Inflammatory pathways in heart failure with preserved left ventricular ejection fraction: implications for future interventions

Abstract

Many patients with symptoms and signs of heart failure have a left ventricular ejection fraction ≥50%, termed heart failure with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous syndrome mainly affecting older people who have many other cardiac and non-cardiac conditions that often cast doubt on the origin of symptoms, such as breathlessness, or signs, such as peripheral oedema, rendering them neither sensitive nor specific to the diagnosis of HFpEF. Currently, management of HFpEF is mainly directed at controlling symptoms and treating comorbid conditions such as hypertension, atrial fibrillation, anaemia and coronary artery disease. HFpEF is also characterised by a persistent increase in inflammatory biomarkers. Inflammation may be a key driver of the development and progression of HFpEF and many of its associated comorbidities. Detailed characterisation of specific inflammatory pathways may provide insights into the pathophysiology of HFpEF and guide its future management. There is growing interest in novel therapies specifically designed to target deregulated inflammation in many therapeutic areas, including cardiovascular disease. However, large-scale clinical trials investigating the effectiveness of anti-inflammatory treatments in HFpEF are still lacking. In this manuscript, we review the role of inflammation in HFpEF and the possible implications for future trials.

The dangerous liaison between epicardial adipose tissue and heart failure with preserved ejection fraction

“…Unsurprisingly, a positive association was reported between EAT thickness and biomarkers related to metabolic syndrome, endothelial dysfunction and heightened systemic inflammation. Indeed, all the aforementioned conditions are associated with both visceral fat accumulation and HFpEF 4,7 . Obesity‐associated variables displayed the highest discriminative power in the analysis, and in fact, there was a significant correlation between EAT and BMI, in keeping with existing literature 1 .…”

“…1-3 EAT appears to have a critical role in balancing the activation of local and systemic inflammatory pathways via the production of adipose tissue-derived cytokines (adipokines). 4 Indeed, increased EAT thickness is associated with diabetes mellitus, metabolic syndrome, microvascular dysfunction, myocardial fibrosis and remodelling. 5,6 All these pathophysiological alterations appear to be of particular importance in the pathogenesis of the so-called 'inflammatory-metabolic' phenotype of HFpEF, 4 where EAT accumulation is overtly evident.…”

Heart failure: an update from the last years and a look at the near future

“…220 Other mechanisms involved in the pathogenesis of HFpEF are venous dysfunction, endothelium-independent microvascular dysfunction, and subclinical inflammation. [221][222][223][224]…”

Inflammatory cytokines and their correlations with different left ventricular geometries and functions in PHT patients

“…In recent years, PHT has been constantly mentioned as a low-grade inflammatory disease, and inflammatory cytokines play an important role in its occurrence, development, and regression. 8,9 In addition, it has been suggested that inflammatory cytokines may also be involved in the process of left ventricular structural and left ventricular functional changes. 10,11 However, most current studies related to PHT only focused on changes within the above three factors independently, while stopping short of investigating their interrelationships.…”

“…In recent years, PHT has been constantly mentioned as a low‐grade inflammatory disease, and inflammatory cytokines play an important role in its occurrence, development, and regression 8,9 . In addition, it has been suggested that inflammatory cytokines may also be involved in the process of left ventricular structural and left ventricular functional changes 10,11 .…”