Clinical Profile of Cardiac Involvement in Danon Disease
Dor Lotan, Joel Salazar‐Mendiguchía, Jens Mogensen, Faizan Rathore, Aris Anastasakis, Juan Pablo Kaski, Pablo García‐Pavía, Iacopo Olivotto, Philippe Charron, Elena Biagini, Anwar Baban, Giuseppe Limongelli, Waddah Ashram, Yishay Wasserstrum, Joseph Galvin, Esther Zorio, Attilio Iacovoni, Lorenzo Monserrat, Paolo Spirito, Maria Iascone, Michael Arad, Chana Mandel, Herminio Morillas, Esther González-López, Fernándo Domínguez, Daniela Marchetti, Laura Pezzoli, Katie Anne Walsh, Catherine McGorrian, Raffaello Ditaranto, Giovanni Vitale, Eric Villard, Pascale Richard, Emanuele Monda, Martina Caiazza, Silvia Passantino, Francesca Girolami, Fabrizio Drago, Rachele Adorisio, Ella Field, Dov Freimark, Ulrik Baandrup
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.