Background and Purpose-Emery-Dreifuss muscular dystrophy (EDMD) is a rare inherited disorder associated with cardiac involvement. We investigated the spectrum and relevance of the cardiac manifestations of EDMD, focusing on bradyarrhythmias and tachyarrhythmias (including atrial fibrillation/flutter), embolic stroke, and heart failure. Methods and Results-Eighteen patients (age 42.8+/-19.6 years) with genetically confirmed X-linked (n=10, including 3 carriers) or autosomal dominant (n=8) EDMD were followed for a period ranging from 1 to 30 years in a research center for neuromuscular diseases and in a university cardiological department. Pacemakers were required by 10 of 18 (56%) patients for bradyarrhythmia, and related complications occurred in 3 of 10 (30%) cases. Atrial fibrillation/flutter developed in 11 of 18 (61%) patients, with atrial standstill subsequently occurring in 5 of 11 (45%) cases and embolic stroke (most often disabling) in 4 of 11 (36%). Heart failure requiring transplantation occurred in 1 of 18 (6%) patients, and asymptomatic left ventricular dysfunction in a further 3 (17%). No relationship was evident between neuromuscular impairment and cardiac involvement. Conclusions-Both X-linked and autosomal dominant EDMD patients risk not only bradyarrhythmia (requiring pacemaker implant) but also atrial fibrillation/flutter, which often anticipates atrial standstill and can cause disabling embolic stroke at a relatively young age. Antithromboembolic prophylaxis has to be recommended in EDMD patients with atrial fibrillation/flutter or atrial standstill. With careful monitoring, survival after pacemaker implant may be long. Heart failure, which seems to occur only in a minority of patients, may be severe.