Fetnat M. Fouad

Left ventricular diastolic function in hypertension: relation to left ventricular mass and systolic function

Initial studies of diastolic cardiac function in hypertension demonstrated that slowing of the maximal rate of left ventricular filling occurred before alterations in either ejection fraction or cardiac output. The present study was undertaken to determine: 1) the relation between hypertension, increased left ventricular mass and impaired left ventricular filling, and 2) the correlation between abnormalities in left ventricular diastolic function and its systolic performance. Eleven normal subjects (Group 1), 5 hypertensive patients without evidence of left ventricular hypertrophy (Group 2) and 18 hypertensive patients with increased left ventricular mass by echocardiography (Group 3) were studied by M-mode echocardiography, radionuclide (technetium-99m human serum albumin) first pass technique and gated blood pool scintigraphy. Indexes of systolic function (ejection fraction, maximal rate of ejection and percent left ventricular shortening) were essentially similar in hypertensive and normotensive subjects. No correlation was found between systolic blood pressure and left ventricular mass (r = 0.20, not significant). Maximal rate of left ventricular filling (P dV/dt) and fast filling fraction decreased progressively from Group 1 to Group 3 (2.36 +/- 0.4 [mean +/- standard deviation], 2.17 +/- 0.3 and 1.97 +/- 0.4 s-1, respectively, for P dV/dt and 46 +/- 7, 48 +/- 9 and 38 +/- 11%, respectively, for fast filling fraction); the difference from values in normal subjects reached statistical significance in hypertensive patients with left ventricular hypertrophy. Left ventricular maximal filling rate correlated inversely with left ventricular mass and left ventricular end-systolic diameter (r = -0.74), but positively with left ventricular fractional shortening and ejection fraction (r = 0.70).(ABSTRACT TRUNCATED AT 250 WORDS)

Clonidine-suppression test: a useful aid in the diagnosis of pheochromocytoma.

THE diagnosis of pheochromocytoma is considered secure when typical signs and symptoms (e.g., hypertension, sweating, palpitation, and headaches) are associated with unequivocal biochemical evidenc...

Reversal of left ventricular hypertrophy in hypertensive patients treated with methyldopa: Lack of association with blood pressure control

Ten patients with essential hypertension and left ventricular hypertrophy were treated with relatively small doses of methyldopa (500 to 750 mg/day) added to long-term diuretic therapy. Sequential M mode echocardiography showed significant reduction in left ventricular mass 36 weeks after addition of methyldopa in four patients (359 +/- 77 [standard error of the mean] to 235 +/- 63 g) although blood pressure was not significantly altered by the added treatment. In three of these patients, reduction of left ventricular mass was observed as early as 12 weeks of treatment (384 to 262 g). Neither left ventricular mass to left ventricular volume ratio nor fractional shortening was significantly altered by reduction in left ventricular mass (3.21 +/- 0.26 to 2.74 +/- 0.24 and 0.42 +/- 0.03 to 0.44 +/- 0.02, respectively). There was no apparent relation in these patients between changes in blood pressure and changes in left ventricular mass. Thus, reversal of cardiac hypertrophy with antihypertensive treatment is possible in human beings; however, it seems to depend on other factors besides blood pressure control.

Regression of left ventricular hypertrophy from systemic hypertension by enalapril

Reversal of left ventricular (LV) hypertrophy with medical therapy has been studied increasingly in patients with systemic hypertension. However, serial changes of LV function are not found during reversal of LV hypertrophy in hypertensive patients. Seven patients with LV hypertension were studied to evaluate serial changes of LV mass and function after the initiation of the new converting enzyme inhibitor MK-421. LV mass and function were determined serially at the end of a placebo period and at 5 days, 1 month, 3 months and 7 months after the initiation of MK-421, using both 2-dimensional (2-D) guided M-mode echocardiography and radionuclide techniques. All patients except 1 had LV hypertrophy and all had normal LV function (ejection fraction derived from gated blood pool method greater than 49%). There was an inverse relation between LV fractional shortening (percent FS) and end-systolic stress before medication (r = -0.81, p less than 0.05). LV mass decreased significantly at 3 months and at 7 months (-10%, p less than 0.05, and -12%, p less than 0.01, respectively) accompanied with persistent decrease of mean blood pressure, which occurred as early as 5 days after start of therapy (133 +/- 5 mm Hg at control, to 112 +/- 4 mm Hg at day 5). During reversal of LV hypertrophy, the inverse correlation between FS and end-systolic stress remained significant (r = -0.80 to -0.95, p less than 0.025 for all), with no difference from the placebo period and from this relation in the normal group. Moreover, percent FS, ejection fraction and stroke index remained unchanged. Thus, LV hypertrophy in patients with systemic hypertension can be reversed without deterioration of LV function. Moreover, overall LV function is likely to be determined by afterload even after reversal of LV hypertrophy.

Hyperkalemia in azotemic patients during angiotensin-converting enzyme inhibition and aldosterone reduction with captopril.

Thirty-three hypertensive patients with a wide range of renal function were studied during initiation of angiotensin-converting enzyme inhibition with captopril to evaluate changes in potassium levels concomitant with reduction of aldosterone excretion. Ten patients (Group I) with low levels of plasma renin activity had no change in either aldosterone excretion or potassium during the first week of therapy. Twenty-three other patients (Group II) had decreased aldosterone excretion of an average of 63 percent, often reversing secondary hyperaldosteronism. This was associated with a rise in serum potassium from 3.6 +/- 0.1 to 4.4 +/- 0.1 mEq/liter (p less than 0.001). Serum potassium levels during captopril therapy were inversely related to glomerular filtration rate (creatinine clearance) and transiently exceeded 6.0 mEq/liter in markedly azotemic subjects. Despite rising potassium levels, nine patients had reduced aldosterone excretion to subnormal levels, sometimes for many months. During initiation of converting-enzyme inhibition, potassium-sparing agents and supplements should be discontinued and serum potassium levels should be monitored closely, particularly in patients with imparied renal function.

Three cases of hypotension and syncope with ventricular pacing: Possible role of atrial reflexes

Hypotension with lightheadedness and near syncope occurred in three patients during effective ventricular pacing. Hemodynamic studies demonstrated a decrease in cardiac output ranging from almost no decrease to 15 percent, presumably related to the loss of effective atrial contraction. The decrease in output was too small to explain by itself the reduced blood pressure, which resulted from paradoxic reduction of total peripheral resistance in one patient and from failure of resistance to increase in two. Baroceptor reflexes (Valsalva response) were normal in all three patients; hence it is suggested that the failure of compensatory increases in total peripheral resistance may be due to a reflex from the sudden atrial distension that occurs during atrioventricular (A-V) dissociation. The fluctuations in arterial pressure during ventricular pacing were synchronous with the appearance of cannon waves in the right atrial pressure tracing. Arterial pressure during A-V dissociation thus appears to be balanced by two opposite reflexes: the baroceptor reflex, which attempts to compensate for reduction in output, and atrial distension, which reduces peripheral resistance.

Determinants of left ventricular hypertrophy and function in hypertensive patients: An echocardiographic study

Hypertensive patients present a wide spectrum of echocardiographic alterations. A review of these changes in 74 patients (37 untreated and 37 treated) revealed left ventricular hypertrophy in 43 (58 percent). There was no significant difference between treated and untreated patients in regard to either the prevalence of left ventricular hypertrophy or of its various subtypes [concentric left ventricular hypertrophy in 15 (20.3 percent), asymmetric septal hypertrophy in 16 (21.6 percent), and combined left ventricular hypertrophy and dilation in 12 (16.2 percent)]. None of the patients who showed asymmetric septal hypertrophy had abnormal motion of the mitral valve. Cardiac performance as judged by left ventricular percent shortening was related inversely to end-systolic stress (p less than 0.001) and positively to the ratio of end-systolic pressure/end-systolic volume (an index of myocardial contractility) (p less than 0.01). Multiple regression analysis showed an increased dependence on afterload (end-systolic stress), when left ventricular hypertrophy developed and especially when it was associated with left ventricular dilation.

A COOPERATIVE MULTICENTER STUDY OF CAPTOPRIL IN CONGESTIVE HEART FAILURE: HEMODYNAMIC EFFECTS AND LONG-TERM RESPONSE

The acute hemodynamic effects, long-term clinical efficacy, and safety of the oral angiotensin-converting enzyme inhibitor, captopril, were assessed in a multicenter cooperative study of 124 patients with heart failure resistant to digitalis and diuretics. The cardiac status of most patients was deteriorating prior to the study. Favorable acute hemodynamic effects consistently occurred with captopril. Maximal mean percentage increases in cardiac index, stroke index, and stroke work index were, respectively, 35%, 44%, and 34%. Systemic and pulmonary vascular resistances were each decreased by approximately 40%, as were the filling pressures of the right and left heart. Infusion of nitroprusside in some of the same patients to an end point of a pulmonary capillary wedge pressure of 12 to 18 mm Hg (equivalent to that after captopril) revealed no significant difference in the effect of either drug on the other hemodynamic parameters. Recatheterization after 8 weeks of captopril therapy revealed sustained hemodynamic changes. Significant and sustained improvements in clinical status were observed in most patients as measured by changes in New York Heart Association (NYHA) functional classification and exercise tolerance times. Seventy-nine percent of patients for whom there were adequate NYHA class data improved. Twenty percent remained unchanged and 1% deteriorated. Those patients who had both pretreatment and post-treatment exercise stress testing exhibited a highly significant mean increase in exercise tolerance times of 34% (317 +/- 32 seconds pretreatment to 425 +/- 34 seconds, final measurement). There was no evidence of tachyphylaxis over an 18-month period.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and volume changes associated with captopril.

SUMMARY The effects of captopril on bemodynamic, rolmne, and neurohumoral indices were inrestigated in 33 patients with essential hypertension or renal arterial disease. Changes associated with treatment were studied under two conditions: immediately (V4 to 1 boar) after administration of the drug, or after 5 to 7 days of therapy. Blood pressure (BP) reduction in both conditions was due to a reduction in total peripheral resistance (TPR) (r = 0.714, p < 0.001 for A MAP / TPR); there was no significant change in either cardiac output or heart rate. The immediate BP and TPR responses were significantly related to pretreatment plasma renin activity (PRA) (r = 0.737, p < 0.001), but this correlation was much weaker (r - 0392, p > 0.50) after maintained treatment. Response to therapy could not be predicted from either bemodynamic or volume characteristics of the patients (r - 0.265, NS for A MAP / TBV and -0.262, NS for A MAP / cardiac output). There was no significant change in body weight during treatment, while plasma volume Increased slightly (+7% ± 2.8 SE, p < 0.05) but only in those patients who maintained a good BP response to captopril. Simultaneously, plasma aldosterone (PA) levels were reduced in relation to pretreatment level (r = 0.955, p < 0.001). Thus, whereas the hemodynamic pattern of response to captopril remained unchanged during therapy, its relationship to pretreatment PRA became progressively weaker. The clinical antihypertensive effectiveness of captopril was therefore not related to either humoral, hemodynamic, or volume characteristics of this group of patients. The unusual pattern of lack of significant plasma volume expansion during therapy might be related in part to sustained reduction of plasma aldosterone levels.

Regulation of Renal Hemodynamics and Glomerular Filtration in Patients with Renovascular Hypertension During Converting Enzyme Inhibition with Captopril

Changes in regional hemodynamics and function of the kidney during inhibition of angiotensin converting enzyme were studied in 25 patients with renovascular hypertension. A variety of patterns were observed depending upon (1) the activity of the renin-angiotensin system and concomitant administration of diuretics, and (2) the presence of bilateral renal artery stenosis. Increase in blood flow, glomerular filtration rate and sodium excretion during angiotensin blockade, in some instances, indicated tonic renal vasoconstriction before therapy. Release of the kidney from these effects may explain, in part, the sustained effectiveness of converting enzyme inhibition in chronic congestive heart failure. When compared with blood pressure reduction due to nitroprusside administration, initial captopril therapy in patients with unilateral stenosis produced a selective decrease in glomerular filtration, despite well-preserved renal blood flow. These results confirm the importance of efferent arteriolar vasoconstriction due to angiotensin II in man. Experimental studies demonstrate that angiotensin may become critical to sustaining glomerular filtration rate in the presence of stenosis during vasodilation. In patients with bilateral stenosis, this effect produces a syndrome of functional renal insufficiency. Taken together, these data demonstrate an intrarenal action of angiotensin II in human renovascular hypertension and underscore the importance of evaluating the functional impact of changes in regional hemodynamics.