Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding

Abstract

Heart failure (HF) is the most rapidly growing cardiovascular health burden worldwide. HF can be classified into three groups based on the percentage of the ejection fraction (EF): heart failure with reduced EF (HFrEF), heart failure with mid-range—also called mildly reduced EF— (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). HFmrEF can progress into either HFrEF or HFpEF, but its phenotype is dominated by coronary artery disease, as in HFrEF. HFrEF and HFpEF present with differences in both the development and progression of the disease secondary to changes at the cellular and molecular level. While recent medical advances have resulted in efficient and specific treatments for HFrEF, these treatments lack efficacy for HFpEF management. These differential response rates, coupled to increasing rates of HF, highlight the significant need to understand the unique pathogenesis of HFrEF and HFpEF. In this review, we summarize the differences in pathological development of HFrEF and HFpEF, focussing on disease-specific aspects of inflammation and endothelial function, cardiomyocyte hypertrophy and death, alterations in the giant spring titin, and fibrosis. We highlight the areas of difference between the two diseases with the aim of guiding research efforts for novel therapeutics in HFrEF and HFpEF.

Catestatin as a New Prognostic Marker in Stable Patients with Heart Failure with Reduced Ejection Fraction in Two-Year Follow-Up

“…The authors included in their analysis patients with completely different pathophysiology of heart failure—those with reduced and preserved left ventricular ejection fraction. Although the prognosis for both HF groups may well be equally serious, the reaction for administered treatment is often different reflecting various pathomechanisms involved in the natural history of the disease [ 20 ].…”

Humanistic burden and economic impact of heart failure – a systematic review of the literature

“…HF is chronic and progressive in nature, and can be classified into New York Heart Association (NYHA) classes I-IV based on physical limitation and objective assessment of the presence of cardiovascular disease 6 or according to percentage ejection fraction 7 . The pathophysiology of HF with reduced ejection fraction (HFrEF) differs from that of HF with preserved ejection fraction (HFpEF), with a higher prevalence of non-cardiac morbidities (including DM and hypertension) in patients with HFpEF than in those with HFrEF.…”

“…The pathophysiology of HF with reduced ejection fraction (HFrEF) differs from that of HF with preserved ejection fraction (HFpEF), with a higher prevalence of non-cardiac morbidities (including DM and hypertension) in patients with HFpEF than in those with HFrEF. Given the differences in aetiology and progression of these diseases 7 , the economic burden of HFrEF and HRpEF may vary [8][9][10] . The signs and symptoms of HF include breathlessness, swelling, fatigue, and fluid retention, which can lead to reduced mobility and impaired daily physical functioning 11 .…”

Targeting Mitochondrial Fission-Fusion Imbalance in Heart Failure

“…These adjustments result in a transient improvement of cardiac output. However, in the mid-to-long term, hyperactivation of sympathetic nervous system and renin angiotensin aldosterone system results in excessive cardiac hypertrophy and fibrosis as well as vascular and kidney dysfunction, which together contribute to the left ventricular dysfunction and progression of heart failure [2,6,7].…”