Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects.

Abstract

Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 ± 1.3 to 3.7 ± 1.3 end-diastolic volumes/sec; p < .001) was associated with an increase in exercise tolerance (from 5.9 ± 3.6 to 8.7 + 4.7 min; p < .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p < .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11 %) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p < .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p < .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil. Circulation 72, No. 4, 853-864, 1985. IMPAIRED RELAXATION and diastolic filling of the left ventricle contribute importantly to the spectrum of symptoms experienced by patients with hypertrophic cardiomyopathy. Several studies of hypertrophic cardiomyopathy indicate that verapamil, administered intravenously or orally, improves indexes of left ventricular relaxation and diastolic filling.`X Verapamil also reduces symptoms and increases exercise tolerance in many patients with this disease.-H owever, the relationship between enhanced left ventricular diastolic filling resulting from verapamil and improved exercise tolerance has not been demonstrated conclusively.

Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force generation during systole.

“…7 B). These results are consistent with reports in the clinical literature documenting hemodynamic improvement of patients with hypertrophic cardiomyopathy after administration of Ca" channel blocking agents (7,(29)(30)(31)(32) Fig. 8, caffeine's effects on the sarcoplasmic reticulum appear predominant, since the drug produced a dose-related negative inotropic effect that was associated with a decrease in the amplitude of LI and a less pronounced decrease in the amplitude of L2.…”

Imaging in hypertrophic cardiomyopathy. Expert consensus statement of the Polish Clinical Forum for Cardiovascular Imaging

“…Użycie głowicy przezprzełykowej z kolei ułatwia ciągły udział w procedurze i zapewnia dobrą jakość badania, ale wymaga zastosowania znieczulenia ogólnego. Pomiaru gradientu w LVOT można dokonać z projekcji przezżołądkowej koniuszkowej czterojamowej (0 o ) oraz środkowoprzełykowej w osi długiej na poziomie zastawki aortalnej (120)(121)(122)(123)(124)(125)(126)(127)(128)(129)(130) o ). Należy pamiętać, że zmierzony gradient w LVOT może być zaniżony z powodu sedacji ogólnej.…”

“…Tempo maksymalnego napełniania jest najczęściej stosowanym wskaźnikiem w celu określania funkcji rozkurczowej. Przydatność tego parametru określono w badaniach nad wpływem werapamilu na zmniejszenie ciś-nienia napełniania LV i poprawę kliniczną u pacjentów z HCM [120]. W ocenie funkcji rozkurczowej metodą referencyjną pozostaje jednak echokardiografia.…”

Asses S Ment of Diastolic Function by Combined Trnsmitral and Pulmo N Ary Venous Flow Velocity Curves

“…15 The negative inotropic and chronotropic properties of the CCBs make them likely to be effective in treating diastolic dysfunction. Studies have yielded conflicting results with many showing improved relaxation, 16,17 but others showing no change in the rate of relaxation. 18 BBs have no direct effects on myocardial relaxation; however, they may be effective by slowing heart rate and reducing myocardial demand and ischemia.…”