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Updated: May 13, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Clinical and plasma proteomic characterization of heart failure with supranormal left ventricular ejection fraction:
Yasuhiko Sakata1,2, Kotaro Nochioka1, Satoshi Yasuda1
1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Insights
Heart failure with supranormal ejection fraction (HFsnEF) presents a significant cardiovascular risk, comparable to reduced ejection fraction heart failure (HFrEF). This emerging condition exhibits distinct structural and proteomic profiles.
Area of Science:
- Cardiology
- Heart Failure Pathophysiology
- Proteomics
Background:
- Current heart failure (HF) guidelines use left ventricular ejection fraction (LVEF) cutoffs that may not fully capture risks in HF with higher LVEF.
- Existing classifications may overlook specific characteristics and risks associated with HF and supranormal LVEF.
Purpose of the Study:
- To characterize heart failure with supranormal ejection fraction (HFsnEF) by exploring novel LVEF cutoffs.
- To compare the clinical, structural, and proteomic profiles of HFsnEF with other HF classifications.
Main Methods:
- Patients from the CHART-Omics study were categorized into four groups: HFrEF, HFmrEF, HFnEF, and HFsnEF based on defined LVEF criteria.
- Hazard ratios for cardiovascular death and HF hospitalization were calculated, adjusting for clinical backgrounds.
- Quantitative analysis of plasma proteins was performed to identify differences between HFsnEF and HFrEF.
Main Results:
- HFsnEF demonstrated an increased hazard ratio (2.71) for adverse cardiovascular outcomes, similar to HFrEF (3.14), when compared to HFnEF.
- HFsnEF was associated with increased relative left ventricular wall thickness and decreased ventricular dimensions.
- Significant differences in plasma proteomic profiles were observed between HFsnEF and HFrEF, indicating distinct underlying pathophysiological pathways.
Conclusions:
- HFsnEF is an emerging heart failure entity with a cardiovascular risk profile comparable to HFrEF.
- HFsnEF possesses unique structural and plasma proteomic characteristics differentiating it from other HF subtypes.
- Re-evaluation of LVEF cutoffs may be necessary to fully understand and manage HFsnEF.
Aims:
The clinical guidelines categorize heart failure (HF) based on left ventricular ejection fraction (LVEF). However, the current LVEF cutoffs, 40% and 50%, may not fully address the underlying characteristics and cardiovascular risk of HF, particularly for HF with higher LVEF. This study aimed to characterize HF with supranormal ejection fraction (HFsnEF) using different LVEF cutoffs (35%, 55%, and 70% for men, and 40%, 60%, and 75% for women).
Methods And Results:
This study divided 442 patients from the CHART-Omics study into four groups: HF with reduced ejection fraction (HFrEF) (n = 55, 65.5 years), HF with mildly reduced ejection fraction (HFmrEF) (n = 125, 69.3 years), HF with normal ejection fraction (HFnEF) (n = 215, 69.0 years) and HFsnEF (n = 47, 67.1 years). When clinical backgrounds were adjusted and HFnEF served as the reference, HFsnEF carried an increased hazard ratio (HR) for the composite of cardiovascular death and HF hospitalization of 2.71 (95% confidence interval [CI] 1.10-6.66, p = 0.030), while HFrEF had a HR of 3.14 (95% CI 1.36-7.23, p = 0.007). HFsnEF was characterized by an increase in relative left ventricular wall thickness and a decrease in left ventricular dimensions, whereas increased left ventricular mass and dimensions characterized HFrEF. Quantitative analysis of 4670 plasma proteins showed essential differences between HFsnEF and HFrEF, for example, 'protein synthesis' versus 'cell morphology', 'cellular assembly and organization' and 'nucleic acid metabolism' for underlying pathophysiology, and 'energy production' versus 'connective tissue disorders' and 'cell-to-cell signalling and interaction' for prognostication.
Conclusions:
Heart failure with supranormal ejection fraction, an unnoticed but emerging entity in HF, carries a similarly increased cardiovascular risk as HFrEF but has unique structural and plasma proteomic characteristics.
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