Effect of calcium channel block on the wall motion abnormality of the idiopathic long QT syndrome

We recently showed the frequent occurrence of an unusual ventricular wall motion abnormality, assessed by echocardiography, in patients with the idiopathic long QT syndrome (LQTS). Two new quantitative indexes were developed: Th1/2 (time needed to reach half of the maximal systolic thickening), which was smaller in LQTS patients than in controls; and TSTh (time spent at a very low thickening rate before rapid relaxation), which was much greater in LQTS patients, indicating the presence of a slow contraction in the late thickening phase. This marked late systolic "plateau," either rectilinear or with a peculiar double peak pattern, was significantly more frequent in patients with a history of syncope or cardiac arrest. The mechanism underlying this puzzling phenomenon remained unexplained. METHODS AND RESULTS: The present study assessed the effects of the calcium channel blocker verapamil on the contraction pattern in 10 LQTS patients (9 females and 1 male; mean age, 19 +/- 7 years) with a marked plateau pattern and in 6 healthy controls (4 females and 2 males; mean age, 28 +/- 5 years). Either verapamil (0.1 mg/kg) or saline was randomly injected over 2 minutes. Saline had no effect. In LQTS patients, verapamil increased Th1/2 by 27%, from 16.9 +/- 3.2% to 21.4 +/- 3.9% of the cardiac cycle (P = .005), and dramatically reduced TSTh by 92%, from 13.7 +/- 5.3% to 1.08 +/- 0.6% of the cardiac cycle (P < .00001). At the peak effect of verapamil, the contraction pattern of all patients was normal. In healthy control subjects, verapamil did not significantly change either Th1/2 (from 17.6 +/- 2.5% to 18.5 +/- 3.5% of the cardiac cycle) or TSTh (from 0.92 +/- 0.47% to 1.17 +/- 0.74%). CONCLUSIONS: This study demonstrates that the wall motion abnormality of LQTS is completely abolished by verapamil. These results suggest that symptomatic LQTS patients may have an abnormal increase in the intracellular calcium concentration before relaxation has completed, possibly linked to an early afterdepolarization, and that the contraction abnormality may be the mechanical equivalent of an early afterdepolarization.