Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction

Diastolic dysfunction may be exacerbated by increased systolic blood pressure (SBP) during exercise. Ang II may contribute to this process. We performed a randomized, double-blind, crossover study of two weeks of candesartan (16 mg) and verapamil (SR 160 mg). The 21 subjects were 64 10 years old with ejection fraction greater than 50%, no ischemia, mitral flow velocity E/A less than 1, normal resting SBP (< 150 turn Hg), and SBP greater than 200 turn Hg during exercise. Exercise tolerance was assessed using a Modified Bruce Protocol at baseline and after each two-week treatment period, separated by a two-week washout Period. Quality of life (QOL) was assessed using the Minnesota Living with Heart Failure questionnaire. During exercise, Ang II levels increased from 29 18 to 33 18 pg/mI (P < 0.05). SBP during exercise was 213 +/- 9 mm Hg at baseline and similarly reduced by candesartan (198 18, P < 0.01) and verapamil (197 +/- 14, P < 0.01). With candesartan, exercise time increased from 793 182 seconds to 845 163 seconds (P < 0.05), and QOL improved from 11 +/- 14 to 5 +/- 6 (P < 0.05). In contrast, verapamil did not significantly improve exercise time or QOL. In patients with mild diastolic dysfunction at rest and a hypertensive response to exercise, both Ang II receptor blockade and verapamil blunted the hypertensive response to exercise. Ang II blockade increased exercise tolerance and improved QOL.