Effect of quinapril or losartan alone and in combination on left ventricular systolic and diastolic functions in asymptomatic patients with diabetic autonomic neuropathy.

OBJECTIVE: To investigate the effect of angiotensin converting enzyme inhibition (ACE-I) or angiotensin receptor blockade (ARB), and their combination, on both diabetic autonomic neuropathy (DAN) and left ventricular (LV) diastolic dysfunction (LVDD) in asymptomatic patients with diabetes mellitus (DM). MATERIALS AND METHODS: Sixty-two patients (34 women) with long-term DM (24 with Type 1) and DAN, aged 51.7+/-13.9 years, free of coronary artery disease (CAD) or arterial hypertension (HT) at baseline, were studied for a 12-month period. Diagnosis of DAN was established if two or more of the standard cardiovascular reflex tests (CRT) were abnormal. Patients were randomly allocated to quinapril (20 mg/day), losartan (100 mg/day), or quinapril plus losartan (20 mg/day+100 mg/day). LV systolic and diastolic function was assessed using radionuclide ventriculography (RNV) at baseline and after 12 months of treatment. RESULTS: In all three treatment groups, abnormal CRT values were improved. In the quinapril group, the first third filling fraction (1/3FF, 48.9+/-17.8% vs. 39.2+/-12.9% at baseline, P=.005) was increased and the atrial contribution to ventricular filling (25.1+/-6.3 vs. 30.1+/-7.8, P=.027) was reduced in the losartan group; the peak filling rate (PFR) was improved (3.41+/-.62 vs. 3.11+/-.44 volumes/s, P=.05), and in the combination group, the 1/3FF (39.4+/-11.8% vs. 29.6+/-11.9%, P=.018) was markedly increased, while the time to peak filling (TPF; 147+/-42 vs. 184+/-33 ms, P=.02) and the TPF/filling time (TPF/FT; 32.5+/-6.2% vs. 38.2+/-5.7%, P=.016) were reduced. CONCLUSIONS: Early ACE-I or ARB improve both DAN and LVDD in asymptomatic patients with Type 1 or 2 DM, after 1 year of treatment. Their combination may be slightly better than monotherapies on DAN and LVDD. The clinical importance of these effects should be validated by larger studies.

Left ventricular systolic and diastolic function in normotensive type 1 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study.

OBJECTIVE: To investigate the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 57 type 1 diabetic patients free of coronary artery disease and arterial hypertension were studied. Diagnosis of DAN was established by autonomic nervous function (ANF) tests, and LV systolic and diastolic functions were assessed by radionuclide ventriculography at rest. RESULTS: There were 24 patients who had definite DAN, established by the presence of two or more abnormal ANF tests, and 33 subjects were without DAN. DAN patients had impaired LV filling pattern, obvious by a reduced peak filling rate (3.1 +/- 1.1 vs. 3.7 +/- 0.7 end-diastolic volume [EDV]/s, P = 0.011) and first third filling fraction (35.3 +/- 19.5 vs. 50.8 +/- 16%, P = 0.002) as well as an increased time to peak filling (159.4 +/- 45.1 vs. 134.2 +/- 33.4 ms, P = 0.02) after correction for age and heart rate. There were no differences between the two groups with regard to ejection fraction, cardiac output, and cardiac index, whereas the peak emptying rate was greater in DAN patients (4.1 +/- 0.8 vs. 3.6 +/- 0.8 EDV/s, P = 0.019), suggesting LV hypercontractility. DAN patients had an increased heart rate (83.4 +/- 11.9 vs. 72.7 +/- 9.3 bpm, P = 0.001) and slightly higher systolic blood pressure. As a result, LV working load at rest was higher in DAN patients (11,109 vs. 9,096 bpm x mmHg, P < 0.001). Moreover, a correlation was found between abnormal LV systolic and diastolic indexes and the number of abnormal ANF tests. CONCLUSIONS: At rest, DAN patients have impaired LV filling pattern, slightly increased LV systolic function, and a higher LV working load, in comparison to non-DAN type 1 diabetic patients.