Understanding heart failure with preserved ejection fraction: where are we today?

Abstract

Heart failure with preserved ejection fraction (HFpEF) represents a complex and heterogeneous clinical syndrome, which is increasingly prevalent and associated with poor outcome. In contrast to heart failure with reduced ejection fraction (HFrEF), modern heart failure pharmacotherapy did not improve outcome in HFpEF, which was attributed to incomplete understanding of HFpEF pathophysiology, patient heterogeneity and lack of insight into primary pathophysiological processes. HFpEF patients are frequently elderly females and patients demonstrate a high prevalence of non-cardiac comorbidities, which independently adversely affect myocardial structural and functional remodelling. Furthermore, although diastolic left ventricular dysfunction represents the dominant abnormality in HFpEF, numerous ancillary mechanisms are frequently present, which also negatively impact on cardiovascular reserve. Over the past decade, clinical and translational research has improved insight into HFpEF pathophysiology and the importance of comorbidities and patient heterogeneity. Recently, a new paradigm for HFpEF was proposed, which states that comorbidities drive myocardial dysfunction and remodelling in HFpEF through coronary microvascular inflammation. Regarding the conceptual framework of HFpEF treatment, emphasis may need to shift from a ‘one fits all’ strategy to an individualised approach based on phenotypic patient characterisation and diagnostic and pathophysiological stratification of myocardial disease processes. This review will describe these novel insights from a pathophysiological standpoint.

Clinical Effectiveness of Telemedicine for Chronic Heart Failure: A Systematic Review and Meta-Analysis

“…HFpEF represents a complex and heterogeneous clinical syndrome with a poor outcome, and a preserved systolic LV function, with LVEF>50% 62. One of the inclusion criteria in studies included in this meta-analysis was the impaired LVEF, defined as LVEF<50%.…”

Vascular and endocardial endothelial dysfunction in heart failure

“…Ona inhibira maladaptivnu hipertrofiju i povećava komplijansu kardiomiocita kroz PKG posredovanu fosforilaciju sarkomernog proteina titina [3]. Krutost kardiomiocita je uglavnom određena titinom, elastičnim proteinom sarkomere.…”

“…Sintetisani cGMP aktivira PKG dozvoljavajući PKG posredovanu fosforilaciju velikog broja ciljnih proteina ispoljavajući širok spektar nishodnih efekata poput pojačanog preuzimanja kalcijuma u sarkoplazmatski retikulum, inhibiciju ulaska kalcijuma, suzbijanja hipertrofije preko inhibicije G proteina vezanog za receptor i inhibicije katjonskih kanala zavisnih od prolaznog potencijala (TRPC). Inhibira i oštećenja koja su posledica ishemije/reperfuzije fosforilacijom ATPsenzitivnog kalijumovog kanala i stimulišu relaksaciju i distensibilitet leve komore preko fosforilacije troponina i (TNI) i segmenta titin N2B [3,5].…”

Heart failure with preserved ejection fraction: current status and challenges for the future

“…Based on recent findings in cardiac tissue samples from HFpEF patients, a novel paradigm on HFpEF pathogenesis was formulated [1]. This paradigm proposes that the different comorbidities initiate chronic systemic inflammation, which via perturbations of the microvasculature of the heart stiffens and damages cardiac muscle cells causing diastolic dysfunction.…”

“…The advances and current status of HFpEF research are described in this special focus issue of the Netherlands Heart Journal. HFpEF is the most common heart failure phenotype in ageing societies, highly prevalent in elderly women and frequently accompanied by comorbidities which result from a detrimental lifestyle, such as obesity, metabolic syndrome, type 2 diabetes mellitus and salt-sensitive arterial hypertension [1]. Despite modern heart failure therapy, the prognosis of HFpEF has not improved over the last decades.…”