Increased Resting Metabolic Rate in Patients with Congestive Heart Failure

Cardiac cachexia, which is characterized by a negative energy balance and subsequent weight loss and systemic wasting, occurs frequently in patients with end-stage heart failure [1]. It is unclear whether reduction in caloric intake or elevated caloric expenditure causes this condition. We know of no recent studies that have systematically investigated resting metabolic rate and body composition in patients with heart failure and documented systolic dysfunction. Thus, we investigated a cohort of patients with heart failure, using indirect calorimetry to measure resting metabolic rate, dual energy x-ray absorptiometry to measure body composition, and food diaries to measure caloric intake. We then compared the results with those from an age-matched cohort of healthy volunteers. Methods Patients Twenty patients with documented dyspnea and fatigue during ordinary physical activity were recruited by the Heart Failure Service at the Baltimore Veterans Affairs Medical Center. Patients were male (7 were black and 13 were white), and each had a mean left ventricular ejection fraction (SD) by radionuclide ventriculography of 0.24 0.10 (range, 0.06 to 0.40). Mean time (SD) since diagnosis was 45 36 months. Patients were taking two or more of the following medications: diuretics, digoxin, and vasodilators (angiotensin-converting enzyme inhibitors or hydralazine-nitrates). Symptoms were stable, patients were in New York Heart Association functional class II (n = 2), III (n = 14), or IV [n = 4], and no concomitant acute disease was present. Forty healthy, age-matched male volunteers served as controls. Reasons for excluding volunteers from the control cohort included 1) cardiomyopathy or clinical evidence of coronary heart disease, such as ST-segment depression 1 mm at rest or exercise; 2) hypertension with resting blood pressure greater than 140/90 mm Hg; and 3) noncardiac disease that limited exercise performance, such as arthritis, peripheral vascular disease, and cerebral vascular disease. This study was approved by the Committee on Human Research at the University of Maryland, and written informed consent was obtained from each patient and control before the investigation. Timing of Tests Methods for the timing of tests have been previously described [2]. At approximately 8:30 a.m., after patients and controls had completed a 12-hour fast in a darkened, temperature-controlled room, their resting metabolic rates were measured for 45 minutes. Each patient or control was placed in a supine position with a clear plastic hood over his head. Room air was continuously drawn through the hood and the flow rate was measured by a pneumotachograph. Oxygen consumption and carbon dioxide production were continuously measured and analyzed and converted to a caloric equivalent (kcal/d) using the Weir equation [3]. Daily caloric intake and daily macronutrient intake were estimated from a 3-day (2 weekdays and 1 weekend day) food diary. Fat-free mass and fat mass were measured using a total body scan with dual-energy x-ray absorptiometry (Model DPX-L, Lunar Radiation Corp., Madison, Wisconsin). Peak oxygen consumption (Vo 2) was assessed by a progressive, symptom-limited treadmill exercise test in which the speed of the treadmill was constant and the incline was increased by 2% every 2 minutes. Statistical Analysis The physical characteristics of cohorts and patients with heart failure were compared using unpaired t-tests. The relation between variables was measured by linear regression analysis. A one-way analysis of covariance examined whether resting metabolic rate differed between controls and patients with heart failure after we statistically controlled for differences in fat-free mass. Values are expressed as mean SD. Results Because no differences were noted between black and white patients, data for all patients were pooled. No differences in age or body weight existed between controls and patients with heart failure Table 1, but because patients with heart failure were shorter than controls (P = 0.08), the body mass index in patients with heart failure was higher than it was in controls (P < 0.05). Fat-free mass tended to be lower in patients with heart failure (P = 0.09), but no difference in fat mass existed. Predictably, peak Vo 2 was lower (P < 0.01) in patients with heart failure. No difference was noted in daily caloric intake between groups. Table 1. Physical Characteristics in Healthy Men and Patients with Congestive Heart Failure* Measured resting metabolic rate (kcal/d) was 18% higher in patients with heart failure (mean, 1828 275 kcal/d [95% CI, 1289 to 2367 kcal/d]) than in controls (1543 219 kcal/d [95% CI, 1114 to 1972 kcal/d]; P < 0.01). Resting metabolic rate correlated with fat-free mass in both groups (Figure 1). When statistically adjusted for differences in fat-free mass, the mean difference in resting metabolic rate between patients with heart failure (1875 178 kcal/d) and controls (1521 171 kcal/d) was magnified. Figure 1. Relation between resting metabolic rate (kcal/d) and fat-free mass in patients with heart failure and controls. Discussion The higher resting metabolic rate in patients with heart failure probably contributes to weight loss and musculoskeletal wasting. The difference in resting metabolic rate between elderly patients with heart failure and healthy elderly persons is clinically significant (18%; 283 kcal/d). When resting metabolic rate data for each group were compared after being normalized for differences in fat-free mass, the higher resting metabolic rate in patients with heart failure compared with that in healthy elderly persons was even more striking ( 354 kcal/d). These data highlight the importance of factors other than simple reduction in caloric intake that contribute to weight loss, which complicates the course of many patients with late-stage heart failure. It is unlikely that abnormalities in the two other components of daily caloric expenditure contribute substantially to weight loss in patients with heart failure; that is, the caloric expenditure associated with meal consumption constitutes only 10% of daily caloric expenditure [4], and the deconditioned state of patients with heart failure diminishes the possibility that a high level of caloric expenditure associated with physical activity is an important factor. A voluntary reduction in caloric intake is commonly thought to contribute to the weight loss of patients with heart failure [1], but we found no difference in reported daily caloric intake between patients with heart failure and controls. However, it should be acknowledged that difficulties and inaccuracies associated with reporting of food intake exist [5]. Resting metabolic rate is frequently used to establish daily caloric requirements in both healthy and diseased elderly persons [6]. Data from our study suggest that such guidelines, if based on the caloric requirements of healthy persons, would be inappropriate for patients with heart failure. Using recent equations generated from a healthy elderly cohort in our laboratory would underestimate resting metabolic rate in patients with heart failure by 270 kcal per day (measured, 1828 kcal/d; predicted, 1556 kcal/d) [7]. The mechanism for the higher resting metabolic rate in patients with heart failure is unknown. Increased myocardial oxygen requirements and the increased metabolic cost of breathing may contribute [1], but it is probable that systemic factors are also important. Circulating levels of tumor necrosis factor are higher in patients with heart failure [8], but the relation of this to resting metabolic rate is unknown. A more likely explanation is elevated sympathetic nervous system activity, which is typically seen in patients with heart failure, especially heart failure in its advanced stages [9]. We have shown that resting metabolic rate increases in relation to increments in the rate of norepinephrine appearance into circulation [2]. Thus, it is likely that overactivity of the sympathetic nervous system is involved in the pathogenesis of the higher resting metabolic rate in patients with heart failure. Future studies in patients with heart failure should address this important hypothesis. A higher resting metabolic rate in patients with heart failure may at least partially account for otherwise unexplained weight loss. Present caloric guidelines established in healthy elderly persons significantly underestimate the resting caloric needs of elderly patients with heart failure. Proper nutritional and physical activity interventions could reverse or prevent weight loss in patients with heart failure, improve their functional capacity and body composition, and possibly alter the long-term evolution of cardiac dysfunction.