Dear Colleagues,

Cardiovascular disease deaths account for 50%–70% of total mortality, with heart failure (HF) as a crucial cause of morbidity and mortality worldwide. It has been historically accepted that the landscape of HF can be classified into three subtypes based on the percentage of the ejection fraction (EF): heart failure with a preserved ejection fraction (HFpEF; LVEF ≥50%), heart failure with mid-range (HFmrEF; LVEF 41%–49%), and heart failure with reduced EF (HFrEF, EF≤40%). Although HFpEF and HFrEF share common presenting signs and symptoms with poor quality of life, they are distinct conditions with different pathophysiologies, comorbidity, risk factor profiles and changed cellular and molecular levels. In particular, HFpEF represents ~50% of all heart failure hospitalizations and forms ~90% of HF cases in elderly women. Although significant and under-recognized, these findings highlight the need for continued research on the assessment of sex and its impact on HFpEF morbidity and mortality, as well as sex-specific mechanisms and sex-specific interventions.

These chronic illnesses have long been a major area of unmet needs in cardiovascular medicine in addition to their enormous burden on the healthcare system. While recent clinical advances have resulted in a better understanding and efficient and specific treatments for HfrEF, treatment disparities for HfpEF remain a pertinent question. It is, therefore, important to advance our understanding of the unique pathogenesis of HFrEF and HFpEF and the basic mechanisms underlying these entities to inform and guide the efforts of both researchers and clinicians to manage HF patients more effectively. There is also a critical need to explore new therapeutic approaches.

This research topic on HFrEF and HFpEF focuses on new insights and developments in research, novel experimental approaches, current challenges and the latest discoveries in therapeutic modalities, and recent advances and future perspectives. This Special Issue aims to inform and provide a thorough overview of HFrEF and HFpEF research over the past decade and to shed light on the progress made and future challenges of the clinical impact of emerging treatment with benefits on cardiovascular outcomes. 

Original research articles and comprehensive reviews are welcome. Potential HFrEF and HFpEF areas of interest may include, but are not limited to:

• Molecular and structural differences.
• Differences in pathological development.
• The role of endothelial cells and microvasculature in cardiac physiology and pathology.
• Molecular mechanisms and signaling pathways.
• Immune cell-mediated mechanisms.
• Single-cell transcriptomics for identifying disease-specific and/or sex-specific mechanisms.
• Genetics and epigenomics.
• Treatment and prognosis.
• The recent development of HF risk prediction tools.
• Optimal HF prevention strategies.
• Personalized medicine.
• Risk prediction and risk assessment models for HFrEF and HFpEF using machine learning and artificial intelligence methods.
• The interplay between different comorbidities and how likely this could result in multiple HFpEF phenotypes.
• Proteomics, metabolomics and lipidomics signatures in HFrEF and HFpEF risk prediction, pathogenesis, etc.
• Sex disparities with respect to 1) clinical characteristics, pathophysiology, and therapeutic responses to HF treatments; 2) causes; 3) mechanisms; 4) potential biomarkers.

Dr. Djamel Lebeche
Guest Editor

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• heart failure
• HFpEF
• HFrEF
• diastolic dysfunction
• fibrosis
• sex differences
• inflammation
• microvascular dysfunction
• pathophysiology
• outcomes
• treatment
• computational biology
• epitranscriptomics