Pubblicazioni - Dott.ssa Frigerio Maria

• Sacubitril/Valsartan: Updates and Clinical Evidence for a Disease-Modifying Approach.
  Drugs

  2019 Sep;79(14):1543-1556. doi: 10.1007/s40265-019-01181-2.
  
  Fabris Enrico, Merlo Marco, Rapezzi Claudio, Ferrari Roberto, Metra Marco, Frigerio Maria, Sinagra Gianfranco
  
  Abstract
  
  New therapeutic strategies aimed to tackle the rising socio-economic burden of heart failure (HF) have become an impelling priority. The new pharmacological class of angiotensin (Ang) receptor-neprilysin inhibitors (ARNI) prompted a real conceptual change in the treatment of HF moving from only the inhibition of the renin-Ang-aldosterone system and sympathetic nervous system to a strategy based on the concomitant pharmacological enhancement of endogenous natriuretic peptides. Sacubitril/valsartan, a first-in-class ARNI, has reduced the primary composite endpoint of cardiovascular death or HF hospitalisation, sudden cardiac death, disease progression and improved quality of life, compared with enalapril, in patients on evidence-based contemporary medical therapy. Our review underlines the increasing body of evidence supporting the efficacy of sacubitril/valsartan, which may be considered a new disease-modifying therapy and, after about 30 years of research, a real step forward in HF pharmacological therapy.
  
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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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• Of hearts, minds, and guts: difficulties in diagnosing heart failure in the young.
  Eur J Heart Fail

  2019 Jul;():. doi: 10.1002/ejhf.1544.
  
  Frigerio Maria, Carugo Stefano, Voltolini Alessandra
  
  
  
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• Psychological outcomes of left ventricular assist device long-term treatment: A 2-year follow-up study.
  Artif Organs

  2019 Jul;():. doi: 10.1111/aor.13531.
  
  Voltolini Alessandra, Salvato Gerardo, Frigerio Maria, Cipriani Manlio, Perna Enrico, Pisu Mirella, Mazza Umberto
  
  Abstract
  
  Left ventricular assist device (LVAD) is an effective therapy for patients with advanced or refractory heart failure. It may represent a temporary treatment in heart transplant (HTX) candidates (Bridge-To-Transplant-BTT), or a permanent therapy for patients unsuitable for HTX (Destination Therapy-DT). Living with the device may be stressful for both the patients and their caregivers. Currently, evidence on the psychological assessment of LVAD recipients, and factors influencing the patients' psychological adaptation to the device in the long-term period is limited. Here, we explored the quality of life in 20 patients who were treated with LVAD with BTT (n = 13) or DT indication (n = 7) before (T0), 1 year (T1) and 2 years (T2) after implantation, using the EuroQoL-5D-5L test. We also analyzed the influence of sociodemographic (eg, age, gender) and clinical variables (eg, the INTERMACS level and number of hospital admissions) on the quality of life at T2. We found a significant improvement in the self-perceived quality of life 2 years after LVAD implantation. Patients significantly improved in the domains of physical activity and anxiety and depression symptoms. Interestingly, we also demonstrated that the treatment indication was related to changes in self-assessed quality of life, which improved over time in patients implanted with DT indication, whereas it decreased from T1 to T2 in patients with BTT indication. Taken together, these findings suggest that LVAD-related emotional distress and coping strategies need to be carefully evaluated before and in the long-term after LVAD implantation.
  
  © 2019 International Center for Artificial Organ and Transplantation and Wiley Periodicals, Inc.
  
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• ["To clip or not to clip" - Additional considerations on transcatheter mitral valve repair for secondary mitral insufficiency in patients with heart failure].
  G Ital Cardiol (Rome)

  2019 Jun;20(6):396-398. doi: 10.1714/3165.31475.
  
  Frigerio Maria, Cipriani Manlio G
  
  
  
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• Recurrent cardiac sarcoidosis after heart transplantation.
  Clin Res Cardiol

  2019 Oct;108(10):1171-1173. doi: 10.1007/s00392-019-01485-z.
  
  Veronese Giacomo, Cipriani Manlio, Petrella Duccio, Geniere Nigra Stefano, Pedrotti Patrizia, Garascia Andrea, Masciocco Gabriella, Bramerio Manuela A, Klingel Karin, Frigerio Maria, Ammirati Enrico
  
  
  
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• Effect of occlusal splint and therapeutic exercises on postural balance of patients with signs and symptoms of temporomandibular disorder.
  Clin Exp Dent Res

  2019 Apr;5(2):109-115. doi: 10.1002/cre2.136.
  
  Oliveira Simone S I, Pannuti Claudio M, Paranhos Klenise S, Tanganeli João P C, Laganá Dalva C, Sesma Newton, Duarte Marcos, Frigerio Maria Luíza M A, Cho Sang-Chon
  
  Abstract
  
  The aim of this study was to investigate the effects of the use of an occlusal splint on postural balance considering the occlusal splint as a device for treating temporomandibular joint disorder. A randomized, controlled, prospective clinical trial was conducted. The research group consisted of 49 patients (36 as test group and 13 as control group) between 18 and 75 years old, both genders, diagnosed as temporomandibular disorder by Research Diagnostic Criteria/Temporomandibular Disorders questionnaire and magnetic resonance imaging of the temporomandibular joints. Test group was treated with orientations for physiotherapeutic exercises and occlusal splint, whereas control group received orientation for physiotherapeutic exercises only. Postural equilibrium was evaluated by means of a force plate. After 12 weeks, the groups were re-evaluated. Patients from both groups presented a significant increase in antero-posterior speed with eyes closed, test group ( < 0.001) and control group ( = 0.046). Only patients of the test group presented a significant increase in antero-posterior speed with eyes opened ( = 0.023). We concluded that the use of occlusal splint affected the postural balance.
  
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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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• Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors.
  PLoS One

  2019 ;14(3):e0214616. doi: 10.1371/journal.pone.0214616.
  
  Merlo Marco, Ammirati Enrico, Gentile Piero, Artico Jessica, Cannatà Antonio, Finocchiaro Gherardo, Barbati Giulia, Sormani Paola, Varrenti Marisa, Perkan Andrea, Fabris Enrico, Aleksova Aneta, Bussani Rossana, Petrella Duccio, Cipriani Manlio, Raineri Claudia, Frigerio Maria, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  Persistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored.
  
  OBJECTIVES:
  To assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission.
  
  METHODS AND RESULTS:
  We retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6-18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF <50% at 1-year, and was observed in 27/48 patients (56.3%). Higher LV end-diastolic diameter at admission (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.04-1.43, p = 0.002), non-fulminant presentation (OR 8.46, 95% CI 1.28-55.75, p = 0.013) and presence of a poor lymphocytic infiltrate (OR 12.40, 95% CI 1.23-124.97, p = 0.010) emerged as independent predictors of persistent LV dysfunction at multivariate analysis (area under the curve 0.91, 95% CI 0.82-0.99). Pre-discharge LVEF was lower in patients with persistent LV dysfunction compared to the others (32%±8 vs. 53%±8, p <0.001), and this single variable showed the best accuracy in predicting the study end-point (area under the curve 0.95, 95% CI 0.89-1.00).
  
  CONCLUSIONS:
  More than half of patients presenting with acute LM and LVEF <50% who survive the acute phase show persistent LV dysfunction after 1-year from hospital discharge. Features of subacute inflammatory process and of established myocardial damage at initial hospitalization emerged as predictors of this end-point.
  
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• Response by Ammirati et al to Letter Regarding Article, "Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis".
  Circulation

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

  2019 05;283():131-133. doi: S0167-5273(18)36049-2.
  
  Ammirati Enrico, Van De Heyning Caroline M, Musca Francesco, Brambatti Michela, Perna Enrico, Cipriani Manlio, Cannata Aldo, Mondino Michele, Moreo Antonella, De Bock Dina, Pretorius Victor, Claeys Marc J, Adler Eric D, Russo Claudio F, Frigerio Maria
  
  Abstract
  
  INTRODUCTION:
  No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD.
  
  METHODS:
  We retrospectively identified 6 patients (median age of 62?years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018.
  
  RESULTS:
  Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282?days (interquartile range 67 to 493), and median time on CF-LVAD support was 401?days (interquartile range 105 to 492?days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications.
  
  CONCLUSIONS:
  Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• Impact of in-hospital cardiac rehabilitation on mortality and readmissions in heart failure: A population study in Lombardy, Italy, from 2005 to 2012.
  Eur J Prev Cardiol

  2019 05;26(8):808-817. doi: 10.1177/2047487319833512.
  
  Scalvini Simonetta, Grossetti Francesco, Paganoni Anna Maria, La Rovere Maria Teresa, Pedretti Roberto Fe, Frigerio Maria
  
  Abstract
  
  AIMS:
  The 2016 European guidelines for the diagnosis and treatment of heart failure classified cardiac rehabilitation as a mandatory class I intervention. We aimed to analyse in heart failure patients the impact of an in-hospital cardiac rehabilitation programme on all-cause mortality and readmissions.
  
  METHODS:
  From the Lombardy healthcare administrative database, we analysed in patients with incident heart failure, from 2005 to 2012, the number of all hospitalisations, cardiac rehabilitation admissions, post-discharge deaths, outpatient drug prescriptions and visits. We divided patients into hospitalised for heart failure in acute care only (group A) versus patients with one or more admission to cardiac rehabilitation for an in-hospital cardiac rehabilitation programme (group B).
  
  RESULTS:
  Of 140,552 incident cases, 100,843 (71%) were in group A and 39,709 (29%) in group B. Patients in group B had 3.26?±?1.78 admissions to acute care before referral to an in-hospital cardiac rehabilitation programme. Male gender, age in women and comorbidities (more than two) were higher in group B ( P?
  CONCLUSION:
  This study showed in a large population of heart failure patients that in-hospital cardiac rehabilitation is associated with a reduction of all-cause mortality and rehospitalisations in heart failure. Given its potential significant benefit, referral of heart failure patients to an in-hospital cardiac rehabilitation programme should be promoted.
  
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• Heart failure prognosis over time: how the prognostic role of oxygen consumption and ventilatory efficiency during exercise has changed in the last 20 years.
  Eur J Heart Fail

  2019 02;21(2):208-217. doi: 10.1002/ejhf.1364.
  
  Paolillo Stefania, Veglia Fabrizio, Salvioni Elisabetta, Corrà Ugo, Piepoli Massimo, Lagioia Rocco, Limongelli Giuseppe, Sinagra Gianfranco, Cattadori Gaia, Scardovi Angela B, Metra Marco, Senni Michele, Bonomi Alice, Scrutinio Domenico, Raimondo Rosa, Emdin Michele, Magrì Damiano, Parati Gianfranco, Re Federica, Cicoira Mariantonietta, Minà Chiara, Correale Michele, Frigerio Maria, Bussotti Maurizio, Battaia Elisa, Guazzi Marco, Badagliacca Roberto, Di Lenarda Andrea, Maggioni Aldo, Passino Claudio, Sciomer Susanna, Pacileo Giuseppe, Mapelli Massimo, Vignati Carlo, Clemenza Francesco, Binno Simone, Lombardi Carlo, Filardi Pasquale Perrone, Agostoni Piergiuseppe,
  
  Abstract
  
  AIMS:
  Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO ) and minute ventilation/carbon dioxide relationship slope (VE/VCO slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO and VE/VCO slope has changed over the last 20?years in parallel with HF prognosis improvement.
  
  METHODS AND RESULTS:
  Data from 6083 HF patients (81% male, age 61?±?13?years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993-2000 (n?=?440), group 2 2001-2005 (n?=?1288), group 3 2006-2010 (n?=?2368), and group 4 2011-2015 (n?=?1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO and VE/VCO slope and to major clinical and therapeutic variables. At 10?years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO 15?mL/min/kg (95% confidence interval 16-13), 9 (11-8), 4 (4-2) and 5 (7-4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO slope value for a 20% risk was 32 (37-29), 47 (51-43), 59 (64-55), and 57 (63-52), respectively.
  
  CONCLUSIONS:
  Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO and VE/VCO slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO and VE/VCO slope must be updated whenever HF prognosis improves.
  
  © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.
  
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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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• [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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• Acute and Fulminant Myocarditis: a Pragmatic Clinical Approach to Diagnosis and Treatment.
  Curr Cardiol Rep

  2018 09;20(11):114. doi: 10.1007/s11886-018-1054-z.
  
  Ammirati Enrico, Veronese Giacomo, Cipriani Manlio, Moroni Francesco, Garascia Andrea, Brambatti Michela, Adler Eric D, Frigerio Maria
  
  Abstract
  
  PURPOSE OF REVIEW:
  To review the clinical features of acute myocarditis, including its fulminant presentation, and present a pragmatic approach to the diagnosis and treatment, considering indications of American and European Scientific Statements and recent data derived by large contemporary registries.
  
  RECENT FINDINGS:
  Patients presenting with acute uncomplicated myocarditis (i.e., without left ventricular dysfunction, heart failure, or ventricular arrhythmias) have a favorable short- and long-term prognosis: these findings do not support the indication to endomyocardial biopsy in this clinical scenario. Conversely, patients with complicated presentations, especially those with fulminant myocarditis, require an aggressive and comprehensive management, including endomyocardial biopsy and availability of advanced therapies for circulatory support. Although several immunomodulatory or immunosuppressive therapies have been studied and are actually prescribed in the real-world practice, their effectiveness has not been clearly demonstrated. Patients with specific histological subtypes of acute myocarditis (i.e., giant cell and eosinophilic myocarditis) or those affected by sarcoidosis or systemic autoimmune disorders seem to benefit most from immunosuppression. On the other hand, no clear evidence supports the use of immunosuppressive agents in patients with lymphocytic acute myocarditis, even though small series suggest a potential benefit. Acute myocarditis is a heterogeneous condition with distinct pathophysiological pathways. Further research is mandatory to identify factors and mechanisms that may trigger/maintain or counteract/repair the myocardial damage, in order to provide a rational for future evidence-based treatment of patients affected by this condition.
  
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• Antithrombotic therapy in ventricular assist device (VAD) management: From ancient beliefs to updated evidence. A narrative review.
  Int J Cardiol Heart Vasc

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

  2018 Dec;273():141-146. doi: S0167-5273(18)34278-5.
  
  Campodonico Jeness, Piepoli Massimo, Clemenza Francesco, Bonomi Alice, Paolillo Stefania, Salvioni Elisabetta, Corrà Ugo, Binno Simone, Veglia Fabrizio, Lagioia Rocco, Sinagra Gianfranco, Cattadori Gaia, Scardovi Angela B, Metra Marco, Senni Michele, Scrutinio Domenico, Raimondo Rosa, Emdin Michele, Magrì Damiano, Parati Gianfranco, Re Federica, Cicoira Mariantonietta, Minà Chiara, Limongelli Giuseppe, Correale Michele, Frigerio Maria, Bussotti Maurizio, Perna Enrico, Battaia Elisa, Guazzi Marco, Badagliacca Roberto, Di Lenarda Andrea, Maggioni Aldo, Passino Claudio, Sciomer Susanna, Pacileo Giuseppe, Mapelli Massimo, Vignati Carlo, Lombardi Carlo, Filardi Pasquale Perrone, Agostoni Piergiuseppe,
  
  Abstract
  
  BACKGROUND:
  The usefulness of ?-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned.
  
  METHODS AND RESULTS:
  We analyzed data from HF patients (958 patients (801 males, 84%, age 67?±?11?years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving ?-blockers (n?=?777, 81%) vs. those not treated with ?-blockers (n?=?181, 19%). We also analyzed the role ?1-selectivity and the role of daily ?-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577-2304) days in the entire population, 1203 (614-2420) and 1325 (569-2300) days in patients not receiving and receiving ?-blockers. 224 (23%, 54/1000?events/year), 163 (21%, 79/1000?events/year), and 61 (34%, 49/1000?events/year) events were recorded, respectively. At 10-year patients treated with ?-blockers had a better outcome (HR 0.447, p?
  CONCLUSION:
  HF patients with AF taking a ?-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards ?1 selectivity) but this does not mean that ?-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with ?-blocker use.
  
  Copyright © 2018. Published by Elsevier B.V.
  
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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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• 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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• Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology.
  Eur J Heart Fail

  2018 11;20(11):1505-1535. doi: 10.1002/ejhf.1236.
  
  Crespo-Leiro Maria G, Metra Marco, Lund Lars H, Milicic Davor, Costanzo Maria Rosa, Filippatos Gerasimos, Gustafsson Finn, Tsui Steven, Barge-Caballero Eduardo, De Jonge Nicolaas, Frigerio Maria, Hamdan Righab, Hasin Tal, Hülsmann Martin, Nalbantgil Sanem, Potena Luciano, Bauersachs Johann, Gkouziouta Aggeliki, Ruhparwar Arjang, Ristic Arsen D, Straburzynska-Migaj Ewa, McDonagh Theresa, Seferovic Petar, Ruschitzka Frank
  
  Abstract
  
  This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.
  
  © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.
  
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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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• A New Life: Motherhood After Heart Transplantation. A Single-center Experience and Review of Literature.
  Transplantation

  2018 09;102(9):1538-1544. doi: 10.1097/TP.0000000000002281.
  
  Macera Francesca, Occhi Lucia, Masciocco Gabriella, Varrenti Marisa, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Pregnancy after heart transplantation (HTx) may expose the recipient to hemodynamic and immunologic risks and the newborn to toxic effects of immunosuppressive therapy. Adequate preconception counseling is crucial to identify optimal timing and to modify immunosuppressive therapy to minimize risks for both the mother and the fetus.
  
  METHODS:
  We describe our experience with 12 pregnancies occurred in 11 women who had undergone HTx at our center.
  
  RESULTS:
  Pregnancies ran without severe complications or rejections, and none of the babies have shown major defects at birth. However, as reported in the literature, weight at birth rated in lower range in most of the newborns, probably due to in utero cyclosporine exposure. Up to now, none of the babies showed clinical signs of heart disease, although more than half of the mothers had an inherited or familial cardiomyopathy.
  
  CONCLUSIONS:
  Despite potential mother and fetal complications, successful pregnancy and delivery are possible after HTx, provided that optimum timing, close monitoring, and therapy adjustments are guaranteed. Becoming a mother appears to be an important achievement for young women after HTx, even when there is a risk to transmit an inheritable heart disease.
  
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• Response by Ammirati et al to Letter Regarding Article, "Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis".
  Circulation

  2018 03;137(13):1427-1428. doi: 10.1161/CIRCULATIONAHA.117.032056.
  
  Ammirati Enrico, Cipriani Manlio, Camici Paolo G, Frigerio Maria
  
  
  
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• Fulminant myocarditis: Characteristics, treatment, and outcomes.
  Anatol J Cardiol

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

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

  2017 Oct;33(5):494-496. doi: 10.1016/j.joa.2017.04.007.
  
  Pedretti Stefano, Cipriani Manlio, Bonacina Edgardo, Vargiu Sara, Gil Ad Vered, Frigerio Maria, Lunati Maurizio
  
  Abstract
  
  In patients with left ventricular assist device (LVAD), a minority of post-operative ventricular tachycardias (VTs) is caused by contact between the inflow cannula and the endocardium. Currently, electrophysiologic characteristics and pathologic features of this condition are lacking. We report on a case of a successfully ablated mechanical VT. After VT recurrence, heart transplantation took place. Pathologic observations were consistent with direct tissue injury and inflammation, eventually contributing to persisting arrhythmias. Radiofrequency catheter ablation can be a safe and effective option to treat arrhythmias caused by inflow cannula interference in the short term, although a high recurrence rate is expected.
  
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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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• Optimal and Equitable Allocation of Donor Hearts: Which Principles Are We Translating Into Practices?
  Transplant Direct

  2017 Aug;3(8):e197. doi: 10.1097/TXD.0000000000000712.
  
  Frigerio Maria
  
  
  
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• An ISHLT consensus document for prevention and management strategies for mechanical circulatory support infection.
  J Heart Lung Transplant

  2017 10;36(10):1137-1153. doi: S1053-2498(17)31872-7.
  
  Kusne Shimon, Mooney Martha, Danziger-Isakov Lara, Kaan Annemarie, Lund Lars H, Lyster Haifa, Wieselthaler Georg, Aslam Saima, Cagliostro Barbara, Chen Jonathan, Combs Pamela, Cochrane Adam, Conway Jennifer, Cowger Jennifer, Frigerio Maria, Gellatly Rochelle, Grossi Paolo, Gustafsson Finn, Hannan Margaret, Lorts Angela, Martin Stanley, Pinney Sean, Silveira Fernanda P, Schubert Stephan, Schueler Stephan, Strueber Martin, Uriel Nir, Wrightson Neil, Zabner Rachel, Huprikar Shirish
  
  
  
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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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• HeartWare-HVAD for end-stage heart failure: a review of clinical experiences with ?50 patients.
  Expert Rev Med Devices

  2017 Jun;14(6):423-437. doi: 10.1080/17434440.2017.1325318.
  
  Botta Luca, De Chiara Benedetta, Macera Francesca, Cannata Aldo, Costetti Alessandro, Voltolini Alessandra, Moreo Antonella, Cipriani Manlio, Frigerio Maria, Russo Claudio Francesco
  
  Abstract
  
  INTRODUCTION:
  Despite the improvements in medical and surgical treatments, the incidence of end-stage heart failure (ESHF) continues to increase. Different mechanical systems have been adopted to support failing left ventricles. Among continuous-flow devices, the HeartWare-HVAD was the first to use a centrifugal pump rather than an axial one. Areas covered: In this review article, we provide an overview of the HeartWare-HVAD as a ventricular assist device for ESHF, discussing indications, echocardiographic assessment, surgical techniques, outcomes, concerns and controversies. Scientific literature was reviewed with a MEDLINE search strategy combining 'HeartWare' or 'HVAD' with 'heart failure'. A total of 263 papers were found using the reported search. From these, 16 were identified to provide the best evidence on the subject reporting outcomes in ?50 patients. Expert commentary: HeartWare-HVAD is a minute device that provides full circulatory support in patients with ESHF. Its main indication remains bridge to heart transplantation (HTx). Median sternotomy is the preferred technique of implantation although less invasive procedures have been described. Early outcomes are satisfactory. Nevertheless, some fearing complications still occur during the mid- and long-term follow-up. Further technical developments and optimal medical management will guarantee better outcomes.
  
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• [Farewell].
  G Ital Cardiol (Rome)

  2017 Mar;18(3):173. doi: 10.1714/2674.27393.
  
  Frigerio Maria
  
  
  
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• Trends in heart failure hospitalizations, patient characteristics, in-hospital and 1-year mortality: A population study, from 2000 to 2012 in Lombardy.
  Int J Cardiol

  2017 Jun;236():310-314. doi: S0167-5273(16)34743-X.
  
  Frigerio Maria, Mazzali Cristina, Paganoni Anna Maria, Ieva Francesca, Barbieri Pietro, Maistrello Mauro, Agostoni Ornella, Masella Cristina, Scalvini Simonetta,
  
  Abstract
  
  BACKGROUND:
  This study was undertaken to evaluate trends in heat failure hospitalizations (HFHs) and 1-year mortality of HFH in Lombardy, the largest Italian region, from 2000 to 2012.
  
  METHODS:
  Hospital discharge forms with HF-related ICD-9 CM codes collected from 2000 to 2012 by the regional healthcare service (n=699797 in 370538 adult patients), were analyzed with respect to in-hospital and 1-year mortality; Group (G) 1 included most acute HF episodes with primary cardiac diagnosis (70%); G2 included cardiomyopathies without acute HF codes (17%); and G3 included non-cardiac conditions with HF as secondary diagnosis (13%). Patients experiencing their first HFH since 2005 were analyzed as incident cases (n=216782).
  
  RESULTS:
  Annual HFHs number (mean 53830) and in-hospital mortality (9.4%) did not change over the years, the latter being associated with increasing age (p<0.0001) and diagnosis Group (G1 9.1%, G2 5.6%, G3 15.9%, p<0.0001). Incidence of new cases decreased over the years (3.62 [CI 3.58-3.67] in 2005 to 3.13 [CI 3.09-3.17] in 2012, per 1000 adult inhabitants/year, p<0.0001), with an increasing proportion of patients aged ?85y (22.3% to 31.4%, p<0.0001). Mortality lowered over time in <75y incident cases, both in-hospital (5.15% to 4.36%, p<0.0001) and at 1-year (14.8% to 12.9%, p=0.0006).
  
  CONCLUSIONS:
  The overall burden and mortality of HFH appear stable for more than a decade. However, from 2005 to 2012, there was a reduction of new, incident cases, with increasing age at first hospitalization. Meanwhile, both in-hospital and 1-year mortality decreased in patients aged <75y, possibly due to improved prevention and treatment.
  
  Copyright © 2017 Elsevier B.V. All rights reserved.
  
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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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• The key clues to reach the diagnosis of Loeffler endomyocardial fibrosis associated with eosinophilic granulomatosis with polyangiitis.
  J Cardiovasc Med (Hagerstown)

  2017 10;18(10):831-832. doi: 10.2459/JCM.0000000000000496.
  
  Ammirati Enrico, Sirico Domenico, Brevetti Linda, Scudiero Laura, Artioli Diana, Pedrotti Patrizia, Frigerio Maria
  
  
  
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• [Psychological evaluation and support in patients with left ventricular assist devices: preliminary data at 6-month follow-up].
  G Ital Cardiol (Rome)

  2016 Nov;17(11):940-946. doi: 10.1714/2498.26204.
  
  Voltolini Alessandra, Minotti Anna, Verde Alessandro, Cipriani Manlio, Garascia Andrea, Turazza Fabio, Macera Francesca, Perna Enrico, Russo Claudio F, Fumagalli Emilia, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Heart disease has an impact on patient's identity and self-perception. Taking into account the wide literature about psychological aspects before and after heart transplant, it clearly emerges that there is a lack of data and results for patients up to implantation of ventricular assist devices (VAD). The aim of the present study was to explore quality of life and factors correlated with psychological adjustment in patients supported with VAD.
  
  METHODS:
  From February 2013 to August 2014, 18 patients (17 male, mean age 57 years) under clinical evaluation before and after VAD implantation were enrolled. During interviews, patients were assessed with EuroQoL-5D questionnaire to monitor improvement of quality of life before implantation and at 3 and 6 months; critical issues, needs and point of views of patients have been described.
  
  RESULTS:
  A significant improvement in the quality of life score was observed at 3 (score 38 [interquartile range 30-40] vs 75 [60-80], p<0.05) and 6 months (38 [30-40] vs 70 [60-80], p<0.05). Overall, patients' psychological state investigated by the test showed a clear and positive trend. All patients need to empower through complete information about the device, related risks and life expectancy. Interdisciplinary approach improved compliance with therapy.
  
  CONCLUSIONS:
  Successful treatment and efficient psychological care are closely related to assessment and continuous clinical support. This approach ensures a better selection of patients and improves their compliance. Further data are needed to support our preliminary observations and to explore long-term quality of life.
  
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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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• 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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• 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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• Prognostic impact of late gadolinium enhancement in the risk stratification of heart transplant patients.
  Eur Heart J Cardiovasc Imaging

  2017 Feb;18(2):130-137. doi: 10.1093/ehjci/jew186.
  
  Pedrotti Patrizia, Vittori Claudia, Facchetti Rita, Pedretti Stefano, Dellegrottaglie Santo, Milazzo Angela, Frigerio Maria, Cipriani Manlio, Giannattasio Cristina, Roghi Alberto, Rimoldi Ornella
  
  Abstract
  
  AIMS:
  The aim of the present study was to assess the association of the presence and amount of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) with cardiovascular adverse events in patients with orthotopic heart transplantation (HTx).
  
  METHODS AND RESULTS:
  We enrolled 48 patients (mean age, 54.7 ± 14.6 years; 37 men) at various stages after HTx. All patients underwent standard CMR at 1.5 T, to characterize both cardiac anatomy and LGE. Late gadolinium enhancement was detected in 26 patients (54%). All-cause and cardiovascular mortalities, and a composite of major adverse cardiovascular events (MACE) recurrence were evaluated during the follow-up period for a median of 5.16 years. Ten patients (21%) died and 26 (54%) were readmitted because of MACE. Multivariate Cox analysis identified as independent predictors of MACE a diagnosis of cardiac allograft vasculopathy (CAV) (HR 3.63; 1.5-8.7 95% CI; P = 0.0039), left ventricular end systolic volume index (HR 1.04; 95% CI 1.01-1.079; P = 0.008), LGE mass (HR 1.04; 1.01-1.06 95% CI; P = 0.0007), LGE % of left ventricular mass (HR 1.083; 1.03-1.13 95% CI; P = 0.0002). Independent predictors of all-cause death were CAV (HR 6.33; 95% CI 1.33-30.03; P = 0.0201), LGE mass (HR 1.04; 1.01-1.07 95% CI; P = 0.005), LGE % of left ventricular mass (HR 1.075; 1.02-1.13 95% CI; P = 0.007). Patients with CAV had a risk of MACE by 5 years of 67% (95% CI 0.309-0.851%); the addition of 7.9 LGE % to the risk model increased the predicted risk to 88% (95% CI 0.572-0.967%).
  
  CONCLUSIONS:
  The current study demonstrated that the presence of CAV and the total amount of LGE have a significant independent association with MACE and mortality in HTx patients.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
  
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• Getting approval for new therapeutic medical devices versus drugs: are the differences justified?
  Eur Respir Rev

  2016 09;25(141):223-6. doi: 10.1183/16000617.0037-2016.
  
  Frigerio Maria
  
  
  
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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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• Methodological issues on the use of administrative data in healthcare research: the case of heart failure hospitalizations in Lombardy region, 2000 to 2012.
  BMC Health Serv Res

  2016 07;16():234. doi: 10.1186/s12913-016-1489-0.
  
  Mazzali Cristina, Paganoni Anna Maria, Ieva Francesca, Masella Cristina, Maistrello Mauro, Agostoni Ornella, Scalvini Simonetta, Frigerio Maria,
  
  Abstract
  
  BACKGROUND:
  Administrative data are increasingly used in healthcare research. However, in order to avoid biases, their use requires careful study planning. This paper describes the methodological principles and criteria used in a study on epidemiology, outcomes and process of care of patients hospitalized for heart failure (HF) in the largest Italian Region, from 2000 to 2012.
  
  METHODS:
  Data were extracted from the administrative data warehouse of the healthcare system of Lombardy, Italy. Hospital discharge forms with HF-related diagnosis codes were the basis for identifying HF hospitalizations as clinical events, or episodes. In patients experiencing at least one HF event, hospitalizations for any cause, outpatient services utilization, and drug prescriptions were also analyzed.
  
  RESULTS:
  Seven hundred one thousand, seven hundred one heart failure events involving 371,766 patients were recorded from 2000 to 2012. Once all the healthcare services provided to these patients after the first HF event had been joined together, the study database totalled about 91 million records. Principles, criteria and tips utilized in order to minimize errors and characterize some relevant subgroups are described.
  
  CONCLUSIONS:
  The methodology of this study could represent the basis for future research and could be applied in similar studies concerning epidemiology, trend analysis, and healthcare resources utilization.
  
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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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• Exercise tolerance can explain the obesity paradox in patients with systolic heart failure: data from the MECKI Score Research Group.
  Eur J Heart Fail

  2016 05;18(5):545-53. doi: 10.1002/ejhf.534.
  
  Piepoli Massimo F, Corrà Ugo, Veglia Fabrizio, Bonomi Alice, Salvioni Elisabetta, Cattadori Gaia, Metra Marco, Lombardi Carlo, Sinagra Gianfranco, Limongelli Giuseppe, Raimondo Rosa, Re Federica, Magrì Damiano, Belardinelli Romualdo, Parati Gianfranco, Minà Chiara, Scardovi Angela B, Guazzi Marco, Cicoira Mariantonietta, Scrutinio Domenico, Di Lenarda Andrea, Bussotti Maurizio, Frigerio Maria, Correale Michele, Villani Giovanni Quinto, Paolillo Stefania, Passino Claudio, Agostoni Piergiuseppe,
  
  Abstract
  
  AIMS:
  Obesity has been found to be protective in heart failure (HF), a finding leading to the concept of an obesity paradox. We hypothesized that a preserved cardiorespiratory fitness in obese HF patients may affect the relationship between survival and body mass index (BMI) and explain the obesity paradox in HF.
  
  METHODS AND RESULTS:
  A total of 4623 systolic HF patients (LVEF 31.5?±?9.5%, BMI 26.2?±?3.6?kg/m(2) ) were recruited and prospectively followed in 24 Italian HF centres belonging to the MECKI Score Research Group. Besides full clinical examination, patients underwent maximal cardiopulmonary exercise test at study enrolment. Median follow-up was 1113 (553-1803) days. The study population was divided according to BMI (<25, 25-30, >30 to ?35?kg/m(2) ) and predicted peak oxygen consumption (peak VO2 , <50%, 50-80%, >80%). Study endpoints were all-cause and cardiovascular deaths including urgent cardiac transplant. All-cause and cardiovascular deaths occurred in 951 (28.6%, 57.4 per person-years) and 802 cases (17.4%, 48.4 per 1000 person-years), respectively. In the high BMI groups, several prognostic parameters presented better values [LVEF, peak VO2 , ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO2 were significant positive predictors of longer survival: both higher BMI and peak VO2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO2 ), the protective role of BMI disappeared.
  
  CONCLUSION:
  Exercise tolerance affects the relationship between BMI and survival. Cardiorespiratory fitness mitigates the obesity paradox observed in HF patients.
  
  © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.
  
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• Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives.
  Eur J Heart Fail

  2016 09;18(9):1106-18. doi: 10.1002/ejhf.541.
  
  Ammirati Enrico, Contri Rachele, Coppini Raffaele, Cecchi Franco, Frigerio Maria, Olivotto Iacopo
  
  Abstract
  
  Hypertrophic cardiomyopathy (HCM) is entering a phase of intense translational research that holds promise for major advances in disease-specific pharmacological therapy. For over 50?years, however, HCM has largely remained an orphan disease, and patients are still treated with old drugs developed for other conditions. While judicious use of the available armamentarium may control the clinical manifestations of HCM in most patients, specific experience is required in challenging situations, including deciding when not to treat. The present review revisits the time-honoured therapies available for HCM, in a practical perspective reflecting real-world scenarios. Specific agents are presented with doses, titration strategies, pros and cons. Peculiar HCM dilemmas such as treatment of dynamic outflow obstruction, heart failure caused by end-stage progression and prevention of atrial fibrillation and ventricular arrhythmias are assessed. In the near future, the field of HCM drug therapy will rapidly expand, based on ongoing efforts. Approaches such as myocardial metabolic modulation, late sodium current inhibition and allosteric myosin inhibition have moved from pre-clinical to clinical research, and reflect a surge of scientific as well as economic interest by academia and industry alike. These exciting developments, and their implications for future research, are discussed.
  
  © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.
  
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• Incremental utility of prognostic variables at discharge for risk prediction in hospitalized patients with acutely decompensated chronic heart failure.
  Heart Lung

  ;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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• [Will big data satisfy the unmet needs of clinical research?].
  G Ital Cardiol (Rome)

  2016 Mar;17(3):186-8. doi: 10.1714/2190.23658.
  
  Frigerio Maria
  
  
  
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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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• 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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• Low incidence of gastrointestinal bleeding and pump thrombosis in patients receiving the INCOR LVAD system in the long-term follow-up.
  Int J Artif Organs

  2015 Oct;38(10):542-7. doi: 10.5301/ijao.5000441.
  
  Iacovoni Attilio, Centofanti Paolo, Attisani Matteo, Verde Alessandro, Terzi Amedeo, Senni Michele, Maiani Massimo, Baronetto Andrea, Livi Ugo, Frigerio Maria, Rinaldi Mauro
  
  Abstract
  
  BACKGROUND:
  Left ventricular assist device (LVAD) implantation improves survival and quality of life in patients with advanced heart failure (HF). Despite these advantages, LVADs are not free from risks. Among all adverse events (AE), pump thrombosis and bleeding, especially of the gastrointestinal (GI) tract, have been reported to occur with increasing frequency in some CF-LVADs. The INCOR LVAD system is a third-generation, continuous flow, axial pump with active magnetic levitation, avoiding the potential downsides of mechanical bearings.
  
  METHODS:
  The aim of this retrospective study was to review the Italian clinical experience with the INCOR LVAD and to determine the prevalence of GI bleeding and pump thrombosis. All patients implanted between January 2006 and May 2012 were considered eligible.
  
  RESULTS:
  The total population consisted of 42 patients. LVAD indication was BTT in 36 (86%) and DT in 6 (14%) patients; 31 patients (74%) were INTERMACS class 1 or 2. Mean support time was 525 ± 570 days. The 1-year and 2-year survival rates were 74% and 60%, respectively. The most frequent AE was driveline infection (0.33 events PPY) followed by stroke with consequence (0.17 events PPY), sepsis (0.07 events PPY), and right HF (0.05 events PPY). No episodes of pump thrombosis or GI bleeding were observed.
  
  CONCLUSIONS:
  In this cohort of high-risk, advanced HF patients, the INCOR LVAD provided effective support with improved survival. Moreover, the absence of GI bleeding and pump thrombosis demonstrates a favorable characteristic of this device. Further prospective studies are needed to confirm these data.
  
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• Letter by Frigerio et al Regarding Article, "Long-Term Outcomes of Inoperable Patients With Aortic Stenosis Randomly Assigned to Transcatheter Aortic Valve Replacement or Standard Therapy".
  Circulation

  2015 Aug;132(6):e117. doi: 10.1161/CIRCULATIONAHA.114.014377.
  
  Frigerio Maria, Bruschi Giuseppe, Klugmann Silvio
  
  
  
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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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• Prognostic role of atrial fibrillation in patients affected by chronic heart failure. Data from the MECKI score research group.
  Eur J Intern Med

  2015 Sep;26(7):515-20. doi: 10.1016/j.ejim.2015.04.023.
  
  Paolillo Stefania, Agostoni Piergiuseppe, Masarone Daniele, Corrà Ugo, Passino Claudio, Scrutinio Domenico, Correale Michele, Cattadori Gaia, Metra Marco, Girola Davide, Piepoli Massimo F, Salvioni Elisabetta, Giovannardi Marta, Iorio Annamaria, Emdin Michele, Raimondo Rosa, Re Federica, Cicoira Mariantonietta, Belardinelli Romualdo, Guazzi Marco, Clemenza Francesco, Parati Gianfranco, Scardovi Angela B, Di Lenarda Andrea, La Gioia Rocco, Frigerio Maria, Lombardi Carlo, Gargiulo Paola, Sinagra Gianfranco, Pacileo Giuseppe, Perrone-Filardi Pasquale, Limongelli Giuseppe,
  
  Abstract
  
  BACKGROUND:
  Atrial fibrillation (AF) is common in heart failure (HF). It is unclear whether AF has an independent prognostic role in HF. The aim of the present study was to assess the prognostic role of AF in HF patients with reduced ejection fraction (EF).
  
  METHODS:
  HF patients were followed in 17 centers for 3.15years (1.51-5.24). Study endpoints were the composite of cardiovascular (CV) death and heart transplant (HTX) and all-cause death. Data analysis was performed considering the entire population and a 1 to 1 match between sinus rhythm (SR) and AF patients. Match process was done for age±5, gender, left ventricle EF±5, peakVO2±3 (ml/min/kg) and recruiting center.
  
  RESULTS:
  A total of 3447 patients (SR=2882, AF=565) were included in the study. Considering the entire population, CV death and HTX occurred in 114 (20%) AF vs. 471 (16%) SR (p=0.026) and all-cause death in 130 (23%) AF vs. 554 (19.2%) SR patients (p=0.039). At univariable Cox analysis, AF was significantly related to prognosis. Applying a multivariable model based on all variables significant at univariable analysis (EF, peakVO2, ventilation/carbon dioxide relationship slope, sodium, kidney function, hemoglobin, beta-blockers and digoxin) AF was no longer associated with adverse outcomes. Matching procedure resulted in 338 couples. CV death and HTX occurred in 63 (18.6%) AF vs. 74 (21.9%) SR (p=0.293) and all-cause death in 71 (21%) AF vs. 80 (23.6%) SR (p=0.406), with no survival differences between groups.
  
  CONCLUSION:
  In systolic HF AF is a marker of disease severity but not an independent prognostic indicator.
  
  Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• [The heart of Nicholas Green - why transplant matters].
  G Ital Cardiol (Rome)

  2015 May;16(5):323-4. doi: 10.1714/1870.20444.
  
  Frigerio Maria
  
  
  
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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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• Palliative needs for heart failure or chronic obstructive pulmonary disease: Results of a multicenter observational registry.
  Int J Cardiol

  2015 Apr;184():552-8. doi: 10.1016/j.ijcard.2015.03.056.
  
  Gavazzi Antonello, De Maria Renata, Manzoli Lamberto, Bocconcelli Paolo, Di Leonardo Antonio, Frigerio Maria, Gasparini Stefano, Humar Franco, Perna Gianpiero, Pozzi Roberto, Svanoni Fausto, Ugolini Marcello, Deales Alberto
  
  Abstract
  
  BACKGROUND:
  Heart failure (HF) and chronic obstructive pulmonary disease (COPD) share a common organ failure trajectory marked by prognostic uncertainty, which is a barrier to appropriate provision of palliative care. We describe in a prospective cohort from specialist hospital services the epidemiology and late clinical course of these chronic diseases to trace criteria for transition to palliative care in the community.
  
  METHODS AND RESULTS:
  Seven centers enrolled 267 patients with advanced HF (n=174) or COPD (n=93) using common (multiple hospitalizations or severely impaired functional status or cachexia) and disease-specific (HF: systolic dysfunction, NYHA classes III-IV, end-organ hypoperfusion; COPD: very severe airflow obstruction, hypoxemia, hypercapnia, or long-term oxygen therapy) entry criteria. These patients represented 7.2% and 13% respectively of the overall HF and COPD population hospitalized during one year. They showed similar symptom burden, functional and quality of life impairment, recurrent hospitalizations, and 6-month mortality (39% and 37%, respectively). Organ failure progression was the cause of death in >75%. In-hospital overall stay during the previous year was the main mortality predictor in both. Disease-specific predictors included anemia, hyponatremia, no beta-blockers in HF; older age, hypercapnia in COPD.
  
  CONCLUSIONS:
  Patients with advanced HF/COPD represent almost 10% of subjects hospitalized yearly with a primary diagnosis of HF or COPD, have similarly impaired functional status, disabling symptoms and reduced survival. Overall days spent in-hospital during the previous year, a "red flag" in the late clinical course of both diseases, might be used as a simple, reliable screening tool for appropriate transition to palliative care in the community.
  
  Copyright © 2015. Published by Elsevier Ireland Ltd.
  
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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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• Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.
  Circ J

  2015 ;79(3):583-91. doi: 10.1253/circj.CJ-14-0806.
  
  Scrutinio Domenico, Agostoni Piergiuseppe, Gesualdo Loreto, Corrà Ugo, Mezzani Alessandro, Piepoli Massimo, Di Lenarda Andrea, Iorio Annamaria, Passino Claudio, Magrì Damiano, Masarone Daniele, Battaia Elisa, Girola Davide, Re Federica, Cattadori Gaia, Parati Gianfranco, Sinagra Gianfranco, Villani Giovanni Quinto, Limongelli Giuseppe, Pacileo Giuseppe, Guazzi Marco, Metra Marco, Frigerio Maria, Cicoira Mariantonietta, Minà Chiara, Malfatto Gabriella, Caravita Sergio, Bussotti Maurizio, Salvioni Elisabetta, Veglia Fabrizio, Correale Michele, Scardovi Angela B, Emdin Michele, Giannuzzi Pantaleo, Gargiulo Paola, Giovannardi Marta, Perrone-Filardi Pasquale, Raimondo Rosa, Ricci Roberto, Paolillo Stefania, Farina Stefania, Belardinelli Romualdo, Passantino Andrea, La Gioia Rocco,
  
  Abstract
  
  BACKGROUND:
  Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V?O2) in heart failure (HF) patients. METHODS?AND?RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV?O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV?O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ?60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV?O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant.
  
  CONCLUSIONS:
  Renal dysfunction is correlated with peakV?O2. A peakV?O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.
  
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• Pathologic correlates of late gadolinium enhancement cardiovascular magnetic resonance in a heart transplant patient.
  Cardiovasc Pathol

  ;24(4):247-9. doi: 10.1016/j.carpath.2015.02.001.
  
  Pedrotti Patrizia, Bonacina Edgardo, Vittori Claudia, Frigerio Maria, Roghi Alberto
  
  Abstract
  
  We report the histopathologic correlates of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) in a patient with heart transplant who died for graft failure a few months after the scan. Extensive late enhancement was present at CMR, and it correlated with extensive fibrosis at histology. To our knowledge, this is the first time the findings on contrast enhancement CMR are compared to the histology of the whole heart in a heart transplantation patient, and the correspondence between LGE and fibrosis, demonstrated in other cardiac pathologies, is confirmed also in this particular setting.
  
  Copyright © 2015 Elsevier Inc. All rights reserved.
  
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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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• [Prognostication in heart failure].
  G Ital Cardiol (Rome)

  2015 Jan;16(1):31-3. doi: 10.1714/1776.19246.
  
  Frigerio Maria, De Maria Renata
  
  
  
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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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• Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein.
  Clin Chem Lab Med

  2015 Aug;53(9):1359-66. doi: 10.1515/cclm-2014-0633.
  
  Caruso Raffaele, Caselli Chiara, Cozzi Lorena, Campolo Jonica, Viglione Federica, Parolini Marina, Nonini Sandra, Trunfio Salvatore, D'Amico Andrea, Pelosi Gualtiero, Giannessi Daniela, Marraccini Paolo, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  In left ventricular assist device (LVAD) recipients, plasma levels of interleukin (IL)-6 are associated with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles, reflecting post-operative risk. However, it is not clear how the cardiac level of IL-6, detectable on the tissue samples at the time of implantation, can contribute to predict the post-operative outcome.
  
  METHODS:
  In 40 LVAD recipients, blood and myocardial samples from LV-apex were collected at the time of implantation to assess plasma and cardiac IL-6 levels. Serum C-reactive protein (CRP) levels were considered as inflammatory variable routinely used in LVAD-based therapy.
  
  RESULTS:
  Cardiac IL-6 levels did not correlate with either plasma IL-6 levels (R=0.296, p=0.063) and tissue IL-6 mRNA expression (R=-0.013, p=0.954). Contrary to what happened for the plasma IL-6 and CRP, no differences were observed in cardiac IL-6 levels with respect to INTERMACS profiles (p=0.090). Furthermore, cardiac IL-6 concentrations, unlike IL-6 and CRP circulating levels, were not correlated with the length of intensive care unit stay and hospitalization.
  
  CONCLUSIONS:
  Cardiac IL-6 levels do not contribute to improve risk profile of LVAD recipients in relation to clinical inpatient post-implantation. Instead, plasma IL-6 and serum CRP concentrations are more effective in predicting the severity of the clinical course in the early phase of LVAD therapy.
  
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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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• Organ allocation around the world: insights from the ISHLT International Registry for Heart and Lung Transplantation.
  J Heart Lung Transplant

  2014 Oct;33(10):975-84. doi: 10.1016/j.healun.2014.08.001.
  
  Stehlik Josef, Stevenson Lynne W, Edwards Leah B, Crespo-Leiro Maria G, Delgado Juan F, Dorent Richard, Frigerio Maria, Macdonald Peter, MacGowan Guy A, Nanni Costa Alessandro, Rogers Joseph G, Shah Ashish S, Taylor Rhiannon, Venkateswaran Rajaiyer V, Mehra Mandeep R
  
  
  
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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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• 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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• Relationship between early inflammatory response and clinical evolution of the severe multiorgan failure in mechanical circulatory support-treated patients.
  Mediators Inflamm

  2014 ;2014():281790. doi: 10.1155/2014/281790.
  
  Caruso Raffaele, Campolo Jonica, Verde Alessandro, Botta Luca, Cozzi Lorena, Parolini Marina, Milazzo Filippo, Nonini Sandra, Martinelli Luigi, Paino Roberto, Marraccini Paolo, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified.
  
  METHODS:
  Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53?MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA).
  
  RESULTS:
  During MCS treatment, 32 patients experienced moderate MOFS (tSOFA?
  CONCLUSIONS:
  The MCS patients of C group show an excessive release to IL-8 and TNF-?, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS.
  
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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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• Heart transplantation in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).
  J Heart Lung Transplant

  2014 Aug;33(8):842-50. doi: 10.1016/j.healun.2014.02.023.
  
  Groh Matthieu, Masciocco Gabriella, Kirchner Elizabeth, Kristen Arnt, Pellegrini Carlo, Varnous Shaïda, Bortman Guillermo, Rosenberg Mark, Brucato Antonio, Waterworth Paul, Bonacina Edgardo, Facchetti Fabio, Calabrese Leonard, Gregorini Gina, Scali Juan Jose, Starling Randall, Frigerio Maria, D'Armini Andrea Maria, Guillevin Loïc
  
  Abstract
  
  BACKGROUND:
  Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) and is more frequent in anti-neutrophil cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once.
  
  METHODS:
  We conducted a retrospective international multicenter study. Patients satisfying the criteria of the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature were identified by collaborating vasculitis and transplant specialists, and the help of the Churg-Strauss Syndrome Association.
  
  RESULTS:
  Nine ANCA(-) patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12 to 288 months for the remaining 4 patients. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients' explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%), but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3 to 60 months, 4 (44%) patients died sudden deaths.
  
  CONCLUSIONS:
  The search for EGPA-related cardiomyopathy is mandatory early in the course of this type of vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve restore cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed, which carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified.
  
  Copyright © 2014 International Society for Heart and Lung Transplantation. All rights reserved.
  
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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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• [Great expectations].
  G Ital Cardiol (Rome)

  2014 Feb;15(2):126-7. doi: 10.1714/1424.15783.
  
  Frigerio Maria
  
  
  
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• Relationship between pre-implant interleukin-6 levels, inflammatory response, and early outcome in patients supported by left ventricular assist device: a prospective study.
  PLoS One

  2014 ;9(3):e90802. doi: 10.1371/journal.pone.0090802.
  
  Caruso Raffaele, Botta Luca, Verde Alessandro, Milazzo Filippo, Vecchi Irene, Trivella Maria Giovanna, Martinelli Luigi, Paino Roberto, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  PURPOSE:
  The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among pre-implant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients.
  
  METHODS:
  In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA ?11 was considered as main adverse outcome. Length of ICU-stay, 1 week-tSOFA score, hospitalisation and 3-month survival were considered additional end-points.
  
  RESULTS:
  During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score ?11. Pre-implant level of IL-6 ? 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p?=?0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p?=?0.048). The ICU-stay and hospitalisation resulted longer in B-group (p?=?0.001 and p?=?0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group.
  
  CONCLUSIONS:
  LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome.
  
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• [Learning from mistakes. Considerations on unsuccessful clinical trials of pharmacological therapies in acute heart failure].
  G Ital Cardiol (Rome)

  2014 Jan;15(1):13-8. doi: 10.1714/1394.15513.
  
  Frigerio Maria
  
  
  
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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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• Beyond age, the need for useful parameters to identify heart failure patients in sinus rhythm that can benefit from oral anticoagulation.
  Int J Cardiol

  2014 ;172(1):e243-4. doi: 10.1016/j.ijcard.2013.12.146.
  
  Ammirati Enrico, Dalla Libera Dacia, Frigerio Maria
  
  
  
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• Left ventricular ejection fraction overcrossing 35% after one year of cardiac resynchronization therapy predicts long term survival and freedom from sudden cardiac death: single center observational experience.
  Int J Cardiol

  2014 Mar;172(1):64-71. doi: 10.1016/j.ijcard.2013.12.005.
  
  Frigerio Maria, Lunati Maurizio, Pasqualucci Daniele, Vargiu Sara, Foti Grazia, Pedretti Stefano, Vittori Claudia, Cattafi Giuseppe, Magenta Giovanni, Campo Claudia, Bisetti Silvia, Mercuro Giuseppe
  
  Abstract
  
  BACKGROUND:
  Reverse remodeling and increased LVEF after CRT correlate with survival and heart failure hospitalizations, but their relationship with the risk of SCD is unclear. We aimed to evaluate whether exceeding a threshold value of 35% for left ventricular ejection fraction (LVEF) 1 year after cardiac resynchronization therapy (CRT) predicts survival and freedom from sudden cardiac death (SCD).
  
  METHODS:
  330 patients who survived ? 6 months after CRT (males 80%, age 62 ± 11 years) were grouped according to 1-year LVEF ? 35% (Group 1, n=187, 57%) or >35% (Group 2, n=143, 43%). According to changes vs. baseline (reduction of left end-systolic volume [LVESV] ? 10% or increase of LVEF% > 10 units), patients were also classified as echocardiographic (Echo) non-responders (Group A, n=152, 46%) or responders (Group B, n=178, 54%).
  
  RESULTS:
  At baseline, LVESV volume was larger and LVEF was lower in Group 1 vs. Group 2 (p<0.001). After 1 year, echocardiographic improvement was greater in Group 2 vs. Group 1 (p<0.001 for changes in both LVESV and LVEF). Over a median follow-up of 49 months, 47 patients (14%) died, 36 in Group 1 vs. 11 in Group 2 (19% vs. 8%, p=0.004). A significantly higher rate of freedom from all-cause mortality (p=0.002), cardiovascular mortality (p<0.001) and SCD (p<0.001) was observed in Group 2. Multivariate analysis demonstrated that only 1-year LVEF >35% was associated with freedom from SCD/VF.
  
  CONCLUSIONS:
  LVEF >35% after 1 year of CRT characterizes a favorable long-term outcome, with a very low risk for SCD.
  
  Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
  
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• Adverse event prediction in patients with left ventricular assist devices.
  Conf Proc IEEE Eng Med Biol Soc

  2013 ;2013():1314-7. doi: 10.1109/EMBC.2013.6609750.
  
  Tsipouras Markos G, Karvounis Evaggelos C, Tzallas Alexandros T, Katertsidis Nikolaos S, Goletsis Yorgos, Frigerio Maria, Verde Alessandro, Trivella Maria G, Fotiadis Dimitrios I
  
  Abstract
  
  This work presents the Treatment Tool, which is a component of the Specialist's Decision Support Framework (SDSS) of the SensorART platform. The SensorART platform focuses on the management of heart failure (HF) patients, which are treated with implantable, left ventricular assist devices (LVADs). SDSS supports the specialists on various decisions regarding patients with LVADs including decisions on the best treatment strategy, suggestion of the most appropriate candidates for LVAD weaning, configuration of the pump speed settings, while also provides data analysis tools for new knowledge extraction. The Treatment Tool is a web-based component and its functionality includes the calculation of several acknowledged risk scores along with the adverse events appearance prediction for treatment assessment.
  
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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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• Home-based telesurveillance program in chronic heart failure: effects on clinical status and implications for 1-year prognosis.
  Telemed J E Health

  2013 Aug;19(8):605-12. doi: 10.1089/tmj.2012.0250.
  
  Giordano Amerigo, Scalvini Simonetta, Paganoni Anna Maria, Baraldo Stefano, Frigerio Maria, Vittori Claudia, Borghi Gabriella, Marzegalli Maurizio, Agostoni Ornella
  
  Abstract
  
  BACKGROUND:
  Studies focusing on the effects of telemanagement programs for chronic heart failure (CHF) on functional status are lacking, and the prognostic value of the clinical response to the programs is unknown. In the Lombardy region of Italy, a home-based telesurveillance program (HTP) including multidisciplinary management and remote telemonitoring for patients with CHF was introduced in 2000 and was formally adopted, as part of the services delivered by the regional healthcare system, in 2006. This article reports the effect of the HTP on the functional status and quality of life and describes the main outcomes observed within 1 year from the end of the program.
  
  MATERIALS AND METHODS:
  Six-month variations of New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), 6-min walking distance (6MWD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score were evaluated in 602 CHF patients. Patients showing at least two of the following conditions-NYHA class reduction, increase in LVEF ?5%, 6MWD >30?m, and a reduction of >24 points of MLHFQ-were defined as "responders." One-year events included unplanned cardiovascular readmissions and mortality.
  
  RESULTS:
  A significant improvement in NYHA class, LVEF, 6MWD, and MLHFQ was observed. Clinical events occurred in 24.1% of non-responders and in 15.9% of responders (p=0.03). An unfavorable response to the program, the presence of an implantable cardioverter defibrillator, and multiple comorbidities were predictors of poor outcome.
  
  CONCLUSIONS:
  The HTP was effective in improving CHF patient functional status, and an unsuccessful response to the intervention seems to be an independent marker of poor prognosis.
  
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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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• [Cardiac resynchronization therapy in women].
  G Ital Cardiol (Rome)

  2012 May;13(5 Suppl 1):31S-34S.
  
  Lunati Maurizio, Landolina Maurizio, Cipriani Manlio, Rordorf Roberto, Bisetti Silvia, Campo Claudia, Ghio Stefano, Frigerio Maria
  
  Abstract
  
  Cardiac resynchronization therapy (CRT) is a well established option in patients with moderate to severe heart failure on optimal medical therapy, NYHA functional class Ill-IV, reduced systolic function (left ventricular ejection fraction < or =35%), broad QRS complex (>120 ms), but data addressing sex differences in response to CRT are lacking. Women are underrepresented in clinical and observational trials on CRT (<30%) but, when examining response across recent studies, there is evidence of a more positive effect of CRT in women. Also our data show that females seem to achieve a greater survival benefit with CRT than male recipients. While larger trials remain the ideal way to specifically address the question of a gender effect, with some uncertainties on the understanding of the greater benefit still present (specific factors intrinsic to women are responsible for this difference? pre-CRT clinical characteristics, prevalence of nonischemic cardiomyopathy and left bundle branch block, other than female gender itself?), current evidence supports the notion of increasing access to CRT for women with the appropriate indication, to allow them to exploit the distinctive benefits associated with this treatment strategy.
  
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• [Heart failure in women: challenges and opportunities].
  G Ital Cardiol (Rome)

  2012 May;13(5 Suppl 1):3S-5S.
  
  Frigerio Maria, De Maria Renata
  
  
  
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• Emergency ECMO support for acute LVAD failure.
  Int J Cardiol

  2013 Jul;167(2):e41-2. doi: 10.1016/j.ijcard.2013.03.072.
  
  Russo Claudio Francesco, Botta Luca, Lanfranconi Marco, De Marco Federico, Frigerio Maria, Paino Roberto, Martinelli Luigi
  
  
  
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• Limited changes in severe functional mitral regurgitation and pulmonary hypertension after left ventricular assist device implantation: a clue to consider concurrent mitral correction?
  Int J Cardiol

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

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

  2013 Feb;14(2):110-9. doi: 10.1714/1218.13523.
  
  Ammirati Enrico, Oliva Fabrizio, Colombo Tiziano, Botta Luca, Cipriani Manlio, Cannata Aldo, Verde Alessandro, Turazza Fabio M, Russo Claudio F, Paino Roberto, Martinelli Luigi, Frigerio Maria
  
  Abstract
  
  Heart transplantation (HTx) is considered to be the gold standard treatment for advanced heart failure (HF) but it is available only for a minority of patients, due to paucity of donor hearts (278 HTx were performed in 2011 in Italy). Patients listed for HTx have a prolonged waiting time (that is about 2.3 years in the 2006-2010 time period in Italy) that is superior compared with patients who receive HTx (median time around 6 months), to underline the presence of an allocation system that prioritizes candidates in critical conditions. Patients listed for HTx have a poor quality of life and their annual mortality is around 8-10%. Another 10-15% of HTx candidates are removed from the waiting list each year because they are no longer suitable for transplantation. On the other hand, continuous-flow left ventricular assist devices (LVADs) have been demonstrated to improve survival and quality of life of patients with advanced/refractory HF. LVAD therapy can represent a valid alternative to HTx, and it is recommended for patients with advanced HF in the recent edition of the European Society of Cardiology guidelines on HF management. In the United States, a larger number of centers compared with European ones started to apply a strategy of LVAD implant for many patients who meet clinical criteria for listing for HTx. Data from our center concerning the last 6 years of LVAD implant (51 implants since 2006) reported a 75.5% survival rate at 1 year. In Italian series, as in our center, current HTx survival is only slightly superior (83% survival rate at 1 year), based on data from the Italian National Transplant Center. We report a proposal for updated listing criteria for HTx and indications for LVAD implant in patients with advanced acute and chronic HF. Criteria for identifying suitable patients for HTx and/or LVAD considering the shortage of donors are discussed.
  
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• 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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• Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7.
  Circulation

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

  2012 Jul;59(1):138-44. doi: 10.1016/j.cyto.2012.04.018.
  
  Caruso Raffaele, Verde Alessandro, Campolo Jonica, Milazzo Filippo, Russo Claudio, Boroni Chiara, Parolini Marina, Trunfio Salvatore, Paino Roberto, Martinelli Luigi, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  This study investigates the impact of early left ventricular (LV)-mechanical unloading on systemic oxidative stress and inflammation in terminal heart failure patients and their impact both on multi organ failure and on intensive care unit (ICU) stay. Circulating levels of urinary 15-isoprostane-F(2t) (8-epi-PGF2(?)) and pro-inflammatory markers [plasma interleukin (IL)-6, IL-8, and urinary neopterin, a monocyte activation index] were analyzed in 20 healthy subjects, 22 stable end-stage heart failure (ESHF) patients and in 23 LV assist device (LVAD) recipients at pre-implant and during first post-LVAD (PL) month. Multi-organ function was evaluated by total Sequential Organ Failure Assessment (tSOFA) score. In LVAD recipients the levels of oxidative-inflammatory markers and tSOFA score were higher compared to other groups. After device implantation 8-epi-PGF2(?) levels were unchanged, while IL-6, and IL-8 levels increased during first week, and at 1month returned to pre-implant values, while neopterin levels increased progressively during LVAD support. The tSOFA score worsened at 1 PL-week with respect to pre-implant value, but improved at 1 PL-month. The tSOFA score related with IL-6 and IL-8 levels, while length of ICU stay related with pre-implant IL-6 levels. These data suggest that hemodynamic instability in terminal HF is associated to worsening of systemic inflammatory and oxidative milieu that do not improve in the early phase of hemodynamic recovery and LV-unloading by LVAD, affecting multi-organ function and length of ICU stay. This data stimulate to evaluate the impact of inflammatory signals on long-term outcome of mechanical circulatory support.
  
  Copyright © 2012 Elsevier Ltd. All rights reserved.
  
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• Percutaneous iatrogenic coronary fistula closure in heart transplant recipient.
  Asian Cardiovasc Thorac Ann

  2012 Apr;20(2):188-90. doi: 10.1177/0218492311421456.
  
  Bruschi Giuseppe, Oreglia Jacopo, Colombo Paola, De Marco Federico, Frigerio Maria, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  A 61-year-old man with ischemic cardiomyopathy underwent orthotopic heart transplantation. On routine coronary angiography 1 year later, a huge fistula was seen between the left anterior descending coronary artery and the right ventricle. When the patient developed symptoms of ischemia 8 years later, the fistula was successfully closed percutaneously, using a covered stent.
  
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• [The relationship between the heart and the kidney in acute heart failure: doubts of the cardiologist and the nephrologist's point of view].
  G Ital Cardiol (Rome)

  2012 Apr;13(4):281-90. doi: 10.1714/1056.11560.
  
  Di Tano Giuseppe, Misuraca Gianfranco, , Ronco Claudio, Zoccali Carmine, Frigerio Maria
  
  Abstract
  
  The pathophysiological interactions that link the heart and kidney in heart failure are multiple and complex. This issue constitutes one of the most vexing and difficult challenges facing cardiologists. In the setting of acute decompensated heart failure, worsening renal function has traditionally been directly associated with poor clinical prognosis and complicates treatment. In the last years, many reports suggest that worsening renal failure may represent the final common pathway of several mechanistically distinct processes, with different prognostic implications. In the clinical scenario, the clinical significance of transient worsening of renal function may be different as compared with irreversible or progressive renal failure. In addition, it can represent a relatively normal response to treatment-induced physiological derangements such as a reduction in renal perfusion and/or intravascular volume. We here focus on these highlights, with special reference to the diagnostic criteria of renal dysfunction and the management of fluid overload. Two expert nephrologists were asked to answer a few important clinical questions: how should renal dysfunction be recognized and monitored? Are there therapies to counteract it and when, and more importantly, for whom should be applied? Their answers serve as touchstones for cardiologists to provide better individualized care for their patients with acute heart failure. Only a multidisciplinary and collaborative management of cardio-renal interactions will help to mitigate the difficult day-to-day clinical practice and improve our understanding of this condition through a concerted and constructive approach.
  
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• The first Caucasian patient with p.Val122Ile mutated-transthyretin cardiac amyloidosis treated with isolated heart transplantation.
  Amyloid

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

  2012 Apr;41(4):e48-52; discussion e52-3. doi: 10.1093/ejcts/ezr321.
  
  Cannata Aldo, Botta Luca, Colombo Tiziano, Russo Claudio F, Taglieri Corrado, Bruschi Giuseppe, Merlanti Bruno, Frigerio Maria, Martinelli Luigi
  
  Abstract
  
  OBJECTIVE:
  The choice of cardioplegic solution for myocardial preservation in heart transplantation (HT) remains debated. We analysed our experience with three different cardioplegic solutions in adult HT performed during past 5 years, in terms of non-immunological intraoperative biventricular graft failure (BVF) and in-hospital mortality.
  
  METHODS:
  A total of 133 patients underwent HT at our hospital from January 2006 to December 2010. Patients were divided into three groups, according to the solution adopted in the donor: HTK-Custodiol (n = 61), Celsior (n = 38) and St Thomas (n = 34). For each patient, solution was chosen according to surgeon's preference.
  
  RESULTS:
  Recipient and donor mean age was 48.2 ± 12.7 and 43.8 ± 13.6 years, respectively. Twenty-four patients (18.0%) were in Status 1 at the transplant. The mean ischaemic time was 187.9 ± 52.6 min. Intraoperative BVF was observed in 18 cases (13.5%). Patients with BVF, and their respective donors, were older than the other patients (patients: 53.3 vs 47.4 years, P = 0.06; donors: 49.4 vs 42.9 years, P 0.06), and experienced significantly higher in-hospital mortality (47.3 vs 7.8%, P = 0.0001). The combination of patients aged 60 years or older with donors aged 60 years or older carried a mortality of 66.6% (6 out of 9). The three groups of patients did not differ significantly in terms of preoperative and intraoperative features and outcomes, including biventricular graft failure and death. At multivariate analysis, predictors of in-hospital death were a combination of both a recipient and a donor aged ? 60 years (OR 27.9), intraoperative BVF (OR 14.8) and previous cardiac surgery (OR 13.0). Cardioplegic solution did not predict mortality.
  
  CONCLUSIONS:
  We did not observe a significant effect of the kind of cardioplegic solution on the early HT outcomes. The combination between both a recipient and a donor aged ? 60 years, reoperation and BVF are strong predictors of in-hospital death.
  
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• Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients.
  J Heart Lung Transplant

  2012 Jun;31(6):625-33. doi: 10.1016/j.healun.2012.02.006.
  
  Caruso Raffaele, Verde Alessandro, Cabiati Manuela, Milazzo Filippo, Boroni Chiara, Del Ry Silvia, Parolini Marina, Vittori Claudia, Paino Roberto, Martinelli Luigi, Giannessi Daniela, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Inflammatory mechanisms are associated with worse prognosis in end-stage heart failure (ESHF) patients who require left ventricular assist device (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles describe patient condition at pre-implant and outcome. This study assessed the relationship among inflammation patterns and INTERMACS profiles in LVAD recipients.
  
  METHOD:
  Thirty ESHF patients undergoing LVAD implantation as bridge to transplant were enrolled. Blood and urine samples were collected pre-operatively and serially up to 2 weeks post-operatively for assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function was evaluated by the total sequential organ failure assessment (tSOFA) score. Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive care unit (ICU) length of stay.
  
  RESULTS:
  Fifteen patients had INTERMACS profiles 1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6 levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6 levels.
  
  CONCLUSIONS:
  The INTERMACS profiles reflect the severity of the pre-operative inflammatory activation and the post-implant inflammatory response, affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may contribute to poor outcome in patients with severe INTERMACS profile.
  
  Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
  
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• Efficacy and Safety of Low-Dose Cyclosporine with Everolimus and Steroids in de novo Heart Transplant Patients: A Multicentre, Randomized Trial.
  J Transplant

  2011 ;2011():535983. doi: 10.1155/2011/535983.
  
  Zuckermann Andreas, Wang Shoei-Shen, Ross Heather, Frigerio Maria, Eisen Howard J, Bara Christoph, Hoefer Daniel, Cotrufo Maurizio, Dong Gaohong, Junge Guido, Keogh Anne M
  
  Abstract
  
  A six-month, multicenter, randomized, open-label study was undertaken to determine whether renal function is improved using reduced-exposure cyclosporine (CsA) versus standard-exposure CsA in 199 de novo heart transplant patients receiving everolimus and steroids ± induction therapy. Mean C(2) levels were at the low end of the target range in standard-exposure patients (n = 100) and exceeded target range in reduced-exposure patients (n = 99) throughout the study. Mean serum creatinine at Month 6 (the primary endpoint) was 141.0 ± 53.1??mol/L in standard-exposure patients versus 130.1 ± 53.7??mol/L in reduced-exposure patients (P = 0.093). The incidence of biopsy-proven acute rejection ?3A at Month 6 was 21.0% (21/100) in the standard-exposure group and 16.2% (16/99) in the reduced-exposure group (n.s.). Adverse events and infections were similar between treatment groups. Thus, everolimus with reduced-exposure CsA resulted in comparable efficacy compared to standard-exposure CsA. No renal function benefits were demonstrated; that is possibly related to poor adherence to reduced CsA exposure.
  
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• Relationship between myocardial redox state and matrix metalloproteinase activity in patients on left ventricular assist device support.
  Circ J

  2011 ;75(10):2387-96.
  
  Caruso Raffaele, Caselli Chiara, Boroni Chiara, Campolo Jonica, Milazzo Filippo, Cabiati Manuela, Russo Claudio, Parolini Marina, Giannessi Daniela, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Redox aminothiols have been reported to modulate the activity of recombinant metalloproteinases (MMP). The aim of the present study was to investigate the effects of myocardial redox state on the activities of MMP-2 and -9 implicated in cardiac remodeling in end-stage heart failure patients supported by left ventricular assist device (LVAD).
  
  METHODS AND RESULTS:
  During heart transplant (HT) surgery, myocardial specimens (MS) from right ventricular walls and LV walls were obtained from 7 LVAD recipients (LVAD group, MS n=35) and from 7 stable HT candidates on medical therapy (MT group, MS n=35). Myocardial MMP-2 and -9 activities and expression, tissue inhibitor of MMP (TIMP)-1 and -4, transforming growth factor (TGF)-?1 and aminothiol concentrations were measured. MMP-2 and -9 activities were evaluated also by incubating MS with different amounts of reduced and oxidized glutathione (GSH). MMP-2 and -9 activities and expression were lower in the LVAD group, whereas myocardial TIMP-1 and -4 concentrations were comparable to those of MT patients. Higher GSH and TGF-?1 concentrations were found in LVAD-recipients. Only GSH concentrations were inversely related to MMP-2 and -9 activities. In vitro, GSH had an inhibitory effect on MMP-2 and -9 activities.
  
  CONCLUSIONS:
  LVAD recipients show reduced myocardial MMP-2 and -9 activities and expression when compared to medically treated patients. Changes of myocardial redox state, predominantly GSH-dependent, appear to modulate MMP-2 and -9 activities by an inhibitory effect dependent on thiol content. These data support a role of GSH cycle in modulating the extracellular matrix in end-stage heart failure patients supported by LVAD.
  
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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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• Transcatheter aortic valve implantation after heart transplantation.
  Ann Thorac Surg

  2010 Nov;90(5):e66-8. doi: 10.1016/j.athoracsur.2010.08.021.
  
  Bruschi Giuseppe, De Marco Federico, Oreglia Jacopo, Colombo Paola, Moreo Antonella, De Chiara Benedetta, Paino Roberto, Frigerio Maria, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  Conventional cardiac surgical procedures after orthotopic heart transplantation are generally uncommon. We report the case of a 67-year-old man who had severe symptomatic aortic stenosis develop 9 years after heart transplantation. After joint evaluation of the cardiovascular team, transcatheter aortic valve implantation was preferred due to patient medical conditions. The CoreValve prosthesis (Medtronic, Minneapolis, MN) was inserted percutaneously into the femoral artery. At 4 months postoperatively, the patient is asymptomatic in New York Heart Association functional class II. This case report provides evidence that transcatheter aortic valve implantation is safe and suitable for selected patients with severe aortic stenosis and a history of heart transplantation that must improve allograft function.
  
  Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• Effect of surface topography of implant abutments on retention of cemented single-tooth crowns.
  Int J Periodontics Restorative Dent

  2010 Aug;30(4):409-13.
  
  de Campos Tomie Nakakuki, Adachi Lena Katekawa, Miashiro Karen, Yoshida Hideki, Shinkai Rosemary Sadami, Neto Pedro Tortamano, Frigerio Maria Luiza Moreira Arantes
  
  Abstract
  
  This study investigated whether surface topography affects the retentive strength of cemented full crowns, comparing the effects of standard machined, sandblasted, and grooved implant abutments. Five metallic crowns per abutment type were cast and cemented with zinc phosphate. After 24 hours, the specimens were submitted to a tensile test. The retentive strength of the cemented crowns was affected by abutment surface topography. The sandblasted and grooved surface groups had approximately 2.4 times greater mean uniaxial retentive strength than the machined surface group (P < .001). The retentive strength of the sandblasted and grooved abutments was similar, despite marked differences in surface profiles and roughness parameters.
  
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• The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients.
  J Heart Lung Transplant

  2010 Aug;29(8):914-56. doi: 10.1016/j.healun.2010.05.034.
  
  Costanzo Maria Rosa, Dipchand Anne, Starling Randall, Anderson Allen, Chan Michael, Desai Shashank, Fedson Savitri, Fisher Patrick, Gonzales-Stawinski Gonzalo, Martinelli Luigi, McGiffin David, Smith Jon, Taylor David, Meiser Bruno, Webber Steven, Baran David, Carboni Michael, Dengler Thomas, Feldman David, Frigerio Maria, Kfoury Abdallah, Kim Daniel, Kobashigawa Jon, Shullo Michael, Stehlik Josef, Teuteberg Jeffrey, Uber Patricia, Zuckermann Andreas, Hunt Sharon, Burch Michael, Bhat Geetha, Canter Charles, Chinnock Richard, Crespo-Leiro Marisa, Delgado Reynolds, Dobbels Fabienne, Grady Kathleen, Kao W, Lamour Jaqueline, Parry Gareth, Patel Jignesh, Pini Daniela, Towbin Jeffrey, Wolfel Gene, Delgado Diego, Eisen Howard, Goldberg Lee, Hosenpud Jeff, Johnson Maryl, Keogh Anne, Lewis Clive, O'Connell John, Rogers Joseph, Ross Heather, Russell Stuart, Vanhaecke Johan,
  
  
  
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• Early expression of pro- and anti-inflammatory cytokines in left ventricular assist device recipients with multiple organ failure syndrome.
  ASAIO J

  ;56(4):313-8. doi: 10.1097/MAT.0b013e3181de3049.
  
  Caruso Raffaele, Trunfio Salvatore, Milazzo Filippo, Campolo Jonica, De Maria Renata, Colombo Tiziano, Parolini Marina, Cannata Aldo, Russo Claudio, Paino Roberto, Frigerio Maria, Martinelli Luigi, Parodi Oberdan
  
  Abstract
  
  To assess whether the combined evaluation of total Sequential Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVAD, we analyzed plasma interleukin (IL)-6, IL-8, IL-10, IL-1ra, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and urine neopterin levels before (day 0) and at 4 hours, 1, 3, 7, 14, and 30 days after LVAD implant in 23 recipients. Eight patients died of MOFS between days 7 and 30 (nonsurvivors). At preimplant, only blood urea nitrogen and age were higher in nonsurvivors than survivors. At 4 hours, IL-8, IL-10, and IL1-ra levels were higher in nonsurvivors than in survivors; t-SOFA was also higher and peaked on day 3 in nonsurvivors. Only IL-8 levels on day 1 were significantly associated with a t-SOFA > or =10 on day 3 (odds ratio 1.10, 95% confidence interval 1.01-1.21, p = 0.04). Neopterin, marker of monocyte activation, increased significantly only in nonsurvivors (p < 0.001). These findings suggest that an activated inflammatory system soon after LVAD implant is implicated in MOFS development. Early monitoring of inflammatory mediators and t-SOFA score may be a valuable tool for outcome prediction in LVAD recipients.
  
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• Percutaneous implantation of CoreValve aortic prostheses in patients with a mechanical mitral valve.
  Ann Thorac Surg

  2009 Nov;88(5):e50-2. doi: 10.1016/j.athoracsur.2009.07.028.
  
  Bruschi Giuseppe, De Marco Federico, Oreglia Jacopo, Colombo Paola, Fratto Pasquale, Lullo Francesca, Paino Roberto, Frigerio Maria, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  Concerns exist in the field of transcatheter aortic valve implantation regarding the treatment of patients with mechanical mitral valve for possible interference between the percutaneous aortic valve and the mechanical mitral prosthesis. We report our experience with percutaneous aortic valve implantation in 4 patients with severe aortic stenosis, previously operated on for mitral valve replacement with a mechanical prosthesis. All patients underwent uneventful percutaneous retrograde CoreValve implantation (CoreValve Inc, Irvine, CA). No deformation of the nitinol tubing of the prostheses (ie, neither distortion nor malfunction of the mechanical valve in the mitral position) occurred in any of the patients. All patients are alive and asymptomatic at a mean follow-up of 171 days.
  
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• Percutaneous device closure of iatrogenic left ventricular wall pseudoaneurysm.
  Ann Thorac Surg

  2009 Oct;88(4):e31-3. doi: 10.1016/j.athoracsur.2009.07.032.
  
  Vignati Gabriele, Bruschi Giuseppe, Mauri Luigi, Annoni Giuseppe, Frigerio Maria, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  A 67-year-old man with ischemic cardiomyopathy was transferred to our hospital in cardiogenic. During a video-assisted mini-thoracotomy for left ventricular epicardial lead implantation, a left ventricular free-wall rupture occurred and an emergency surgical repair was performed. Postoperatively patients experience left ventricular wall pseudoaneurysm. After stabilization of clinical conditions with aggressive medical treatment, we decided to attempt a minimally invasive procedure (ie, a transcatheter pseudoaneurysm closure). To date, few cases of device closure of left ventricle pseudoaneurysm are reported in the literature, usually secondary to myocardial infarction, and we believe this is the first case of left ventricle pseudoaneurysm after iatrogenic left ventricle laceration and surgical closure.
  
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• Design of the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study to assess the ability of remote monitoring to treat and triage patients more effectively.
  Trials

  2009 Jun;10():42. doi: 10.1186/1745-6215-10-42.
  
  Marzegalli Maurizio, Landolina Maurizio, Lunati Maurizio, Perego Giovanni B, Pappone Alessia, Guenzati Giuseppe, Campana Carlo, Frigerio Maria, Parati Gianfranco, Curnis Antonio, Colangelo Irene, Valsecchi Sergio
  
  Abstract
  
  BACKGROUND:
  Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier.
  
  METHODS:
  The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink monitor for remote transmission or the conventional method of in-person evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations.
  
  TRIAL REGISTRATION:
  ClinicalTrials.gov: NCT00873899.
  
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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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• Failure and off-pump replacement of Incor LVAD system.
  ASAIO J

  ;55(1):121-2. doi: 10.1097/MAT.0b013e3181906e2a.
  
  Pelenghi Stefano, Colombo Tiziano, Montorsi Emanuela, Newcomb Andrew, Frigerio Maria, Martinelli Luigi
  
  Abstract
  
  An Incor (Berlin Heart AG, Berlin) left ventricular assist device (LVAD) was implanted; 6 months later the patient was admitted to our department for intravenous antibiotic therapy for a driveline infection. Two days after admission under direct echocardiographic monitoring, the pump failure was noted to be entirely dependent on the position of the cable. The pump was successfully replaced without cardiopulmonary bypass as a matter of urgency.
  
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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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• Long-term results of lung cancer after heart transplantation: single center 20-year experience.
  Lung Cancer

  2009 Jan;63(1):146-50. doi: 10.1016/j.lungcan.2008.04.018.
  
  Bruschi Giuseppe, Conforti Serena, Torre Massimo, Colombo Tiziano, Russo Claudio F, Pedrazzini Giovanna, Frigerio Maria, Ravini Mario
  
  Abstract
  
  OBJECTIVE:
  The present study analyses, long-term lung cancer survival rate in the Niguarda heart transplant population and the results of surgical treatments.
  
  METHODS:
  From November 1985 to December 2006, 786 heart transplants were performed in our Center; we underwent a retrospective review of patients developing primary lung cancer.
  
  RESULTS:
  Among 660 heart transplant recipients valuable in this study, 22 (3.3%) developed a primary lung cancer (20 male, 91%), their mean age at time of heart transplant was 54.5+/-5.2 years (range, 42-65). The mean time from transplantation to lung cancer diagnosis was 73.7+/-30 months. Eleven patients (50%) were in stage IIIB or higher at the time of presentation. The 5-year survival rate of the entire study population was 21.4%, with a median survival time (MST) of 10.1 months. Ten patients underwent surgical resection (9 lobectomies and 1 wedge resection) and demonstrated improved long-term survival with 5-year survival of 56% and MST 70.4 months, compared to patients who did not undergo any surgical procedure, all of whom died during follow-up, with 1-year survival of 33%.
  
  CONCLUSIONS:
  Long-term results following lung cancer surgery in heart transplant recipients are satisfactory when performed at the early stage of the disease. Preventive computed tomography screen should be considered as a routine method for early diagnosis in this group of high-risk patients.
  
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• Clinical outcome and bridge to transplant rate of left ventricular assist device recipient patients: comparison between continuous-flow and pulsatile-flow devices.
  Eur J Cardiothorac Surg

  2008 Aug;34(2):275-80; discussion 280. doi: 10.1016/j.ejcts.2008.02.019.
  
  Garatti Andrea, Bruschi Giuseppe, Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Milazzo Filippo, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  BACKGROUND:
  Long-term implantable continuous axial-flow pumps are increasingly used in bridging heart failure patients to heart transplant. Compared to pulsatile left ventricular assist devices (LVADs), they offer smaller dimensions, less surgical trauma and less thromboembolisms. However concerns still remain about the long-term effects of continuous-flow on patients' outcome. The aim of this study was to review our mechanical bridge to transplant experience to compare pre- and post-transplant outcomes between pulsatile and continuous-flow LVAD recipients.
  
  METHODS:
  Thirty-six patients with a continuous-flow device (Micromed DeBakey, Houston, TX or InCor Berlin Heart, Berlin, Germany--group A) were compared with 41 patients supported with a pulsatile device (Novacor, WorldHeart, Oakland, CA--group B).
  
  RESULTS:
  Mean age (48.6+/-12.4 vs 47.2+/-12.5) and LVAD duration (119.3+/-115.4 vs 128.3+/-198.3) were similar in the two groups. Group A recipients were smaller compared to group B (mean body surface area=1.77+/-0.18 vs 1.93+/-0.16; p<0.001). Idiopathic dilated cardiomyopathy was not significantly greater between the two groups (78% vs 58.3%; p=0.085). Successful bridging to transplantation was similar in group A compared to group B (52.8% vs 63.4%; p=non significant). On-VAD mortality was similar between the two groups (A vs B=33.3% vs 36.6%; p=non significant). Thirty-day mortality after HTx in group A was 10.5% compared to 7.7% in group B (p=non significant). First year post-transplant incidence of treated rejections (36.8% vs 46%; p=non significant) as the mean number of rejection/patient (0.38+/-0.5 vs 0.53+/-0.83; p=non significant) were similar in group A compared to group B.
  
  CONCLUSIONS:
  In our experience, when compared to pulsatile LVAD, continuous-flow pumps are similarly effective in transplant rate and post-transplant outcome.
  
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• Thromboaspiration during acute myocardial infarction in a heart transplant patient.
  J Cardiovasc Med (Hagerstown)

  2008 Mar;9(3):293-5. doi: 10.2459/JCM.0b013e328216240a.
  
  Colombo Paola, Bruschi Giuseppe, Agozzino Manuela, Silva Pedro, Frigerio Maria, Vitali Ettore, Arbustini Eloisa, Klugmann Silvio
  
  Abstract
  
  Each year, an estimated 10% of heart transplant recipients develop coronary allograft vasculopathy, an aggressive form of coronary artery disease that limits survival after transplantation. The pathologic characteristics of coronary allograft vasculopathy are not uniform and both the clinical importance and pathophysiological significance of thrombosis and vasospasm in this setting are not completely understood. Mechanical reperfusion is a better alternative to systemic thrombolysis in patients with acute myocardial infarction and thrombus removal before standard percutaneous coronary intervention improves coronary epicardial flow. We report the case of a 38-year-old male admitted to the emergency room of our hospital with acute inferior myocardial infarction complicated by cardiogenic shock. He underwent heart transplant because of ischemic cardiomyopathy. Coronary angiography showed acute coronary thrombosis of the circumflex coronary artery. Percutaneous coronary intervention with thrombus extraction was successfully attempted. This case represents an unusual clinical presentation and treatment of cardiac allograft vasculopathy.
  
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• Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure.
  Eur Heart J

  2008 Apr;29(8):1019-28. doi: 10.1093/eurheartj/ehn020.
  
  Borggrefe Martin M, Lawo Thomas, Butter Christian, Schmidinger Herwig, Lunati Maurizio, Pieske Burkert, Misier Anand Ramdat, Curnis Antonio, Böcker Dirk, Remppis Andrew, Kautzner Joseph, Stühlinger Markus, Leclerq Christophe, Táborsky Milos, Frigerio Maria, Parides Michael, Burkhoff Daniel, Hindricks Gerhard
  
  Abstract
  
  AIMS:
  We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients.
  
  METHODS AND RESULTS:
  One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter).
  
  CONCLUSION:
  In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period.
  
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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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• Pre-operative redox state affects 1-month survival in patients with advanced heart failure undergoing left ventricular assist device implantation.
  J Heart Lung Transplant

  2007 Nov;26(11):1177-81.
  
  Caruso Raffaele, Garatti Andrea, Sedda Valentina, Milazzo Filippo, Campolo Jonica, Colombo Tiziano, Catena Emanuele, Cighetti Giuliana, Russo Claudio, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Left ventricular assist device (LVAD) implantation has proven effective as a bridge to transplantation in end-stage heart failure patients (ESHFPs), although survival during device support is critical. Oxidative stress has been implicated in the development of heart failure, but the influence of redox state on in-hospital post-LVAD outcome has not been clarified.
  
  METHODS AND RESULTS:
  In this report we describe the oxidant/anti-oxidant profiles of 15 ESHFPs before LVAD placement, 5 of whom did not survive to 1 month, and in 30 subjects without cardiac disease, representing the control group.
  
  CONCLUSIONS:
  Preliminary findings suggest that adequate activity of the GPx-1-based anti-oxidant system before device placement is associated with patient survival up to 1 month, despite comparable baseline oxidative stress in patients who both survived and died (within 2 weeks post-LVAD).
  
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• Long-term follow-up of simultaneous heart and kidney transplantation with single donor allografts: report of nine cases.
  Ann Thorac Surg

  2007 Aug;84(2):522-7.
  
  Bruschi Giuseppe, Busnach Ghil, Colombo Tiziano, Radaelli Loredana, Pedrazzini Giovanna, Garatti Andrea, Sansalone Cosimo V, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  BACKGROUND:
  Combined heart-kidney transplantation is an accepted therapeutic option for patients with end-stage heart disease associated with severely impaired renal function. We report our single-institutional experience with this combined procedure and long-term follow-up.
  
  METHODS:
  Between April 1989 and August 2006, 9 patients underwent combined simultaneous heart-kidney transplantation at our center. Seven patients were male (mean age, 45.2 +/- 10.12 years); 7 patients were on dialysis at transplantation. Whenever possible, donors were selected on the basis of ABO identity, weight (ratio > or = 0.9), on-site or short-distance procurement, young age, low inotropic support, and normal renal function.
  
  RESULTS:
  Mean ischemic time was 132.2 +/- 57.0 minutes for the cardiac allograft and 6.0 +/- 1.0 hours for the kidney. Surgical procedure was uneventful in all patients. One patient died in the intensive care unit 41 days after transplantation. Three patients died during follow-up, 1 of lung neoplasm after 6 years, 1 of cerebral stroke after 34 months, and 1 of infection and multiorgan failure after 148 months. The mortality rates led to an overall actuarial survival of 88.9% +/- 10.4% at 1 year, 77.8% +/- 13.6% at 5 years, and 64.8% +/- 16.5% at 10 years. Seven patients lived beyond 5 years, 4 beyond 10 years, and the patient who has longest survival is patient no. 1, with 17 years of follow-up. One patient lost kidney function after 113 months.
  
  CONCLUSIONS:
  In selected patients, with coexisting end-stage cardiac and renal failure, combined heart-kidney transplantation with allograft from the same donor proved to have satisfactory short- and long-term results, with a low incidence of both cardiac and renal allograft rejection.
  
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• [Prognostic value of serial measurements of left ventricular function and exercise performance in chronic heart failure].
  Rev Esp Cardiol

  2006 Sep;59(9):905-10.
  
  Moreo Antonella, de Chiara Benedetta, Cataldo Gabriella, Piccalò Giacomo, Lobiati Elisabetta, Parolini Marina, Frigerio Maria, Ciliberto Guglielma Rita, Mauri Francesco
  
  Abstract
  
  INTRODUCTION AND OBJECTIVES:
  The prognostic value of a single measurement of ejection fraction and peak oxygen uptake in chronic heart failure has been extensively investigated. The aim of our study was to evaluate the prognostic significance of serial changes in ejection fraction and exercise performance in moderate to severe chronic heart failure.
  
  METHODS:
  182 patients (156 men, 53 [47-58] years) underwent echocardiography and cardiopulmonary exercise testing at baseline and after 10 [8-12] months. Most patients had idiopathic dilated cardiomyopathy (69%) and all patients presented left ventricular ejection fraction <45%. Median follow-up was 21 [14-34] months; cardiac death and heart transplantation were the end-points. Hazard ratio (HR, per unit) is presented with its 95% confidence interval (CI).
  
  RESULTS:
  During follow-up 18 patients (9.9%) died and 14 (7.7%) underwent heart transplantation. Baseline ejection fraction (HR, 0.94, 95% CI, 0.89-0.98 P=.006) and mitral regurgitation (HR, 4.22, 95% CI, 1.63-10.92, P=.003), and delta (second examination-baseline) ejection fraction (HR, 0.93, 95% CI, 0.88-0.98, P=.01) were the only significant variables at univariate analysis. Both ejection fraction and delta ejection fraction remained independently associated with events at multivariate analysis. The prognostic power significantly increased between a model including ejection fraction alone and another one including ejection fraction plus delta ejection fraction.
  
  CONCLUSIONS:
  In clinically stable patients with chronic heart failure, ejection fraction and its changes were independently associated with outcome; on the contrary, serial cardiopulmonary exercise testing did not provide significant prognostic value. Baseline plus changes in ejection fraction showed better prognostic performance than baseline ejection fraction alone.
  
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• Bone mass index analysis in elderly people before and after change prosthesis.
  Gerodontology

  2006 Sep;23(3):187-91.
  
  Gomes Vanessa Neves, Frigerio Maria Luiza Moreira Arantes, Fidelix Marcia
  
  Abstract
  
  OBJECTIVES:
  To evaluate the bone mass index (BMI) of senescent patients before and after prosthetic rehabilitation by complete dentures and evaluating any correlations between prosthetic rehabilitation and changes in BMI.
  
  SUBJECTS:
  Thirty-two edentulous elder patients who were in need of new complete dentures.
  
  SETTING:
  Dental clinic of the Prosthodontics Department (Dental Branch) of the University of São Paulo, Brazil.
  
  MATERIALS AND METHODS:
  The study was performed in three different phases: the first one took place before any procedures relating to the new complete dentures had started and consisted of clinical records and a prosthetic anamnesis. The second and third phases took place after the prosthetic rehabilitation was completed, normally after 3 and 5-6 months respectively. The data collected in the different phases were analysed by using BIOESTAT 3.0; the level of significance was p < 0.05, in a bilateral proof.
  
  RESULTS:
  The non-parametric statistical analysis of BMI did not show any significant differences when compared with the three phases analysed during the study.
  
  CONCLUSION:
  There was no evidence that accurate prosthetic rehabilitation could influence BMI.
  
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• Blood glutathione as independent marker of lipid peroxidation in heart failure.
  Int J Cardiol

  2007 Apr;117(1):45-50.
  
  Campolo Jonica, De Maria Renata, Caruso Raffaele, Accinni Roberto, Turazza Fabio, Parolini Marina, Roubina Elèna, De Chiara Benedetta, Cighetti Giuliana, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated.
  
  AIM:
  To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients.
  
  METHODS:
  Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I-III).
  
  RESULTS:
  MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56-1.60) microM vs. 0.70 (0.40-0.83) microM, p=0.006]. Blood reduced GSH concentrations were significantly higher [662 (327-867) microM vs. 416 (248-571) microM, p=0.016], while alpha-tocopherol levels were significantly lower [15 (13-19) microM vs. 21 (17-32) microM, p=0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by MDA levels > or = 1.00 microM, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p=0.008), ischemic (OR 20, 95% CI 2.6 to 155, p=0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p=0.026).
  
  CONCLUSIONS:
  Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.
  
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• Left ventricular mechanical support with the Impella Recover left direct microaxial blood pump: a single-center experience.
  Artif Organs

  2006 Jul;30(7):523-8.
  
  Garatti Andrea, Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Milazzo Filippo, Catena Emanuele, Bruschi Giuseppe, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  The Impella Recover left direct (LD) is a new intravascular microaxial blood pump, intended as a short-term mechanical support especially in case of acutely reduced left ventricular function. From September 2002 to October 2004, Impella was used to support 12 patients: six patients were supported as bridge-to-heart transplant (HTx); three patients were treated for fulminant acute myocarditis, and three patients for postcardiotomy low-output syndrome. Mean support time was 8.8 +/- 2.3 days. Overall mortality was 50%. Four patients were successfully HTxed; two patients supported as bridge-to-HTx died on left ventricular assist device. Two patients with myocarditis died of septic shock; two patients in the group of postcardiotomy died of multiorgan failure. The latter two patients were slowly weaned from the device, and at 3-months follow-up showed good improvement of the left ventricular function. Our initial experience with Impella Recover LD as mechanical support for patients in cardiogenic shock of various etiology is promising, yielding a good survival in a population of particularly compromised patients.
  
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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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• [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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• Programme to improve the use of beta-blockers for heart failure in the elderly and in those with severe symptoms: results of the BRING-UP 2 Study.
  Eur J Heart Fail

  2006 Oct;8(6):649-57.
  
  Opasich Cristina, Boccanelli Alessandro, Cafiero Massimo, Cirrincione Vincenzo, Sindaco Donatella Del, Lenarda Andrea Di, Luzio Silvia Di, Faggiano Pompilio, Frigerio Maria, Lucci Donata, Porcu Maurizio, Pulignano Giovanni, Scherillo Marino, Tavazzi Luigi, Maggioni Aldo P,
  
  Abstract
  
  BACKGROUND:
  Beta-blockers are underused in HF patients, thus strategies to implement their use are needed.
  
  OBJECTIVES:
  To improve beta-blocker use in elderly and/or patients with severe heart failure (HF) and to evaluate safety and outcome.
  
  METHODS:
  Patients with symptomatic HF and age>/=70 years or left ventricular EF<25% and symptoms at rest were enrolled, including those already on beta-blocker treatment. Patients who were not receiving a beta-blocker were considered for carvedilol treatment. All patients were followed up for 1-year.
  
  RESULTS:
  Of the 1518 elderly patients, 505 were already on beta-blockers, and carvedilol was newly prescribed in 419 patients. At 1-year, patients treated with carvedilol had a lower incidence of death [10.8% vs. 18.0% in already treated (adjusted RR 0.68; 95%CI 0.49-0.96) and 11.2% in newly treated patients (adjusted RR 0.68; 95%CI 0.48-0.97)]. Of the 709 patients with severe HF, 38.4% were already on beta-blockers, and carvedilol was newly prescribed in 189 patients. Patients not treated with carvedilol showed the worst clinical outcome. Total rate of discontinuation (including adverse reaction and non-compliance) was 14% and 9%, respectively, in elderly and severe patients.
  
  CONCLUSIONS:
  In a real world setting, beta-blocker treatment was not associated with an increased risk of adverse events in elderly and severe HF patients.
  
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• Oral lesions in elderly population: a biopsy survey using 2250 histopathological records.
  Gerodontology

  2006 Mar;23(1):48-54.
  
  Corrêa Luciana, Frigerio Maria Luiza Moreira Arantes, Sousa Suzana Cantanhede Orsini Machado, Novelli Moacyr Domingos
  
  Abstract
  
  OBJECTIVE:
  To perform an oral biopsy survey focused on the incidence of oral lesions in Brazilian elderly patients.
  
  METHODS:
  A total of 17 329 oral biopsy records were analysed and divided into two age groups: elderly patients, > or =60 years old; and non-elderly patients, <60 years old. Information about sex, race, age and histopathological diagnosis (categorised in non-neoplastic and neoplastic lesions) was collected. Differences of diagnosis incidence were tested by comparison between two proportions (binomial test).
  
  RESULTS:
  The incidence of epithelial malignant neoplasms and pre-malignant lesions in the elderly group was higher than non-elderly group, as well as autoimmune diseases and salivary gland tumours. The three most prevalent lesions in the elderly group were inflammatory fibrous hyperplasia, squamous cell carcinoma, and fibroma.
  
  CONCLUSION:
  The distribution of oral diseases using biopsies allows greater accuracy in data about oral health of elderly patients, especially when considering malignant and pre-malignant lesions.
  
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• Different clinical scenarios for circulatory mechanical support in acute and chronic heart failure.
  Am J Cardiol

  2005 Dec;96(12A):34L-41L.
  
  Vitali Ettore, Colombo Tiziano, Bruschi Giuseppe, Garatti Andrea, Russo Claudio, Lanfranconi Marco, Frigerio Maria
  
  Abstract
  
  Chronic heart failure (HF) is a leading cause of death in developed countries. Over the last 2 decades, mechanical circulatory support (MCS) devices have steadily evolved in the clinical management of end-stage HF and have emerged as a standard of care for the treatment of acute and chronic HF refractory to conventional medical therapy. Possible indications for using MCS are acute cardiogenic shock, as a bridge to transplantation, as a bridge to recovery, and more recently, as destination therapy in dilated cardiomyopathy, of either ischemic or idiopathic etiology. We reviewed the different clinical scenarios in which we think there are currently indications to implant different kinds of MCS systems.
  
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• Drugs for left ventricular remodeling in heart failure.
  Am J Cardiol

  2005 Dec;96(12A):10L-18L.
  
  Frigerio Maria, Roubina Elena
  
  Abstract
  
  Left ventricular (LV) remodeling (ie, enlargement and functional deterioration occurring over time) is among the main mechanisms of progression in heart failure (HF). LV dilatation and dysfunction are major negative prognostic markers in patients with HF. Treatments that are effective in limiting or even reversing this process can be expected to provide clinical benefit. Changes in LV dimensions rather than in ejection fraction should be used to monitor remodeling. Ejection fraction can be influenced by transient loading conditions and by agents that stimulate contractility at the expense of increased oxygen demand, whereas dimensional changes probably reflect structural modifications occurring in the myocardium. The neurohormonal antagonists that have been demonstrated to reduce mortality and morbidity in HF (angiotensin-converting enzyme inhibitors [ACE], beta-blockers, angiotensin receptor blockers, and aldosterone antagonists) are also able to inhibit or reverse remodeling. In reverse remodeling, beta-blockers appear to be superior to the other classes of drugs, with a stronger correlation between dose and effect, but it must be remembered that they have been tested as an addition to background therapy that may include ACE inhibitors. With regard to nonpharmacologic strategies, biventricular pacing is associated with functional improvement and reverse remodeling in patients with advanced HF and electromechanical dyssynchrony, and it recently has been demonstrated to improve survival in a randomized clinical trial.
  
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• [Use of imaging in the evaluation of heart transplant recipients].
  Ital Heart J Suppl

  2005 Sep;6(9):561-8.
  
  De Chiara Benedetta, Roubina Elèna, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  Common complications after heart transplantation include acute rejection and coronary allograft vasculopathy. In order to detect the presence of rejection, tissue Doppler imaging echocardiography provides high accuracy and allows to optimize the timing of endomyocardial biopsies, which remain the cornerstone in rejection diagnosis. Coronary allograft vasculopathy is often a diffuse disease so that it is difficult to recognize by imaging modalities, such as myocardial perfusion scintigraphy, which are based on intra-patient comparison of different areas. Quantitative assessment of the myocardial blood flow by positron emission tomography overcomes this issue. Dobutamine stress echocardiography provides accurate diagnosis as well as useful prognostic information. Nevertheless, intracoronary ultrasound is nowadays considered the gold standard for vasculopathy assessment, since it is able to detect a minimum intimal thickening which represents the early feature of disease. Magnetic resonance represents the most attractive approach, though it has not yet gained widespread clinical use.
  
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• [What's essential, what's useful and what's superfluous in patients with dilated cardiomyopathy].
  Ital Heart J

  2005 May;6 Suppl 2():28S-34S.
  
  Frigerio Maria, Garascia Andrea, Foti Grazia, Masciocco Gabriella, Distefano Giada, Roubina Elena, Resta Davide
  
  
  
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• Blood glutathione as a marker of cardiac allograft vasculopathy in heart transplant recipients.
  Clin Transplant

  2005 Jun;19(3):367-71.
  
  De Chiara Benedetta, Bigi Riccardo, Campolo Jonica, Parolini Marina, Turazza Fabio, Masciocco Gabriella, Frigerio Maria, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV.
  
  METHODS:
  Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis.
  
  RESULTS:
  CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008).
  
  CONCLUSIONS:
  In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.
  
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• Different applications for left ventricular mechanical support with the Impella Recover 100 microaxial blood pump.
  J Heart Lung Transplant

  2005 Apr;24(4):481-5.
  
  Garatti Andrea, Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Milazzo Filippo, Catena Emanuele, Bruschi Guiseppe, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  The "Impella Recover 100" (IR100) is a new intravascular microaxial blood pump for use as short-term mechanical support for cases of acutely reduced left ventricular function. From September 2002 to April 2003, we used the IR100 to support 5 patients: 2 patients were bridged to heart transplant; 2 were being treated for fulminant acute myocarditis; and 1 for post-cardiotomy low-output syndrome. Only 1 patient with myocarditis died of septic shock, 2 had successful heart transplants; and the latter 2 were slowly weaned from the device and, at 3-month follow-up, showed moderate improvement of left ventricular (LV) function. Our initial experience with the IR100 as mechanical support for patients in cardiogenic shock of varying etiology has been positive, yielding good survival in a population of particularly compromised patients.
  
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• One-year clinical experience with the Acorn CorCap cardiac support device: results of a limited market release safety study in Italy and Sweden.
  Ital Heart J

  2005 Jan;6(1):59-65.
  
  Livi Ugolino, Alfieri Ottavio, Vitali Ettore, Russo Claudio, Frigerio Maria, Tursi Vincenzo, Albanese Maria Cecilia, De Bonis Michele, Fragasso Gabriele, Franco-Cereceda Anders, Forssell Gunilla, Rorke Rebecca, Kubo Spencer H
  
  Abstract
  
  BACKGROUND:
  The Acorn CorCap cardiac support device (CSD) is a mesh-like device intended to provide end-diastolic support and reduce ventricular wall stress. Animal studies with the CorCap CSD have demonstrated beneficial reverse remodeling, and preliminary safety studies in patients with heart failure have shown that the device is safe and associated with improved left ventricular (LV) structure and function. The objective of the current study was to further evaluate the safety and efficacy of the CorCap CSD in patients with advanced heart failure.
  
  METHODS:
  Twenty-four patients with dilated cardiomyopathy, severe LV dysfunction, and advanced heart failure (NYHA class II-IV) were enrolled at four centers in Italy and Sweden. All patients underwent CorCap CSD implantation either alone (n = 3) or in combination with mitral valve repair/replacement (n = 13), coronary artery bypass surgery (n = 6), combined mitral valve repair/coronary artery bypass surgery (n = 1) or aneurysmectomy (n = 1).
  
  RESULTS:
  The LV end-diastolic diameter decreased from 69.3 +/- 7.2 to 60.1 +/- 9.0 mm at 3 months, 60.9 +/- 9.6 mm at 6 months, and 58.9 +/- 8.0 mm at 12 months (all p < 0.05). A trend toward an improved LV ejection fraction (28.8 +/- 10.5% at baseline and 32.4 +/- 12.7, 33.1 +/- 10.8, and 33.8 +/- 13.9% at 3, 6 and 12 months respectively) was also noted. The NYHA functional class, 6-min walking distance, and quality of life as measured using Uniscale were all improved. There were no differences in response among the patients submitted to the different types of concomitant surgery.
  
  CONCLUSIONS:
  In agreement with earlier safety studies, even the present investigation demonstrated improvements in cardiac structure and function as well as in patient functional status after Cor Cap CSD implantation. Randomized controlled trials are in progress.
  
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• Association between nutrition and the prosthetic condition in edentulous elderly.
  Gerodontology

  2004 Dec;21(4):205-8.
  
  de Oliveira Terezinha R C, Frigerio Maria L M A
  
  Abstract
  
  OBJECTIVES:
  The aim of this study was to assess the possible risk of malnutrition among the elderly population.
  
  SUBJECTS:
  twenty-three pairs of complete dentures were made for a group of patients and 17 upper complete dentures with implant-supported lower dentures were made for a different group.
  
  METHODS:
  The study was performed at the University of São Paulo--Dental Branch, Brazil. The patients were submitted to a nutritional test, as well as to a clinical examination and interview. Chewing ability and patient's satisfaction with their prostheses were evaluated. The nonparametric statistics proof of chi-squared, level 0.05 was performed and because of the low frequencies. The Fischer test was also used.
  
  RESULTS:
  Patients wearing mandibular implant-supported dentures were considered well nourished (76.47%) when compared with complete dentures users (43.48%). There was a significant difference between the two groups, concerning to chewing ability (chi2 = 5.79) and nutritional status (chi2 = 4.35).
  
  CONCLUSION:
  The risk of malnutrition was higher for elderly wearing complete dentures. The psychological state influences the interest in diet and choice of food.
  
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• Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.
  Br J Haematol

  2004 Jul;126(1):85-92.
  
  Cugno Massimo, Mari Daniela, Meroni Pier Luigi, Gronda Edoardo, Vicari Francesco, Frigerio Maria, Coppola Raffaella, Bottasso Bianca, Borghi Maria Orietta, Gregorini Luisa
  
  Abstract
  
  Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.
  
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• Diastolic heart failure.
  Ital Heart J

  2004 Jun;5 Suppl 6():48S-54S.
  
  Frigerio Maria, Aguggini Giovanni
  
  Abstract
  
  Diastolic heart failure is characterized by the presence of heart failure with preserved left ventricular ejection fraction (LVEF): documentation of diastolic dysfunction, usually by Doppler echocardiography, is strongly recommended. Heart failure with preserved LVEF is a heterogeneous and common condition, especially in the elderly, among whom represents up to 50% of all heart failure patients. Mortality is generally lower than in patients with heart failure and low LVEF, and depends on etiology, patient conditions, and comorbidities. Anyway, morbidity is very high. So far, treatment of diastolic heart failure is empirical, and is aimed to maintain cardiac output, reduce filling pressure, control heart rate and rhythm, and antagonize disease progression with diuretics, inhibitors of the renin-angiotensin-aldosterone system, nitrates, and digoxin.
  
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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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• First successful bridge to recovery with the Impella Recover 100 left ventricular assist device for fulminant acute myocarditis.
  Ital Heart J

  2003 Sep;4(9):642-5.
  
  Colombo Tiziano, Garatti Andrea, Bruschi Giuseppe, Lanfranconi Marco, Russo Claudio, Milazzo Filippo, Catena Emanuele, Frigerio Maria, Vitali Ettore
  
  Abstract
  
  A patient with septic and cardiogenic shock secondary to acute fulminant myocarditis was successfully treated by mechanical offloading of the left ventricle using the Impella Recover 100, a new implantable micro-axial blood pump designed for short-term circulatory support (for a maximum of 7 days). The possibility of implanting this device without using cardiopulmonary bypass allowed as to manage the septic shock, to reverse cardiac and hepatorenal failure and to wean the patient off treatment after 18 days of support. At 3 months the left and right ventricular function was satisfactory. The widespread application of this kind of support depends on the availability of an inexpensive "mini-invasive" blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.
  
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• Usefulness of chronotropic incompetence to dipyridamole in predicting myocardial perfusion defects in heart transplant recipients.
  Am J Cardiol

  2003 Oct;92(8):1001-4.
  
  De Chiara Benedetta, Bigi Riccardo, Devoto Emmanuela, Cavenaghi Giorgio, Turazza Fabio, Sara Roberto, Colombo Tiziano, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.
  
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• Prognostic value of contractile response during high-dose dipyridamole echocardiography test in heart transplant recipients.
  J Heart Lung Transplant

  2003 May;22(5):526-32.
  
  Ciliberto Guglielma Rita, Parodi Oberdan, Cataldo Gabriella, Mangiavacchi Maurizio, Alberti Antonia, Parolini Marina, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Coronary allograft vasculopathy (CAV) remains a main factor limiting long-term survival after heart transplantation (HTX). The diagnosis of CAV is still based on serial coronary angiography. In this study, we evaluated the prognostic value of high-dose dipyridamole echocardiography in HTX.
  
  METHODS:
  Sixty-eight patients underwent dipyridamole echocardiography within 48 hours of their scheduled annual coronary angiography. Coronary allograft vasculopathy was defined as CAV 1 (focal or diffuse stenosis <50%) or CAV 2 (focal or diffuse stenosis >or=50%). Wall-motion score index (WMSI) was evaluated at rest and after dipyridamole administration.
  
  RESULTS:
  Results of coronary angiography were normal in 43 patients (63%), showed CAV 1 in 11 (16%), and showed CAV 2 in 14 (21%). Rest wall motion was normal in 39 patients and abnormal in 29. After dipyridamole administration, wall motion remained normal in all 39 (Group 1, no CAV in 34 and CAV 1 in 5). Of 29 patients with rest wall-motion abnormalities, all reversed to normal after dipyridamole in 8 patients (Group 2, no CAV in 7 and CAV 1 in 1) and remained or worsened in 21 (Group 3, CAV 2 in 14 and no CAV or CAV 1 in 7). During follow-up (6 +/- 3 years), 15 patients had major cardiac events: 11 occurred in Group 3, whereas 4 occurred in Groups 1 and 2. Wall motion at rest and after dipyridamole administration and CAV were independent predictors for cardiac events; only dipyridamole WMSI >1 remained significant (p < 0.0001) at multivariate analysis.
  
  CONCLUSIONS:
  Dipyridamole echocardiography is a simple, non-invasive test that after HTX may identify patients with altered wall motion who deserve stricter surveillance.
  
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• Surgical therapy in advanced heart failure.
  Am J Cardiol

  2003 May;91(9A):88F-94F.
  
  Vitali Ettore, Colombo Tiziano, Fratto Pasquale, Russo Claudio, Bruschi Giuseppe, Frigerio Maria
  
  Abstract
  
  Congestive heart failure (CHF) affects about 1% of adults in the United States and is a contributing factor in >250,000 deaths per year. In an increasingly elderly population, the surgical treatment of CHF made great progress during the past 3 decades, consuming enormous health care resources. Heart transplantation is still the most effective therapy for end-stage heart disease, with the 10-year survival rate after transplantation approaching 50%. Efforts to increase the supply of donor organs have failed to improve the shortage, underscoring the crucial need for alternatives to cardiac allotransplantation. Alternative surgical options to end-stage heart transplantation are rapidly evolving. Left ventricular assist devices have been used as a bridge to heart transplantation for patients who otherwise might die awaiting a new heart. There is also continued interest in the use of these devices either to bridge patients to full recovery or to destination therapy, without the need for heart replacement. Left ventricular reconstruction, including the Batista and Dor procedures, along with mitral valve repair, cardiomyoplasty, and extreme coronary artery bypass graft surgery, are now being increasingly performed as alternative options. The history, status, and personal experience of surgical treatment of end-stage heart disease are discussed.
  
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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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• Cardiac resynchronization and implantable cardioverter defibrillator therapy: preliminary results from the InSync Implantable Cardioverter Defibrillator Italian Registry.
  Pacing Clin Electrophysiol

  2003 Jan;26(1P2):148-51.
  
  Gasparini Maurizio, Lunati Maurizio, Bocchiardo Mario, Mantica Massimo, Gronda Edoardo, Frigerio Maria, Caponi Domenico, Carboni Angelo, Boriani Giuseppe, Zanotto Gabriele, Ravazzi Pier Antonio, Curnis Antonio, Puglisi Andrea, Klersy Catherine, Vicini Ilaria, Cavaglià Sergio
  
  Abstract
  
  The aim of this study was to evaluate ventricular arrhythmias occurring in recipients of the InSync ICD for the primary and secondary prevention of sudden death. The InSync ICD was implanted in 142 patients (128 men; mean age 65 +/- 10 years) with heart failure (mean NYHA functional Class 3.0 +/- 0.7) and wide QRS (mean 159 +/- 33 ms). The underlying etiology was ischemic in 55%, idiopathic in 33%, and valvular or hypertensive cardiomyopathy in 12% of patients. The numbers of arrhythmic episodes/100 patient-months was computed with their 95% CI, assuming a Poisson distribution. Implants were performed in 48 (34%) patients who did not have an ACC/AHA guidelines Class I indication for ICD therapy. A total of 104 patients were compliant for follow-up visits. During a 9-month median (range 0.1-24) follow-up of 104 compliant patients, 19 experienced a total of 94 ventricular arrhythmias, all successfully interrupted or self-terminated, with a median number of two separate episodes, corresponding to a rate of 10 episodes/100 person-month (95% CI 8-12). A rate of 12 episodes/100 person-months (95% CI 10-15) was measured in the subgroup of patients with ACC/AHA class I indications, versus two episodes/100 person-months (95% CI 1-5) in the remainder of the population. Among 12 deaths, 9 were due to heart failure, 1 to a non-cardiovascular cause, and 2 to unknown causes. The implantation of ICD in heart failure patients has been prominently extended to primary prevention. Patients without standard ICD indications experienced life-threatening arrhythmic events. The impact of ICD combined with cardiac resynchronization therapy on arrhythmic profile, mortality, and costs in this subgroup of patients need to be more precisely studied, with a particular focus on the various types of underlying heart disease.
  
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• Successful experience in bridging patients to heart transplantation with the MicroMed DeBakey ventricular assist device.
  Ann Thorac Surg

  2003 Apr;75(4):1200-4.
  
  Vitali Ettore, Lanfranconi Marco, Ribera Elena, Bruschi Giuseppe, Colombo Tiziano, Frigerio Maria, Russo Claudio
  
  Abstract
  
  BACKGROUND:
  Pulsatile left ventricular assist devices are used with increasing frequency to bridge patients with end-stage heart failure to heart transplantation (HTx). Implantation of pulsatile devices is a cumbersome surgical procedure that is associated with major complications, such as bleeding, thromboembolism, and infection. Recently, a continuous axial flow left ventricular assist device (DeBakey ventricular assist device) has been introduced with the goal of reducing the incidence of major complications.
  
  METHODS:
  We reviewed our experience with 11 patients who received a DeBakey ventricular assist device axial flow pump for bridge to HTx from April 2000 through November 2001.
  
  RESULTS:
  Two patients (18.2%) died of multiple-organ failure while on left ventricular assist device support. Bleeding requiring thoracotomy occurred in 2 patients (18.2%). One patient had a minor neurologic event, and one patient developed left ventricular assist device thrombosis, which was successfully treated without pump exchange. Renal failure developed in 1 patient and hepatic dysfunction in 2 patients. There were no instances of right heart failure. No device, pocket, or drive-line infections occurred. Nine patients (9 of 11, 81.8%) had HTx within 51 +/- 49 days (range, 11 to 141 days) after left ventricular assist device implant. One patient died 29 days after HTx because of acute rejection.
  
  CONCLUSIONS:
  The continuous axial flow DeBakey ventricular assist device had reliable features, including a high rate of bridge to HTx. This device had low complication and system failure rates. We consider the DeBakey ventricular assist device a favorable alternative to pulsatile heart assist devices as a bridge to HTx.
  
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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. Surgery of the left ventricle and mitral insufficiency].
  Ital Heart J Suppl

  2002 Aug;3(8):822-30.
  
  Frigerio Maria, Rocco Francesco
  
  Abstract
  
  The high number of patients with advanced heart failure despite optimal medical therapy and the limited availability of radical therapeutic solutions (including heart transplantation) increase the interest in alternative surgical procedures. In this paper, the correction of secondary mitral valve regurgitation, left ventriculectomy, and aneurysmectomy/ventriculoplasty will be reviewed. Secondary mitral valve regurgitation worsens both symptoms and prognosis in patients with left ventricular dysfunction of ischemic and non-ischemic etiology. Its correction, mostly by conservative repair, can be performed with an acceptable perioperative risk in patients with compensated heart failure. Concomitant correction of mitral insufficiency is advisable in patients with significant regurgitation undergoing revascularization surgery. On the other hand, data regarding the improvement in clinical and objective parameters after mitral valve surgery in patients with severe mitral regurgitation and idiopathic or ischemic cardiomyopathy who are unsuitable for revascularization are discordant. In view of its feasibility and presumed efficacy, partial left ventriculectomy or the Batista operation seemed attractive but the expectations were not met: success cannot be predicted in individual patients, the initial improvement may be of short duration, and the peri and postoperative mortalities are relevant. Postinfarction surgical reconstruction and reshaping of the left ventricle is performed mostly together with revascularization surgery; the surgical experience, indications and results reported in various studies are however discordant. In conclusion, multicenter cooperation including randomized studies or registries is worthwhile in order to define the role of surgery of the mitral valve and left ventricle in patients with advanced heart failure.
  
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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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