This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of β-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Complications and mortality of heart failure are high, despite the availability of several forms of treatment. Uric acid, the end product of purine metabolism would actively participate in the pathophysiology of heart failure. However, there is no consensus about its action in cardiovascular disease. Serum uric acid would have a protective antioxidant activity. This action could help to reduce or counteract the processes that cause or appear as a result of heart failure. However, these protective properties would vanish in the intracellular environment or in highly hydrophobic areas such as atherosclerotic plaques and adipose tissue. This review discusses the paradoxical action of uric acid in the pathophysiology of heart failure.

Primary pulmonary hypertension (PPH) is a progressive disease leading to right heart failure and death. Right heart catherization and maximal or submaximal tests are employed to assess the course of the disease. A neurohormonal parameter such as pro-brain natriuretic peptide (BNP) would be helpful in the assessment of these patients. To study the correlation of BNP with functional status and non-invasive hemodynamic determinations in patients with PPH. Twelve patients (mean age: 48 years; 58% female) were evaluated with 6 minutes walk distance test (6-min WT), plasma BNP, systolic pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and cardiac output (CO) determined by echocardiogram. Plasma BNP levels were compared with normal subjects. BNP levels were increased in PPH patients (1270+/-547 vs 48+/-8 pg/ml, p-value <0.01). Mean PAPs was 82+/-27 mmHg and the mean distance walked in 6 minutes was 407+/-113 meters. BNP levels were positively correlated with PVR (r=0.58, p-value=0.006) and negatively correlated with 6-min WT (r=-0.83, p-value <0.001). No correlation was found between BNP levels, PAPs and CO. In PPH patients, BNP levels are increased and correlate with functional class and PVR. Follow-up studies are needed to evaluate the role of BNP as a marker of progression and therapeutic response in PPH patients.