- Email: [email protected]
Cardiac remodeling after substantial weight loss: a prospective cardiac magnetic resonance study after bariatric surgery
Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Original article
Cardiac remodeling after substantial weight loss: a prospective cardiac magnetic resonance study after bariatric surgery Rahul R. Jhaveri, M.D.a, Kyle K. Pond, M.D.a, Thomas H. Hauser, M.D.a, Kraig V. Kissinger, R.T.a, Lois Goepfert, R.N.a, Benjamin Schneider, M.D.b, Daniel B. Jones, M.D.b, Warren J. Manning, M.D.a,c,* a
Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts b Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts c Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Abstract
Background: Obesity is a risk factor for left ventricular (LV) hypertrophy and excess cardiovascular disease and mortality. Substantial weight loss is associated with a decrease in cardiovascular mortality. Using volumetric cardiovascular magnetic resonance (CMR) imaging, we studied changes in cardiac anatomy and systolic function in women undergoing substantial weight loss in a university hospital. Methods: A total of 17 women (body mass index [BMI] 44.1 ⫾ 4.2 kg/m2; age 44 ⫾ 11 yr) scheduled for bariatric surgery underwent volumetric CMR imaging before and 3 and 17 months after surgery. Results: The body weight declined by 37.2 ⫾ 10.5 kg (32%) with a decrease in BMI to 29.9 ⫾ 4.7 kg/m2 (32%, P ⬍ .004) during 17 months of observation. The LV mass decreased from 120 ⫾ 23 g to 82 ⫾ 11 g (32%, P ⬍ .004), with a linear relationship between the decrease in BMI and decrease in LV mass (P ⫽ .008) for the duration of the observation period. After adjustment for systolic and/or diastolic blood pressure, the relationship remained significant (P ⬍ .001). The right ventricular (RV) mass declined from 31.7 ⫾ 6.7 g preoperatively to 26.6 ⫾ 4.5 g at 3 months (16%, P ⬍ .001) but without additional changes at 17 months. No change was found in the LV or RV end-diastolic volume or ejection fraction. Conclusion: In morbidly obese women, substantial weight loss was associated with a reduction of LV and RV mass. The decrease in LV mass was linearly related to the reduction in BMI, independent of changes in blood pressure, and might partially explain the reduction in cardiovascular mortality associated with substantial weight loss. The BMI was a predictor of LV mass in this population. (Surg Obes Relat Dis 2009;5:648 – 652.) © 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Cardiac mass; Cardiovascular magnetic resonance; Obesity
The prevalence of obesity has been increasing for several decades, with up to one third of men and women in the United States now estimated to be obese [1,2]. Abdominal obesity, in particular, is an independent risk factor for car-
*Reprint requests: Warren J. Manning, M.D., Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: [email protected]
diovascular disease and is associated with excess mortality [3–5]. Obesity is associated with an increased left ventricular (LV) mass and volume and an increased right ventricular (RV) mass [6 – 8]. Obesity is also associated with increased LV end-diastolic pressure and volume, which can lead to ventricular dilation. Ventricular dilation and its associated increase in wall stress might drive the development of LV hypertrophy among the obese [5]. Concomitant hyperten-
1550-7289/09/$ – see front matter © 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved. doi:10.1016/j.soard.2009.01.011
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
sion, regardless of the presence of the metabolic syndrome, might also contribute to LV hypertrophy among the obese [9]. Obesity is also associated with a decrease in LV systolic and diastolic function [10,11]. Substantial weight loss is associated with a decrease in mortality [12,13]. Previous transthoracic two-dimensional (2D) and M-mode echocardiographic studies have suggested that a regression of LV hypertrophy and improvement in cardiac function occur with weight reduction [14 –17]. These data, however, have been derived from a relatively select group of subjects with good echocardiographic windows, because only 70% of transthoracic echocardiographic examinations are interpretable in morbidly obese subjects [14,16,18,19]. Volumetric cardiovascular magnetic resonance (CMR) imaging obtains a better definition of the cardiac structure and function than 2D or M-mode echocardiography and provides more reproducible measurements of cardiac anatomy [20,21]. CMR imaging also allows for accurate anatomic delineation of the heart in the presence of significant amounts of subcutaneous fat [8]. To better understand the cardiac effects of rapid weight loss, we prospectively studied a group of obese women before and after bariatric surgery. Methods Study population A total of 17 women (age 44.5 ⫾ 11.6 yr) recruited from the Beth Israel Deaconess Medical Center Weight Loss Center were enrolled after their acceptance for bariatric surgery. One woman underwent preoperative CMR imaging but relocated after surgery and was unavailable for the follow-up CMR studies. The data from this patient were excluded from the study. Three other patients were unavailable or declined to undergo the 17-month follow-up CMR study. Thus, 16 subjects underwent the 3-month follow-up CMR study and 13 underwent the 17-month follow-up CMR study. Of these women, 10 had a history of hypertension and 6 had a diagnosis of obstructive sleep apnea. The Hospital Committee on Clinical Investigation approved the study, and all the women provided written informed consent. Bariatric surgery Bariatric surgery was performed using standard techniques [22] at an American College of Surgeons–accredited bariatric program. Of the 16 women, 4 (25%) underwent laparoscopic adjustable gastric banding and 12 (75%) underwent laparoscopic Roux-en-Y gastric bypass. No clinical evidence of a cardiovascular complication was found in any patient postoperatively. CMR imaging All imaging was performed on a commercial 1.5T Philips Achieva whole body scanner (Philips Medical Systems,
649
Best, The Netherlands) with a 60-cm scanner bore. After the initial localizing scans, short axis cine images were obtained, as previously described [23], using a breath-hold, steady-state, free precession cine CMR sequence, with contiguous 10-mm slices and a temporal resolution of 30 –35 ms. The patients’ blood pressure, weight, and heart rate were recorded at each scan. Data analysis The CMR data were independently analyzed by 2 observers (R.R.J and K.K.P) unaware of the clinical findings using a commercial workstation (EasyVision 5, Philips Medical Systems). The LV and RV endocardial borders were manually traced at end-diastole and end-systole. The LV and RV epicardial borders were traced at end-diastole [23]. The LV and RV end-diastolic volume and end-systolic volume were determined using a summation of the slice thickness multiplied by the slice area. The mass was determined by multiplying the myocardial muscle volume by the density of the myocardium (1.05 g/cm3). Statistical analysis Continuous variables are presented as the mean ⫾ standard deviation. The individual patients’ preoperative and postoperative values were compared using a paired Student t test with the Bonferroni adjustment for multiple comparisons among the baseline and 3- and 17-month studies. The relationship between the preoperative and postoperative values was assessed using standard correlation and linear regression analysis. Multivariate regression analysis using a retrospective selection of variables was performed to account for potential confounding variables. Statistical analyses were done using Statistical Analysis Systems for Windows, version 9.1 (SAS Institute, Cary, NC). Results The blood pressure and body habitus data are summarized in Table 1. The total body weight had declined by 18.4 ⫾ 3.8 Table 1 Baseline data Variable
Weight (kg) BMI (kg/m2) BSA (m2) Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (bpm)
Preoperative
116.1 ⫾ 14.8 44.1 ⫾ 4.2 2.16 ⫾ .16 128 ⫾ 16 80 ⫾ 10 76 ⫾ 11
Postoperative (mo) 3
17
97.7 ⫾ 14.7* 37.1 ⫾ 4.4* 2.01 ⫾ .16* 129 ⫾ 20 72 ⫾ 14* 68 ⫾ 11*
79.3 ⫾ 14.4*† 29.9 ⫾ 4.7*† 1.84 ⫾ .17*† 127 ⫾ 13 58 ⫾ 11*† 60 ⫾ 11*
BMI ⫽ body mass index; BSA ⫽ Body surface area; BP ⫽ blood pressure. * P ⬍ .001 versus preoperatively. † P ⬍ .001 versus 3 mo postoperatively.
650
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Table 2 Left ventricular data Variable
Preoperative
LV EDV (mL) LV ESV (mL) Stroke volume (mL) LV ejection fraction (%) LV mass (g) LV mass/height (g/m) LV mass/BSA (g/m2) LV mass/BMI (g/kg/m2)
152 ⫾ 26 50 ⫾ 18 103 ⫾ 14 68.1 ⫾ 6.4 120 ⫾ 23 74 ⫾ 12 55 ⫾ 7 2.72 ⫾ 0.41
Postoperative (mo) 3
17
152 ⫾ 29 54 ⫾ 18 97 ⫾ 19 64.5 ⫾ 6.5 98 ⫾ 15* 60 ⫾ 8* 49 ⫾ 5* 2.66 ⫾ 0.40
163 ⫾ 26 61 ⫾ 19* 102 ⫾ 15 63.0 ⫾ 6.6 82 ⫾ 11*† 50 ⫾ 7*† 45 ⫾ 6* 2.78 ⫾ 0.53
LV ⫽ left ventricular; EDV ⫽ end-diastolic volume; ESV ⫽ endsystolic volume; other abbreviations as in Table 1. * P ⬍ .004 versus preoperatively. † P ⬍ .004 versus 3 mo.
kg (16%, P ⬍ .001) at 3 months and by 37.2 ⫾ 10.5 kg (32%, P ⬍ .001) at 17 months. The body mass index (BMI) had declined by 16% and 32% at 3 and 17 months, respectively (both, P ⬍ .001). LV changes with weight loss The changes in LV anatomy are summarized in Table 2. The LV mass had declined by 21.8 ⫾ 12.7 g (18%, P ⬍ .001) at 3 months postoperatively. The results were similar if we excluded the 3 women who did not undergo CMR imaging at 17 months. After 17 months, the LV mass had declined by 40.0 ⫾ 19.8 g (32% compared with preoperatively, P ⬍ .001). No change was seen in the LV enddiastolic volume or ejection fraction during the observation period. The baseline BMI and LV mass exhibited a significant linear relationship (R ⫽ .50, P ⫽ .049). A significant linear relationship was also seen between changes in the BMI and changes in the LV mass after surgery (P ⫽ .008;
Fig. 2. LV mass/BMI ratio over time for individual subjects.
Fig. 1). The effect of the changes in BMI on LV mass remained significant on multivariate analysis, which included changes in the systolic and diastolic blood pressure as parameters (P ⫽ .001 after adjustment for either or both). In addition, the LV mass/BMI ratio remained unchanged with weight loss (Fig. 2). In contrast, both the LV mass/ body surface area ratio (⫺11% at 3 months and ⫺18% at 17 months, both P ⬍ .004) and the LV mass/height ratio (⫺19% at 3 months and ⫺32% at 17 months, both P ⬍ .004) declined (Table 2). RV changes with weight loss The RV anatomic measures are summarized in Table 3. The RV mass correlated with body weight preoperatively and at 3 and 17 months (R ⫽ .74, R ⫽ .83, and R ⫽ .63 and P ⬍ .004, P ⬍ .001, and P ⫽ .066, respectively). The RV mass had declined by 16% at 3 months (P ⬍ .001) but did not exhibit additional changes at 17 months. The RV ejection fraction and volumes remained unchanged with weight loss (Table 3).
Table 3 Right ventricular data Variable
RV RV RV RV Fig. 1. LV mass versus BMI for individual subjects.
mass (g) EDV (mL) ESV (mL) ejection fraction (%)
Preoperative
31.7 ⫾ 6.7 157 ⫾ 27 74 ⫾ 23 54 ⫾ 8
Postoperative (mo) 3
17
26.6 ⫾ 4.4* 160 ⫾ 30 75 ⫾ 24 54 ⫾ 7
27.5 ⫾ 6.0* 156 ⫾ 30 71 ⫾ 18 54 ⫾ 6
RV ⫽ right ventricular; other abbreviations as in Table 2. * P ⬍ .001 versus preoperatively.
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Discussion Both obesity and LV hypertrophy are risk factors for cardiovascular mortality. Using a volumetric CMR approach in the morbidly obese population, we found that substantial weight reduction was associated with a significant regression of LV mass, with no change in LV volume or ejection fraction. The regression in LV mass was linearly related to the magnitude of weight loss after bariatric surgery. When normalized for BMI, the LV mass remained constant, despite a 32% weight loss within 17 months. A regression of the RV mass occurred during the period of rapid weight loss (3 months) after bariatric surgery, with little change thereafter. To our knowledge, these are the first data regarding RV mass changes, identifying a differential response of the 2 ventricles and highlighting the close relationship of the LV mass and BMI in this population. Several studies have demonstrated that bariatric surgery for morbid obesity is associated with a long-term survival advantage [12,13,24,25]. In a prospective study, Sjöström et al. [12] found a hazard ratio of .76 for overall mortality among subjects who had undergone bariatric surgery compared with matched controls. In a retrospective cohort study, Adams et al. [13] found a 40% decline in mortality in patients who had undergone gastric bypass surgery compared with an age-, gender-, and BMI-matched control group. The LV mass is an independent risk predictor for cardiac mortality [26,27]. Our finding of LV mass regression with weight loss could partially explain these findings. Other investigators have used surface echocardiography to examine the LV mass changes in this population. Cunha et al. [28] demonstrated LV mass regression at 6 months after bariatric surgery using M-mode echocardiography in a group of 23 patients. Leichman et al. [29] identified a smaller decrease in the LV mass at 3 months. Using volumetric CMR methods, we found regression of the LV mass as soon as 3 months after bariatric surgery, with the degree of LV mass regression linearly related to the decrease in total body weight, with maintenance of the LV mass/BMI ratio. The change in LV mass was independent of changes in blood pressure. Additionally, using volumetric CMR imaging, with its improved reproducibility compared with echocardiography, we demonstrated these differences with a relatively modest sample size. Previous studies have shown that weight loss, through intensive dieting or weight loss surgery, has led to changes in LV dimensions, including a reduction of the calculated LV mass and wall thickness [14 –17,30]. Using 2D echocardiography, Karason et al. [16] examined the effects of weight loss at 1 year after bariatric surgery in 41 obese subjects. They found a significant reduction in the LV mass and wall thickness compared with 31 “conventionally treated” obese subjects and 43 non– obese-matched controls. However, 13% of their obese subjects were excluded
651
from the analysis of LV wall thickness and mass and 28% of their subjects were excluded from the estimations of LV volumes because of suboptimal echocardiographic data, highlighting the limitations of echocardiography in this population [16]. We were able to acquire data from all subjects at both baseline and all follow-up points. Himeno et al. [20] used M-mode echocardiography to characterize a decrease in LV mass among 22 obese subjects after a 12-week exercise and dietary intervention program. Similar to our findings, the change in LV mass was independent of blood pressure. Again, 12% of their study population were excluded because of uninterpretable echocardiographic data. Hinderliter et al. [14] used 2D echocardiography to study 82 subjects, 63 of whom had been randomized to a 6-month exercise or weight management program, and 19 controls. The intervention group had a decreased relative LV wall thickness, with a trend toward a decrease in LV mass relative to the control group. As with the other echocardiographic studies, 42 patients (29%) of the overall study population of 144 had echocardiograms “in which left ventricular dimensions or wall thicknesses could not be quantified with confidence” [14]. Unlike previous 2D and M-mode echocardiographic studies in the morbidly obese population, we did not find a decrease in LV end-diastolic volume with weight loss. The reasons for this conflict are uncertain, but they might reflect the volumetric approach of CMR imaging compared with the geometric modeling of 2D and M-mode echocardiography. None of the previously cited echocardiographic studies were able to address RV mass or volume. Our data demonstrated a decrease in RV mass in the early period of weight loss. The reason for the initial parallel decline in RV mass and weight but subsequent maintenance of RV mass despite ongoing total body weight loss is unexplained. Our report had several limitations. The study population consisted of entirely middle-age women. Our findings might not be applicable to all age groups or to men. The mechanism by which cardiac remodeling occurs is not fully explained, but it appears to be independent of a reduction in blood pressure or other metabolic factors (e.g., hyperlipidemia). We did not assess the metabolic or inflammatory parameters that might affect LV mass. The potential confounder of 2 different surgical approaches could not be addressed by the present study. Also, we could not determine whether the decline in LV mass reflects a decrease in fatty infiltration of the myocardium or a decrease in LV myocyte hypertrophy. Whether the RV changes we observed were a direct result of weight loss or were possibly due to improvements in obstructive sleep apnea or a decline in pulmonary artery pressure in this population is uncertain.
652
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Conclusion In morbidly obese women, rapid weight loss was associated with significant regression of the LV and RV mass, with maintenance of the LV mass/BMI ratio and no change in LV or RV volume or ejection fraction. The decline in LV mass was linearly related to the weight reduction, independent of changes in blood pressure, and might partially explain the reduction in cardiovascular mortality associated with substantial weight loss. Disclosures The authors claim no commercial associations that might be a conflict of interest in relation to this article. References [1] Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the united states, 1999 –2004. JAMA 2006;295:1549 –55. [2] Parikh NI, Pencina MJ, Wang TJ, et al. Increasing trends in incidence of overweight and obesity over 5 decades. Am J Med 2007;120:242–50. [3] Hu FB. Obesity and mortality: watch your waist, not just your weight. Arch Intern Med 2007;167:875– 6. [4] Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med 2004;351:2694 –703. [5] Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006;113:898 –918. [6] Heckbert SR, Post W, Pearson GD, et al. Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: the multiethnic study of atherosclerosis. J Am Coll Cardiol 2006;48:2285–92. [7] Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry: the Framingham heart study. JAMA 1991;266:231– 6. [8] Danias PG, Tritos NA, Stuber M, Kissinger KV, Salton CJ, Manning WJ. Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study. J Cardiovasc Magn Reson 2003; 5:431– 8. [9] Ferrara LA, Guida L, Ferrara F, et al. Cardiac structure and function and arterial circulation in hypertensive patients with and without metabolic syndrome. J Hum Hypertens 2007;21:729 –35. [10] Wong CY, O’Moore-Sullivan T, Leano R, Byrne N, Beller E, Marwick TH. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation 2004;110:3081–7. [11] Zarich SW, Kowalchuk GJ, McGuire MP, Benotti PN, Mascioli EA, Nesto RW. Left ventricular filling abnormalities in asymptomatic morbid obesity. Am J Cardiol 1991;68:377– 81. [12] Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741–52.
[13] Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Eng J Med 2007;357:753– 61. [14] Hinderliter A, Sherwood A, Gullette EC, et al. Reduction of left ventricular hypertrophy after exercise and weight loss in overweight patients with mild hypertension. Arch Intern Med 2002; 162:1333–9. [15] Alpert MA, Lambert CR, Panayiotou H, et al. Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss. Am J Cardiol 1995;76: 1194 –7. [16] Karason K, Wallentin I, Larsson B, Sjöström L. Effects of obesity and weight loss on left ventricular mass and relative wall thickness: survey and intervention study. BMJ 1997;315:912– 6. [17] Poirier P, Martin J, Marceau P, Biron S, Marceau S. Impact of bariatric surgery on cardiac structure, function and clinical manifestations in morbid obesity. Expert Rev Cardiovasc Ther 2004;2:193–201. [18] Chuang ML, Danias PG, Riley MF, Hibberd MG, Manning WJ, Douglas PS. Effect of increased body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection fraction, and mass. Am J Cardiol 2001;87:371, 4, A10. [19] Alpert MA, Hashimi MW. Obesity and the heart. Am J Med Sci 1993;306:117–23. [20] Himeno E, Nishino K, Nakashima Y, Kuroiwa A, Ikeda M. Weight reduction regresses left ventricular mass regardless of blood pressure level in obese subjects. Am Heart J 1996;131:313–9. [21] Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ. Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2000;2:271– 8. [22] McNatt SS, Longhi JJ, Goldman CD, McFadden DW. Surgery for obesity: a review of the current state of the art and future directions. J Gastrointest Surg 2007;11:377–97. [23] Salton CJ, Chuang ML, O’Donnell CJ, et al. Gender differences and normal left ventricular anatomy in an adult population free of hypertension: a cardiovascular magnetic resonance study of the Framingham heart study offspring cohort. J Am Coll Cardiol 2002;39:1055– 60. [24] Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416, 423– 4. [25] Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 2004;199:543–51. [26] Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991;114:345–52. [27] Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study. N Engl J Med 1990;322: 1561– 6. [28] Cunha Lde C, da Cunha CL, de Souza AM, Chiminacio Neto N, Pereira RS, Suplicy HL. Evolutive echocardiographic study of the structural and functional heart alterations in obese individuals after bariatric surgery. Arq Bras Cardiol 2006;87:615–22. [29] Leichman JG, Aguilar D, King TM, et al. Improvements in systemic metabolism, anthropometrics, and left ventricular geometry 3 months after bariatric surgery. Surg Obes Relat Dis 2006;2:592–9. [30] MacMahon SW, Wilcken DE, MacDonald GJ. The effect of weight reduction on left ventricular mass: a randomized controlled trial in young, overweight hypertensive patients. N Engl J Med 1986;314: 334 –9.
Original article
Cardiac remodeling after substantial weight loss: a prospective cardiac magnetic resonance study after bariatric surgery Rahul R. Jhaveri, M.D.a, Kyle K. Pond, M.D.a, Thomas H. Hauser, M.D.a, Kraig V. Kissinger, R.T.a, Lois Goepfert, R.N.a, Benjamin Schneider, M.D.b, Daniel B. Jones, M.D.b, Warren J. Manning, M.D.a,c,* a
Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts b Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts c Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Abstract
Background: Obesity is a risk factor for left ventricular (LV) hypertrophy and excess cardiovascular disease and mortality. Substantial weight loss is associated with a decrease in cardiovascular mortality. Using volumetric cardiovascular magnetic resonance (CMR) imaging, we studied changes in cardiac anatomy and systolic function in women undergoing substantial weight loss in a university hospital. Methods: A total of 17 women (body mass index [BMI] 44.1 ⫾ 4.2 kg/m2; age 44 ⫾ 11 yr) scheduled for bariatric surgery underwent volumetric CMR imaging before and 3 and 17 months after surgery. Results: The body weight declined by 37.2 ⫾ 10.5 kg (32%) with a decrease in BMI to 29.9 ⫾ 4.7 kg/m2 (32%, P ⬍ .004) during 17 months of observation. The LV mass decreased from 120 ⫾ 23 g to 82 ⫾ 11 g (32%, P ⬍ .004), with a linear relationship between the decrease in BMI and decrease in LV mass (P ⫽ .008) for the duration of the observation period. After adjustment for systolic and/or diastolic blood pressure, the relationship remained significant (P ⬍ .001). The right ventricular (RV) mass declined from 31.7 ⫾ 6.7 g preoperatively to 26.6 ⫾ 4.5 g at 3 months (16%, P ⬍ .001) but without additional changes at 17 months. No change was found in the LV or RV end-diastolic volume or ejection fraction. Conclusion: In morbidly obese women, substantial weight loss was associated with a reduction of LV and RV mass. The decrease in LV mass was linearly related to the reduction in BMI, independent of changes in blood pressure, and might partially explain the reduction in cardiovascular mortality associated with substantial weight loss. The BMI was a predictor of LV mass in this population. (Surg Obes Relat Dis 2009;5:648 – 652.) © 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Cardiac mass; Cardiovascular magnetic resonance; Obesity
The prevalence of obesity has been increasing for several decades, with up to one third of men and women in the United States now estimated to be obese [1,2]. Abdominal obesity, in particular, is an independent risk factor for car-
*Reprint requests: Warren J. Manning, M.D., Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: [email protected]
diovascular disease and is associated with excess mortality [3–5]. Obesity is associated with an increased left ventricular (LV) mass and volume and an increased right ventricular (RV) mass [6 – 8]. Obesity is also associated with increased LV end-diastolic pressure and volume, which can lead to ventricular dilation. Ventricular dilation and its associated increase in wall stress might drive the development of LV hypertrophy among the obese [5]. Concomitant hyperten-
1550-7289/09/$ – see front matter © 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved. doi:10.1016/j.soard.2009.01.011
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
sion, regardless of the presence of the metabolic syndrome, might also contribute to LV hypertrophy among the obese [9]. Obesity is also associated with a decrease in LV systolic and diastolic function [10,11]. Substantial weight loss is associated with a decrease in mortality [12,13]. Previous transthoracic two-dimensional (2D) and M-mode echocardiographic studies have suggested that a regression of LV hypertrophy and improvement in cardiac function occur with weight reduction [14 –17]. These data, however, have been derived from a relatively select group of subjects with good echocardiographic windows, because only 70% of transthoracic echocardiographic examinations are interpretable in morbidly obese subjects [14,16,18,19]. Volumetric cardiovascular magnetic resonance (CMR) imaging obtains a better definition of the cardiac structure and function than 2D or M-mode echocardiography and provides more reproducible measurements of cardiac anatomy [20,21]. CMR imaging also allows for accurate anatomic delineation of the heart in the presence of significant amounts of subcutaneous fat [8]. To better understand the cardiac effects of rapid weight loss, we prospectively studied a group of obese women before and after bariatric surgery. Methods Study population A total of 17 women (age 44.5 ⫾ 11.6 yr) recruited from the Beth Israel Deaconess Medical Center Weight Loss Center were enrolled after their acceptance for bariatric surgery. One woman underwent preoperative CMR imaging but relocated after surgery and was unavailable for the follow-up CMR studies. The data from this patient were excluded from the study. Three other patients were unavailable or declined to undergo the 17-month follow-up CMR study. Thus, 16 subjects underwent the 3-month follow-up CMR study and 13 underwent the 17-month follow-up CMR study. Of these women, 10 had a history of hypertension and 6 had a diagnosis of obstructive sleep apnea. The Hospital Committee on Clinical Investigation approved the study, and all the women provided written informed consent. Bariatric surgery Bariatric surgery was performed using standard techniques [22] at an American College of Surgeons–accredited bariatric program. Of the 16 women, 4 (25%) underwent laparoscopic adjustable gastric banding and 12 (75%) underwent laparoscopic Roux-en-Y gastric bypass. No clinical evidence of a cardiovascular complication was found in any patient postoperatively. CMR imaging All imaging was performed on a commercial 1.5T Philips Achieva whole body scanner (Philips Medical Systems,
649
Best, The Netherlands) with a 60-cm scanner bore. After the initial localizing scans, short axis cine images were obtained, as previously described [23], using a breath-hold, steady-state, free precession cine CMR sequence, with contiguous 10-mm slices and a temporal resolution of 30 –35 ms. The patients’ blood pressure, weight, and heart rate were recorded at each scan. Data analysis The CMR data were independently analyzed by 2 observers (R.R.J and K.K.P) unaware of the clinical findings using a commercial workstation (EasyVision 5, Philips Medical Systems). The LV and RV endocardial borders were manually traced at end-diastole and end-systole. The LV and RV epicardial borders were traced at end-diastole [23]. The LV and RV end-diastolic volume and end-systolic volume were determined using a summation of the slice thickness multiplied by the slice area. The mass was determined by multiplying the myocardial muscle volume by the density of the myocardium (1.05 g/cm3). Statistical analysis Continuous variables are presented as the mean ⫾ standard deviation. The individual patients’ preoperative and postoperative values were compared using a paired Student t test with the Bonferroni adjustment for multiple comparisons among the baseline and 3- and 17-month studies. The relationship between the preoperative and postoperative values was assessed using standard correlation and linear regression analysis. Multivariate regression analysis using a retrospective selection of variables was performed to account for potential confounding variables. Statistical analyses were done using Statistical Analysis Systems for Windows, version 9.1 (SAS Institute, Cary, NC). Results The blood pressure and body habitus data are summarized in Table 1. The total body weight had declined by 18.4 ⫾ 3.8 Table 1 Baseline data Variable
Weight (kg) BMI (kg/m2) BSA (m2) Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (bpm)
Preoperative
116.1 ⫾ 14.8 44.1 ⫾ 4.2 2.16 ⫾ .16 128 ⫾ 16 80 ⫾ 10 76 ⫾ 11
Postoperative (mo) 3
17
97.7 ⫾ 14.7* 37.1 ⫾ 4.4* 2.01 ⫾ .16* 129 ⫾ 20 72 ⫾ 14* 68 ⫾ 11*
79.3 ⫾ 14.4*† 29.9 ⫾ 4.7*† 1.84 ⫾ .17*† 127 ⫾ 13 58 ⫾ 11*† 60 ⫾ 11*
BMI ⫽ body mass index; BSA ⫽ Body surface area; BP ⫽ blood pressure. * P ⬍ .001 versus preoperatively. † P ⬍ .001 versus 3 mo postoperatively.
650
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Table 2 Left ventricular data Variable
Preoperative
LV EDV (mL) LV ESV (mL) Stroke volume (mL) LV ejection fraction (%) LV mass (g) LV mass/height (g/m) LV mass/BSA (g/m2) LV mass/BMI (g/kg/m2)
152 ⫾ 26 50 ⫾ 18 103 ⫾ 14 68.1 ⫾ 6.4 120 ⫾ 23 74 ⫾ 12 55 ⫾ 7 2.72 ⫾ 0.41
Postoperative (mo) 3
17
152 ⫾ 29 54 ⫾ 18 97 ⫾ 19 64.5 ⫾ 6.5 98 ⫾ 15* 60 ⫾ 8* 49 ⫾ 5* 2.66 ⫾ 0.40
163 ⫾ 26 61 ⫾ 19* 102 ⫾ 15 63.0 ⫾ 6.6 82 ⫾ 11*† 50 ⫾ 7*† 45 ⫾ 6* 2.78 ⫾ 0.53
LV ⫽ left ventricular; EDV ⫽ end-diastolic volume; ESV ⫽ endsystolic volume; other abbreviations as in Table 1. * P ⬍ .004 versus preoperatively. † P ⬍ .004 versus 3 mo.
kg (16%, P ⬍ .001) at 3 months and by 37.2 ⫾ 10.5 kg (32%, P ⬍ .001) at 17 months. The body mass index (BMI) had declined by 16% and 32% at 3 and 17 months, respectively (both, P ⬍ .001). LV changes with weight loss The changes in LV anatomy are summarized in Table 2. The LV mass had declined by 21.8 ⫾ 12.7 g (18%, P ⬍ .001) at 3 months postoperatively. The results were similar if we excluded the 3 women who did not undergo CMR imaging at 17 months. After 17 months, the LV mass had declined by 40.0 ⫾ 19.8 g (32% compared with preoperatively, P ⬍ .001). No change was seen in the LV enddiastolic volume or ejection fraction during the observation period. The baseline BMI and LV mass exhibited a significant linear relationship (R ⫽ .50, P ⫽ .049). A significant linear relationship was also seen between changes in the BMI and changes in the LV mass after surgery (P ⫽ .008;
Fig. 2. LV mass/BMI ratio over time for individual subjects.
Fig. 1). The effect of the changes in BMI on LV mass remained significant on multivariate analysis, which included changes in the systolic and diastolic blood pressure as parameters (P ⫽ .001 after adjustment for either or both). In addition, the LV mass/BMI ratio remained unchanged with weight loss (Fig. 2). In contrast, both the LV mass/ body surface area ratio (⫺11% at 3 months and ⫺18% at 17 months, both P ⬍ .004) and the LV mass/height ratio (⫺19% at 3 months and ⫺32% at 17 months, both P ⬍ .004) declined (Table 2). RV changes with weight loss The RV anatomic measures are summarized in Table 3. The RV mass correlated with body weight preoperatively and at 3 and 17 months (R ⫽ .74, R ⫽ .83, and R ⫽ .63 and P ⬍ .004, P ⬍ .001, and P ⫽ .066, respectively). The RV mass had declined by 16% at 3 months (P ⬍ .001) but did not exhibit additional changes at 17 months. The RV ejection fraction and volumes remained unchanged with weight loss (Table 3).
Table 3 Right ventricular data Variable
RV RV RV RV Fig. 1. LV mass versus BMI for individual subjects.
mass (g) EDV (mL) ESV (mL) ejection fraction (%)
Preoperative
31.7 ⫾ 6.7 157 ⫾ 27 74 ⫾ 23 54 ⫾ 8
Postoperative (mo) 3
17
26.6 ⫾ 4.4* 160 ⫾ 30 75 ⫾ 24 54 ⫾ 7
27.5 ⫾ 6.0* 156 ⫾ 30 71 ⫾ 18 54 ⫾ 6
RV ⫽ right ventricular; other abbreviations as in Table 2. * P ⬍ .001 versus preoperatively.
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Discussion Both obesity and LV hypertrophy are risk factors for cardiovascular mortality. Using a volumetric CMR approach in the morbidly obese population, we found that substantial weight reduction was associated with a significant regression of LV mass, with no change in LV volume or ejection fraction. The regression in LV mass was linearly related to the magnitude of weight loss after bariatric surgery. When normalized for BMI, the LV mass remained constant, despite a 32% weight loss within 17 months. A regression of the RV mass occurred during the period of rapid weight loss (3 months) after bariatric surgery, with little change thereafter. To our knowledge, these are the first data regarding RV mass changes, identifying a differential response of the 2 ventricles and highlighting the close relationship of the LV mass and BMI in this population. Several studies have demonstrated that bariatric surgery for morbid obesity is associated with a long-term survival advantage [12,13,24,25]. In a prospective study, Sjöström et al. [12] found a hazard ratio of .76 for overall mortality among subjects who had undergone bariatric surgery compared with matched controls. In a retrospective cohort study, Adams et al. [13] found a 40% decline in mortality in patients who had undergone gastric bypass surgery compared with an age-, gender-, and BMI-matched control group. The LV mass is an independent risk predictor for cardiac mortality [26,27]. Our finding of LV mass regression with weight loss could partially explain these findings. Other investigators have used surface echocardiography to examine the LV mass changes in this population. Cunha et al. [28] demonstrated LV mass regression at 6 months after bariatric surgery using M-mode echocardiography in a group of 23 patients. Leichman et al. [29] identified a smaller decrease in the LV mass at 3 months. Using volumetric CMR methods, we found regression of the LV mass as soon as 3 months after bariatric surgery, with the degree of LV mass regression linearly related to the decrease in total body weight, with maintenance of the LV mass/BMI ratio. The change in LV mass was independent of changes in blood pressure. Additionally, using volumetric CMR imaging, with its improved reproducibility compared with echocardiography, we demonstrated these differences with a relatively modest sample size. Previous studies have shown that weight loss, through intensive dieting or weight loss surgery, has led to changes in LV dimensions, including a reduction of the calculated LV mass and wall thickness [14 –17,30]. Using 2D echocardiography, Karason et al. [16] examined the effects of weight loss at 1 year after bariatric surgery in 41 obese subjects. They found a significant reduction in the LV mass and wall thickness compared with 31 “conventionally treated” obese subjects and 43 non– obese-matched controls. However, 13% of their obese subjects were excluded
651
from the analysis of LV wall thickness and mass and 28% of their subjects were excluded from the estimations of LV volumes because of suboptimal echocardiographic data, highlighting the limitations of echocardiography in this population [16]. We were able to acquire data from all subjects at both baseline and all follow-up points. Himeno et al. [20] used M-mode echocardiography to characterize a decrease in LV mass among 22 obese subjects after a 12-week exercise and dietary intervention program. Similar to our findings, the change in LV mass was independent of blood pressure. Again, 12% of their study population were excluded because of uninterpretable echocardiographic data. Hinderliter et al. [14] used 2D echocardiography to study 82 subjects, 63 of whom had been randomized to a 6-month exercise or weight management program, and 19 controls. The intervention group had a decreased relative LV wall thickness, with a trend toward a decrease in LV mass relative to the control group. As with the other echocardiographic studies, 42 patients (29%) of the overall study population of 144 had echocardiograms “in which left ventricular dimensions or wall thicknesses could not be quantified with confidence” [14]. Unlike previous 2D and M-mode echocardiographic studies in the morbidly obese population, we did not find a decrease in LV end-diastolic volume with weight loss. The reasons for this conflict are uncertain, but they might reflect the volumetric approach of CMR imaging compared with the geometric modeling of 2D and M-mode echocardiography. None of the previously cited echocardiographic studies were able to address RV mass or volume. Our data demonstrated a decrease in RV mass in the early period of weight loss. The reason for the initial parallel decline in RV mass and weight but subsequent maintenance of RV mass despite ongoing total body weight loss is unexplained. Our report had several limitations. The study population consisted of entirely middle-age women. Our findings might not be applicable to all age groups or to men. The mechanism by which cardiac remodeling occurs is not fully explained, but it appears to be independent of a reduction in blood pressure or other metabolic factors (e.g., hyperlipidemia). We did not assess the metabolic or inflammatory parameters that might affect LV mass. The potential confounder of 2 different surgical approaches could not be addressed by the present study. Also, we could not determine whether the decline in LV mass reflects a decrease in fatty infiltration of the myocardium or a decrease in LV myocyte hypertrophy. Whether the RV changes we observed were a direct result of weight loss or were possibly due to improvements in obstructive sleep apnea or a decline in pulmonary artery pressure in this population is uncertain.
652
R. R. Jhaveri et al. / Surgery for Obesity and Related Diseases 5 (2009) 648 – 652
Conclusion In morbidly obese women, rapid weight loss was associated with significant regression of the LV and RV mass, with maintenance of the LV mass/BMI ratio and no change in LV or RV volume or ejection fraction. The decline in LV mass was linearly related to the weight reduction, independent of changes in blood pressure, and might partially explain the reduction in cardiovascular mortality associated with substantial weight loss. Disclosures The authors claim no commercial associations that might be a conflict of interest in relation to this article. References [1] Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the united states, 1999 –2004. JAMA 2006;295:1549 –55. [2] Parikh NI, Pencina MJ, Wang TJ, et al. Increasing trends in incidence of overweight and obesity over 5 decades. Am J Med 2007;120:242–50. [3] Hu FB. Obesity and mortality: watch your waist, not just your weight. Arch Intern Med 2007;167:875– 6. [4] Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med 2004;351:2694 –703. [5] Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006;113:898 –918. [6] Heckbert SR, Post W, Pearson GD, et al. Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: the multiethnic study of atherosclerosis. J Am Coll Cardiol 2006;48:2285–92. [7] Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry: the Framingham heart study. JAMA 1991;266:231– 6. [8] Danias PG, Tritos NA, Stuber M, Kissinger KV, Salton CJ, Manning WJ. Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study. J Cardiovasc Magn Reson 2003; 5:431– 8. [9] Ferrara LA, Guida L, Ferrara F, et al. Cardiac structure and function and arterial circulation in hypertensive patients with and without metabolic syndrome. J Hum Hypertens 2007;21:729 –35. [10] Wong CY, O’Moore-Sullivan T, Leano R, Byrne N, Beller E, Marwick TH. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation 2004;110:3081–7. [11] Zarich SW, Kowalchuk GJ, McGuire MP, Benotti PN, Mascioli EA, Nesto RW. Left ventricular filling abnormalities in asymptomatic morbid obesity. Am J Cardiol 1991;68:377– 81. [12] Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741–52.
[13] Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Eng J Med 2007;357:753– 61. [14] Hinderliter A, Sherwood A, Gullette EC, et al. Reduction of left ventricular hypertrophy after exercise and weight loss in overweight patients with mild hypertension. Arch Intern Med 2002; 162:1333–9. [15] Alpert MA, Lambert CR, Panayiotou H, et al. Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss. Am J Cardiol 1995;76: 1194 –7. [16] Karason K, Wallentin I, Larsson B, Sjöström L. Effects of obesity and weight loss on left ventricular mass and relative wall thickness: survey and intervention study. BMJ 1997;315:912– 6. [17] Poirier P, Martin J, Marceau P, Biron S, Marceau S. Impact of bariatric surgery on cardiac structure, function and clinical manifestations in morbid obesity. Expert Rev Cardiovasc Ther 2004;2:193–201. [18] Chuang ML, Danias PG, Riley MF, Hibberd MG, Manning WJ, Douglas PS. Effect of increased body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection fraction, and mass. Am J Cardiol 2001;87:371, 4, A10. [19] Alpert MA, Hashimi MW. Obesity and the heart. Am J Med Sci 1993;306:117–23. [20] Himeno E, Nishino K, Nakashima Y, Kuroiwa A, Ikeda M. Weight reduction regresses left ventricular mass regardless of blood pressure level in obese subjects. Am Heart J 1996;131:313–9. [21] Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ. Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2000;2:271– 8. [22] McNatt SS, Longhi JJ, Goldman CD, McFadden DW. Surgery for obesity: a review of the current state of the art and future directions. J Gastrointest Surg 2007;11:377–97. [23] Salton CJ, Chuang ML, O’Donnell CJ, et al. Gender differences and normal left ventricular anatomy in an adult population free of hypertension: a cardiovascular magnetic resonance study of the Framingham heart study offspring cohort. J Am Coll Cardiol 2002;39:1055– 60. [24] Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416, 423– 4. [25] Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 2004;199:543–51. [26] Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991;114:345–52. [27] Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study. N Engl J Med 1990;322: 1561– 6. [28] Cunha Lde C, da Cunha CL, de Souza AM, Chiminacio Neto N, Pereira RS, Suplicy HL. Evolutive echocardiographic study of the structural and functional heart alterations in obese individuals after bariatric surgery. Arq Bras Cardiol 2006;87:615–22. [29] Leichman JG, Aguilar D, King TM, et al. Improvements in systemic metabolism, anthropometrics, and left ventricular geometry 3 months after bariatric surgery. Surg Obes Relat Dis 2006;2:592–9. [30] MacMahon SW, Wilcken DE, MacDonald GJ. The effect of weight reduction on left ventricular mass: a randomized controlled trial in young, overweight hypertensive patients. N Engl J Med 1986;314: 334 –9.