Clinical and plasma proteomic characterization of heart failure with supranormal left ventricular ejection fraction: An emerging entity of heart failure.

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.