To define the mechanisms of unexpected cardiac arrest in advanced heart failure, we reviewed the causes of cardiac arrest as established from electrocardiographic monitoring and from clinical and autopsy data in patients hospitalized for cardiac transplantation evaluation and management of advanced heart failure (mean left ventricular ejection fraction, 0.18 +/- 0.08) who were stable while on vasodilator and diuretic therapy such that hospital discharge to home was anticipated. Twenty-one cardiac arrests occurred in 20 of 216 (9%) such patients during a 4-year period. Heart failure was due to coronary artery disease with prior myocardial infarction in 13 patients and nonischemic cardiomyopathy in seven patients. The rhythm at the time of arrest was severe bradycardia or electromechanical dissociation (BA/EMD) in 13 (62%) patients. The precipitating cause of the BA/EMD arrest was coronary artery thrombosis or embolism in two patients, pulmonary embolism in one patient, hyperkalemia in two patients, and unexplained hypoglycemia in one patient. In seven of 13 (54%) patients, a precipitating cause of the bradycardia arrest could not be established. Only eight of 21 (38%) arrests were due to ventricular tachycardia or fibrillation (VT/VF), and all occurred in patients with prior myocardial infarction (p = 0.02 vs. BA/EMD arrests). Two VT/VF arrests were due to acute or recent infarction, and one patient had hyperkalemia. The patients who suffered a BA/EMD arrest were similar to those who had a VT/VF arrest in age, ventricular arrhythmia history, ventricular function, and serum potassium levels. Serum sodium levels were lower in patients with BA/EMD arrests (129 +/- 3 vs. 133 +/- 4 meq/l, p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)