Effects of one-year treatment with rilmenidine on systemic hypertension-induced left ventricular hypertrophy in hypertensive patients

In patients with essential hypertension, left ventricular hypertrophy (LVH) increases the risk for cardiovascular morbidity and mortality. Thus its reversal represents one of the principal endpoints of antihypertensive treatment. We assessed the cardiovascular effects of 1-year antihypertensive treatment with rilmenidine (1 or 2 mg/day orally), a new oxazoline with a potent antihypertensive action that acts selectively through imidazoline-preferring receptors. In 11 hypertensive patients (mean age, 49 ± 2 years) with LVH, we measured systemic hemodynamics, large artery compliance, cardiac anatomy, and endocrine function. Patients underwent M-mode and 2-dimensional echocardiography as well as Doppler and peripheral pulsed Doppler flowmetry, determination of plasma atrial natriuretic factor (ANF) levels and renin activity (PRA), and of 24-hour urinary electrolyte and creatinine excretion in control conditions (systolic/diastolic blood pressure, 148 ± 3/102 ± 1 mm Hg), 4 weeks after blood pressure normalization (131 ± 2/84 ± 2 mm Hg; p < 0.01), after 1 year of satisfactory antihypertensive treatment (142 ± 3/90 ± 1 mm Hg; p <0.01) and, finally, 1 month after therapy withdrawal (155 ± 3/106 ± 2 mm Hg; difference not significant [NS]). One-year of rilmenidine treatment induced an improvement in brachial artery compliance (from 0.92 ± 0.06 to 1.16 ± 0.08 cm⁴/dyne; p <0.05), which persisted after withdrawal of treatment (1.17 ± 0.06 cm⁴/ dyne; p <0.05). LVH was reversed after 1 year of rilmenidine treatment (from 152 ± 5 to 131 ± 4 g/m² body surface area; p <0.05). Finally, PRA and urinary electrolyte excretion did not change throughout the study, and ANF remained unchanged after blood pressure normalization (48.4 ± 6.2 vs 44.7 ± 2.9 pg/mL; difference not significant) but fell after reversal of LVH (28.6 ± 3.4 pg/mL; p <0.05) and remained significantly lower than in control conditions after therapy withdrawal (27.5 ± 2.9 pg/mL; p <0.05). Our results demonstrate that long-term antihypertensive treatment with rilmenidine is able to induce a reversal of LVH and of the vascular structural changes associated with essential hypertension. In addition, they indicate that rilmenidine-induced regression of LVH is associated with significant and persistent reduction of ANF levels, which may suggest a favorable influence of the drug with the biosynthetic properties of ventricular myocardium.     

Experimental right ventricular hypertrophy and failure in swine.

Following pulmonary arterial constriction, 22 pigs developed right ventricular failure and 10 right ventricular hypertrophy. Comparing results with those obtained in 21 normal pigs (no pulmonary artery constriction), it was found the right ventricular peak systolic and end-diastolic pressures, cardiac output, and right ventricular weight distinguished hypertrophied and failing hearts from normal ones. Cardiac output was lower in failing hearts than in hypertrophied hearts and was the only variable which significantly differentiated between these two groups. Left ventricular pressures and left ventricular and right ventricular dP/dtmax, and maximum [(dP/dt)/P] did not distinguish failing from hypertrophied hearts. Left ventricular pressure, maximum [(dP/dt)/P] and left ventricular and right ventricular dP/dtmax were not significantly different in the three groups.     

Usefulness of echocardiographic right ventricular measurements in estimating right ventricular hypertrophy and right ventricular systolic pressure

Right ventricular wall thickness (T) measurements were made in 111 patients by echocardiography to evaluate their usefulness in diagnossing right ventricular hypertrophy (RVH) and in predicting right ventricular peak systolic pressure (P). Anatomic and echocardiographic findings of RVH were compared in 36 of 111 subjects: diastolic T (dT) and systolic T (sT) had a sensitivity of 90 and 34% and a specificity of 94 and 100%, respectively, in the diagnosis of RVH. Echocardiographic and hemodynamic findings were compared in the remaining 75 of 111 patients undergoing cardiac catheterization: dt was 6.5 +/- 2.7 mm in 46 patients with elevated P (58.2 +/- 30.2 mm Hg) versus 3.8 +/- 0.9 in 29 patients with normal P (26.3 +/- 2.7 mm Hg) (p less than 0.01). The dT and P had a linear correlation (r = 0.92) in 40 patients with right ventricular end-diastolic dimension less than 13 mm/m2. Estimates of P in 22 patients with atrial septal defect and right ventricular end-diastolic dimension greater than 13 mm/m2 were fairly good (r = 0.83). It is concluded that echocardiographic measurements of T are useful in diagnosing RVH and in estimating P.     

Significance of ventricular arrhythmias in systemic hypertension with left ventricular hypertrophy.

Hypertensive patients with the electrocardiographic (ECG) pattern of left ventricular (LV) hypertrophy and strain are at increased risk of sudden death. It has been suggested that ventricular arrhythmias may be responsible. The prevalence and significance of ventricular arrhythmias was therefore studied in 90 hypertensive patients with LV hypertrophy and strain by undertaking 48-hour ambulatory ECG monitoring, ECG signal-averaging and programmed ventricular stimulation. Complex ventricular ectopic activity (Lown grade greater than or equal to 3) was detected in 59 patients (66%). Eleven patients (12%) had episodes of nonsustained ventricular tachycardia. There were no sustained arrhythmias either on ambulatory ECG monitoring or induced by programmed ventricular stimulation. Only 1 patient had ventricular late potentials recorded by the signal-averaged electrocardiogram. Therefore, there was little to suggest an underlying arrhythmogenic substrate in these patients. In conclusion, whereas ventricular arrhythmias occur often in patients with LV hypertrophy associated with systemic hypertension, their significance, if any, remains to be established.     

Echocardiographic detection of right ventricular hypertrophy

M-mode echocardiographic right ventricular wall thickness (RVW) and diastolic right ventricular internal diameter (RVID), when above the accepted normal range (RVW less than or equal to 5 mm, RVID less than or equal to 26 mm), are frequently used clinically to predict the presence of right ventricular hypertrophy. RVID was compared to anatomic right ventricular mass (RVM) in 27 patients and to RVW in 13 patients to determine their accuracy for predicting right ventricular hypertrophy (RVM greater than 65 gm). When increased, both measurements were specific for right ventricular hypertrophy. The specificity for RVW above 5 mm was 100% and for RVID greater than 26 mm was 79%. Neither was a sensitive indicator of hypertrophy. Only 36% of those with anatomic right ventricular hypertrophy had an echocardiographically dilated ventricle, and 67% had a thickened free wall. Neither measurement proved to be an accurate predictor of RVM, with a correlation for RVW of 0.56 and for diastolic RVID of 0.19.     

Left ventricular midwall mechanics in systemic arterial hypertension. Myocardial function is depressed in pressure-overload hypertrophy

BACKGROUND. Left ventricular (LV) midwall geometry has been described conventionally as the sum of the chamber radius and half of the wall thickness; this convention is based on the assumption of uniform transmural thickening during systole. However, theoretical considerations and experimental data indicate that the inner half (inner shell) of the LV wall thickens more than the outer half (outer shell). Thus, an end-diastolic circumferential midwall fiber exhibits a relative migration toward the epicardium during systole. As a result, the conventional method provides an overestimate of the extent of the midwall fiber shortening. METHODS AND RESULTS. We developed an ellipsoidal model with a concentric two-shell geometry (nonuniform thickening) to assess midwall fiber length transients throughout the cardiac cycle. This modified midwall method was used in the analysis of LV cineangiograms from 15 patients with systemic arterial hypertension and 14 normal subjects. Study groups were classified according to LV mass index (LVMI): 14 normal subjects (group I), eight hypertensive patients with a normal LVMI (group II), and seven hypertensive patients with an increased LVMI (group III). There were no significant differences in LV end-diastolic pressure or volume among the three groups; the ejection fraction was slightly greater in group II (70 +/- 5%) than in groups I (65 +/- 8%) and III (66 +/- 4%), but this trend did not achieve statistical significance. Values for endocardial and conventional midwall fractional shortening (FS) were also similar in the three groups. By contrast, FS by the concentric two-shell geometry (modified midwall method) in group III (16 +/- 2%) was significantly less than that seen in groups I and II (21 +/- 4% and 21 +/- 5%, respectively; both p less than 0.05). This difference achieves greater importance when it is recognized that mean systolic circumferential stress was lower in group III (151 +/- 22 g/cm2) than in groups I and II (244 +/- 37 g/cm2 and 213 +/- 38 g/cm2, respectively; both p less than 0.01). The midwall stress-shortening coordinates in six of the seven group III patients were outside the 95% confidence limits for the normal (group I) subjects. Thus, despite a normal ejection fraction, systolic function is subnormal in hypertensive patients with LV hypertrophy. CONCLUSIONS. Chamber dynamics provide an overestimate of myocardial function, especially when LV wall thickness is increased. This is due to a relatively greater contribution of inner shell thickening in pressure-overload hypertrophy.     

Electrocardiographic recognition of right ventricular hypertrophy

The electrocardiogram (ECG) is a relatively insensitive tool for the detection of right ventricular hypertrophy (RVH), but some criteria have high specificity. The recommended ECG screening criteria for RVH are not sufficiently sensitive or specific for screening for mild RVH in adults without clinical cardiovascular disease. The greatest accuracy of the ECG is in congenital heart disease, with intermediate accuracy in acquired heart disease and primary pulmonary hypertension in adults.     

Effects of indapamide on left ventricular mass and function in systemic hypertension with left ventricular hypertrophy

Left ventricular hypertrophy (LVH) is frequently associated with hypertension and constitutes a major cardiovascular risk factor, the reduction of which should be considered when initiating antihypertensive therapy. To assess the effects of indapamide on LVH, 18 hypertensive patients were included in the study (11 men and 7 women, age 53.6 +/- 2.9 years, mean +/- standard deviation) whose supine diastolic blood pressure was greater than 95 mm Hg without (n = 11) or with (n = 7:6 beta blockers, 1 calcium antagonist) antihypertensive therapy. All presented with LVH, echocardiographically defined by a left ventricular mass index greater than 110 g/m2. After a 2-week preinclusion period, all patients received indapamide, 2.5 mg/day, for a period of 6 months. Physical examination including blood pressure measurement was performed on selection (M-1/2), before (M0), and after 1 (M1), 3 (M3) and 6 (M6) months of indapamide treatment, and echocardiography was performed at M0 and M6. Quality of life was evaluated by means of questionnaires completed by the patient and the physician, and a visual analog scale was completed by the patient at M-1/2, M0 and M6. All clinical parameters remained stable during the 2-week preinclusion period. Indapamide administration induced a highly significant reduction in both supine systolic and diastolic blood pressures from 173.9 +/- 2.9/100.5 +/- 1.2 mm Hg at M0 to 150.9 +/- 1.9/90.5 +/- 1.3 mm Hg at M1 (p less than 0.001), and 145.0 +/- 1.7/86.0 +/- 1.5 mm Hg at M6 (p less than 0.001). Similar favorable effects were observed in the upright position.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular function in exercise-induced hypertrophy in dogs.

Indexes of left ventricular function and diastolic compliance were studied in 10 awake exercise-trained greyhounds with left ventricular hypertrophy. Mean left ventricular to body weight ratio and mean myocardial cell diameter were significantly greater than in normal dogs (8.73 +/- 2.7 [standard error of the mean] versus 4.63 +/- 0.24 g/kg, P less than 0.01; and 18.3 +/- 0.67 versus 12.5 +/- 0.71 mu, P less than 0.01, respectively). In awake resting animals, 7 to 50 days after implantation of a high fidelity micromanometer and sonomicrometer crystals, left ventricular contractility indexes were similar to those measured previously in normal dogs (maximal derivative of left ventricular pressure [dP/dt] 3,800 +/- 250 versus 3,810 +/- 330 mm Hg/sec, difference not significant; and mean rate of circumferential fiber shortening 1.54 +/- 0.12 versus 1.43 +/- 0.12 sec-1, difference not significant). During volume loading sufficient to produce a left ventricular end-diastolic pressure of 20 mm Hg, changes in contractility indexes were similar to those in normal dogs; however, heart rate increased significantly (74 percent, P less than 0.005) in the trained greyhounds but not in normal dogs. Left ventricular diastolic stiffness did not differ from normal (51.6 +/- 3.0 versus 45.9 +/- 5.9 mm Hg/cm, P less than 0.01). These findings suggest that left ventricular function in exercise-induced left ventricular hypertrophy is substantially normal.     

Transient severe isolated right ventricular hypertrophy in neonates

We report two instances of transient isolated right-sided myocardial hypertrophy in patients with an intact ventricular septum, normal thickness of the posterior wall of the left ventricle, and normal ventricular function, diagnosed by echocardiography on the third day of life. The two neonates, born at 36 and 38 weeks gestation respectively, had perinatal distress. Both were diagnosed as having isolated right ventricular hypertrophy with mild pulmonary hypertension, which disappeared in both cases within 8 weeks without any specific therapy. Though the cause of the ventricular hypertrophy remains unclear, we believe that it is the consequence of remodeling of pulmonary vasculature secondary to acute perinatal distress, resulting in persistent pulmonary hypertension and producing pressure overload on the right ventricle, and hence right ventricular hypertrophy. The finding of early and transient right ventricular hypertrophy, with normal left-sided structures and normal ventricular function, has thus far failed to gain attention in the paediatric cardiologic literature.     

Myocyte morphological characteristics differ between the phases of pulmonary hypertension-induced ventricular hypertrophy and failure

Pulmonary hypertensive model rats were prepared by treating them with monochrotaline (MCT). Using these model rats, we examined myocyte remodeling in the right ventricle in response to increased right ventricular pressure. Male Sprague-Dawley rats were divided into 2 groups. Group M received MCT and group C received physiological saline. The 2 groups were examined at weeks 2, 5, and 7 after MCT or saline injection, respectively. At week 2, a significant difference in cell form was not observed in either group. At week 5, cell volume and myocyte cross-sectional area (CSA) of the right ventricle in group M were significantly greater than those in group C. At week 7, cell volume, CSA, and cell length of the right ventricle in group M were all significantly greater than those in group C. These results suggest that pulmonary hypertension causes hypertrophy, accompanying the enlargement of CSA in the right ventricle, and that cells lengthen in the phase of right ventricular failure. These results are similar to the changes observed in left ventricular myocytes due to overload pressure. Both right and left ventricular myocytes may share a common mechanism for myocyte remodeling as an adaptive and maladaptive response to increased ventricular pressure.     

Roentgenometry in the diagnosis of right ventricular hypertrophy

The diagnostic value of roentgenometrically enlarged second arc of the anterior heart's shadow outline, a roentgenologic sign of right ventricular hypertrophy, is discussed. A study of 30 patients with various acquired and congenital valvular defects showed the enlargment of this arc, which is normally not more than 3.5 cm long and 0.5 cm wide, to be a reliable sign of right ventricular hypertrophy, as verified by ECG findings, and direct as well as the second oblique roentgenographic projections. Three degrees of the enlargment of the second arc in the heart's shadow anterior outline were distinguished in the first oblique projection. This arc is not evident in patients with electrocardiographic signs of right ventricular diastolic overloading.