Regression of left ventricular hypertrophy in patients with essential hypertension. Results of 6 month treatment with indapamide.

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity in hypertensive patients. The effects of diuretics on LVH have raised controversies, but recent studies suggest that diuretics are able to reduce LVH in hypertensive patients, mainly through a reduction in ventricular diameter. The present multicenter open study was designed to test the effects of indapamide, a widely used nonthiazide diuretic, on LVH in patients with essential hypertension. Patients had to have mild-to-moderate essential hypertension (supine diastolic blood pressure [sDBP] 95 to 115 mm Hg) with echocardiographic evidence of LVH (left ventricular mass index [LVMI] > 130 g/m2 for men and > 110 g/m2 for women). After a 2 week placebo run-in period, eligible patients underwent a 6 month treatment with 2.5 mg indapamide daily. All echograms were performed by the same investigator before and after 6 months of indapamide. Clinical and biological acceptability and quality of life (visual analog scale) were also studied. One hundred and thirty patients were included in the study and 112 completed the trial. Indapamide induced a significant reduction i systolic and diastolic blood pressures. Indapamide induced a marked reduction in posterior wall thickness (from 12.1 +/- 2.0 to 11.2 +/- 1.6 mm) and in interventricular wall thickness (from 12.7 +/- 1.7 to 11.8 +/- 1.9 mm; each P < .001) and a slight decrease in left ventricular diameter (P = .049). This resulted in a 13% reduction in LVMI (from 161.9 +/- 37.9 to 140.7 +/- 33.8 g/m2, P < .001). Left ventricular fractional shortening remained unchanged. There was no significant relation between changes in LVMI and changes in systolic, diastolic, or mean blood pressure. No significant adverse clinical or biological effects were reported during the study. The increased score of the visual analog scale indicated that overall well-being was improved (P < .001). Our study indicates that indapamide, in addition to blood pressure control, is able to reduce LVH. This effect was achieved mainly through a reduction in wall thicknesses rather than in internal cavity diameter.

[Renal hemosiderosis caused by chronic hemolysis in a patient with a Saint-Jude mitral valve prosthesis]. / Hémosidérose rénale par hémolyse chronique sur valve de Saint-Jude en position mitrale.

The authors report a case of renal hemosiderosis in a 33 year old patient with mitral valve replacement with a Saint Jude Medical prosthesis. Chronic, well-tolerated hemolysis developed after surgery and a peri-prosthetic leak was demonstrated. Alteration of renal function and abnormalities on urinalysis led to renal biopsy which showed massive localised hemosiderosis, mainly in the interstitial tissues. Repeat mitral valve replacement led to a regression of the hemolysis. Significant hemolysis in patients with mechanical cardiac valves prostheses should lead to investigation of prosthetic valve function and, if dysfunction is demonstrated, the patient should be considered for reoperation because of the potential severity of renal complications.

Improvement in left ventricular hypertrophy and left ventricular diastolic function following verapamil therapy in mild to moderate hypertension.

We evaluated the effect of verapamil therapy on left ventricular hypertrophy and left ventricular diastolic function in 13 patients with mild to moderate hypertension. Left ventricular hypertrophy was determined by M-mode echocardiographic measurements of interventricular septal thickness (IVST), posterior wall thickness (PWT) and left ventricular mass index (LVMI) both before (T0) and after 3 months (T3) of verapamil therapy. Left ventricular diastolic transmitral flow was measured by pulsed Doppler indices of early (E) and atrial (A) velocity, E/A ratio, total area (Ta), A area (Aa), Aa/Ta ratio, E-pressure half-time (E-PHT). A-pressure half-time (A-PHT) and E-PHT/A-PHT ratio both before and after 3 months of verapamil therapy. No significant changes occurred in mean heart rate, systolic function or body weight. We conclude that 3 months' therapy with verapamil resulted in an improvement in left ventricular hypertrophy and left ventricular diastolic function and a normalization of blood pressure, without a corresponding deterioration in left ventricular systolic function.

Correlations between M-mode markers of left ventricular hypertrophy and radionuclide angiographic indices of left ventricular diastolic function in mild to moderate hypertension.

This study was undertaken to determine the correlations between left ventricular hypertrophy and left ventricular diastolic function in mild to moderate essential hypertension. M-mode echocardiography and rest equilibrium radionuclide angiography were performed in 53 hypertensive subjects. The following M-mode echocardiographic parameters were measured: interventricular septal thickness, posterior wall thickness, left ventricular mass index, left atrial diameter and relative wall thickness. The following radionuclide angiography parameters were measured: ejection fraction, peak filling rate, time to peak filling rate, first third filling fraction and atrial contribution to total filling. Weak correlations were shown between left ventricular diastolic function and the M-mode echocardiographic parameters. The peak filling rate was negatively correlated with the interventricular septal thickness (r = -0.345; P less than 0.05), with the sum of the interventricular septal thickness and the posterior wall thickness (r = -0.395; P less than 0.01), with the left atrial diameter (r = -0.345; P less than 0.05), and with the relative wall thickness (r = -0.297; P less than 0.05). The time to peak filling rate was positively correlated with the left ventricular mass index (r = + 0.310; P less than 0.05) and with the left atrial diameter (r = + 0.323; P less than 0.05). These findings suggest that diastolic abnormalities in hypertensive heart disease are only in part related to the degree of left ventricular hypertrophy.

Verapamil interacts in vitro with alpha 2-adrenoceptors but does not modify alpha 2-receptivity in vivo.

The kind of interaction of two structurally different calcium channel blockers (verapamil and nicardipine) with both alpha 2-adrenergic agonist and antagonist binding on human platelets was investigated. Only verapamil, but not nicardipine, interacted in vitro with platelet alpha 2-adrenoceptors on [3H]-yohimbine or [3H]-UK 14,304 binding. Verapamil behaves as a weak antagonist competitor for alpha 2-adrenoceptors. In patients with mild essential arterial hypertension, the number of platelet alpha 2-adrenoceptors as well as velocity of aggregatory response to adrenaline, are significantly decreased: -21 and -25%, respectively (p less than 0.05). Verapamil (120 mg t.i.d. orally during 1 month) failed to modify the platelet alpha 2-adrenoceptor number or the adrenaline-induced platelet aggregation in hypertensive patients. These results show that, although interacting in vitro, verapamil does not modify the alpha 2-adrenergic receptivity after 1 month treatment in humans.

[Study of left ventricular diastolic function using pulsed Doppler in myocardial infarct in hypertensive subjects]. / Etude de la fonction ventriculaire gauche diastolique par doppler pulsé dans l'infarctus du myocarde chez l'hypertendu.

To determine if impairment of left ventricular filling is influenced by acute myocardial infarction in patients with arterial hypertension, left ventricular diastolic function was assessed by pulsed doppler echocardiography in 46 patients (pts) subdivided into four groups (Gr): G.1 (n = 12 pts) with acute myocardial infarction and hypertensive heart disease. G.2 (n = 12 pts) acute myocardial infarction without arterial hypertension. G.3 (n = 10 pts) arterial hypertension without history of coronary artery disease. G.4 (n = 12 pts) healthy subjects. Coronary angiography and left ventricular cineangiogram was performed in 24 pts (G.1 + G.2). Peak mitral flow velocity (cm/s) in early diastole (E), atrial systole (A), A/E and int A/int E ratios were measured by pulsed doppler. Age and heart rate were statistically similar in all groups. No difference was found among G.1 and G.2 in ejection fraction, and left ventricular segmental kinetic. (tables; see text) Conclusion left ventricular filling is impaired in pts with arterial hypertension and in pts with acute myocardial infarction; acute myocardial infarction increase the impairment of left ventricular diastolic function in pts with hypertensive heart disease.

[Alpha 2-adrenergic receptors and arterial pressure]. / Récepteurs alpha 2-adrénergiques et pression artérielle.

The aim of this work was to investigate the influence of blood pressure levels on human platelet alpha 2-adrenergic receptivity. The study was carried out on 12 mild essential hypertensive patients and 7 normotensive parkinsonians with orthostatic hypotension. Alpha 2-adrenoceptors number and affinity were determined by 3H-yohimbine binding, plasma catecholamines were measured by HPLC and adrenaline-induced platelet aggregation by turbidimetry. Results obtained were compared with those of two groups of 12 normotensive control subjects. In hypertensive patients, both platelet alpha 2-adrenoceptors (139 +/- 6 vs 176 +/- 18 fmol/mg protein) and velocity of adrenaline-induced platelet aggregation were decreased whereas plasma adrenaline and noradrenaline remained unchanged. In patients with orthostatic hypotension, there was an increased number of platelet alpha 2-adrenoceptors (313 +/- 52 vs 168 +/- 8 fmol/mg protein) associated with a significant decrease in plasma noradrenaline (62 +/- 11 vs 190 +/- 25 pg/ml). In none of the two groups of patients there was any change in receptor affinity for 3H-yohimbine. These results indicate that human platelet alpha 2-adrenoceptors levels are related to blood pressure values. Moreover, up-regulation in orthostatic hypotension and lack of down-regulation in essential hypertension suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptors regulatory mechanisms. These variations can represent tentative compensatory mechanisms for normalization of blood pressure levels.

A multicenter double-blind comparative study of rilmenidine and clonidine in 333 hypertensive patients.

The efficacy and acceptability of rilmenidine were studied in a double-blind clonidine-controlled multicenter trial; after a 4-week placebo run-in period, patients with supine diastolic blood pressure (BP) between 95 and 115 mm Hg received as monotherapy either rilmenidine or clonidine over 6 weeks. The initial dose (rilmenidine 1 mg/day or clonidine 0.15 mg/day) was doubled (1 mg or 0.15 mg twice a day, respectively) after 2 weeks if diastolic BP remained greater than or equal to 90 mm Hg. Three hundred and thirty-three patients (mean age 57.8 +/- 0.7 years) with a systolic BP of 170.53 +/- 0.92 mm Hg and a diastolic BP of 101.57 +/- 0.30 mm Hg were randomly divided into 2 homogenous groups (rilmenidine, n = 162 and clonidine, n = 171). All patients taking rilmenidine completed the trial. Seventeen patients taking clonidine (10%, p less than 0.01 vs rilmenidine) were withdrawn because of severe side effects. Systolic and diastolic BP were significantly reduced in both groups at every examination (at 2, 4 and 6 weeks). The mean decreases in supine and erect BP were identical in both groups: systolic BP 19 mm Hg and diastolic BP 12 mm Hg after 6 weeks. BP was normalized (systolic BP less than 160 and diastolic BP less than or equal to 90 mm Hg) in 57% of patients taking rilmenidine and 56% of patients taking clonidine (60% of normalized patients had been taking the single dose in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)