Gentile Dott. Piero

Pubblicazioni su PubMed

• [The pulmonary artery catheter in the intensive cardiac care unit].
  G Ital Cardiol (Rome)

  2024 Sep;25(9):624-639. doi: 10.1714/4318.43037.
  
  Baldetti Luca, Gentile Piero, Gori Mauro, Scandroglio Anna Mara, Gasparetto Nicola, Trambaiolo Paolo, Valente Serafina, Marini Marco
  
  Abstract
  
  More than 50 years after its introduction in clinical practice, the increase in the intensity of care offered by the cardiac intensive care units, the shift in the population of patients treated and the wider availability of circulatory supports, still makes the pulmonary artery catheter (PAC) an essential tool for diagnosis, monitoring and prognosis in patients suffering from cardiogenic shock. In this review, we will discuss how to identify those patients who can benefit most from its use, the configuration and the correct insertion technique of a PAC. A pragmatic guide will also be provided for the interpretation of the hemodynamic indexes (direct and calculated) that the PAC is able to reveal as well as a summary of the most common errors in reading or interpreting the pressure curves provided by the PAC. In this article, we will then present a practical guide on how to use the PAC in a modern cardiac intensive care unit.
  
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• Charting the Unseen: How Non-Invasive Imaging Could Redefine Cardiovascular Prevention.
  J Cardiovasc Dev Dis

  2024 Aug;11(8):. doi: 245.
  
  Trimarchi Giancarlo, Pizzino Fausto, Paradossi Umberto, Gueli Ignazio Alessio, Palazzini Matteo, Gentile Piero, Di Spigno Francesco, Ammirati Enrico, Garascia Andrea, Tedeschi Andrea, Aschieri Daniela
  
  Abstract
  
  Cardiovascular diseases (CVDs) remain a major global health challenge, leading to significant morbidity and mortality while straining healthcare systems. Despite progress in medical treatments for CVDs, their increasing prevalence calls for a shift towards more effective prevention strategies. Traditional preventive approaches have centered around lifestyle changes, risk factors management, and medication. However, the integration of imaging methods offers a novel dimension in early disease detection, risk assessment, and ongoing monitoring of at-risk individuals. Imaging techniques such as supra-aortic trunks ultrasound, echocardiography, cardiac magnetic resonance, and coronary computed tomography angiography have broadened our understanding of the anatomical and functional aspects of cardiovascular health. These techniques enable personalized prevention strategies by providing detailed insights into the cardiac and vascular states, significantly enhancing our ability to combat the progression of CVDs. This review focuses on amalgamating current findings, technological innovations, and the impact of integrating advanced imaging modalities into cardiovascular risk prevention, aiming to offer a comprehensive perspective on their potential to transform preventive cardiology.
  
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• Iron deficiency and supplementation in patients with heart failure: Results from the IRON-HF international survey.
  Eur J Heart Fail

  2024 Jul;():. doi: 10.1002/ejhf.3356.
  
  Camilli Massimiliano, Ballacci Federico, Rossi Valentina Alice, Cannatà Antonio, Monzo Luca, Mewton Nathan, Girerd Nicolas, Gentile Piero, Marini Marco, Mapelli Massimo, Flammer Andreas J, Aspromonte Nadia, Montone Rocco Antonio, Lombardo Antonella, Lanza Gaetano Antonio, Savarese Gianluigi, Ruschitzka Frank, Crea Filippo
  
  Abstract
  
  AIMS:
  Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, regardless of anaemia status. Iron supplementation has been demonstrated to improve exercise capacity and quality of life in patients with HF with an ejection fraction
  METHODS AND RESULTS:
  We designed and distributed an online survey (23 questions) regarding ID screening and management in the HF setting. Overall, 256 cardiologists completed the survey (59.8% male, mostly between 30 and 50?years). The majority of physicians defined ID according to the most recent HF recommendations (98.4%) and reported screening for ID in more than half of their patients (68.4%). However, only 54.3% of the respondents performed periodic screening (every 6?months to 1?year). A total of 93.0% of participants prescribed and/or administered iron supplementation, using intravenous iron as the preferred method of administration (86.3%). After iron supplementation, 96.1% of the respondents reassessed ID, most frequently at 3-6?months (67.6%). Most physicians (93.8%) perceived ID as an underestimated comorbidity in HF. Cardiologists' age, training status, subspecialty and work setting (academic vs. non-academic hospitals) were associated with heterogeneity in the answers.
  
  CONCLUSIONS:
  The results of this survey highlight the need for more consistent strategies of ID screening and treatment for patients with HF.
  
  © 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• Phenotype and outcomes according to loop diuretic use in pulmonary arterial hypertension.
  ESC Heart Fail

  2024 Oct;11(5):3146-3154. doi: 10.1002/ehf2.14818.
  
  Savonitto Giulio, Barbisan Davide, Ameri Pietro, Lombardi Carlo Maria, Monti Simonetta, Driussi Mauro, Gentile Piero, Howard Luke, Toma Matteo, Pagnesi Matteo, Collini Valentino, Bauleo Carolina, Adamo Marianna, D'Angelo Luciana, Nalli Chiara, Giannoni Alberto, Vecchiato Veronica, Di Poi Emma, Airo Edoardo, Metra Marco, Garascia Andrea, Sinagra Gianfranco, Lo Giudice Francesco, Stolfo Davide
  
  Abstract
  
  AIMS:
  The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics.
  
  METHODS AND RESULTS:
  Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low-dose loop diuretic and high-dose loop diuretic. Primary outcome was 5 year all-cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ?25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high-dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high-dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome.
  
  CONCLUSIONS:
  Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.
  
  © 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• Recurrent Coronary Artery Vasospasm Complicated by Cardiac Arrests in Heart Transplant Recipient: An Unusual Enemy.
  Transplantation

  2024 Jun;108(6):e86-e87. doi: 10.1097/TP.0000000000004975.
  
  Tedeschi Andrea, Ianni Umberto, Gentile Piero, Palazzini Matteo, Masciocco Gabriella, Ammirati Enrico, Garascia Andrea
  
  
  
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• Heart Failure Management through Telehealth: Expanding Care and Connecting Hearts.
  J Clin Med

  2024 Apr;13(9):. doi: 2592.
  
  Tedeschi Andrea, Palazzini Matteo, Trimarchi Giancarlo, Conti Nicolina, Di Spigno Francesco, Gentile Piero, D'Angelo Luciana, Garascia Andrea, Ammirati Enrico, Morici Nuccia, Aschieri Daniela
  
  Abstract
  
  Heart failure (HF) is a leading cause of morbidity worldwide, imposing a significant burden on deaths, hospitalizations, and health costs. Anticipating patients' deterioration is a cornerstone of HF treatment: preventing congestion and end organ damage while titrating HF therapies is the aim of the majority of clinical trials. Anyway, real-life medicine struggles with resource optimization, often reducing the chances of providing a patient-tailored follow-up. Telehealth holds the potential to drive substantial qualitative improvement in clinical practice through the development of patient-centered care, facilitating resource optimization, leading to decreased outpatient visits, hospitalizations, and lengths of hospital stays. Different technologies are rising to offer the best possible care to many subsets of patients, facing any stage of HF, and challenging extreme scenarios such as heart transplantation and ventricular assist devices. This article aims to thoroughly examine the potential advantages and obstacles presented by both existing and emerging telehealth technologies, including artificial intelligence.
  
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• [The IN-HF Registry: the history and the scientific production for the Italian cardiology community].
  G Ital Cardiol (Rome)

  2024 May;25(5):301-308. doi: 10.1714/4252.42293.
  
  Rizzello Vittoria, Tinti Maria Denitza, Gori Mauro, Marini Marco, Palmieri Vittorio, De Gennaro Luisa, Manca Paolo, Matassini Maria Vittoria, Di Nora Concetta, Bianco Matteo, Carigi Samuela, Gentile Piero, Leonardi Giuseppe, Orso Francesco, Gorini Marco, Gonzini Lucio, Lucci Donata, Maggioni Aldo Pietro, De Maria Renata, Tavazzi Luigi
  
  Abstract
  
  The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.
  
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• SARS-CoV2 infections in heart transplant recipients: Vaccines still are our greatest weapon.
  Int J Cardiol Heart Vasc

  2024 Apr;51():101379. doi: 101379.
  
  Tedeschi Andrea, Gentile Piero, Palazzini Matteo, Masciocco Gabriella, Leidi Filippo, Monticelli Massimiliano, Ammirati Enrico, Garascia Andrea
  
  
  
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• Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.
  Clin Res Cardiol

  2024 Apr;():. doi: 10.1007/s00392-024-02448-9.
  
  Toma Matteo, Savonitto Giulio, Lombardi Carlo Maria, Airò Edoardo, Driussi Mauro, Gentile Piero, Howard Luke, Moschella Martina, Di Poi Emma, Pagnesi Matteo, Monti Simonetta, Collini Valentino, D'Angelo Luciana, Vecchiato Veronica, Giannoni Alberto, Adamo Marianna, Barbisan Davide, Bauleo Carolina, Garascia Andrea, Metra Marco, Sinagra Gianfranco, Giudice Francesco Lo, Stolfo Davide, Ameri Pietro
  
  Abstract
  
  AIM:
  To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD).
  
  METHODS AND RESULTS:
  By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD.
  
  CONCLUSIONS:
  In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.
  
  © 2024. The Author(s).
  
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• Clinical characteristics, treatment, trajectories and outcome of patients with dilated cardiomyopathy in a national heart failure registry.
  Int J Cardiol

  2024 Jul;407():131986. doi: 10.1016/j.ijcard.2024.131986.
  
  Carigi Samuela, Gentile Piero, Gori Mauro, Tinti Denitza, De Gennaro Luisa, Leonardi Giuseppe, Orso Francesco, Felici Anna Rita, Catalano Maria Rosaria, Floresta Marina, Rizzello Vittoria, Lucci Donata, Gonzini Lucio, De Maria Renata, Marini Marco,
  
  Abstract
  
  BACKGROUND:
  Available data on the clinical characteristics and prognosis of patients with heart failure (HF) due to dilated cardiomyopathy (DCM) derive mainly from tertiary care centres for cardiomyopathies or from drug trial sub-studies, which may entail a referral bias.
  
  METHODS:
  From 2008 to 2021, we enrolled in a nationwide HF Registry 1886 DCM patients and 3899 with ischemic heart disease (IHD).
  
  RESULTS:
  Patients with DCM were younger, more often female, had more commonly recent onset HF, left bundle branch block, and showed higher LV end-diastolic volume and lower LVEF than IHD. With respect to IHD, DCM patients received more often mineralocorticoid receptor antagonists, renin angiotensin system inhibitors and betablockers, the latter more commonly at doses ?50% of target, and triple guideline-directed medical therapy (GDMT) (adjusted OR 1.411, 95% CI 1.247-1.595, p 40% (p 
  CONCLUSIONS:
  DCM patients have a different clinical profile, greater uptake of GDMT and better outcomes than IHD subjects. A comprehensive management approach is needed to further address the risk of unfavorable outcomes in DCM.
  
  Copyright © 2024 Elsevier B.V. All rights reserved.
  
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• Current Treatment and Immunomodulation Strategies in Acute Myocarditis.
  J Cardiovasc Pharmacol

  2024 May;83(5):364-376. doi: 10.1097/FJC.0000000000001542.
  
  Ferone Emma, Segev Amitai, Tempo Erika, Gentile Piero, Elsanhoury Ahmed, Baggio Chiara, Artico Jessica, Bhatti Prashan, Scott Paul, Bobbio Emanuele, Merlo Marco, Ameri Pietro, Sinagra Gianfranco, Tschöpe Carsten, Bromage Daniel, Cannata Antonio
  
  Abstract
  
  Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.
  
  Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
  
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• Estimation of Right Atrial Pressure by Ultrasound-Assessed Jugular Vein Distensibility in Patients With Heart Failure.
  Circ Heart Fail

  2024 Feb;17(2):e010973. doi: 10.1161/CIRCHEARTFAILURE.123.010973.
  
  Ammirati Enrico, Marchetti Davide, Colombo Giada, Pellicori Pierpaolo, Gentile Piero, D'Angelo Luciana, Masciocco Gabriella, Verde Alessandro, Macera Francesca, Brunelli Dario, Occhi Lucia, Musca Francesco, Perna Enrico, Bernasconi Davide P, Moreo Antonella, Camici Paolo G, Metra Marco, Oliva Fabrizio, Garascia Andrea
  
  Abstract
  
  BACKGROUND:
  Clinical evaluation of central venous pressure is difficult, depends on experience, and is often inaccurate in patients with chronic advanced heart failure. We assessed the ultrasound-assessed internal jugular vein (JV) distensibility by ultrasound as a noninvasive tool to identify patients with normal right atrial pressure (RAP ?7 mm?Hg) in this population.
  
  METHODS:
  We measured JV distensibility as the Valsalva-to-rest ratio of the vein diameter in a calibration cohort (N=100) and a validation cohort (N=101) of consecutive patients with chronic heart failure with reduced ejection fraction who underwent pulmonary artery catheterization for advanced heart failure therapies workup.
  
  RESULTS:
  A JV distensibility threshold of 1.6 was identified as the most accurate to discriminate between patients with RAP ?7 versus >7 mm?Hg (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.64-0.84]) and confirmed in the validation cohort (receiver operating characteristic, 0.82 [95% CI, 0.73-0.92]). A JV distensibility ratio >1.6 had predictive positive values of 0.86 and 0.94, respectively, to identify patients with RAP ?7 mm?Hg in the calibration and validation cohorts. Compared with patients from the calibration cohort with a high JV distensibility ratio (>1.6; n=42; median RAP, 4 mm?Hg; pulmonary capillary wedge pressure, 11 mm?Hg), those with a low JV distensibility ratio (?1.6; n=58; median RAP, 8 mm?Hg; pulmonary capillary wedge pressure, 22 mm?Hg;
  CONCLUSIONS:
  Ultrasound-assessed JV distensibility identifies patients with chronic advanced heart failure with normal RAP and better outcomes.
  
  REGISTRATION:
  URL: https://www.clinicaltrials.gov; Unique identifier: NCT03874312.
  
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• [Pulmonary hypertension associated with left heart diseases: pathophysiology, diagnosis, treatment].
  G Ital Cardiol (Rome)

  2024 Feb;25(2):88-97. doi: 10.1714/4187.41757.
  
  Caravita Sergio, Gori Mauro, Garascia Andrea, Baratto Claudia, Camassa Nino, Carigi Samuela, De Gennaro Luisa, De Maria Renata, Enea Iolanda, Gentile Piero, Giordana Francesca, Leonardi Giuseppe, Lo Giudice Francesco, Orso Francesco, Romaniello Antonella, Roncon Loris, Tinti Maria Denitza, Vatrano Marco, Vedovati Maria Cristina, Marini Marco, Picariello Claudio
  
  Abstract
  
  Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure. Left atrial hypertension is the initial driver of post-capillary PH. However, several mechanisms may lead in a subset of patients to structural changes in the pulmonary vessels with development of a pre-capillary component. The right ventricle may be frequently affected, leading to right ventricular failure and a worse outcome. The differential diagnosis of PH associated with left heart disease vs pulmonary arterial hypertension (PAH) is challenging in patients with cardiovascular comorbidities, risk factors for PAH and/or a preserved left ventricular ejection fraction. Multidimensional clinical phenotyping is needed to identify patients in whom hemodynamic confirmation is deemed necessary, that may be completed by provocative testing in the cath lab. In contrast with PAH, management of PH associated with left heart disease should focus on the treatment of the underlying condition. There is currently no approved therapy for PH associated with left heart disease: some PAH-specific treatments have led to an increase in adverse events in these patients.
  
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• Biomarkers in Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Updated Review of the Literature.
  J Clin Med

  2023 Nov;12(23):. doi: 7214.
  
  Crisci Giulia, Bobbio Emanuele, Gentile Piero, Bromage Daniel I, Bollano Entela, Ferone Emma, Israr Muhammad Zubair, Heaney Liam M, Polte Christian L, Cannatà Antonio, Salzano Andrea
  
  Abstract
  
  Myocarditis is a disease caused by cardiac inflammation that can progress to dilated cardiomyopathy, heart failure, and eventually death. Several etiologies, including autoimmune, drug-induced, and infectious, lead to inflammation, which causes damage to the myocardium, followed by remodeling and fibrosis. Although there has been an increasing understanding of pathophysiology, early and accurate diagnosis, and effective treatment remain challenging due to the high heterogeneity. As a result, many patients have poor prognosis, with those surviving at risk of long-term sequelae. Current diagnostic methods, including imaging and endomyocardial biopsy, are, at times, expensive, invasive, and not always performed early enough to affect disease progression. Therefore, the identification of accurate, cost-effective, and prognostically informative biomarkers is critical for screening and treatment. The review then focuses on the biomarkers currently associated with these conditions, which have been extensively studied via blood tests and imaging techniques. The information within this review was retrieved through extensive literature research conducted on major publicly accessible databases and has been collated and revised by an international panel of experts. The biomarkers discussed in the article have shown great promise in clinical research studies and provide clinicians with essential tools for early diagnosis and improved outcomes.
  
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• Editorial: Myocarditis and inflammatory cardiomyopathies: diagnosis, treatment and future directions.
  Front Cardiovasc Med

  2023 ;10():1321494. doi: 1321494.
  
  Gentile Piero, Bollano Entela, Vergaro Giuseppe, Bobbio Emanuele
  
  
  
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• Intravenous continuous home inotropic therapy in advanced heart failure: Insights from an observational retrospective study.
  Eur J Intern Med

  2023 Oct;116():65-71. doi: 10.1016/j.ejim.2023.06.010.
  
  Gentile Piero, Masciocco Gabriella, Palazzini Matteo, Tedeschi Andrea, Ruzzenenti Giacomo, Conti Nicolina, D'Angelo Luciana, Foti Grazia, Perna Enrico, Verde Alessandro, Ammirati Enrico, Sinagra Gianfranco, Oliva Fabrizio, Garascia Andrea
  
  Abstract
  
  INTRODUCTION:
  Intravenous inotropic support represents an important therapeutic option in advanced heart failure (HF) as bridge to heart transplantation, bridge to mechanical circulatory support, bridge to candidacy or as palliative therapy. Nevertheless, evidence regarding risks and benefits of its use is lacking.
  
  METHODS:
  we conducted a retrospective single center study, analysing the effect of inotropic therapies in an outpatient cohort, evaluating the burden of hospitalizations, the improvement in quality of life, the incidence of adverse events and the evolution of organ damage.
  
  RESULTS:
  twenty-seven patients with advanced HF were treated in our Day Hospital service from 2014 to 2021. Nine patients were treated as bridge to heart transplant while eighteen as palliation. Comparing data regarding the year before and after the beginning of inotropic infusion, we observed a reduction of hospitalization (46 vs 25, p
  CONCLUSIONS:
  in a selected population of advanced HF patients, continuous home inotropic infusion were able to reduce hospitalizations, improving end organ damage and quality of life. We provide a practical guidance on starting and maintaining home inotropic infusion while monitoring a challenging group of patients.
  
  Copyright © 2023. Published by Elsevier B.V.
  
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• Outcome and Morphofunctional Changes on Cardiac Magnetic Resonance in Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination.
  Circ Heart Fail

  2023 Jun;16(6):e010315. doi: 10.1161/CIRCHEARTFAILURE.122.010315.
  
  Ammirati Enrico, Lupi Laura, Palazzini Matteo, Ciabatti Michele, Rossi Valentina A, Gentile Piero, Uribarri Aitor, Vecchio Chiara R, Nassiacos Daniele, Cereda Alberto, Conca Cristina, Tumminello Gabriele, Piriou Nicolas, Lelarge Coline, Pedrotti Patrizia, Stucchi Miriam, Peretto Giovanni, Galasso Michele, Huang Florent, Ianni Umberto, Procopio Antonio, Saponara Gianluigi, Cimaglia Paolo, Tomasoni Daniela, Moroni Francesco, Turco Annalisa, Sala Simone, Di Tano Giuseppe, Bollano Entela, Moro Claudio, Abbate Antonio, Della Bona Roberta, Porto Italo, Carugo Stefano, Campodonico Jeness, Pontone Gianluca, Grosu Aurelia, Bolognese Leonardo, Salamanca Jorge, Diez-Villanueva Pablo, Ozieranski Krzysztof, Tyminska Agata, Sardo Infirri Loren, Bromage Daniel, Cannatà Antonio, Hong Kimberly N, Adamo Marianna, Quattrocchi Giuseppina, Foà Alberto, Potena Luciano, Garascia Andrea, Giannattasio Cristina, Adler Eric D, Sinagra Gianfranco, Ruschitzka Frank, Camici Paolo G, Metra Marco, Pieroni Maurizio
  
  
  
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• Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.
  Int J Cardiol

  2023 Jul;383():82-88. doi: 10.1016/j.ijcard.2023.05.004.
  
  De Angelis Elena, Bochaton Thomas, Ammirati Enrico, Tedeschi Andrea, Polito Maria Vincenza, Pieroni Maurizio, Merlo Marco, Gentile Piero, Van De Heyning Caroline M, Bekelaar Thalia, Cipriani Alberto, Camilli Massimiliano, Sanna Tommaso, Marra Martina Perazzolo, Cabassi Aderville, Piepoli Massimo F, Sinagra Gianfranco, Mewton Nathan, Bonnefoy-Cudraz Eric, Ravera Amelia, Hayek Ahmad
  
  Abstract
  
  OBJECTIVE:
  There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS.
  
  METHODS:
  We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS.
  
  RESULTS:
  Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days.
  
  CONCLUSIONS:
  PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.
  
  Copyright © 2023 Elsevier B.V. All rights reserved.
  
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• Advanced heart failure: from definitions to therapeutic options.
  Eur Heart J Suppl

  2023 May;25(Suppl C):C283-C291. doi: 10.1093/eurheartjsupp/suad028.
  
  Garascia Andrea, Palazzini Matteo, Tedeschi Andrea, Sacco Alice, Oliva Fabrizio, Gentile Piero
  
  Abstract
  
  Advanced heart failure (AHF) represents an ominous stage of heart failure (HF), where the expected prognosis remains poor regardless of the improvement in medical knowledge. In this review, we summarize the definition, prognosis, physiopathology, and clinical/therapeutic management of the disease, focusing on the fast and timely referral of the patient to the AHF facilities. We provide an insight of the diagnostic and therapeutic 'work up' performed in an Italian AHF hub, implying a deep phenotypical patients characterization in order to evaluate candidacy to the therapeutic gold standards as heart transplantation (HTx) and left ventricular assist device (LVAD).
  
  © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
  
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• Immune checkpoint inhibitor-associated myocarditis: from pathophysiology to rechallenge of therapy - a narrative review.
  Future Cardiol

  2023 Feb;19(2):91-103. doi: 10.2217/fca-2022-0120.
  
  Tedeschi Andrea, Camilli Massimiliano, Ammirati Enrico, Gentile Piero, Palazzini Matteo, Conti Nicolina, Verde Alessandro, Masciocco Gabriella, Foti Grazia, Giannattasio Cristina, Garascia Andrea
  
  Abstract
  
  Even if immune checkpoint inhibitors have revolutionized the landscape of cancer therapy, their use may be complicated by immune-related adverse events. Among these, myocarditis is the most severe complication. The clinical suspicion often arises after clinical symptoms onset and increase in cardiac biomarkers or electrocardiographic manifestations. Echocardiography and cardiac magnetic resonance imaging are recommended for each patient. However, since they may be misleadingly normal, endomyocardial biopsy remains the gold standard for establishing the diagnosis. Until now, treatment has been based on glucocorticoids even if increasing interest has risen in other immunosuppressive agents. Although myocarditis currently imposes immunotherapy discontinuation, case reports have suggested a safety rechallenge in low-grade myocarditis paving the way for further studies to respond to this unmet clinical need.
  
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• Performance of risk stratification scores and role of comorbidities in older vs younger patients with pulmonary arterial hypertension.
  J Heart Lung Transplant

  2023 Aug;42(8):1082-1092. doi: 10.1016/j.healun.2023.02.1707.
  
  Stolfo Davide, Barbisan Davide, Ameri Pietro, Lombardi Carlo Mario, Monti Simonetta, Driussi Mauro, Zovatto Isabella Carlotta, Gentile Piero, Howard Luke, Toma Matteo, Pagnesi Matteo, Collini Valentino, Bauleo Carolina, Guglielmi Giulia, Adamo Marianna, D'Angelo Luciana, Nalli Chiara, Sciarrone Paolo, Moschella Martina, Zorzi Barbara, Vecchiato Veronica, Milani Martina, Di Poi Emma, Airò Edoardo, Metra Marco, Garascia Andrea, Sinagra Gianfranco, Lo Giudice Francesco
  
  Abstract
  
  BACKGROUND:
  Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown.
  
  METHODS:
  Patients with PAH enrolled from 2001 to 2021 were divided in ?65 years old vs
  RESULTS:
  Among 383 patients, 152 (40%) were ?65 years old. They had more comorbidities (number of comorbidities 2, IQR 1-3, vs 1, IQR 0-2 in
  CONCLUSIONS:
  Risk scores have similar accuracy in the prognostic stratification of older vs younger PAH patients. REVEAL 2.0 had the best performance in older patients and COMPERA 2.0 had it in younger patients. Comorbidities increased the accuracy of risk scores only in younger patients.
  
  Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
  
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• [Heart failure with improved ejection fraction: practical guidance for the clinician].
  G Ital Cardiol (Rome)

  2022 Dec;23(12):924-931. doi: 10.1714/3913.38959.
  
  Gori Mauro, Tinti Maria Denitza, Gentile Piero, De Maria Renata, Carigi Samuela, De Gennaro Luisa, Leonardi Giuseppe, Orso Francesco, Navazio Alessandro, Marini Marco, Gabrielli Domenico, Oliva Fabrizio, Colivicchi Furio
  
  Abstract
  
  Heart failure with improved ejection fraction (HFimpEF) represents a nosological entity that has recently been recognized and has little evidence from the literature. Available data indicate an increasing incidence of this patient group, consistent with the progressive improvement and implementation of medical therapy of heart failure with reduced ejection fraction (HFrEF). Furthermore, it is important to underline that the therapy itself should not be suspended after ejection fraction recovery, to avoid the recurrence of worse systolic dysfunction and patient outcomes. Only recently a randomized clinical study has been published, which enrolled also this patient subgroup, the DELIVER trial. Other data will soon become available, given the interest of the scientific community for this subgroup of patients, whose best management remains controversial. Since many studies suggest that the probability of myocardial recovery in HFrEF patients might be as high as 40%, depending on the case series taken into account, whereas the time to recovery might even be 12 months, the appropriate timing of device implantation, such as the defibrillator, in this setting deserves careful consideration.
  
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• [Ten questions on cardiac magnetic resonance in patients with heart failure: from etiological diagnosis to prognostic stratification].
  G Ital Cardiol (Rome)

  2022 Dec;23(12):912-923. doi: 10.1714/3913.38958.
  
  Carigi Samuela, De Gennaro Luisa, Gentile Piero, De Maria Renata, Di Giannuario Giovanna, Khoury Georgette, Polizzi Vincenzo, Gori Mauro, Orso Francesco, Tinti Maria Denitza, Leonardi Giuseppe, D'Andrea Antonello, Mantovani Francesca, Pergola Valeria, Rabia Granit, Gimelli Alessia, Rizzo Massimiliano, Campana Marco, Marini Marco, Oliva Fabrizio, Colivicchi Furio
  
  Abstract
  
  Cardiac magnetic resonance (CMR) imaging has progressively become part of the imaging methods recommended in patients with heart failure. CMR represents the gold standard for assessing volumes, function, biventricular kinetics and providing tissue characterization through scans with and without contrast medium. In patients with heart failure with reduced ejection fraction (HFrEF) and ischemic dilated cardiomyopathy, CMR allows to search for viability, accurately estimate volumes and ejection fraction. It can assess scar extent for predicting response to cardiac resynchronization therapy and for establishing an indication for implanting a defibrillator in borderline cases. In patients with HFrEF and non-ischemic dilated cardiomyopathy, CMR helps to identify specific etiological subgroups and to estimate the arrhythmic risk beyond ejection fraction. In patients with heart failure with preserved ejection fraction, CMR offers the possibility of diagnosing specific phenotypes, including sarcomeric hypertrophic cardiomyopathy, amyloidosis or Fabry disease, and adds prognostic information. Both clinical and scientific interest in this imaging method is constantly expanding; the clinicians dealing with heart failure cannot fail to know the technique, the indications and all the potential that CMR can offer.
  
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• Combined Neuro-Humoral Modulation and Outcomes in Patients with Chronic Heart Failure and Mildly Reduced or Preserved Ejection Fraction.
  J Clin Med

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

  2022 Nov;24(Suppl I):I111-I113. doi: 10.1093/eurheartjsupp/suac083.
  
  Gentile Piero, Palazzini Matteo, Garascia Andrea, Oliva Fabrizio
  
  Abstract
  
  Proteomics in heart failure (HF) is aimed to study and identify proteins involved in the pathophysiology of this clinical syndrome. Proteins have a role as diagnostic, prognostic and therapeutic markers. This review will unravel the developments and impact of proteomics in HF, focusing on its role in the diagnosis, prognosis and definition of new HF therapies. Proteomics promises to change our approach to HF in the near future, accepting the need for precision medicine, tailored on the characteristics of the single patient.
  
  © The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.
  
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• Acute Myocarditis Associated With Desmosomal Gene Variants.
  JACC Heart Fail

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

  2023 Mar;112(3):392-400. doi: 10.1007/s00392-022-02103-1.
  
  Peretto Giovanni, Merlo Marco, Gentile Piero, Porcari Aldostefano, Palmisano Anna, Vignale Davide, Sormani Paola, Rizzo Stefania, De Gaspari Monica, Basso Cristina, Bella Paolo Della, Sala Simone, Ammirati Enrico, Sinagra Gianfranco, Esposito Antonio, Pedrotti Patrizia
  
  Abstract
  
  BACKGROUND:
  Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB).
  
  METHODS:
  From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM.
  
  RESULTS:
  Among 74 patients [mean age 38?±?15 years, 65% males, left ventricular ejection fraction (LVEF) 40?±?18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p?0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p?=?0.006).
  
  CONCLUSION:
  In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.
  
  © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
  
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• Cardiovascular Damage in COVID-19: What We Know Two Years Later.
  Curr Cardiol Rep

  2022 Sep;24(9):1085-1091. doi: 10.1007/s11886-022-01730-4.
  
  Nuzzi Vincenzo, Del Mestre Eva, Degrassi Alessia, Bromage Daniel I, Manca Paolo, Piper Susan, Artico Jessica, Gentile Piero, Scott Paul A, Chiatto Mario, Merlo Marco, Pareek Nilesh, Giacca Mauro, Sinagra Gianfranco, McDonagh Theresa A, Cannata Antonio
  
  Abstract
  
  PURPOSE OF THE REVIEW:
  The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting.
  
  RECENT FINDINGS:
  The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications.
  
  © 2022. The Author(s).
  
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• Takotsubo syndrome after BNT162b2 mRNA Covid-19 vaccine: Emotional or causative relationship with vaccination?
  Int J Cardiol Heart Vasc

  2022 Jun;40():101002. doi: 101002.
  
  Tedeschi Andrea, Camilli Massimiliano, Ianni Umberto, Tavecchia Giovanni, Palazzini Matteo, Cartella Iside, Gentile Piero, Quattrocchi Giuseppina, Maria Spanò Francesca, Cipriani Manlio, Garascia Andrea, Ammirati Enrico
  
  
  
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• Haemodynamic effects of sacubitril/valsartan in advanced heart failure.
  ESC Heart Fail

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

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

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

  2021 Feb;324():108-114. doi: 10.1016/j.ijcard.2020.09.036.
  
  Paldino Alessia, De Angelis Giulia, Dal Ferro Matteo, Faganello Giorgio, Porcari Aldostefano, Barbati Giulia, Korcova Renata, Gentile Piero, Artico Jessica, Cannatà Antonio, Gigli Marta, Pinamonti Bruno, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  The early diagnosis of genetically determined dilated cardiomyopathy (DCM) could improve the prognosis in mutation carriers. Left ventricular global longitudinal strain (LV GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of subtle systolic and diastolic dysfunction. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives.
  
  METHODS AND RESULTS:
  In this retrospective study, we analyzed echocardiograms of forty-one GPFN relatives of DCM patients. They were compared with age and sex matched healthy individuals (control group). Reduced LV GLS and PALS were defined as >18% and
  CONCLUSIONS:
  Despite standard echocardiographic parameters are within the normal range, LV GLS and PALS are lower in GPFN relatives of DCM patients when compared to healthy individuals, suggesting a consistent proportion of subtle systolic and diastolic dysfunction in this population.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Sex-Specific Prognostic Implications in Dilated Cardiomyopathy After Left Ventricular Reverse Remodeling.
  J Clin Med

  2020 Jul;9(8):. doi: 2426.
  
  Cannata Antonio, Manca Paolo, Nuzzi Vincenzo, Gregorio Caterina, Artico Jessica, Gentile Piero, Pio Loco Carola, Ramani Federica, Barbati Giulia, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  Women affected by Dilated Cardiomyopathy (DCM) experience better outcomes compared to men. Whether a more pronounced Left Ventricular Reverse Remodelling (LVRR) might explain this is still unknown.
  
  AIM:
  We investigated the relationship between LVRR and sex and its long-term outcomes.
  
  METHODS:
  A cohort of 605 DCM patients with available follow-up data was consecutively enrolled. LVRR was defined, at 24-month follow-up evaluation, as an increase in left ventricular ejection fraction (LVEF) ? 10% or a LVEF > 50% and a decrease ? 10% in indexed left ventricular end-diastolic diameter (LVEDDi) or an LVEDDi ? 33 mm/m. Outcome measures were a composite of all-cause mortality/heart transplantation (HTx) or ventricular assist device (VAD) and a composite of Sudden Cardiac Death (SCD) or Major Ventricular Arrhythmias (MVA).
  
  RESULTS:
  181 patients (30%) experienced LVRR. The cumulative incidence of LVRR at 24-months evaluation was comparable between sexes (33% vs. 29%; = 0.26). During a median follow-up of 149 months, women experiencing LVRR had the lowest rate of main outcome measure (global = 0.03) with a 71% relative risk reduction compared to men with LVRR, without significant difference between women without LVRR and males. A trend towards the same results was found regarding SCD/MVA (global = 0.06). Applying a multi-state model, male sex emerged as an independent adverse prognostic factor even after LVRR completion.
  
  CONCLUSIONS:
  Although the rate of LVRR was comparable between sexes, females experiencing LVRR showed the best outcomes in the long term follow up compared to males and females without LVRR. Further studies are advocated to explain this difference in outcomes between sexes.
  
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• Viral presence-guided immunomodulation in lymphocytic myocarditis: an update.
  Eur J Heart Fail

  2021 Feb;23(2):211-216. doi: 10.1002/ejhf.1969.
  
  Sinagra Gianfranco, Porcari Aldostefano, Gentile Piero, Artico Jessica, Fabris Enrico, Bussani Rossana, Merlo Marco
  
  Abstract
  
  Latest statements from European and American societies recommend to rule out viral presence in endomyocardial biopsy (EMB) via polymerase chain reaction (PCR) analysis before starting immunosuppression or immunomodulation in acute lymphocytic myocarditis presenting with life-threatening scenarios. However, recommendations in myocarditis are mostly based on heterogeneous studies enrolling patients with inflammatory cardiomyopathies and established heart failure rather than acute myocarditis. Thus, definitive evidence of a survival benefit from immunomodulation guided by viral presence is currently lacking. Finally, distinguishing innocent bystanders from causative agents among EMB-detected viruses remain challenging and a major goal to achieve in the near future. Therefore, considerable divergence remains between official recommendations and clinical practice, including the possibility of starting immunosuppressive therapy empirically, without knowing viral PCR results. This review systematically discusses the unsolved issues of immunomodulation guided by viral presence in acute lymphocytic myocarditis, namely (i) virus epidemiology and prognosis, (ii) variability of viral presence rates, (iii) the role of potential viral bystander findings, and (iv) the main results of immunosuppression controlled trials in lymphocytic myocarditis. Furthermore, a practical approach for the critical use of viral presence analysis in guiding immunomodulation is provided, highlighting its importance before starting immunosuppression or immunomodulation. Future, multicentre?studies are needed to address specific scenarios such as fulminant lymphocytic myocarditis and a virus-tailored management as for parvovirus B19.
  
  © 2020 European Society of Cardiology.
  
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• Lymphocytic Myocarditis: A Genetically Predisposed Disease?
  J Am Coll Cardiol

  2020 Jun;75(24):3098-3100. doi: 10.1016/j.jacc.2020.04.048.
  
  Artico Jessica, Merlo Marco, Delcaro Giulia, Cannatà Antonio, Gentile Piero, De Angelis Giulia, Paldino Alessia, Bussani Rossana, Ferro Matteo Dal, Sinagra Gianfranco
  
  
  
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• Echocardiographic evaluation of centenarians in Trieste.
  J Cardiovasc Med (Hagerstown)

  2020 Aug;21(8):556-561. doi: 10.2459/JCM.0000000000000984.
  
  Cannatà Antonio, Gentile Piero, Paldino Alessia, Nuzzi Vincenzo, Camparini Luca, Ciucci Giulio, Manca Paolo, Artico Jessica, Dal Ferro Matteo, Marcon Gabriella, Tettamanti Mauro, Merlo Marco, Sinagra Gianfranco, Loffredo Francesco S
  
  Abstract
  
  BACKGROUND:
  Population aging has increased together with the need for cardiovascular care. Understanding the relevance of cardiovascular conditions in the very old is crucial to developing a specific and rationale therapeutic approach. Centenarians can be considered a model of successful aging, although the impact of cardiovascular disease in this population is still unclear.
  
  AIM:
  To evaluate the cardiovascular health status of a subset of centenarians enrolled in the Centenari a Trieste study and living in the province of Trieste to describe the prevalence of cardiovascular conditions among them.
  
  METHODS:
  The current study included 20 individuals born before 1919 and living in the province of Trieste as of 1 May 2019. All centenarians were able to give consent and were subjected to an in-home complete clinical assessment focused on cardiovascular conditions, ECG and echocardiography.
  
  RESULTS:
  The majority of centenarians were women (85%) and were not taking any chronic cardiovascular medication (55%). No centenarians had a history of ischemic heart disease while about one-third had signs suggestive of heart failure at examination (20%). Atrial fibrillation was present in 20% of individuals and conduction disorders were uncommon. Although the majority of individuals had a preserved left ventricular function, diastolic function was abnormal in 80% of enrolled centenarians that, however, was mild in 73% of cases.
  
  CONCLUSION:
  This is the second study to perform in-home echocardiography in centenarians and the first to characterize the cardiovascular status of centenarians living in Trieste. The majority of centenarians had asymptomatic diastolic dysfunction and were naïve from cardiovascular therapy. The recruitment of new individuals from the Trieste area is continuing to perform analyses on clinical, genetic and environmental factors that may predict greater longevity in this geographical context and unveil mechanisms that regulate cardiac aging associated with increased lifespan.
  
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• Contemporary survival trends and aetiological characterization in non-ischaemic dilated cardiomyopathy.
  Eur J Heart Fail

  2020 Jul;22(7):1111-1121. doi: 10.1002/ejhf.1914.
  
  Merlo Marco, Cannatà Antonio, Pio Loco Carola, Stolfo Davide, Barbati Giulia, Artico Jessica, Gentile Piero, De Paris Valerio, Ramani Federica, Zecchin Massimo, Gigli Marta, Pinamonti Bruno, Korcova Renata, Di Lenarda Andrea, Giacca Mauro, Mestroni Luisa, Camici Paolo G, Sinagra Gianfranco
  
  Abstract
  
  AIM:
  Contemporary survival trends in dilated cardiomyopathy (DCM) are largely unknown. The aim of this study is to investigate clinical descriptors, survival trends and the prognostic impact of aetiological characterization in DCM patients.
  
  METHODS AND RESULTS:
  Dilated cardiomyopathy patients were consecutively enrolled and divided into four groups according to the period of enrolment (1978-1984; 1985-1994; 1995-2004; and 2005-2015). A subset of patients with DCM of specific aetiology, enrolled from 2005 to 2015, was also analysed. Over a mean follow-up of 12?±?8?years, 1284 DCM patients (52 in the 1978-1984 group, 326 in the 1985-1994 group, 379 in the 1995-2004 group, and 527 in the 2005-2015 group) were evaluated. Despite older age (mean age 51?±?15, 43?±?15, 45?±?14, and 52?±?15?years for the 1978-1984, 1985-1994, 1995-2004, and 2005-2015 groups, respectively; P?0.001), most of the baseline clinical characteristics improved in the 2005-2015 group, suggesting a less advanced disease stage at diagnosis. Similarly, at competing risk analysis, the annual incidence of all outcome parameters progressively decreased over time (global P?0.001). At multivariable analysis, the last period of enrolment emerged as independently associated with a reduction in all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD) implantation (1.46 events/100 patients/year), cardiovascular death/HTx/VAD implantation (0.82 events/100 patients/year) and sudden cardiac death (0.15 events/100 patients/year). Lastly, in 287 patients with DCM of specific aetiology, patients with environmental, toxic, or removable factors appeared to have different phenotypes and prognosis compared to those with genetic, post-myocarditis, or idiopathic DCM (P?0.001).
  
  CONCLUSIONS:
  Contemporary survival trends in DCM significantly improved, mainly due to a reduction of cardiovascular events. Appropriate aetiological characterization might help in prognostication of DCM patients.
  
  © 2020 European Society of Cardiology.
  
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• Long-term prognostic role of diabetes mellitus and glycemic control in heart failure patients with reduced ejection fraction: Insights from the MECKI Score database.
  Int J Cardiol

  2020 Oct;317():103-110. doi: 10.1016/j.ijcard.2020.04.079.
  
  Paolillo Stefania, Salvioni Elisabetta, Perrone Filardi Pasquale, Bonomi Alice, Sinagra Gianfranco, Gentile Piero, Gargiulo Paola, Scoccia Alessandra, Cosentino Nicola, Gugliandolo Paola, Badagliacca Roberto, Lagioia Rocco, Correale Michele, Frigerio Maria, Perna Enrico, Piepoli Massimo, Re Federica, Raimondo Rosa, Minà Chiara, Clemenza Francesco, Bussotti Maurizio, Limongelli Giuseppe, Gravino Rita, Passantino Andrea, Magrì Damiano, Parati Gianfranco, Caravita Sergio, Scardovi Angela B, Arcari Luca, Vignati Carlo, Mapelli Massimo, Cattadori Gaia, Cavaliere Carlo, Corrà Ugo, Agostoni Piergiuseppe,
  
  Abstract
  
  BACKGROUND:
  The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population.
  
  METHODS:
  3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70-6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): 8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death.
  
  RESULTS:
  For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p 
  CONCLUSION:
  In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Acute inflammatory cardiomyopathy: apparent neutral prognostic impact of immunosuppressive therapy.
  Eur J Heart Fail

  2020 Jul;22(7):1280-1282. doi: 10.1002/ejhf.1821.
  
  Merlo Marco, Gentile Piero, Ballaben Andrea, Artico Jessica, Castrichini Matteo, Porcari Aldostefano, Cannatà Antonio, Perkan Andrea, Bussani Rossana, Sinagra Gianfranco
  
  
  
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• Tissue Doppler indices of diastolic function as prognosticator in patients without heart failure in primary care.
  J Cardiol

  2020 Jul;76(1):18-24. doi: 10.1016/j.jjcc.2020.01.015.
  
  Nistri Stefano, Mazzone Carmine, Cioffi Giovanni, Barbati Giulia, Gentile Piero, Ballo Piercarlo, Borca Endria Casanova, Faganello Giorgio, Cherubini Antonella, Bussani Rossana, Sinagra Gianfranco, Di Lenarda Andrea
  
  Abstract
  
  BACKGROUND:
  Tissue Doppler imaging (TDI) indices of left ventricular (LV) diastolic function provide incremental prognostic information on mortality and morbidity in the general population and in several clinical scenarios. Their independent, additional role in outpatients with normal LV ejection fraction (LVEF) and without heart failure (HF) is undefined.
  
  METHODS:
  We reviewed clinical and echocardiographic records of 2628 consecutive outpatients 52.8% male, median age 71 years) with LVEF > 50% without concurrent or prior HF, from the Cardiovascular Center of Trieste. We analyzed septal early mitral annular velocity (e') and its combination with mitral peak early filling velocity (E/e') in relation to the composite end-point of death and cardiovascular hospitalizations.
  
  RESULTS:
  During follow-up of 26 months (interquartile range: 12-41), 392 (15%) patients experienced the endpoint (88 deaths). Increasing E/e' showed an overall association with the clinical end-point (log rank p 
  CONCLUSIONS:
  In outpatients with normal LVEF and without HF, e' and E/e' are both associated with clinical end-points, though only e' is an independent and incremental predictor of outcome. These findings suggest a potential role for e' as a prognosticator, and spread a cautionary word about the utilization of septal E/e' alone as a surrogate for a comprehensive assessment of diastolic function in this context.
  
  Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
  
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• Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy beyond ejection fraction.
  Heart

  2020 May;106(9):656-664. doi: 10.1136/heartjnl-2019-315942.
  
  Cannatà Antonio, De Angelis Giulia, Boscutti Andrea, Normand Camilla, Artico Jessica, Gentile Piero, Zecchin Massimo, Heymans Stephane, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  Sudden cardiac death and arrhythmia-related events in patients with non-ischaemic dilated cardiomyopathy (NICM) have been significantly reduced over the last couple of decades as a result of evidence-based pharmacological and non-pharmacological therapeutic strategies. Nevertheless, the arrhythmic stratification in patients with NICM remains extremely challenging, and the simple indication based on left ventricular ejection fraction appears to be insufficient. Therefore, clinicians need to go beyond the current criteria for implantable cardioverter-defibrillator implantation in the direction of a multiparametric evaluation of arrhythmic risk. Several parameters for arrhythmic risk stratification, ranging from electrocardiographic, echocardiographic, imaging-derived and genetic markers, are crucial for proper arrhythmic risk stratification and a multiparametric evaluation of risk in patients with NICM. In particular, integration of cardiac magnetic resonance parameters (mostly late gadolinium enhancement) and specific genetic information (ie, presence of mutations) appears fundamental for proper implementation of the current arrhythmic risk stratification. Finally, a novel approach focused on both arrhythmic risk and prediction of left ventricular reverse remodelling during follow-up might be useful for effective multiparametric and dynamic arrhythmic risk stratification in NICM. In the future, a complete and integrated evaluation might be mandatory to implement arrhythmic risk prediction in patients with NICM and to discriminate the competing risk between heart failure-related events and life-threatening arrhythmias.
  
  © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
  
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• Viral genome search in myocardium of patients with fulminant myocarditis.
  Eur J Heart Fail

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

  2020 Jan;36(1):37-44. doi: 10.1016/j.cjca.2019.05.031.
  
  Cannatà Antonio, Fabris Enrico, Merlo Marco, Artico Jessica, Gentile Piero, Pio Loco Carola, Ballaben Andrea, Ramani Federica, Barbati Giulia, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  Dilated cardiomyopathy (DCM) represents a specific phenotype of heart failure. Sex differences in the long-term prognosis of patients with DCM are unknown. The aim of this study is to investigate the long-term prognostic role of gender in a large cohort of patients with DCM.
  
  METHODS:
  A total of 1113 patients with DCM were prospectively enrolled. To investigate the impact of sex, a propensity score-matching analysis was performed on a sample of 586 patients. Univariable and multivariable Cox models and competing-risk analyses were estimated on both cohorts for the following outcome measures: (1) all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD); (2) cardiovascular mortality/HTx/VAD; and (3) sudden cardiac death or malignant ventricular arrhythmias.
  
  RESULTS:
  Women were older than men (50 ± 15 years vs 47 ± 15 years, respectively, P = 0.004) and more frequently had moderate to severe left ventricular dilation (P
  CONCLUSION:
  The long-term outcomes of women affected by DCM are more favourable than those of men, and sex emerged as an important independent factor, particularly for cardiovascular outcomes.
  
  Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
  
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• Dilated Cardiomyopathy With Mid-Range Ejection Fraction at Diagnosis: Characterization and Natural History.
  J Am Heart Assoc

  2019 Sep;8(17):e010705. doi: e010705.
  
  Gentile Piero, Merlo Marco, Cannatà Antonio, Gobbo Marco, Artico Jessica, Stolfo Davide, Gigli Marta, Ramani Federica, Barbati Giulia, Pinamonti Bruno, Sinagra Gianfranco
  
  Abstract
  
  Background Limited data are available on mid-range ejection fraction (mrEF) patients with dilated cardiomyopathy. We sought to define the characteristics, evolution, and long-term prognosis of dilated cardiomyopathy patients with mrEF at diagnosis. Methods and Results We analyzed all dilated cardiomyopathy patients consecutively evaluated in the Trieste Heart Muscle Disease Registry from 1988 to 2013. mrEF and reduced ejection fraction (rEF) were defined as baseline left ventricular (LV) ejection fraction values between 40% and 49% and
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• Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.
  J Am Coll Cardiol

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

  2019 Oct;293():119-124. doi: 10.1016/j.ijcard.2019.06.072.
  
  Artico Jessica, Ceolin Roberto, Franco Stefania, Paldino Alessia, Biondi Federico, Barbati Giulia, Gentile Piero, Cannatà Antonio, Zecchin Massimo, Carriere Cosimo, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  Implantable cardioverter-defibrillators (ICD) have a pivotal role in preventing major arrhythmic events in patients with severely reduced left ventricular ejection fraction (LVEF). Device replacement strategy is still controversial in patients without severely reduced left ventricular ejection fraction (LVEF) at the end of battery life.
  
  OBJECTIVE:
  To evaluate the long-term arrhythmic outcome of patients with ICD or and cardiac resynchronization therapy defibrillators (CRT-D) with normal or intermediate LVEF at the time of device replacement.
  
  METHODS:
  All consecutive patients with reduced ejection fraction heart failure, both from ischemic and non-ischemic origin, implanted with ICD or CRT-D for primary prevention from 2002 to 2009, were considered. The study population included patients without previous ICD interventions and without severe dysfunction (i.e. LVEF???35%) 60 [53-65] months after implantation (average battery duration). The outcome measure was the occurrence of appropriate ICD interventions in the long-term.
  
  RESULTS:
  Among the 255 patients (150 ICDs; 105 CRT-D) evaluated, 45 (18%) had LVEF???35% without ICD interventions 5-year follow-up after implantation (15 ICD [10%]; 30 CRT-D [29%]). In the long term, ICD interventions were 4 (27%) in the ICD group and 5 (17%) in the CRT-D group.
  
  CONCLUSIONS:
  Despite the absence of severe left ventricular dysfunction at the time of battery replacement, a not negligible number of patients with ICD and CRT-D maintained a high risk of appropriate interventions in the long term, suggesting the opportunity of replacing the ICD regardless the amount of LV dysfunction.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• 
  

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• Myocarditis evolving in cardiomyopathy: when genetics and offending causes work together.
  Eur Heart J Suppl

  2019 Mar;21(Suppl B):B90-B95. doi: 10.1093/eurheartj/suz033.
  
  Cannata' Antonio, Artico Jessica, Gentile Piero, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  Myocarditis is an infectious-inflammatory disease often superimposed to individual genetic background which could favour or inhibit its progression into a chronic heart muscle disorder (most often dilated cardiomyopathy, rarely arrhythmogenic, or right-sided cardiomyopathy). Post-myocarditis cardiomyopathy is likely caused by a complex interaction between the viral infection and an individual predisposition. Some viruses are able to highlight a clinical phenotype replicating a model similar to the genetically determined conditions, while other can affect the resolution or the progressive remodelling of the left ventricle after the infectious process. The identification of specific individual genetic backgrounds, or genes favouring the progression of the disease, are important future research goals for aiming at a specific and individualized treatment for patients affected with myocarditis.
  
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• Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors.
  PLoS One

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

  2019 May;20(5):343-350. doi: 10.2459/JCM.0000000000000792.
  
  Merlo Marco, Gentile Piero, Artico Jessica, Cannatà Antonio, Paldino Alessia, De Angelis Giulia, Barbati Giulia, Alonge Marco, Gigli Marta, Pinamonti Bruno, Ramani Federica, Zecchin Massimo, Pirozzi Fabrizio, Stolfo Davide, Sinagra Gianfranco
  
  Abstract
  
  AIMS:
  Arrhythmic risk stratification is a challenging issue in patients with dilated cardiomyopathy (DCM), particularly when left ventricular ejection fraction (LVEF) is more than 35%. We studied the prevalence and predictors of sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs) in DCM patients categorized at low arrhythmic risk because of intermediate left ventricular dysfunction under optimal medical treatment (OMT).
  
  METHODS:
  DCM patients considered at low arrhythmic risk (LVEF >35% and New York Heart Association class I-III after 6?±?3 months of OMT) were analysed. An arrhythmogenic profile was defined as the presence of at least one among a history of syncope, nonsustained ventricular tachycardia, at least 1000 premature ventricular contractions/24?h, at least 50 ventricular couplets/24?h at Holter ECG monitoring. SCD/MVAs was considered as the study end-point.
  
  RESULTS:
  During a median follow-up of 152 months (interquartile range 100-234), 30 out of 360 (8.3%) patients at low arrhythmic risk (LVEF 47?±?7%) experienced the study end-point [14 (3.9%) SCD and 16 (4.4%) MVA]. Compared with survivors, patients who experienced SCD/MVAs had more frequently an arrhythmogenic profile and a larger left atrium. Their LVEF at the last available evaluation before the arrhythmic event was 36?±?12%. At multivariable analysis, left atrial end-systolic area [hazard ratio 1.107; 95% confidence interval (95% CI) 1.039-1.179, P?=?0.002 for 1?mm increase] and arrhythmogenic profile (hazard ratio 3.667; 95% CI 1.762-7.632, P?=?0.001) emerged as predictors of SCD/MVAs during follow-up.
  
  CONCLUSION:
  A consistent quota of DCM patients with intermediate left ventricular dysfunction receiving OMT experienced SCD/MVA during follow-up. Left atrial dilatation and arrhythmogenic pattern were associated with a higher risk of SCD/MVA.
  
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• Isocapnic buffering period: From physiology to clinics.
  Eur J Prev Cardiol

  2019 Jul;26(10):1107-1114. doi: 10.1177/2047487319829950.
  
  Carriere Cosimo, Corrà Ugo, Piepoli Massimo, Bonomi Alice, Salvioni Elisabetta, Binno Simone, Magini Alessandra, Sciomer Susanna, Pezzuto Beatrice, Gentile Piero, Schina Mauro, Sinagra Gianfranco, Agostoni Piergiuseppe
  
  Abstract
  
  BACKGROUND:
  During cardiopulmonary exercise test, the isocapnic buffering period ranges between anaerobic threshold (AT) and respiratory compensation point (RCP). We investigated whether oxygen uptake (VO) increase during the isocapnic buffering period (?VOAT-RCP) is related to heart failure severity and prognosis.
  
  METHODS:
  We retrospectively analysed reduced ejection fraction heart failure patients who attained RCP at cardiopulmonary exercise test. The study endpoint was the composite of cardiovascular mortality and urgent heart transplantation/left ventricular assist device implantation. Hazard ratio was assessed to identify the increase of risk associated with ?VOAT-RCP (below and above the median of ?VOAT-RCP).
  
  RESULTS:
  AT and RCP were both identified in 782 (39.2%) out of 1995 reduced ejection fraction heart failure cases. Left ventricular ejection fraction and peak VO were 33?±?9% and 16.5?±?4.5?mL/kg per min (61?±?16% of predicted value), suggesting moderate heart failure. At five years, endpoint did not vary between patients below and above the median ?VOAT-RCP (3.85?mL/min per kg (25-75th interquartile range?=?2.69-5.46)). ?VOAT-RCP correlated with several parameters associated to heart failure prognosis, such as peak VO, VE/VCO slope, brain natriuretic peptide and left ventricular ejection fraction. The ?VOAT-RCP value was associated with prognosis at univariate but not at multivariable analysis, where only VE/VCO slope endured.
  
  CONCLUSION:
  ?VOAT-RCP correlates with several parameters linked to heart failure severity. Isocapnic buffering period stratifies heart failure patients, but not more than other prognostic indices.
  
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• Current diagnostic strategies for dilated cardiomyopathy: a comparison of imaging techniques.
  Expert Rev Cardiovasc Ther

  2019 Jan;17(1):53-63. doi: 10.1080/14779072.2019.1550719.
  
  Porcari Aldostefano, De Angelis Giulia, Romani Simona, Paldino Alessia, Artico Jessica, Cannatà Antonio, Gentile Piero, Pinamonti Bruno, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  Dilated cardiomyopathy (DCM) is generally thought as a final common pathway of several conditions leading to the same clinical phenotype. Multiple imaging modalities play a fundamental role in recognizing the underlying pathological substrate in DCM. Areas covered: Echocardiography represents the first reliable and easily accessible diagnostic tool, allowing the identification of associated cardiac abnormalities, such as valve disease and highlighting features associated with an adverse prognosis. Recent advances in technology such as strain analysis and 3D-echocardiography have improved the diagnostic and prognostic capabilities of this technique. Cardiac magnetic resonance (CMR) is considered the gold standard for an accurate and reproducible assessment of ventricular volumes and ejection fraction. In addition, CMR allows us to perform tissue characterization that, through new sophisticated sequences, could be obtained even without gadolinium. Nuclear images could be useful to identify specific causes of left ventricular dysfunction, such as cardiac sarcoidosis and amyloidosis. Finally, endomyocardial biopsy is generally performed if acute myocarditis is suspected in high-risk patients. Expert commentary: Strengths and limitations are different for every method, but multiparametric evaluation of patients and family members could progressively improve current understanding of the disease. This is fundamental to specifically target therapy, allowing us to improve patients' prognosis.
  
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• Left bundle branch block in dilated cardiomyopathy with intermediate left ventricular dysfunction: Clinical phenotyping and outcome correlates.
  Int J Cardiol

  2019 Mar;278():180-185. doi: 10.1016/j.ijcard.2018.11.005.
  
  Gentile Piero, Paldino Alessia, Cannatà Antonio, Artico Jessica, Barbati Giulia, Ramani Federica, Fabris Enrico, Aleksova Aneta, Stolfo Davide, Zecchin Massimo, Merlo Marco, Sinagra Gianfranco
  
  Abstract
  
  BACKGROUND:
  Left bundle branch block (LBBB) negatively affects prognosis in heart failure patients with a reduced left ventricular ejection fraction (LVEF). Less is known about the prognostic role of LBBB in dilated cardiomyopathy (DCM) with intermediate LVEF (between 36% and 50%). We sought to assess the role of LBBB in optimally treated DCM patients with mildly to moderately reduced LVEF and to determine the possible variables associated with subsequent LVEF reduction.
  
  METHODS:
  We retrospectively analyzed DCM patients with LVEF >35% after 3-to-9?months of optimal medical treatment (OMT) consecutively evaluated from 1990 to 2010. All-cause mortality or heart transplantation (D/HTx) and sudden cardiac death (SCD) or major ventricular arrhythmias (MVA) were considered as outcome measures. LVEF deterioration during follow-up was also considered.
  
  RESULTS:
  Among 280 (49%) patients that met the study criteria, 76 had LBBB (27%). During a mean follow-up of 151?months, the rates of D/HTx and SCD/MVA were similar between LBBB and not LBBB patients (p value?=?0.52 and p?=?0.39, respectively). Twenty-six out of 76 (34%) patients with LBBB experienced LVEF deterioration below 36%. The persistence of moderate-severe mitral regurgitation (MR), left atrial end-systolic area index and LV end-diastolic volume index emerged as independent predictors of LVEF deterioration and were associated with an increased risk of D/HTx during follow-up.
  
  CONCLUSIONS:
  LBBB does not affect mortality in DCM patients with intermediate LVEF after OMT. However, among these patients those with persistent significant MR, left atrial and LV remodeling carries a higher risk of LVEF deterioration during follow-up.
  
  Copyright © 2018 Elsevier B.V. All rights reserved.
  
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• Cardiovascular aging: the unveiled enigma from bench to bedside.
  J Cardiovasc Med (Hagerstown)

  2018 Oct;19(10):517-526. doi: 10.2459/JCM.0000000000000694.
  
  Cannata' Antonio, Merlo Marco, Artico Jessica, Gentile Piero, Camparini Luca, Cristallini Jacopo, Porcari Aldostefano, Loffredo Francesco, Sinagra Gianfranco
  
  Abstract
  
  : The rapid increase in the median age of the world's population requires particular attention towards older and more fragile people. Cardiovascular risk factors, time and comorbidities play a vicious role in the development of heart failure, both with reduced and preserved ejection fraction, in the elderly. Understanding the mechanisms underlying the pathophysiological processes observed with aging is pivotal to target those patients and their therapeutic needs properly. This review aims to investigate and to dissect the main pathways leading to the aging cardiomyopathy, helping to understand the relationship from bench to bedside of the clinical phenotype.
  
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• Mineralocorticoid receptor antagonists for heart failure: a real-life observational study.
  ESC Heart Fail

  2018 Jun;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 
  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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• Corrigendum to "Contribution of central and peripheral factors at peak exercise in heart failure patients with progressive severity of exercise limitation." [Int. J. Cardiol. 248 (2017) 252-256].
  Int J Cardiol

  2018 Feb;253():198. doi: 10.1016/j.ijcard.2017.11.085.
  
  Del Torto Alberico, Corrieri Nicoletta, Vignati Carlo, Gentile Piero, Cattadori Gaia, Paolillo Stefania, Agostoni Piergiuseppe
  
  
  
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• Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison.
  Eur J Heart Fail

  2018 Apr;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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• Contribution of central and peripheral factors at peak exercise in heart failure patients with progressive severity of exercise limitation.
  Int J Cardiol

  2017 Dec;248():252-256. doi: 10.1016/j.ijcard.2017.07.071.
  
  Del Torto Alberico, Corrieri Nicoletta, Vignati Carlo, Gentile Piero, Cattadori Gaia, Paolillo Stefania, Agostoni Piergiuseppe
  
  Abstract
  
  BACKGROUND:
  A reduced cardiac output (CO) response during exercise is a major limiting factor in heart failure (HF). Oxygen consumption (VO) is directly proportional to CO. Peripheral mechanisms via arteriovenous oxygen difference (?(a-v)O) play a pivotal role in chronic HF. We hypothesized a weak correlation between peak VO and peak CO with a greater ?(a-v)O variability in most severe HF.
  
  METHODS:
  We analyzed 278 HF patients (NYHA II-III) who performed maximal cardiopulmonary exercise test with non-invasive CO measurement by inert gas rebreathing.
  
  RESULTS:
  Median peakVO, CO and ?(a-v)O were 0.96 (0.78-1.28) L/min, 6.3 (5.1-8.0) L/min and 16.0 (14.2-18.0) mL/100mL respectively, with a linear relationship between VO and CO: CO=5.3×VO+1.13 (r=0.705, p
  CONCLUSIONS:
  With worsening HF we observed a progressive reduction of peak CO and peak VO. However in most compromised patients also peripheral mechanisms play a role as indicated by reduced ?(a-v)O.
  
  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 Jul;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?0.0001], while also considering potential confounders. A comparable prognosis was observed at 5?years in the ?1-/?2-receptor-blocker (n?=?2219) vs. ?1-selective group (n?=?2216) (HR 0.95, P?=?ns). A better prognosis was observed in high-dose (>2?5?mg carvedilol equivalent daily dose, n?=?1005) patients than in both medium dose (12.5-25?mg, n?=?1431) and low dose (
  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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• Interleukin-1? levels predict long-term mortality and need for heart transplantation in ambulatory patients affected by idiopathic dilated cardiomyopathy.
  Oncotarget

  2017 Apr;8(15):25131-25140. doi: 10.18632/oncotarget.15349.
  
  Aleksova Aneta, Beltrami Antonio Paolo, Carriere Cosimo, Barbati Giulia, Lesizza Pierluigi, Perrieri-Montanino Martina, Isola Miriam, Gentile Piero, Salvioni Elisabetta, Not Tarcisio, Agostoni Piergiuseppe, Sinagra Gianfranco
  
  Abstract
  
  AIMS:
  The prognostic stratification of patients with Idiopathic Dilated Cardiomyopathy (iDCM) is a difficult task. Here, we assessed the additive value of the evaluation of biomarkers of inflammasome activation and systemic inflammation for the long-term risk stratification of iDCM patients.
  
  METHODS AND RESULTS:
  We studied 156 ambulatory iDCM patients (mean age 58 years, 77% men, 79% in NYHA class 1-2, median Left Ventricular Ejection Fraction (LVEF) 35%, mean sodium 139 mEq/L, median BNP 189 pg/mL, median IL-1 beta (IL-1?) 1.08 pg/mL, median IL-6 1.7 pg/mL and median IL-10 2.7 pg/mL).During the follow-up period of 89.6 months, 35 patients (22%) died/underwent heart transplantation. Patients who died/underwent heart transplantation were more likely to be male, to be in NYHA class III, to have atrial fibrillation, to have lower LVEF and higher BNP levels. IL-1?, IL-6 and IL-10 levels did not differ significantly between the groups of patients with good or bad prognosis. IL-1? levels did not vary significantly among either the different NYHA classes or the quartiles of LVEF. In a multivariable model, however, IL-1? was a strong and independent predictor of all-cause mortality (HR 1.193, 95% CI 1.056 - 1.349, p=0.005 for log squared transformed values). Other factors associated with the outcome were: male gender, presence of atrial fibrillation and sodium concentration. The estimated time-dependent ROC curve of the multivariable model showed an AUC 0.74 (95% CI 0.65-0.86).
  
  CONCLUSIONS:
  Serum levels of IL-1? could be useful to predict the long-term outcome of patients with iDCM.
  
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• Reference Values for Peak Exercise Cardiac Output in Healthy Individuals.
  Chest

  2017 Jun;151(6):1329-1337. doi: 10.1016/j.chest.2017.01.009.
  
  Agostoni Piergiuseppe, Vignati Carlo, Gentile Piero, Boiti Costanza, Farina Stefania, Salvioni Elisabetta, Mapelli Massimo, Magrì Damiano, Paolillo Stefania, Corrieri Nicoletta, Sinagra Gianfranco, Cattadori Gaia
  
  Abstract
  
  BACKGROUND:
  Cardiac output (Q?) is a key parameter in the assessment of cardiac function, its measurement being crucial for the diagnosis, treatment, and prognostic evaluation of all heart diseases. Until recently, Q? determination at peak exercise has been possible through invasive methods, so that normal values were obtained in studies based on small populations.
  
  METHODS:
  Nowadays, peak Q? can be measured noninvasively by means of the inert gas rebreathing (IGR) technique. The present study was undertaken to provide reference values for peak Q? in the normal general population and to obtain a formula able to estimate peak exercise Q? from measured peak oxygen uptake (V?o).
  
  RESULTS:
  We studied 500 normal subjects (age, 44.9 ± 1.5 years; range, 18-77 years; 260 men, 240 women) who underwent a maximal cardiopulmonary exercise test with peak Q? measurement by IGR. In the overall study sample, peak Q? was 13.2 ± 3.5 L/min (men, 15.3 ± 3.3 L/min; women, 11.0 ± 2.0 L/min; P 
  CONCLUSIONS:
  The simultaneous measurement of Q? and V?o at peak exercise in a large sample of healthy subjects provided an equation to predict peak Q? from peak V?o values.
  
  Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
  
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• The natural history of dilated cardiomyopathy: how has it changed?
  J Cardiovasc Med (Hagerstown)

  2017 Jan;18 Suppl 1():e161-e165. doi: 10.2459/JCM.0000000000000459.
  
  Merlo Marco, Gentile Piero, Naso Paola, Sinagra Gianfranco
  
  
  
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• Primary Cardiac Angiosarcoma.
  J Card Surg

  2016 Jan;31(1):63-4. doi: 10.1111/jocs.12672.
  
  Cottini Marzia, Pergolini Amedeo, Gentile Piero, Musumeci Francesco
  
  
  
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