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Olivotto I, Camici PG, Merlini PA, Rapezzi C, Patten M, Climent V, Sinagra G, Tomberli B, Marin F, Ehlermann P, Maier LS, Fornaro A, Jacobshagen C, Ganau A, Moretti L, Hernandez Madrid A, Coppini R, Reggiardo G, Poggesi C, Fattirolli F, Belardinelli L, Gensini G, Mugelli A. Efficacy of Ranolazine in Patients With Symptomatic Hypertrophic Cardiomyopathy: The RESTYLE-HCM Randomized, Double-Blind, Placebo-Controlled Study. Circ Heart Fail 2019; 11:e004124. [PMID: 29321131 DOI: 10.1161/circheartfailure.117.004124] [Citation(s) in RCA: 100] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 12/18/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. METHODS AND RESULTS In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO2 compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E' ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO2 peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus -0.02±4.25 mL/kg per minute; P=0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P=0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], -3 pg/mL [-107, 142 pg/mL] versus 78 pg/mL [-71, 242 pg/mL]; P=0.251). Furthermore, E/E' ratio and quality of life scores showed no significant difference. CONCLUSIONS In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20.
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Affiliation(s)
- Iacopo Olivotto
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Paolo G Camici
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Piera Angelica Merlini
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Claudio Rapezzi
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Monica Patten
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Vicent Climent
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Gianfranco Sinagra
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Benedetta Tomberli
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.).
| | - Francisco Marin
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Philipp Ehlermann
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Lars S Maier
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Alessandra Fornaro
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Claudius Jacobshagen
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Antonello Ganau
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Luciano Moretti
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Antonio Hernandez Madrid
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Raffaele Coppini
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Giorgio Reggiardo
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Corrado Poggesi
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Francesco Fattirolli
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Luiz Belardinelli
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Gianfranco Gensini
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
| | - Alessandro Mugelli
- >From the Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O., B.T., A.F.); Vita Salute University and Scientific Institute San Raffaele, Milan, Italy (P.G.C.); Dipartimento Cardiotoracovascolare, Ospedale Niguarda, Milan, Italy (P.A.M.); Ospedale S. Orsola Malpighi, Bologna, Italy (C.R.); Clinic of General and Interventional Cardiology, University Heart Center, Hamburg, Germany (M.P.); Cardiology Department, Hospital General Universitario de Alicante, ISABIAL - FISABIO, Alicante, Spain (V.C.); Cardiovascular Department, Ospedale di Cattinara, Trieste, Italy (G.S.); Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain (F.M.); University Hospital, Heidelberg, Germany (P.E.); University Hospital Regensburg, Germany (L.S.M.); Herz zentrum Georg-August-Universitaet, Göttingen, Germany (C.J.); Department of Clinical and Experimental Medicine, Cardiology, Sassari Hospital, Sassari, Italy (A.G.); Ospedale Mazzoni, Ascoli Piceno, Italy (L.M.); Hospital Ramòn y Cajal, Alcalá University, Madrid, Spain (A.H.M.); Department Neurofarba, University of Florence, Italy (R.C., A.M.); Medi Service, Genoa, Italy (G.R.); Department of Experimental and Clinical Medicine, University of Florence, Italy (C.P., F.F.); Gilead Sciences, Foster City, CA (L.B.); and CESMAV, Florence, Italy (G.G.)
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18
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Pasqualucci D, Fornaro A, Castelli G, Rossi A, Arretini A, Chiriatti C, Targetti M, Girolami F, Corda M, Orrù P, Matta G, Stefàno P, Cecchi F, Porcu M, Olivotto I. Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy. Circ Heart Fail 2015; 8:1014-21. [PMID: 26446673 DOI: 10.1161/circheartfailure.114.001843] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 09/17/2015] [Indexed: 11/16/2022]
Abstract
BACKGROUND The clinical course of patients with hypertrophic cardiomyopathy and advanced heart failure (HF) subtended by progressive left ventricular dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator and heart transplantation (HT) in patients with hypertrophic cardiomyopathy evaluated at 2 Italian referral centers >3 decades. METHODS AND RESULTS All-cause mortality and a combined end point including death, HT, or appropriate implantable cardioverter-defibrillator shock were assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire hypertrophic cardiomyopathy cohort) followed up for 6.1±6.9 years after development of New York Heart Association class III to IV symptoms. At enrollment, left ventricular ejection fraction was <50% in 55 patients and >50% in 16; all had restrictive left ventricular filling. During follow-up, 35 patients died (49%%; 5-year rate, 49%) and 53 met the combined end point (75%; 5-year rate, 62%). Most events occurred in the 3 years after HF onset (17% per year compared with only 3% per year subsequently). Appropriate implantable cardioverter-defibrillator shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed, and 13 excluded; 2 early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. CONCLUSIONS In hypertrophic cardiomyopathy, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first 3 years after onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favorable but requires early consideration, as the window of opportunity may be short.
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Affiliation(s)
- Daniele Pasqualucci
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.).
| | - Alessandra Fornaro
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Gabriele Castelli
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Alessandra Rossi
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Anna Arretini
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Chiara Chiriatti
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Mattia Targetti
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Francesca Girolami
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Marco Corda
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Pierpaolo Orrù
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Gildo Matta
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Pierluigi Stefàno
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Franco Cecchi
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Maurizio Porcu
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
| | - Iacopo Olivotto
- From the Departments of Cardiology (D.P., M.C., P.O., M.P.) and Radiology (G.M.), Brotzu Hospital, Cagliari, Italy; Referral Center for Cardiomyopathies (A.F., G.C., A.R., A.A., C.C., M.T., I.O.), Genetic Diagnostics Unit (F.G.), and Cardiac Surgery (P.S.), Careggi University Hospital, Florence, Italy; and Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy (F.C.)
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