Hemodynamic and electrophysiologic studies were performed in 30 survivors of sudden cardiac arrest with hypertrophic cardiomyopathy (HC) to determine responsible factors. Electrophysiologic abnormalities alone were present in 27 patients (90%): sinus node dysfunction in 14 (47%), delayed atrioventricular nodal conduction in 1 (3%), abnormal His-Purkinje conduction in 7 (23%), an inducible atrial tachycardia in 7 (23%), and inducible sustained ventricular arrhythmia in 21 (70%). Sustained ventricular arrhythmia was polymorphic ventricular tachycardia (VT) in 18 patients (86%), monomorphic VT in 2 patients (7%) and ventricular fibrillation in 1 patient (3%). In 1 patient the arrhythmia recorded during an episode of cardiac arrest and induced at electrophysiologic study was polymorphic VT. VT was induced with less-than-or-equal-to 2 extra-stimuli in only 1 patient (3%) but with less-than-or-equal-to 3 extra-stimuli in 20 patients (97%). Potential causes of sudden cardiac arrest were found in all patients and were multiple in 13 patients (43%). These were (1) ventricular electrical instability in 21 patients (70%), (2) severe left ventricular outflow tract obstruction in 8 patients (27%), (3) bradycardia in 5 patients (17%), (4) myocardial ischemia associated with hypotension in 5 patients (17%), and (5) atrial tachycardia resulting in hypotension in 4 patients (13%). Of the 21 patients with inducible sustained ventricular arrhythmia, 17 received an implantable defibrillator device and 4 were treated with antiarrhythmic drugs. Seven patients underwent left ventricular septal myectomy. Three patients with atrial tachycardia received antiarrhythmic medication. One patient had catheter ablation of a concealed posteroseptal accessory pathway. Three patients with myocardial ischemia as the only abnormality were treated with verapamil and propranolol (2 also received implantable defibrillators). During a mean follow-up period of 18 +/- 19 months (maximum 75), 4 patients died suddenly and 4 patients received a total of 13 defibrillator shocks (1-year survival rate of 93% and a 1-year event-free rate of 80%). Thus, electrophysiologic studies identify potential mechanisms for cardiac arrest in most patients with HC. Although most cardiac arrest survivors with HC have an inducible sustained VT and may benefit from an implantable defibrillator, hemodynamic plus hemodynamic studies in many patients identify other potential etiologic or aggravating factors that may also require treatment.