Focal mechanisms underlying ventricular tachycardia during prolonged ischemic cardiomyopathy.

BACKGROUND: The present study was performed to define the mechanisms underlying spontaneously occurring ventricular arrhythmias in the failing heart. METHODS AND RESULTS: Three-dimensional cardiac mapping from as many as 232 intramural sites was performed in five dogs with ischemic cardiomyopathy induced by multiple intracoronary embolizations. After 5 to 10 weekly embolizations with 90-microns latex microspheres into the left anterior and circumflex coronary arteries, left ventricular ejection fraction decreased from 63 +/- 3% to 22 +/- 3%. Subsequent weekly Holter monitoring of dogs in the conscious state demonstrated frequent multiform premature ventricular complexes (PVCs) (< or = 2000/d), couplets, and runs of ventricular tachycardia (VT) (< or = 70 beats in duration and < or = 560 beats per minute) in all dogs. Three-dimensional mapping of spontaneous rhythm for 60 minutes was performed an average of 6.4 weeks after the last embolization, during which time each dog demonstrated multiform PVCs, couplets, and runs of nonsustained VT at rates comparable to those in the conscious state. Mapping was of sufficient density to define the mechanism for 31 PVCs, 45 beats of ventricular couplets, and 99 beats of VT. Sinus beats preceding PVCs (n = 36) initiated in the septum and spread rapidly with a total activation time (46 +/- 1 milliseconds) that did not differ from that of sinus beats not preceding PVCs or VT (46 +/- 2 milliseconds, n = 10, P = .69). PVCs and the first beat of couplets or VT were initiated primarily in the subendocardium by a focal mechanism, based on the lack of intervening electrical activity between the termination of the preceding (sinus) beat and initiation of the ectopic beat (225 +/- 23 milliseconds), despite the presence of multiple intervening intramural recording sites. All subsequent beats of VT also were initiated by a focal mechanism, and their total activation time (89 +/- 1 milliseconds) did not differ from that of the initiating ectopic beats (86 +/- 2 milliseconds, P = .14), despite acceleration of VT to a cycle length of 200 milliseconds. Monomorphic VT was due to repetitive focal activation of subendocardial sites. Polymorphic VT was due to sequential focal activation from multiple sites arising in the subendocardium and, at times, in the subepicardium. Comparison of mapping data with results of detailed anatomic analysis of tissue demonstrated that focal sites of initiation exhibited patchy nontransmural fibrosis. Functional conduction delay of a moderate degree was evident only when fibrosis extended transmurally. CONCLUSIONS: Spontaneously occurring PVCs, couplets, and VT in a model of ischemic cardiomyopathy are initiated and maintained by focal mechanisms with no evidence of macroreentry. Thus, therapeutic regimens to treat or prevent VT in the presence of ischemic cardiomyopathy will likely require interruption of these focal mechanisms.