Dor Lotan1, Joel Salazar-Mendiguchía2,3, Maria Iascone4, Michael Arad1, Jens Mogensen5, Faizan Rathore6, Aris Anastasakis7, Juan Kaski8,9, Pablo Garcia-Pavia10,11,9, Iacopo Olivotto12, Philippe Charron13,14,15,16,9, Elena Biagini17, Anwar Baban18,9, Giuseppe Limongelli19,9, Waddah Ashram6, Yishay Wasserstrum1, Joseph Galvin6, Esther Zorio20, Attilio Iacovoni21, Lorenzo Monserrat22, Paolo Spirito23. 1. Leviev Heart Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Israel (D.L., Y.W., M.A.). 2. Cardiomyopathy Unit, Hospital Universitari de Bellvitge, Barcelona, Spain (J.S.-M.). 3. Health in Code, Spain (J.S.-M.). 4. Molecular Genetics Laboratory, A.O. Papa Giovanni XXIII, Bergamo, Italy (M.I.). 5. Department of Cardiology, Odense University Hospital, Denmark (J.M.). 6. Department of Cardiology, University College Dublin School of Medicine, Mater Misericordiae University Hospital, Ireland (F.R., W.A., J.G.). 7. Unit of Inherited Diseases, Onassis Cardiac Surgery Center, Athens, Greece (A.A.). 8. Great Ormond Street Hospital Center for Inherited Cardiovascular Diseases, University College London Institute of Cardiovascular Science, United Kingdom (J.K.). 9. European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (J.K., P.G.-P., P.C., A.B., G.L.). 10. Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, CIBERCV, Madrid, Spain (P.G.-P.). 11. Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain (P.G.-P.). 12. Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (I.O.). 13. Sorbonne Université, Paris, France (P.C.). 14. APHP, Centre de référence des maladies cardiaques héréditaires ou rares, Paris, France (P.C.). 15. INSERM UMR S1166, ICAN, Paris, France (P.C.). 16. Hôpital Pitié-Salpêtrière, Paris, France (P.C.). 17. Cardio-Thoracic-Vascular Department, S. Orsola Hospital, University of Bologna, Bologna, Italy (E.B.). 18. Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children Hospital and Research Institute, Rome (A.B.). 19. Monaldi Hospital, AO Colli, Second University of Naples, Italy (G.L.). 20. Inherited Heart Diseases Unit and CaFaMuSMe Research Group, Hospital Universitari i Politècnic La Fe and IIS La Fe, Valencia and Center for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Madrid, Spain (E.Z.). 21. Department of Cardiology, ASST Papa Giovanni XXIII, Bergamo, Italy (A.I.). 22. Health in Code, Hospital Marítimo de Oza, As Xubias, A Coruña, Spain (L.M.). 23. Hypertrophic Cardiomyopathy Center, Policlinico di Monza, Italy (P.S.).
Abstract
BACKGROUND: The X-linked Danon disease manifests by severe cardiomyopathy, myopathy, and neuropsychiatric problems. We designed this registry to generate a comprehensive picture of clinical presentations and outcome of patients with Danon disease in cardiomyopathy centers throughout Europe. METHODS: Clinical and genetic data were collected in 16 cardiology centers from 8 European countries. RESULTS: The cohort comprised 30 male and 27 female patients. The age at diagnosis was birth to 42 years in men and 2 to 65 in women. Cardiac involvement was observed in 96%. Extracardiac manifestations were prominent in men but not in women. Left ventricular (LV) hypertrophy was reported in 73% of male and 74% of female patients. LV systolic dysfunction was reported in 40% of men (who had LV ejection fraction, 34±11%) and 59% of women (LV ejection fraction, 28±13%). The risk of arrhythmia and heart failure was comparable among sexes. The age of first heart failure hospitalization was lower in men (18±6 versus 28±17 years; P<0.003). Heart failure was the leading cause of death (10 of 17; 59%), and LV systolic dysfunction predicted an adverse outcome. Eight men and 8 women (28%) underwent heart transplantation or received an LV assist device. Our cohort suggests better prognosis of female compared with male heart transplant recipients. CONCLUSIONS: Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications. Cardiomyopathy features, heart failure and arrhythmia, are similar among the sexes. Clinical diagnosis and management is extremely challenging in women due to phenotypic diversity and the absence of extracardiac manifestations.
BACKGROUND: The X-linked Danon disease manifests by severe cardiomyopathy, myopathy, and neuropsychiatric problems. We designed this registry to generate a comprehensive picture of clinical presentations and outcome of patients with Danon disease in cardiomyopathy centers throughout Europe. METHODS: Clinical and genetic data were collected in 16 cardiology centers from 8 European countries. RESULTS: The cohort comprised 30 male and 27 female patients. The age at diagnosis was birth to 42 years in men and 2 to 65 in women. Cardiac involvement was observed in 96%. Extracardiac manifestations were prominent in men but not in women. Left ventricular (LV) hypertrophy was reported in 73% of male and 74% of female patients. LV systolic dysfunction was reported in 40% of men (who had LV ejection fraction, 34±11%) and 59% of women (LV ejection fraction, 28±13%). The risk of arrhythmia and heart failure was comparable among sexes. The age of first heart failure hospitalization was lower in men (18±6 versus 28±17 years; P<0.003). Heart failure was the leading cause of death (10 of 17; 59%), and LV systolic dysfunction predicted an adverse outcome. Eight men and 8 women (28%) underwent heart transplantation or received an LV assist device. Our cohort suggests better prognosis of female compared with male heart transplant recipients. CONCLUSIONS:Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications. Cardiomyopathy features, heart failure and arrhythmia, are similar among the sexes. Clinical diagnosis and management is extremely challenging in women due to phenotypic diversity and the absence of extracardiac manifestations.
Entities:
Keywords:
cardiomyopathies; heart failure; hypertrophy; metabolic; sex characteristics
Authors: Yishay Wasserstrum; José M Larrañaga-Moreira; Cristina Martinez-Veira; Edward Itelman; Dor Lotan; Avi Sabbag; Rafael Kuperstein; Yael Peled; Dov Freimark; Roberto Barriales-Villa; Michael Arad Journal: ESC Heart Fail Date: 2022-04-30
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