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Failure of calcium channel blockers to improve ventricular relaxation in humans
R A Nishimura1, R S Schwartz, D R Holmes
1Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Insights
Calcium channel blockers like verapamil may not improve diastolic dysfunction as indicated by peak filling rates. Invasive measurements showed worsening ventricular relaxation and increased pressure, suggesting cautious use of these drugs.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Diastolic dysfunction is characterized by depressed left ventricular filling rates, often linked to impaired ventricular relaxation.
- Calcium channel blockers have shown potential to reverse these low filling rates, but their true impact on relaxation is debated.
Purpose of the Study:
- To determine if improved peak filling rates after calcium channel blocker administration reflect genuine enhancement of ventricular relaxation and reduced left ventricular end-diastolic pressure.
- To assess the efficacy of verapamil in improving diastolic function parameters in patients with coronary artery disease.
Main Methods:
- Doppler echocardiography was used to measure peak filling rates in 20 patients with coronary artery disease and preserved ejection fraction.
- Invasive high-fidelity manometer-tipped pressures were recorded before and after intravenous verapamil administration (0.1 mg/kg).
- Measurements included early transmitral (E) flow velocity, left ventricular end-diastolic pressure, and time constant of relaxation.
Main Results:
- Verapamil significantly increased peak filling rates (E flow velocity) from 0.57 to 0.77 m/s (p < 0.01).
- Concurrently, left ventricular end-diastolic pressure significantly increased from 18.0 to 24.1 mm Hg (p < 0.001).
- The time constant of relaxation showed a significant increase from 45.8 to 53.2 ms (p = 0.01), indicating prolonged relaxation.
Conclusions:
- Reversal of decreased peak filling rates by verapamil does not accurately indicate improved ventricular relaxation or reduced left ventricular end-diastolic pressure.
- The drug led to increased ventricular filling pressures and prolonged relaxation time, despite improving filling rates.
- Caution is advised when using calcium channel blockers empirically for treating diastolic dysfunction.
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.