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Use of calcium-channel blocking drugs in hypertrophic cardiomyopathy
Insights
Verapamil effectively reduces left ventricular outflow tract obstruction in hypertrophic cardiomyopathy (HC) patients by improving diastolic function. Long-term use enhances quality of life and exercise capacity, though adverse effects require monitoring.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Hypertrophic cardiomyopathy (HC) presents significant hemodynamic challenges.
- Beta-receptor blockers are a common therapy, but alternatives are sought.
Purpose of the Study:
- To evaluate the hemodynamic effects of verapamil in HC patients.
- To assess verapamil's efficacy in reducing left ventricular (LV) outflow tract obstruction.
- To compare verapamil's long-term effects on exercise capacity and symptoms against placebo and other drugs.
Main Methods:
- Intravenous verapamil administration in a catheterization laboratory setting.
- Radionuclide angiography to assess LV diastolic function.
- Double-blind, placebo-controlled studies for short-term exercise capacity.
- Long-term follow-up of patients on verapamil therapy.
Main Results:
- Verapamil significantly decreased systolic blood pressure and LV outflow tract gradients.
- LV diastolic function improved, appearing to be the primary mechanism for obstruction reduction.
- Verapamil improved exercise time and duration compared to placebo and nifedipine.
- Long-term therapy improved quality of life and maintained exercise capacity, with some patients showing reduced septal thickness.
Conclusions:
- Verapamil is an effective alternative to beta-blockers for managing HC, particularly for reducing LV outflow tract obstruction.
- It improves diastolic function, exercise capacity, and subjective symptoms.
- Adverse electrophysiologic and hemodynamic effects necessitate careful patient monitoring.
Abstract:
Verapamil exerts a wide spectrum of hemodynamic effects in patients with hypertrophic cardiomyopathy (HC), and its administration offers an important alternative to beta-receptor blocker therapy in such patients. The intravenous administration of verapamil to 62 patients in the catheterization laboratory decreased systolic blood pressure from 118 +/- 17 to 102 +/- 17 mm Hg (p less than 0.001). It had no significant effect on heart rate, mean pulmonary artery wedge pressure, left ventricular (LV) end-diastolic pressure or cardiac output; however, LV outflow gradient in the basal state decreased from 62 +/- 34 to 29 +/- 34 mm Hg (p less than 0.05). These findings demonstrate a decrease in LV outflow tract obstruction. Radionuclide angiography indicated the major action responsible for the reduction in obstruction appears to be an improvement in LV diastolic function. Short-term nifedipine administration to patients with HC produced no significant effect on LV outflow tract gradients and early diastolic filling. Short-term double-blind studies showed that verapamil improved exercise time by 26 +/- 35% (p less than 0.005) compared with placebo, whereas propranolol improved it by 21 +/- 35% (p less than 0.025). In a separate study, verapamil improved exercise duration by 38 +/- 58% (p = 0.02) compared with placebo, whereas nifedipine improved it by 20 +/- 47% (difference is not significant). Verapamil resulted in a more beneficial subjective symptomatic response than propranolol or nifedipine when compared with placebo. Long-term verapamil therapy was instituted in 227 patients; 133 of these patients have continued taking the medication for an average of 25 +/- 13 months because their quality of life improved compared with what they experienced with their former therapy (usually beta blocker). Improved exercise capacity of 40% has been maintained in 32 patients for 2 years. A decrease in ventricular septal thickness of 1.5 +/- 2.6 mm was also found in 32 patients studied after 39 +/- 8 months of verapamil therapy. Nine patients died during follow-up study, but it is unclear whether the drug increased survival or, conversely, whether any of the deaths could be attributed to verapamil administration. Significant adverse electrophysiologic and hemodynamic effects were seen in 59 instances. The electrophysiologic events, atrioventricular block and sinus arrest, were definitely verapamil-related, but it is uncertain how many of the hemodynamic problems of hypotension and pulmonary congestion were drug-related.(ABSTRACT TRUNCATED AT 400 WORDS)