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

MlSCElJANEOUS

Factors Influencing Left Ventricular Systolic Function in Nonhypertensive Morbidly Obese Patients, and Effect of Weight Loss Induced by Gastroplasty Martin A. Alpert, MD, Boyd E. Terry, MD, Charles R. Lambert, MD, PhD, Diana L. Kelly, RDMS, Hercules Panayiotou, MD, Vaskar Mukerji, MD, Clara V. Massey, Mb, and Michael V. Cohen, MD

HMtrat0WdblOOdpESSU~W~measUred,

and ech~~Gigraphy was performed in 39 pzk tim whose actual body wei& was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function inmorbidlyobesepatientsandassesstheeffect of weight loss on LV systolic function. Patients were studii before and after weight loss induced bygastroplasty.7hestudycohortwas133~8% overwei~

Igore

weight

loss and 39 + 7% over

weight at the nadir of weight loss. Before Weight loss, LV fractional shortening varied inversely witb l.V internal dimension in diastole (an indirect index of preload), LV endqstolic wall stress and systolic blood pressure (indexes of aftetlhd). The weight Wnduced tige in LV fractioiial shortening vrwied directly with the -wei@ loss LV internal dimension in diastole, LV endsystdic wall stress and systolic blood pressure, and irr versely with the -weight loss LV fhctiinal shorte@&The weight loss-induced change in LV hc$ional shortehing varied inversely with the weight loss-indrlti changes in LV end-systolic stress and systolic blood pressure. In patients with rediwed LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a signScant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that l.V loading m ditionS have an important ro@ in detennining LV systolic function in morbidly obese patients. III+ provement in LV systolic function in the&e p tients is closely related to weight loss-induced alterations in LV loading condiiions. (Am J Cardiol1993;71:73S737)

From the Division of Cardiology, University of South Alabama College of Medicine, Mobile, Alabama, and the Department of Surgery, University of Missouri, Columbia, Missouri. Manuscript received February 1, 1992; revised manuscript received and accepted October 5, 1992. Address for reprints: Martin A. Alp&, MD, Division of Cardiology, Suite C, 10th Floor, University of South Alabama Medical Center, 2451 Fillingim Street, Mobile, Alabama 36617.

xtreme obesity produces hemodynamic and cardiac structural alterations that may predispose a subject to left ventricular (LVj dysfunction in the absence of systemic hypertension and underlying organic heart disease.‘-l9 Increased total blood volume aiid cardiac output related to excessive adi&se acctiul&ion result in LV dilatation.1s~7~8 LV dilat&lon $oduces an increase in systolic! wall stress in acchrdance with thi: 1avLof LaPlace. In the nonhypertensiLe obese subject this provides a stimulus for eccentric LV hypertrophy that acts as a mechanism for normalizing systolic wall &eds.‘,21 Eccentric LV hypertrdphy provides the substrate for LV diastolic dysfunction.1,21 Systolic LV dysfunction is thought to ensue if eccentric LV hypertrophy does not keep pace with dilatation, thus allowing systolic wall stress to remain high.121 Prior studies demonstrated that many hemodynamic alteraiioiis associated with. extreme obesity are reversible after weight 10~s.~~~~~~~~~~ However, there is little information concerning the impact of weight loss on LV systolic tiction in extremely obese patients. This study assessesfact&s inlluencing LV systolic function in morbid obesity with specific reference to the effect of weight loss on these factors and LV systolic function itself.

E

METHODS Patient selectii

Study patients were required to weigh at least twice their ideal body weight for 25 years. All patients studied were candidates for and underwent gastroplasty.20 Patients With history of systemic hypertension, overt congestive heart failure and clinical, electrocardiographic, radiographic or echocardiographic evidence of organic heart disease not directly related to obesity were excluded from the study. Protocok Each patient studied underwent a complete medical history and physical examination before gastroplasty.20 A resting electrocardiogram, chest, X-ray and echocardiogrti (M-mode and 2-dim&signal) were also obtained before gastroplasty. Echocardiqgaj?hy was repeated at the nadir of each patient’s postoperative weight loss (4:6 f 1.1 months after suriery). Echocardiobaphy was performer tising a Varian V34OOR or HCwlett-Packard Sonos l&lo ultrasonograph and a 2.25 MHz transducer. Echocardiography was performed and echocardiographic measurements were obtained in accordance with American Society of EchocarLEFT VENTRICLE IN MORBID OBESITY

733

diography recommendations and criteria.22 Two-dimensionally directed M-mode LV dimension measurements were obtained at the papillary muscle level. Key echocardiographic measurements and their normal values included LV internal dimensions in diastole (3.8 to 5.6 cm) and systole (cm), LV posterior wall thickness in diastole (0.6 to 1.1 cm) and systole (cm), and ventricular septal thickness in diastole (0.6 to 1.1 cm). LV fractional shortening (28 to 44%) was used to assessLV systolic function. LV fractional shortening (%) was calculated by dividing the difference between the LV internal dimensions in diastole and systole by the LV internal dimension in diastole, and then multiplying by 100. LV end-systolic stress was calculated using the formula of Quinones et al.23 LV mass was calculated using the formula of Devereaux and Reichek.M Increased LV mass

R=0.78

P=O.O001

was dehned in accordance with American Society of Echocardiography criteria.22 Blood pressure was measured in the right arm immediately before each echocardiographic examination using a thigh cuff and mercury sphygmomanometer. Mean blood pressure was calculated by adding one third of the pulse pressure to the diastolic blood pressure. Ideal body weight was calculated using Metropolitan Life Insurance Tables.25 Severity of obesity was expressed as percentage greater than ideal body weight (overweight). For example, a patient whose actual weight was twice their ideal body weight would be 100% overweight. Statistical analysis: Student’s t test was used to compare paired and nonpaired data. Pearson correlation coefficients were derived from least-squares linear regression analysis. A p value ~0.05 was required to achieve statistical significance. RESULTS Patient characteristics: The original study cohort comprised 43 patients. Four patients were excluded from the study because interpretable echocardiograms could not be obtained. The eventual study cohort comprised 39 patients (33 women and 6 men; mean age 37 f 8 years). The mean percentage greater than ideal body weight was 133 f: 8%. There were no significant dilferences in gender distribution or mean age between subgroups with normal and reduced LV fractional shortening before weight loss. Factors tion before

R=0.83 P=O.OOl

l&

LV Fractional Shortening Prior to Weight Loss (%)

! 1. Left venti-icular (WV) fractional shortening before correlated inversely with LV internal dimension in di ias tale, LV endsystolic strees and eystolic blood preeW&i

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left

ventricuhr

systolic

func

There were significant inverse correlations between LV fractional shortening and LV internal dimensions in diastole (r = 0.78, p = 0.0001; Figure 1) and systole (r = 0.89, p = O.OOOl), LV end-systolic stress (r = 0.89, p = 0.0001; Figure l), systolic blood pressure (r = 0.83, p = 0.001; Figure l), LV mass (r = 0.91, p = 0.0001) and percent overweight (r = 0.68, p = 0.0001) before weight loss. There was no correlation between LV fractional shortening and heart rate, mean blood pressure or diastolic blood pressure. All 14 patients with reduced LV fractional shortening before weight loss had increased LV mass.

250

“O’

influencing

w loss

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 71

weight

Effect of weight function in patients ventricular fractional

loss:

loss on left ventricular systolic with nomal and reduced left shortening. Table I shows the

effect of weight loss on LV fractional shortening in the subgroups with normal and reduced LV fractional shortening. Table I also shows the effect of weight loss on mean heart rate, blood pressure, systolic blood pressure, LV internal dimension in diastole and systole, and LV end-systolic stress in these subgroups. In the subgroup with normal LV fractional shortening, weight loss produced a significant decrease in mean systolic blood pressure, but no signiiicant change in mean heart rate, blood pressure, diastolic blood pressure, LV internal dimension in diastole or systole, LV fractional shortening and LV end-systolic stress. In the subgroup with reduced LV fractional shortening, weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in mean systolic blood pressure, LV internal dimensions in diastole MARCH 15, 1993

and systole, and LV end-systolic stress. Weight loss produced no significant change in mean heart rate, blood pressure or diastolic blood pressure in this subgroup. Factors influencing tion: effect of weight

left ventricular

systolic

func

loss: The relation between the weight loss-induced changes in LV fractional shortening and variables with the potential to intluence LV systolic function was examined in 2 ways. Initially, the relation between the weight loss-induced change in LV fractional shortening and the following variables before weight loss was assessed: heart rate, mean blood pressure, systolic blood pressure, diastolic blood pressure, LV internal dimensions in diastole and systole, LV fracTABLE

I

Effect

of Weight

Loss

Group Normal LV fractional shortening (n = 25) Before After p value Depressed LV fractional shortening (n = 14) Before After p value All pts. (n = 39) Before After p value

on Clinical,

Hemodynamic

% Overweight

and

tional shortening, LV end-systolic stress, LV mass and percent overweight. Then, the relation between the weight loss-induced changes in LV fractional shortening and in the aforementioned variables was assessed. There were significant direct correlations between weight loss-induced changes in LV fractional shortening and pre-weight loss LV internal dimensions in diastole (r = 0.58, p = 0.0001; Figure 2) and systole (r = 0.711, p = O.OOOl), LV en d- systolic stress (r = 0.78, p = 0.00011; Figure 2), LV mass (r = 0.65, p = O.OOOl), systolic blood pressure (r = 0.72, p = 0.0001; Figure 2) and percent overweight (r = 0.59, p = 0.0001) (i.e., the greater the L’V internal dimensions, LV end-systolic stress, systolic

Echocardiographic

Heart Rate (beats/min)

Variables

Mean Blood Pressure (mm Hg)

Systolic Blood Pressure (mm Hg)

LV Internal Dimension (cm) Diastole

Systole

LV EndSystolic Stress (g/cm*)

LV Fractional Shortening (%)

135 f 8 39 2 8 10.00001

82 + 6 80 k 9 NS

98 f 6 95 k 8 NS

128 zk 3 122 + 3
5.4 k 0.4 5.0 f 0.3 NS

3.6 -+ 0.3 3.3 k 0.3 NS

141 121

+ 34 -+ 21 NS

33 k 4 34 z!z 3 NS

131 2 8 38 2 6 <0.00001

80 2 7 78 + 8 NS

99 + 6 95 k 7 NS

135 2 3 129 z!r 3 10.025

6.3 2 0.4 5.7 -t 0.3
4.8 f 0.3 3.9 + 0.3
207 zk 44 149 + 25
24 + 3 30 * 4 <0.025

133 5 8 39 k 7 <0.00001

81 k 6 79 + 8 NS

98 + 6 95 k 5 NS

131 f 3 125 f 3 <0.025

5.7 + 0.4 5.2 f 0.3 10.025

4.0 * 0.3 3.5 t 0.3 <0.025

165 f 38 131 AZ 22 <0.025

30 k 4 33 k 3 NS

LV = left ventricular.

FIGURE 2. Weight loss++ duced change in left ventrh uler (LV) fractional shortening correlated directly with LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure before weight loss and inversely with LV fractional shortening before weight lose.

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2

4

6

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125

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LEFT VENTRICLE

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(%) IN MORBID

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blood pressure, LV mass and percent overweight before weight loss, the greater the improvement in LV fractional shortening resulting from weight loss). There was a significant inverse correlation between the weight loss-induced change in LV fractional shortening and LV fractional shortening before weight loss (r = 0.77, p = 0.0001, Figure 1) (i.e., the less the LV fractional shortening before weight loss, the greater the improvement resulting from the weight loss). There was no correlation between heart rate, mean blood pressure or diastolic blood pressure before weight loss and the weight loss-induced change in LV fractional shortening. There were significant inverse correlations between the weight loss-induced changes in LV fractional shortening and in LV internal dimension in systole (r = 0.74, p = O.OOOl), LV end-systolic stress (r = 0.81, p = 0.0001; Figure 3), systolic blood pressure (r = 0.55, p = 0.0003; Figure 3), LV mass (r = 0.51, p = 0.0009) and percent overweight (r = 0.64, p = 0.0001) (i.e., the greater the weight loss-induced decrease in the LV internal dimension in systole, LV end-systolic stress, systolic blood pressure, LV mass and percent overweight, the greater the improvement in LV fractional shortening resulting from weight loss). There was no correlation between the weight loss-induced changes in LV fractional shortening and in heart rate, mean blood pressure, diastolic blood pressure or LV internal dimension in diastole. The

R=0.81 P=0.0001

R=0.55 P=O.O003

0 -14

,,,,,,,,(,,,,,,,(,,I(,,,,,II,,,,,II -4 -2 0 2 4

6

8

10

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Change in LV Fractional Shortening W FlGURE 3. Weight lossinduced change in left ventricular (LV) fractional shortening correlated inversely with weight lossinduced changes in left ventricular end-systolic streee and systolic blood pressure.

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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME ‘1

left ventricle maintained a prolate ellipsoid shape before and after weight loss. DISCUSSION

Postmortem, echocardiographic and angiographic studies have demonstrated that LV cavity size tends to be larger in nonhypertensive, morbidly obese subjects than in lean subjects. l-l9 LV systolic wall stress in these subjects has been examined indirectly by measurement of LV radius/thickness ratios.1,8J3J4 In nonhypertensive, morbidly obese subjects, LV radius/thickness ratios tend to be greater than in lean subjects, suggesting the presence of increased systolic wall stress.1,8,13J4 These hemodynamic alterations may predispose a subject to eccentric LV hypertrophy. The reported frequency of LV systolic dysfunction in morbid obesity varies widely.‘-l9 LV systolic dysfunction in these subjects has been attributed to “inadequate” LV hypertrophy (inability of hypertrophy to keep pace with dilatation), a state in which LV systolic wall stress remains high.‘s20 In a previous study, we demonstrated that LV systolic function improves after weight loss in morbidly obese patients with reduced LV systolic function.4 This study extends these observations by exploring the relations between factors likely to influence LV systolic function and LV systolic function per se, and by assessing the effect of weight loss on these factors and on LV systolic function itself. LV internal dimension in diastole varied inversely with LV fractional shortening. This suggests that in morbidly obese patients, increased preload predisposes a subject to decreasing LV systolic function. LV fractional shortening and end-systolic wall stress also varied inversely. This demonstrates that LV systolic function tends to decrease as afterload increases in these subjects. These findings support previous observations by Alexander et al,‘~~ which showed that LV fractional shortening varied inversely with LV radius/thickness ratio in 23 morbidly obese patients. Systolic (but not mean or diastolic) blood pressure also varied inversely with LV fractional shortening, even in the normotensive range. This suggests that systolic blood pressure may influence LV systolic function in nonhypertensive, morbidly obese subjects to a greater extent than was previously recognized. Our methodology did not permit assessment of LV inotropy; thus, we cannot exclude impairment of intrinsic myocardial contractility as a cause of LV systolic dysfunction. The results demonstrate that LV loading conditions have an extremely important role in determining LV systolic function in morbidly obese subjects. Two previous studies examined the effect of weight reduction on systemic and pulmonary hemodynamics in extreme obesity.18,19Alexander and Peterson’* studied 9 morbidly obese patients before and after weight loss. Weight loss in this study population ranged from 24 to 54% of peak body weight. The investigators reported a significant decrease in total blood volume, mean arterial pressure, cardiac output, LV stroke volume, LV stroke work and LV work. There were no sign&ant changes in heart rate, systemic vascular resistance, pulmonary artery pressure and LV end-diastolic pressure. Backman

MARCH 15,1993

et all9 performed hemodynamic studies before and after REFERENCES 1. Alexander JK. The cadiomyopatby of obesity. Prog Cardiovasc Dis 1985;27: weight loss-induced jejeunoileostomy in 22 extremely 325-333, obese subjects. The mean percent overweight in this 2. Amad RH, Bremun JC, Alexander JK. The cardiac pathology of chronic exe@group decreased from 104 to 39%. Hemodynamic mea- nous obesity. Circulation 1965;32374@745. Wanes CA, Roberts WC. ‘I&e heart in massive (more than 300 pounds or 136 surements after weight loss were obtained an average of 3.kilograms) obesity: analysis of 12 patients studied at necropsy. Am J Cardiol 1985; 2 years after surgery. Weight loss was associated with a 54:10s7-1~1. 4. Alpert MA, Terry BE, Kelly DL. Effect of weight loss on cardiac chamber size, signiticant decrease in maximal oxygen consumption, thickness and left venhicular function in morbid obesity. Am J Cardiol 1985; cardiac output, stroke volume and mean blood pressure. wall 55:783-786. 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Echocardiograpbic determination of left venhicutolic function, may serve as a marker defining the interin man: anatomic validation of the method. Circulation 1977;55:613618. play of these loading conditions rather than as a func- lar25. mass Metropolitan Life Insurance Body Weight Tables, Metropolitan Lie Insurance tional determinant of LV systolic function. Company, New York, 1983.

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