NONREENTRANT MECHANISMS UNDERLYING SPONTANEOUS VENTRICULAR ARRHYTHMIAS IN A MODEL OF NONISCHEMIC HEART-FAILURE IN RABBITS

Background The goal of this study was to define the mechanisms of spon taneously occurring ventricular arrhythmias in the setting of nonische mic heart failure. Methods and Results Three-dimensional cardiac mappi ng from 232 intramural sites was performed in four rabbits with heart failure induced by combined aortic regurgitation and aortic stenosis a nd in four control rabbits. During the development of heart failure, s erial echocardiographic examination demonstrated a progressive increas e in left ventricular (LV) chamber dimensions and a decrease in LV sys tolic function over 19+/-2 months. Serial Holter monitoring demonstrat ed spontaneously occurring premature ventricular complexes (PVCs) (up to 13 000 per day) and couplets in all four rabbits with heart failure , and runs of nonsustained ventricular tachycardia (VT) up to 26 beats long in three. Mapping of spontaneous rhythm was performed for up to 60 minutes. None of the control rabbits demonstrated spontaneous arrhy thmias during mapping. Three rabbits with heart failure demonstrated i solated PVCs, and two demonstrated couplets and runs of nonsustained V T up to 4 beats long. The three-dimensional activation sequence of 50 sinus beats (42 from rabbits with heart failure; 8 from control rabbit s), 19 PVCs, and 37 beats of couplets and nonsustained VT was determin ed and the mechanism of arrhythmia defined for all ventricular ectopic beats analyzed. Normal sinus beats from the failing rabbits activated rapidly, with a total activation time of 28+/-1 ms (P=.18 versus sinu s beats from control hearts, 26+/-1 ms). Sinus beats preceding PVCs in the rabbits with heart failure activated in a similar fashion, with a total activation time of 26+/-1 ms. In each case, these PVCs initiate d in the subendocardium by a nonreentrant mechanism based on the absen ce of intervening electrical activity between the termination of the p receding beat and the initiation of the next (225+/-7 ms), despite the presence of multiple intervening electrode recording sites. Couplets and monomorphic and polymorphic VTs were due to repetitive nonreentran t activation at the same or different subendocardial sites. Total acti vation time of beats of VT averaged 44+/-1 ms and did not differ from that of isolated PVCs (43+/-2 ms, P=.65). Pathological analysis of tis sue demonstrated myocardial fiber hypertrophy, degenerative changes, a nd interstitial fibrosis throughout the failing hearts. Conclusions Sp ontaneously occurring PVCs, couplets, and VT in a model of nonischemic heart failure are due to nonreentrant mechanisms such as triggered ac tivity or abnormal automaticity. Approaches to the treatment of sponta neously occurring ventricular arrhythmias in patients with nonischemic heart failure should be directed at nonreentrant mechanisms.