese Carloandrea, Vago Luca, Oliva Fabrizio, Distefano Giada, Frigerio Maria, Paino Roberto, Violin Michela, Agati Salvatore, Vitali Ettore
  
  Abstract
  
  A 32-year-old male was admitted to our intensive care unit for low cardiac output syndrome. Echocardiography was suggestive of extensive hypokinesia and the ejection fraction was 0.22. Serological tests, including anti-HIV antibodies (ELISA), were negative. The patient was intubated and an intra-aortic balloon pump was inserted. Twenty-four hours after admission a paracorporeal left ventricular assist device (LVAD-MEDOS) was implanted. The left ventricular function showed progressive improvement with normalization of the ejection fraction on day 19. The device was removed on day 20. Before discharge, the patient admitted that he had had unprotected sex with numerous male acquaintances; anti-HIV testing turned positive. The final diagnosis was fulminant myocarditis during HIV seroconversion.
  
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• [Heart failure in the elderly: do differences in etiology and pathophysiology require different therapeutic strategies? Pros].
  Ital Heart J

  2003 Dec;4 Suppl 8():39S-44S.
  
  Frigerio Maria, Oliva Fabrizio
  
  
  
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• [Is it time to organize a "new " campaign against congestive heart failure?].
  Ital Heart J Suppl

  2003 Mar;4(3):232-6.
  
  Mangia Rolando, Senni Michele, Cacciatore Giuseppe, Del Sindaco Donatella, Pozzi Roberto, Di Lenarda Andrea, Oliva Fabrizio, Clemenza Francesco, Porcu Maurizio
  
  
  
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• Prevention and management of chronic heart failure in management of asymptomatic patients.
  Am J Cardiol

  2003 May;91(9A):4F-9F.
  
  Frigerio Maria, Oliva Fabrizio, Turazza Fabio M, Bonow Robert O
  
  Abstract
  
  Symptomatic heart failure is preceded by a somewhat prolonged asymptomatic stage in many patients. The number of patients with asymptomatic heart dysfunction is about 4-fold greater than the number of patients with clinically overt heart failure. Pharmacologic treatment with angiotensin-converting enzyme inhibitors and beta-blockers (in particular carvedilol) of asymptomatic patients with systolic left ventricular (LV) dysfunction can prevent or delay the occurrence of symptoms and reduce mortality in the long term. Thus, it would be of utmost importance to recognize and appropriately treat these patients before they develop heart failure symptoms. The cost-effectiveness of screening for asymptomatic heart dysfunction in the general population and in cohorts at risk has not been extensively evaluated. A normal electrocardiogram has a high negative predictive value in patients at risk. Echocardiography is the best tool for diagnosis and characterization of heart dysfunction, but extensive use is limited by availability and cost. Natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) are very sensitive markers of heart dysfunction and volume overload, and their measurement has been proposed as a first-line test to select patients who need echocardiography. The definition of the etiology of LV dysfunction--in particular, of the ischemic etiology--has prognostic and therapeutic implications. In addition to revascularization, pharmacologic treatment with antiplatelets and statins is helpful in preventing new ischemic events and the development of heart failure. The prevention, or at least the delay, of clinical manifestations of heart failure is strongly related to an effective approach to the asymptomatic stage. Therefore, it is important to educate the entire medical community, particularly physicians in the primary care setting, about recognition and treatment of these patients.
  
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• [Advanced heart failure: therapeutic options. Opinion of the surgeon cardiologist].
  Ital Heart J

  2002 Oct;3 Suppl 6():65S-70S.
  
  Bruschi Giuseppe, Colombo Tiziano, Garatti Andrea, Fratto Pasquale, Ribera Elena, Garascia Andrea, Oliva Fabrizio, Frigerio Maria, Vitali Ettore
  
  
  
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• [Refractory heart failure. Models of hospital, ambulatory, and home management].
  Ital Heart J Suppl

  2002 Aug;3(8):837-50.
  
  Oliva Fabrizio, Alunni Gianfranco
  
  Abstract
  
  Chronic heart failure is an enormous and growing public health problem and is reaching epidemic proportions. Its economic impact is dramatic; two thirds of expenses are for hospitalizations and relatively little is being spent for medications and outpatient visits. Most of the hospitalizations, deaths and costs are incurred by a relatively small minority of patients who may be described as having "complex", "advanced", "refractory" or "end-stage" heart failure; however, in essence they are patients who have severe symptoms and/or recurrent hospitalizations and/or emergency department visits despite maximal oral therapy. Many of the recommendations regarding the management of these patients are based more on experience than on evidence from controlled trials. This, because such patients require an individualized therapy which limits their inclusion in large trials and because support is less easily available when testing specific strategies than when testing specific agents. Improving the treatment of this group of patients by optimizing their medical regimen, aggressive monitoring and providing early intervention to avert heart failure can reduce their morbidity, mortality and costs of care. Refractory heart failure is not a single disease and it is extremely unlikely that all patients should be treated in a similar manner; before selecting the appropriate therapy, the clinician must categorize and profile the patient. The first step should be a re-evaluation of the previous treatment because many patients are treated suboptimally. It is also important to identify reversible or precipitating factors. For patients with advanced heart failure, the initial goal of therapy is to improve symptoms; the next goal is to maintain the improvement and to prevent later deterioration. The appropriate treatment plan will reflect the presence of comorbidities, the patients' history regarding previous responses to therapy, their own expectations with regard to daily life. The most common symptoms causing hospitalizations are those related to congestion; the distinction between the rising filling pressures and low cardiac output puts the focus on the adjustment of further medical therapy. The persistence of congestion confers a worse prognosis and urgency for the consideration of surgical therapies. It has been repeatedly shown that in case of heart failure, fewer hospitalizations and lower costs are necessary after referral to programs that provide multidisciplinary care. This care includes heart failure physician specialists with specifically trained clinical nurses. Other important components of a comprehensive management program for advanced heart failure are patient education, rehabilitation and the availability of adequate social service. We have entered a difficult era marked by a collision course between increasing scientific discoveries and restricted resources; a better care for heart failure, integrating improved medical practice with the necessity of bearing the financial pressures in mind, constitutes a great opportunity for medicine.
  
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• Patient selection for biventricular pacing.
  J Cardiovasc Electrophysiol

  2002 Jan;13(1 Suppl):S63-7.
  
  Lunati Maurizio, Paolucci Marco, Oliva Fabrizio, Frigerio Maria, Magenta Giovanni, Cattafi Giuseppe, Vecchi Rita, Vicini Ilaria, Cavaglià Sergio
  
  Abstract
  
  INTRODUCTION:
  Biventricular pacing improves functional status in the majority of patients with drug-refractory heart failure, dilated cardiomyopathy, and interventricular conduction delay. The aim of this study was to analyze the baseline clinical and functional data of a cohort of patients implanted with a biventricular stimulation system in a single-center experience, to verify if the pathophysiologic characteristics of patients affect outcome, and to determine if preliminary identification of the right candidates for the new therapy is possible with noninvasive parameters.
  
  METHODS AND RESULTS:
  Since March 1999, 52 patients with advanced heart failure (idiopathic cardiomyopathy 50%, ischemic cardiomyopathy 35%, other etiology 15%) and left bundle branch block underwent cardiac resynchronization and were followed prospectively. Paired analysis over mean (+/- SD) follow-up of 348 +/- 154 days showed an overall significant decrease of QRS width (baseline 194 +/- 33.2 msec vs follow-up 159.6 +/- 20.1 msec), New York Heart Association (NYHA) functional class (baseline 3.2 +/- 0.5 vs follow-up 2.3 +/- 0.5), quality-of-life score (baseline 54 +/- 25 vs follow-up 25 +/- 16), and increase of maximal VO2 (baseline 12.6 +/- 2.5 mL/kg/min vs follow-up 15.0 +/- 3.3 mL/kg/min). There were 80% responders (documented, persistent decrease > or = 1 NYHA class) and 20% nonresponders (same NYHA class or decline of status; need for heart transplant; death due to progressive pump failure). No significant differences in baseline clinical and functional variables between the two subgroups were observed. In responders, there was a highly significant global improvement of all variables; in nonresponders, no parameters changed between baseline and follow-up.
  
  CONCLUSION:
  These data confirm the role of biventricular pacing in improving the functional status of the great majority of a selected patient population having advanced heart failure and left bundle branch block with wide QRS complex. Basal demographic, clinical, and functional characteristics are not helpful in preliminary selection of responders. Simple evaluation of NYHA class confirms favorable outcome (improvement of functional and hemodynamic status).
  
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