Left ventricular function before and after diltiazem in patients with coronary artery disease

Left ventricular contraction, relaxation and diastolic mechanics were investigated before and after intravenous administration of 15 mg of diltiazem in 15 patients with coronary artery disease. High fidelity left ventricular pressure measurements were performed in all 15 patients, with simultaneous biplane cineangiography in 13. The time constant of left ventricular isovolumic pressure decay was calculated from the linear relation of left ventricular pressure and its rate of change with time (negative dP/dt). Frame by frame volume analysis through one cardiac cycle was completed to construct volume-time and pressure-volume curves before and after the administration of diltiazem.After diltiazem, left ventricular peak systolic pressure decreased from 124 to 113 mm Hg (p < 0.001), while left ventricular end-diastolic pressure and heart rate were not altered. Maximal positive dP/dt also remained unchanged. End-diastolic volume was not changed after diltiazem, but end-systolic volume increased from 48 to 52 ml/m2(p < 0.025); as a result, ejection fraction decreased slightly from 57 to 55% (p < 0.025). The time constant of left ventricular pressure decay and maximal negative dP/dt decreased from 58 to 54 ms (p < 0.025) and from −1,404 to −1,321 mm Hg/s (p < 0.025), respectively. Peak early diastolic filling rate increased from 621 to 752 ml/s (p < 0.01) in association with an increase in filling volume during the first half of diastole from 60 to 68% (p < 0.005). No consistent displacement of the diastolic pressure-volume curve was observed after diltiazem.This study indicates that diltiazem reduces afterload and depresses myocardial contractility in patients with coronary artery disease. In contrast, it improves left ventricular relaxation, which may contribute in part to the enhancement of early diastolic filling. However, left ventricular passive diastolic properties remain uninfluenced

Left ventricular systolic series elastic properties in aortic stenosis before and after valve replacement

In seven patients with aortic valve disease the time course of an auxotonic beat was compared with that of an isovolumetric beat produced by aortic cross clamping during open heart surgery. The rate of systolic stress rise (dS/dt; g·cm−2) of the isovolumetric beat at peak meridional wall stress (Sp; g·cm−2) of the auxotonic beat was determined by tipmanometry and simultaneous sonomicrometry and was found to be 87% of maximum dS/dt. In the second part of the study the stiffness index (k) was calculated in patients undergoing cardiac catheterisation according to: k = 0.87·(max·dS/dt)/Sp·Vcf, where Vcf = normalised midwall circumferential fibre shortening velocity (circ·s−1). In 22 patients, 10 controls and 12 patients with aortic stenosis before (pre) and after (post) valve replacement the systolic stiffness index k (circ−1) was determined using tipmanometry and frame by frame angiocardiography. Muscle fibre diameter and interstitial fibrosis were assessed from left ventricular endomyocardial biopsies. The systolic stiffness index k was 15 circ−1 in controls, 14 in preoperative patients with aortic stenosis and 12 (p<0.01 v controls) in postoperative patients. There was a significant correlation between k and muscle fibre diameter (r = 0.55; p<0.01) but not between k and interstitial fibrosis or ejection fraction. We conclude that systolic stiffness index k is normal despite marked left ventricular hypertrophy in preoperative patients with aortic stenosis. Following successful valve replacement systolic stiffness index decreased and was significantly lower than in controls. Series elasticity appears to be determined by structures related to the muscle cell rather than to interstitial fibrosi

Silent myocardial ischemia: Hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris

The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 ± 4,828 [SD] versus 19,247 ± 4,117 beats/min x mm Hg [NS] in the study and control groups without prior infarction, and 19,665 ± 3,950 versus 17,701 ± 4,600 beats/min x mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 ± 4 to 36 ± 11 and from 13 ± 5 to 29 ± 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 ± 7 to 32 ± 13 and from 19 ± 7 to 36 ± 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 ± 7 to 50 ± 15 and from 60 ± 4 to 52 ± 9% in the study and control groups without prior infarction and from 54 ± 9 to 47 ± 10 and 55 ± 9 to 50 ± 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction.Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion

Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis

Background Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. Methods and Results We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7+/-0.2 cm(2)) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35+/-4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25+/-2 to 20+/-2 mm Hg (P<.05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22+/-2 to 18+/-2 mm Hg (P<.05) was accompanied by a significant fall in right atrial pressure (9+/-1 to 6+/-1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. Conclusions Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function