(Circulation. 1995;92:421-429.)
© 1995 American Heart Association, Inc.
Articles |
Mechanism of Repetitive Monomorphic Ventricular Tachycardia
From the Department of Medicine and the Division of Cardiology, New York Hospital–Cornell Medical Center, New York, NY.
Correspondence and reprint requests to Bruce B. Lerman, MD, Division of Cardiology, New York Hospital–Cornell Medical Center, 525 E 68th St, Starr Pavilion, 4th Floor, New York, NY 10021.
Background The most common form of idiopathic ventricular
tachycardia (VT) is repetitive monomorphic VT (RMVT), which is
characterized by frequent ventricular ectopy and salvos of nonsustained
VT with intervening sinus rhythm. Unlike most other forms of idiopathic
VT, this tachycardia typically occurs at rest and is nonsustained. The
mechanism of RMVT is undefined. Because of a common site of origin, the
right ventricular outflow tract (RVOT), we hypothesized that RMVT is
mechanistically related to paroxysmal sustained, exercise-induced VT,
which has been shown to be consistent with cAMP-mediated triggered
activity. Therefore, in this study, we sought to identify (1) the
mechanism of RMVT at the cellular level by using electropharmacological
probes known to activate either stimulatory or inhibitory G proteins
and thereby modify intracellular cAMP levels, (2) potential autonomic
triggers of RMVT through analysis of heart rate variability, and
(3) whether well-characterized somatic activating mutations in the
stimulatory G protein, G
s, underlie RMVT.
Methods and Results Twelve patients with RMVT underwent
electrophysiological study. Sustained monomorphic VT was reproducibly
initiated and terminated with programmed stimulation and/or
isoproterenol infusion in 11 of the 12 patients (the other patient had
incessant RMVT). Induction of VT demonstrated cycle length dependence
and was facilitated by rapid atrial or ventricular pacing. Termination
of VT occurred in response to interventions that either lowered
stimulated levels of intracellular cAMP (and thus decreased
intracellular Ca2+)—ie, adenosine (12 of 12), vagal
maneuvers or edrophonium (8 of 9), and ß-blockade (3 of 5)—or
directly decreased the slow-inward calcium current—ie, verapamil (10
of 12). Analysis of heart rate variability during 24-hour ambulatory
monitoring in 7 patients showed that the sinus heart rate is increased
and accelerates before nonsustained VT (P<.05), whereas
high-frequency heart rate variability is unchanged. These findings are
consistent with transient increases in sympathetic tone preceding
nonsustained VT. Finally, myocardial biopsy samples were obtained from
the site of origin of the VT (typically the RVOT) and from the right
ventricular apex from 9 patients. Genomic DNA was extracted from each
biopsy sample, and three exons of Gs in which activating
mutations have previously been described were amplified by polymerase
chain reaction. All sequences from these regions were found to be
identical to that of control.
Conclusions Although the arrhythmia occurs at rest, the constellation of findings in idiopathic VT that is characterized by RMVT is consistent with the mechanism of cAMP-mediated triggered activity. Therefore, the spectrum of VT resulting from this mechanism includes not only paroxysmal exercise-induced VT but also RMVT.
Key Words: tachycardia • G proteins • adenosine
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