Our knowledge of obesity as it relates to HF is evolving as more research becomes available. There are several ways to define obesity, i.e., body mass index (BMI) greater than 30, increased waist circumference, increased waist-to-hip ratio, skinfold estimates, or increased fat mass compared to lean muscle mass.  We can also classify obesity by BMI and further divide that into the obesity phenotypes of metabolically healthy obesity (MHO) versus metabolically unhealthy obesity (MUO).  Individuals with MHO do not show any signs or symptoms of cardiometabolic disease, whereas those with MUO are at an increased risk for cardiometabolic and cardiovascular disease (April-Sanders & Rodriguez, 2021).

Within the already complex pathophysiology of HF, there are specific hemodynamic abnormalities and structural cardiac changes specifically observed in obesity that frequently result in either high output heart failure (HOHF) or heart failure with preserved ejection fraction (HFpEF).  Normal cardiac output (CO) is 4-8 L/min, but in HOHF the CO is above 8 L/min, and in some cases of severe obesity, it has been reported to be as high as 10 L/min (Shen et al., 2021).  Rarely are the conditions that incite HOHF actually the sole cause of HF.  Often, systolic and/or diastolic dysfunction already exists, thus, the provider should investigate some other underlying cardiovascular problem (Givertz & Haghighat, 2021). 

In the setting of obesity, excessive vasodilation seems to be perhaps the most critical component in HOHF, resulting in reduced systemic vascular resistance (SVR) and inefficient tissue perfusion, although the mechanism for dilation is not quite clear.  Increased central blood volume and stroke volume occur leading to an increase in cardiac output at a rate that is proportional to the degree of obesity.  There is a larger amount of lean muscle mass in obesity, which requires significantly more blood flow; however, the heart rate is either not augmented or perhaps only mildly increased, therefore, the increase in CO appears to arise mainly from the increased stroke volume so long as the preload and cardiac contractility are maintained. 

Chronic volume overload eventually leads first to left ventricular dilation followed by a compensatory left ventricular hypertrophic response.  There may be some level of protection because of left ventricular hypertrophy (LVH) secondary to the reduction of stress on the wall of the ventricle due to a lower SVR.  Neurohormonal reactions are triggered due to the decreased arterial-venous oxygen gradient to compensate for the diminished oxygen and blood supply.  Long term activation of these compensatory mechanisms eventually leads to increased sodium and water retention, plasma volume expansion, and hypertension, which ultimately creates cardiac structure deterioration and function (Shen et al., 2021). 

Insulin resistance, found frequently in obesity, can lead to increased oxidation of fatty acids in cardiac myocytes and myocardial inefficiency by up to 50% that results in an altered myocardial metabolism.  This occurrence leads to impairment in contractility of the left ventricle (LV), conclusively having a major effect on the evolution and progression of diastolic dysfunction.  Proinflammatory cytokines activate the sympathetic nervous system and trigger a neurohormonal response, which leads to sodium and water retention.  In addition, neprilysn levels increase, thereby degrading the production of B-type natriuretic peptides (BNP) and diminishing the cardioprotective effect of BNP (Shen et al., 2021).

HFpEF can be defined as having a left ventricular ejection fraction (LVEF) of > 50% in combination with diastolic dysfunction.  Coronary microvascular endothelial dysfunction stemming from a systemic inflammatory state brought on by common comorbidities that frequently occur with obesity, such as hypertension, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), sedentary lifestyle, and iron deficiency anemia, ultimately lead to HFpEF (Borlaug, 2021). HOHF is observed as CO> 8L/min with systemic vasodilation. Signs of pulmonary or venous congestion are noted with dyspnea, abdominal and peripheral edema, exercise intolerance, and generalized fatigue. Table 1 displays similarities and differences between HOHF and HFpEF.

Interestingly, although the incidence of HF rises in the obese, there seems to be a protective mechanism in some individuals that exerts an improved prognosis in HF when compared to their leaner counterparts (Carbone et al., 2017).  This phenomenon is called the obesity paradox.  It has yet to be determined if this is due to elderly being unable to gain weight or even lose weight which can contribute to worsening health outcomes or if there might be a protective effect of adipose tissue in those with chronic disease.  Research has demonstrated a J-curve such that there is a lower mortality risk amongst the overweight and obese, and increased risk of mortality amongst those at normal, low, or morbidly obese body weights (Carbone, 2017).

Clinical management of the obese patient with heart failure can be difficult, as there currently are no clinical practice guidelines for it and HOHF is often misdiagnosed as HFpEF (Shen et al., 2021).  Some guideline principles include:

• Cardiopulmonary exercise testing is a valuable diagnostic tool to help differentiate the two, allowing for a more specific diagnosis and classification of HF and better management. 
• Evidence suggests that weight reduction through lifestyle changes, such as increased physical activity and diet modification, is beneficial in improving overall health and reducing the detrimental effects of HF (Carbone et al., 2021). 
• Pharmacological interventions may be offered when lifestyle and dietary interventions fail to be effective. 
• Bariatric surgery may be considered in the morbidly obese, which can result in an inhibition of the sympathetic nervous system because of the large amount of weight loss and has been linked to HF prevention (Koutroumpakis et al., 2021). 
• Any combination of diet, exercise, increased physical activity, and surgical intervention has shown to have a positive effect on hemodynamics and cardiac morphology (Carbone et al., 2017). Unfortunately, treating some of these patients using traditional guideline-medical therapy drugs, such as angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBI) can cause vasodilation to an already low systemic vascular resistance found in obesity-related high output HF and must be used with caution.
• Aldosterone antagonists offer relief of sodium and water retention and have demonstrated improvement in myocardial fibrosis and LV function in obese individuals (Koutroumpakis et al., 2021). 
• Neprilysin inhibitors have shown promise due to increased levels of neprilysin found in the obese patient, which causes degradation of natriuretic peptide (Shen et al., 2021). 
• Sodium-glucose co-transporter-2 (SGLT2) inhibitors suppress myocardial proinflammatory and profibrotic processes and reduce epicardial fat and, therefore, ameliorates the development of HFpEF (Koutroumpakis et al., 2021).

The complexity of more intricately involved pathophysiologic mechanisms in the production and development of obesity-related HF is not completely understood.  More research is needed to support and develop more specific guidelines of treatment.  Providers should recognize the importance of differentiating obesity-related HOHF and HFpEF and understand the two require distinct paths of treatment.