Boyd E. Terry

Relation of Duration of Morbid Obesity to Left Ventricular Mass, Systolic Function, and Diastolic Filling, and Effect of Weight loss

Longer duration of morbid obesity is associated with higher LV mass, poorer LV systolic function, and greater impairment of LV diastolic filling. Weight loss-induced decreases in LV mass and improvements in LV systolic function and diastolic filling are due in part to favorable alterations in LV loading conditions.

Cardiac Morphology and Left Ventricular Function in Normotensive Morbidly Obese Patients With and Without Congestive Heart Failure, and Effect of Weight Loss

To assess cardiac morphology and left ventricular (LV) function in normotensive morbidly obese patients with and without congestive heart failure (CHF) we performed a physical examination and obtained a transthoracic echocardiogram and cardiac Doppler studies before and after substantial weight loss in patients whose actual body weight was initially equal to or more than twice their ideal body weight and who were free from systemic hypertension and underlying organic heart disease. There were 24 patients with CHF, 14 of whom were studied after weight loss. There were 50 patients without CHF, 39 of whom were studied after weight loss. Compared to patients without CHF, those with CHF had significantly greater mean LV internal dimension in diastole, LV end-systolic wall stress, LV mass/height index values, left atrial dimension and right ventricular internal dimension values, significantly lower mean LV fractional shortening, and transmitral Doppler E/A ratio values, and significantly longer mean transmitral E-wave deceleration time and duration of morbid obesity than patients without CHF. Substantial weight loss in those with and without CHF produced comparable reductions in mean LV internal dimension in diastole, LV end-systolic wall stress, LV mass/height index, transmitral Doppler E-wave deceleration time, and left atrial dimension, and comparable increases in LV fractional shortening and transmitral Doppler E/A ratio. Linear regression analysis identified duration of morbid obesity as the strongest predictor of CHF (p <0.00000002). Thus, LV mass is greater and LV systolic function and diastolic filling are more impaired in normotensive morbidly obese subjects with CHF than in those without CHF. Duration of morbid obesity is the strongest predictor of CHF among the variables studied. Substantial weight loss produces comparable changes in cardiac morphology and function in those with and without CHF.

Effect of weight loss on cardiac chamber size, wall thickness and left ventricular function in morbid obesity

To determine cardiac chamber size, wall thickness and left ventricular (LV) systolic function in morbidly obese patients, M-mode and cross-sectional echocardiography was performed in 62 patients whose body weight was greater than or equal to twice their ideal weight but who were free from underlying organic heart disease and systemic hypertension. The initial clinical protocol consisted of a medical history, physical examination, electrocardiogram at rest, chest x-ray and echocardiogram. Thereafter, each patient underwent gastric restriction. Thirty-four patients returned for follow-up echocardiography 4.3 +/- 0.3 months after substantial weight loss was achieved. For the whole group (n = 62) and LV internal dimension in diastole was enlarged in 24 (39%), the right ventricular internal dimension was enlarged in 20 (32%), the left atrial dimension was enlarged in 25 (40%) and the ventricular septal and LV posterior wall thickness was increased in 35 (56%). In the 34 patients who returned for follow-up, mean body weight decreased significantly, from 135 +/- 8 to 79 +/- 6 kg (73 +/- 4% of the amount over ideal body weight). In the subgroup with low preoperative LV fractional shortening (n = 13), mean LV fractional shortening increased from 22 +/- 2% to 31 +/- 2% (p less than 0.01). This was accompanied by a significant decrease in the mean LV internal dimension in diastole and mean blood pressure. The results indicate that cardiac chamber enlargement, LV hypertrophy and LV systolic dysfunction occur frequently in morbidly obese patients and that LV systolic dysfunction in such persons may improve following substantial weight loss.

Pharmacological Characterizations of Adrenergic Receptors in Human Adipocytes

Three types of adrenergic receptors, beta, alpha-1, and alpha-2, were identified in human adipocytes, isolated from properitoneal adipose tissue, using both the binding of radioactive ligands and the effects of adrenergic agents on receptor-specific biochemical responses. Adrenergic binding studies showed the following results: [(3)H]dihydroalprenolol binding (beta adrenergic) B(max) 280 fmol/mg protein, K(D) 0.38 nM; [(3)H]para-aminoclonidine binding (alpha-2 adrenergic) B(max) 166 fmol/mg protein, K(D) 0.49 nM; [(3)H]WB 4101 binding (alpha-1 adrenergic) B(max) 303 fmol/mg protein, K(D) 0.86 nM. In adipocytes from subcutaneous adipose tissue, [(3)H]dihydroergocryptine binding indicated the presence of alpha-2 but not alpha-1 receptors. Beta and alpha-2 adrenergic receptors appeared to be positively and negatively coupled to adenylate cyclase, respectively. Cells or cell membranes were incubated with epinephrine (10 muM) alone and in combination with the antagonists yohimbine (alpha-2) and prazosin (alpha-1). Epinephrine alone prompted a modest increase in adenylate cyclase activity, cyclic AMP, and glycerol release, an index of lipolysis. Yohimbine (0.1 muM) greatly enhanced these actions whereas prazosin was without effect. The beta agonist, isoproterenol, stimulated glycerol release, whereas the alpha-2 agonist, clonidine, inhibited lipolysis and cyclic AMP accumulation. To assess further alpha-1 receptors, cells were incubated with [(32)P]phosphate and epinephrine (10 muM) alone and in combination with prazosin and yohimbine. Epinephrine alone caused a three- to fourfold increase in (32)P incorporation into phosphatidylinositol. Prazosin (0.1 muM) blocked this action whereas yohimbine (0.1 muM) was without effect. Thus, in a homogeneous cell preparation, the human adipocyte appears to have three different adrenergic receptors, each of which is coupled to a distinct biochemical response.

Influence of left ventricular mass on left ventricular diastolic filling in normotensive morbid obesity

To identify factors influencing left ventricular (LV) diastolic filling in patients with morbid obesity, we performed transthoracic and Doppler echocardiography on 50 subjects whose actual body weight was > or = twice their ideal body weight and on 50 normal lean control subjects. The transmitral Doppler E/A ratio and E wave deceleration half-time were used to assess LV diastolic filling. Significant negative correlations were seen between the E/A ratio and the LV internal dimension in diastole (r = 0.819, p = 0.0001), systolic blood pressure (r = 0.751, p = 0.0001), LV end-systolic wall stress (r = 0.782, p = 0.0001), and LV mass/height index (r = 0.901, p = 0.0001). Significant positive correlations were seen between the E wave deceleration half-time and the LV internal dimension in diastole (r = 0.743, p = 0.0001), systolic blood pressure (r = 0.789, p = 0.0001), LV end-systolic wall stress (r = 0.828, p = 0.0001), and LV mass/height index (r = 0.831, p = 0.0001). No correlation was seen between diastolic blood pressure and either index of LV diastolic filling. Thus increasing LV mass is associated with progressive impairment of LV diastolic filling in morbidly obese individuals. The aforementioned alterations in LV loading conditions may contribute to impairment of LV diastolic filling directly or by increasing LV mass.

The electrocardiogram in morbid obesity

Electrocardiographic variables that occurred with significantly higher frequency in morbidly obese patients than in lean controls were low QRS voltage, leftward shift of the P, QRS, and T axes and multiple electrocardiographic criteria for left ventricular hypertrophy and left atrial enlargement. P-terminal force, RaVL, SaVR, and R/S ratio in lead V1 values were significantly higher in morbidly obese than in lean subjects.

Factors influencing left ventricular systolic function in nonhypertensive morbidly obese patients, and effect of weight loss induced by gastroplasty

Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions.

Effect of weight loss on left ventricular mass in nonhypertensive morbidly obese patients

Extreme obesity produces increases in circulating blood volume and cardiac output, which are proportional to the excess in adipose accumulation.1-20 In the absence of systemic hypertension, systemic vascular resistance decreases to accommodate the increase in cardiac output.l-‘o Left ventricular enlargement results from the increases in circulating blood volume and cardiac output, and in turn, predisposes the left ventricle to increased wall stress, in accordance with the law of LaPlace.‘-” Eccentric left ventricular hypertrophy is thought to develop in response to, and as a mechanism for, reducing left ventricular wall stress.” Prior postmortem and echocardiographic studies showed that left ventricular hypertrophy frequently occurs in extremely obese subjects, even in the absence of systemic hypertension.4-10 There has been no systematic assessment of factors influencing left ventricular mass in extremely obese subjects or of the effect of weight loss on left ventricular mass in these cases. The present study examines these issues.

Effect of weight loss on left ventricular diastolic filling in morbid obesity.

Abstract Substantial weight loss in morbidly obese subjects produces improvement in LV diastolic filling that is associated with weight loss-related decreases in LV mass and favorable alterations in LV loading conditions.

Effect of exercise on left ventricular systolic function and reserve in morbid obesity

To assess the effect of exercise on left ventricular (LV) systolic function and reserve in morbid obesity, radionuclide left ventriculography was performed before and during supine, symptom-limited bicycle exercise in 23 patients whose body weight was greater than or equal to twice their ideal body weight. Echocardiography was performed before exercise. Resting LV ejection fraction was depressed in 13 patients and LV mass was increased in 10 patients. Exercise produced nonsignificant increases (of similar magnitude) in mean LV ejection fraction in the subgroups with normal and depressed resting LV ejection fraction. Exercise produced a significant increase in LV ejection fraction from 54 +/- 8 to 65 +/- 12% (p less than 0.005) in the subgroup with normal LV mass, but produced no significant change in LV ejection fraction in the subgroup with increased LV mass (53 +/- 10 at rest, 50 +/- 12% during exercise). Moreover, the LV exercise response (change in LV ejection fraction during exercise) in the subgroup with normal LV mass was significantly different from that in the subgroup with increased LV mass (p less than 0.005). There was a strong positive correlation between LV mass and the percent over ideal body weight (r = 0.912, p = 0.01) and a strong negative correlation between LV mass and LV exercise response (r = 0.829, p = 0.01). The results suggest that increased LV mass predisposes morbidly obese patients to impairment of LV systolic function during exercise.