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(Circulation. 1995;92:1034-1048.)
© 1995 American Heart Association, Inc.
Articles |
Nonreentrant Mechanisms Underlying Spontaneous Ventricular Arrhythmias in a Model of Nonischemic Heart Failure in Rabbits
From the Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Mo.
Background The goal of this study was to define the mechanisms of spontaneously occurring ventricular arrhythmias in the setting of nonischemic heart failure.
Methods and Results Three-dimensional cardiac mapping from 232 intramural sites was performed in four rabbits with heart failure induced by combined aortic regurgitation and aortic stenosis and in four control rabbits. During the development of heart failure, serial echocardiographic examination demonstrated a progressive increase in left ventricular (LV) chamber dimensions and a decrease in LV systolic function over 19±2 months. Serial Holter monitoring demonstrated 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 arrhythmias during mapping. Three rabbits with heart failure demonstrated isolated PVCs, and two demonstrated couplets and runs of nonsustained VT up to 4 beats long. The three-dimensional activation sequence of 50 sinus beats (42 from rabbits with heart failure; 8 from control rabbits), 19 PVCs, and 37 beats of couplets and nonsustained VT was determined 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 sinus 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 initiated in the subendocardium by a nonreentrant mechanism based on the absence of intervening electrical activity between the termination of the preceding 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 nonreentrant activation at the same or different subendocardial sites. Total activation 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 tissue demonstrated myocardial fiber hypertrophy, degenerative changes, and interstitial fibrosis throughout the failing hearts.
Conclusions Spontaneously occurring PVCs, couplets, and VT in a model of nonischemic heart failure are due to nonreentrant mechanisms such as triggered activity or abnormal automaticity. Approaches to the treatment of spontaneously occurring ventricular arrhythmias in patients with nonischemic heart failure should be directed at nonreentrant mechanisms.
Key Words: tachycardia • heart failure • mapping
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