Improvement of left ventricular filling by ivabradine during chronic hypertension: involvement of contraction-relaxation coupling
Patients with systemic hypertension and coronary artery disease (CAD) often manifest abnormalities at rest in left ventricular (LV) diastolic function and reduced exercise tolerance. It is possible that abnormalities in filling persist during exercise and are partially related to abnormal exercise tolerance. We examined rest and exercise peak filling rate (PFR) to determine if changes in PFR during exercise influence exercise performance. We studied 20 patients with systemic hypertension who had no evidence of CAD (negative thallium-201 stress imaging) and 15 patients with prior myocardial infarction, preserved ejection fraction, and no ischemia by thallium-201 stress imaging. Results were compared with 20 normal subjects. All 55 subjects had rest and exercise radionuclide angiograms Peak workload, exercise time, and LV ejection fraction were reduced in subjects with CAD (57 +/- 24 W, 7.41 +/- 2.91 min, and 60 +/- 9%) compared with subjects with hypertension (72 +/- 21 W, 9.69 +/- 3.03 min, and 70 +/- 6%, p <0.05) and controls (80 +/- 30 W, 10.82 +/- 3.50 min, and 67 +/- 6%, p <0.05). PFR at rest was reduced in CAD subjects (2.40 +/- 0.70 end-diastolic volume per second [EDV/s]) compared with those with hypertension (2.89 +/- 0.70 EDV/s, p <0.02) and controls (3.23 +/- 0.52 EDV/s, p <0.0002). The increments in PFR during exercise were reduced in CAD patients (+1.76 +/- 0.95 EDV/s) compared with hypertensive subjects (+2.93 +/- 1.7 EDV/s) and controls (+3.22 +/- 1.4 EDV/s, p <0.05). The increment in PFR during exercise was related to exercise performance (r = 0.49, p <0.0002). These findings suggest that alterations in LV diastolic filling during exercise are important determinants of exercise performance.