Weight Loss in Obese Patients With Heart Failure

BackgroundCardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.MethodsWe prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double‐blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.ResultsPatients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14–48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12–66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.ConclusionsCarvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.

show abstract

“…However, weight loss is also associated with a poor prognosis, particularly in those patients who are obese at baseline. 24…”

Section: Discussionmentioning

confidence: 99%

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

Clark

Coats

Krum

et al. 2017

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…131 Other studies estimate a prevalence of cardiac cachexia of 5-15% in CHF. 133 Patients with cardiac cachexia show higher rates of atrial fibrillation, 134 possibly contributing to the increased mortality. 4 Cardiac cachexia has a dramatic prognostic impact with an 18 month mortality rate of up to 50%, 132 mortality is particularly high in obese cachectic CHF patients.…”

Section: Transition To Cardiac Cachexiamentioning

confidence: 99%

Skeletal muscle wasting in chronic heart failure

2018

View full text Add to dashboard Cite

Patients suffering from chronic heart failure (CHF) show an increased prevalence (~20% in elderly CHF patients) of loss of muscle mass and muscle function (i.e. sarcopenia) compared with healthy elderly people. Sarcopenia, which can also occur in obese patients, is considered a strong predictor of frailty, disability, and mortality in older persons and is present in 5–13% of elderly persons aged 60–70 years and up to 50% of all octogenarians. In a CHF study, sarcopenia was associated with lower strength, reduced peak oxygen consumption (peak VO2, 1173 ± 433 vs. 1622 ± 456 mL/min), and lower exercise time (7.7 ± 3.8 vs. 10.22 ± 3.0 min, both P < 0.001). Unfortunately, there are only very limited therapy options. Currently, the main intervention remains resistance exercise. Specialized nutritional support may aid the effects of resistance training. Testosterone has significant positive effects on muscle mass and function, and low endogenous testosterone has been described as an independent risk factor in CHF in a study with 618 men (hazard ratio 0.929, P = 0.042). However, the use of testosterone is controversial because of possible side effects. Selective androgen receptor modulators have been developed to overcome these side effects but are not yet available on the market. Further investigational drugs include growth hormone, insulin‐like growth factor 1, and several compounds that target the myostatin pathway. The continuing development of new treatment strategies and compounds for sarcopenia, muscle wasting regardless of CHF, and cardiac cachexia makes this a stimulating research area.

show abstract

“…However, in the LIVE trial, liraglutide was associated with an increased risk of adverse cardiac events (including ventricular tachycardia, atrial fibrillation, acute coronary syndrome, and worsening HF; 12 with liraglutide vs. 3 with placebo; P = 0.04). An obesity paradox has been demonstrated among patients with HF, and unexpected weight loss among patients with chronic HF is associated with an increased risk of death 21,22 ; this risk extends to obese patients with HF. Furthermore, HbA1c was significantly reduced in the liraglutide arm compared with placebo (mean difference À0.4%; P < 0.0001).…”

Section: Discussionmentioning

confidence: 99%

“…17 Our results did align with the finding in the LIVE trial that demonstrated that liraglutide treatment was associated with a weight loss of 2.2 ± 3.1 kg compared with placebo (0.0 ± 3.0 kg) (mean difference À2.2 kg; P < 0.0001). 22 Prior analyses have also suggested that weight loss may decrease arterial stiffness 23 and weight gain may be associated with increased ventricular stiffness. 17 Despite the challenges of identifying HF events in a high risk population, 18 concern was raised regarding a possible increase in HF risk among patients with a higher BMI.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest a possible discordance between weight loss and clinical outcomes in patients with HF who have a higher BMI. An obesity paradox has been demonstrated among patients with HF, and unexpected weight loss among patients with chronic HF is associated with an increased risk of death 21,22 ; this risk extends to obese patients with HF. 22 Prior analyses have also suggested that weight loss may decrease arterial stiffness 23 and weight gain may be associated with increased ventricular stiffness.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation