Heart Failure with Reduced Ejection Fraction (HFrEF) and Preserved Ejection Fraction (HFpEF): The Diagnostic Value of Circulating MicroRNAs

Abstract

Circulating microRNAs offer attractive potential as epigenetic disease biomarkers by virtue of their biological stability and ready accessibility in liquid biopsies. Numerous clinical cohort studies have revealed unique microRNA profiles in different disease settings, suggesting utility as markers with diagnostic and prognostic applications. Given the complex network of microRNA functions in modulating gene expression and post-transcriptional modifications, the circulating microRNA landscape in disease may reflect pathophysiological status, providing valuable information for delineating distinct subtypes and/or stages of complex diseases. Heart failure (HF) is an increasingly significant global health challenge, imposing major economic liability and health care burden due to high hospitalization, morbidity, and mortality rates. Although HF is defined as a syndrome characterized by symptoms and findings on physical examination, it may be further differentiated based on left ventricular ejection fraction (LVEF) and categorized as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). The presenting clinical syndromes in HFpEF and HFrEF are similar but mortality differs, being somewhat lower in HFpEF than in HFrEF. However, while HFrEF is responsive to an array of therapies, none has been shown to improve survival in HFpEF. Herein, we review recent HF cohort studies focusing on the distinct microRNA profiles associated with HF subtypes to reveal new insights to underlying mechanisms and explore the possibility of exploiting these differences for diagnostic/prognostic applications.

Subtypes identification on heart failure with preserved ejection fraction via network enhancement fusion using multi-omics data

“…In our analysis, hsa-miR-106a-5p , hsa-miR-193b-3p , hsa-miR-193b-5p , hsa-miR-191-5p and hsa-miR-660-5p showed significantly differential expression between the low- and high-risk group. Existing literature revealed that these miRNAs were associated with several mechanisms of potential HF [38] , [39] .…”

“…For example, HF biomarker-NT-proBNP was increased moderately in HFpEF and showed poor predictive value for HFpEF [39] . A study showed that biomarker panels of microRNAs demonstrated higher discriminative power for distinguishing HFpEF compared to the result using plasma NT-proBNP levels alone [38] . Additionally, studies of HFpEF from the 1980s to the present have shifted from the perspective of mechanistic understanding to multi-organ focused disease study [61] including pulmonary arterial hypertension, obesity and metabolic diseases, vascular stiffness, chronological impotence, skeletal muscle disease, and renal insufficiency [62] .…”

The Anti-Inflammatory and Antioxidant Properties of n-3 PUFAs: Their Role in Cardiovascular Protection

“…In recent years, numerous studies have been conducted concerning the heterogeneous and complex syndrome known as heart failure (HF). In particular, heart failure with reduced ejection fraction (EF) and heart failure with preserved ejection fraction (HFpEF) were defined [100][101][102][103]. The majority of the population is affected by heart failure with preserved ejection fraction, prevalent in the ageing population.…”

Targeting Mitochondrial Fission-Fusion Imbalance in Heart Failure

“…Half of heart failure patients display reduced left ventricular ejection fraction, termed HFrEF (heart failure with reduced ejection fraction), and the other half present preserved left ventricular ejection fraction, termed HFpEF (heart failure with preserved ejection fraction) [2,3]. Most of the available therapies for heart failure were developed to treat HFrEF, but not HFpEF [2][3][4][5]. Considering these are diseases with different pathophysiology, there is still uncertainty about the effectiveness of HFrEF interventions to treat HFpEF patients.…”