Reducing the risk of heart failure exacerbation by bariatric surgery in obese patients

KEYWORDS:

• Heart failure exacerbation
• obesity
• bariatric surgery
• self-controlled case series study
• hospitalization

1. Links between obesity and heart failure

1.1. Pathophysiologic evidence

1.1.1. Left ventricular remodeling and neurohormonal changes associated with obesity

Abundant evidence supports that obesity is associated with diastolic dysfunction [1]. Obese individuals tend to have larger left ventricular (LV) mass, greater LV wall thickness, and larger LV chamber size than those who are not obese [1]. Moreover, the ratio between LV wall thickness and chamber radius (i.e. the relative wall thickness) is larger in obese than in lean individuals [2]. LV hypertrophy has been shown to be a risk factor for incident HF, and the association may even be stronger than conventional risk factors [3–5]. Multiple studies demonstrated higher LV diastolic filling pressure in obese patients relative to lean subjects [6,7]. Furthermore, the degree of impairment of LV diastolic filling was related to severity of obesity [8].

In contrast to the association between obesity and diastolic dysfunction, studies comparing obese and non-obese patients have produced mixed results in terms of systolic function [9]. Some studies showed no significant difference in LV systolic function between obese and lean patients, whereas others reported significantly lower LV ejection fraction (EF) or LV fractional shortening in obese subjects [1,10]. These results suggest that obesity leads to HF mainly through diastolic dysfunction rather than systolic dysfunction.

Certain neurohormonal and metabolic alterations may also contribute to the development of LV hypertrophy and dysfunction in obesity. Animal and human studies have demonstrated an association of obesity with activation of the renin–angiotensin–aldosterone system, hyperinsulinemia due to insulin resistance, and hyperleptinemia [1]. All of these factors can lead to HF exacerbation in obese patients.

1.1.2. Concept of obesity cardiomyopathy

Excessive epicardial fat is present in 95% of obese subjects, and more than 40% have ventricular fatty infiltration [11]. The adipocytes can also mediate direct cardiotoxicity that can lead to obesity cardiomyopathy [12]. Both animal and human studies on obesity-related HF revealed an increase in the prevalence of myocardial fibrosis among obese patients [13], which was proportional to the degree of obesity [14]. These morphological findings allude to obesity as a factor directly contributing to HF, reinforcing the concept of obesity cardiomyopathy. In addition to adverse LV remodeling and neurohormonal modifications, such direct effects from excessive adipocytes can contribute to impaired LV function and result in HF.

1.2. Epidemiologic evidence

Obesity is an independent risk factor for development of incidence HF [15]. It has also been reported that its severity and duration are strong predictors of new onset HF [16]. In terms of HF-related morbidities, HF exacerbation contributes to a substantial burden on the health care system, accounting for 1.02 million hospitalizations per year in the United States [17]. Approximately 40% of patients admitted to the hospital with HF exacerbation are obese [10]. Studies have demonstrated an association between obesity and HF-related morbidity. Epidemiological studies report a dose–effect relationship between body mass index (BMI) and risk of hospitalization for HF exacerbation in patients with obesity, suggesting that obesity may be on the causal pathway leading to HF exacerbation [18–20].

Some studies suggested ‘obesity paradox’ (i.e. increased morbidity and mortality with lower BMI compared to obese or overweight individuals) in patients with HF [21]. However, more recent investigations have reported absence of such paradox among patients with HF and good cardiorespiratory fitness (e.g. peak oxygen uptake > 14 ml/kg/min) [22,23]. Several reports suggest that obesity paradox may be due to confounding factors such as physical fitness and disappear after adjusting for these factors [24–29].

2. Weight reduction and improvement of heart failure morbidities

2.1. Pathophysiologic evidence

Many studies demonstrate that weight reduction may have a beneficial effect on LV geometry [30]. Most studies have shown a decrease in LV diastolic chamber size and wall thickness after substantial weight loss [30,31]. For instance, a retrospective cohort study involving 72 patients with obesity showed significant reductions in wall thickness and LV mass at 1 year after bariatric surgery [32]. These changes were more closely related to change in weight than to concomitant change in blood pressure. Regarding changes in hemodynamic parameters, LV end-diastolic pressure and pulmonary capillary wedge pressure were decreased in some, but not all studies, after weight reduction [1]. The benefits of weight loss have been observed more in diastolic dysfunction than systolic dysfunction. This observation is consistent with the fact that systolic dysfunction is not a universal finding in obesity.

2.2. Epidemiologic and clinical evidence

In a self-controlled case-series study, 34 obese patients with HF were enrolled in a 6-month dietary weight reduction program. Only responders (defined as having >3 kg weight loss) showed significant improvement in New York Heart Association functional class, LVEF, and quality of life questionnaire scores [33]. Other studies have also shown that bariatric surgery improves leg edema, frequency of exertional dyspnea, fatigue, and orthopnea in patients with HF [34]. However, no study had evaluated the effects of substantial weight loss on health care utilization for HF exacerbation until our most recent study.

3. Summary of the most recent study

We performed a self-controlled case series study looking at the impact of bariatric surgery on HF hospitalizations and emergency department (ED) visits [35]. By focusing on an objective clinical HF end point that is equally relevant to patients, physicians, and payers, we aimed at determining whether bariatric surgery or other weight loss interventions relieve the social burden of morbidities experienced by obese patients with HF [35]. In this study, we utilized data sampled from 3 states including 1,664 obese patients with HF who underwent bariatric surgery. All ED visits and hospitalizations for HF within the study states were captured for a period of 4 years (2 years before and 2 years after bariatric surgery). The study showed that, in the reference period (i.e. 13–24 months before bariatric surgery), 16.2% (95% confidence interval [CI]: 13.1%–19.4%) of patients had an ED visit or hospitalization for HF, compared with 9.9% in postsurgery months 13–24 (95% CI: 7.4%–12.5%; adjusted odds ratio 0.57; 95% CI: 0.39–0.82; p = 0.003). This corresponds to a >40% reduction in the risk of ED visits or hospitalizations for HF exacerbation after bariatric surgery. Our study based on a large real-world population provides the best evidence on the effectiveness of substantial weight loss on the risk of HF exacerbation.

4. Conclusions and future research considerations

More studies need to be done to understand the mechanism with which substantial weight loss leads to reduction in HF exacerbation. In addition, further investigation is warranted to discern whether the observed effects on HF exacerbation is specific to bariatric surgery or can be achieved with other nonsurgical measures of significant weight reduction. Although our data exhibited relationship between bariatric surgery and HF-associated morbidity, it is still unknown if bariatric surgery offers mortality benefit in obese patients with HF. Since there is no proven intervention to date that can improve survival in patients with HF with preserved EF, we believe bariatric surgery has a potential to be the first treatment to reduce mortality in this patient population. A randomized controlled trial would be necessary to answer this important question on the efficacy of bariatric surgery on mortality and cardiovascular outcomes in patients with HF. Such a trial would overcome some of the limitations that our study had (e.g. lack of BMI, LVEF, and mortality data, possible confounding by time-variable parameters, inability to obtain objective cardiorespiratory function data), with a caveat that it would consume significant time and resources. We believe, while waiting for such a large and high-quality randomized controlled trial to be performed and completed, our self-controlled case series study would serve as the most robust evidence to support the concept that significant weight reduction can reduce HF-related morbidities.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

YJ Shimada was supported, in part, by an unrestricted grant from the American Heart Association National Clinical and Population Research Award and an unrestricted grant from Honjo International Scholarship Foundation. The funding organizations did not have any role in the study design, analysis, or interpretation of data, in writing of the report, or in the decision to submit the article for publication. The researchers were independent from the funding organizations.