Sm. Pogwizd, NONREENTRANT MECHANISMS UNDERLYING SPONTANEOUS VENTRICULAR ARRHYTHMIAS IN A MODEL OF NONISCHEMIC HEART-FAILURE IN RABBITS, Circulation, 92(4), 1995, pp. 1034-1048
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.