Failure of calcium channel blockers to improve ventricular relaxation in humans

Abstract

Objectives: The objective of this study was to ascertain whether the reversal of low peak filling rates after administration of calcium channel blockers in patients with diastolic dysfunction indicates true improvement in the rate of ventricular relaxation and left ventricular end-diastolic pressure measured by invasive indexes.

Background: Depressed filling rates measured noninvasively have been associated with diastolic dysfunction, specifically abnormal relaxation of the left ventricle. There is a reversal of these low peak filling rates after administration of calcium channel blockers.

Methods: Doppler echocardiographic measurements of peak filling rates were made and invasive high fidelity manometer-tipped pressures were measured before and after administration of verapamil (0.1 mg/kg body weight) in 20 patients with coronary artery disease who had an ejection fraction > 40% and decreased peak filling rates.

Results: Verapamil caused significant increases in the peak filling rate, as measured by early transmitral (E) flow velocity, from 0.57 +/- 0.16 m/s to 0.77 +/- 0.15 m/s (p < 0.01), indicating reversal of decreased peak filling rates. Concomitantly, left ventricular end-diastolic pressure increased from 18.0 +/- 7.7 mm Hg to 24.1 +/- 9.0 mm Hg (p < 0.001). The time constant of relaxation was variable, with an overall significant increase from 45.8 +/- 10.4 ms to 53.2 +/- 14.6 ms (p = 0.01).

Conclusions: Verapamil administered intravenously produced reversal of decreased peak filling rates in patients with coronary artery disease and normal ventricular function. However, there was an increase in left ventricular end-diastolic pressure as well as an overall prolongation of the time constant of relaxation. Therefore, changes in peak filling rates do not accurately reflect the response of ventricular relaxation to drug interactions. Thus, calcium channel blockers should be used cautiously in the empiric treatment of patients with diastolic dysfunction.