Heart Failure Phenotypes Require Sex-Specific Criteria Which Are Based on Ventricular Dimensions

Ejection fraction (EF) is often used as a criterion to establish diagnostic phenotypes of heart failure (HF). Because EF is a derived metric based on end-systolic volume (ESV) and end-diastolic volume (EDV), it is more logical to consider ESV or EDV as cut-off marker. We concentrate on the impact of ESV, which has the advantage of being linearly related to EDV and nonlinearly with EF, both with highly significant correlations. In particular we also analyze if HF classification should distinguish between females and males.ESV and EDV were determined by biplane angiography in 197 HF patients (67 women). As body surface indexed (i) ESVi values for adult healthy females are smaller than for males, we employ classes of ESVi (bins of 10 mL/m²) to group preserved and reduced EF's (cut-off at 50%) for HF. Reference values regarding mean and standard deviation for ESVi are based on a control group (N=155, 65 women) without HF. For interpretation of the findings we use the documented universal relationship connecting EF to ESV: EF = 1 + c₁ {ESV / (c₂ - ESV)}, where c₁ and c₂ are population-based sex-independent constants. In the reference group ESVi (mL/m²) in women (27.4 ± 27.6) is smaller (P=0.0026) than in their male counterparts (43.6 ± 37.5). Similarly, for HF the ESVi in women (45.7 ± 41.4) is smaller (P=0.0033) than in men (64.2 ± 41.4). This signifies (see formula above) that women have higher values for EF, primarily resulting from smaller ventricular size related to their sex, and not exclusively reflecting disease state. Current phenotype classification based on pooled data for males and females may be inappropriate for either sex.The significantly smaller ESVi observed in women has direct consequences for the traditional classification based on EF cutoff values for HF. Sex-specific criteria (regarding ESVi or EF) for HF phenotypes are warranted, and expectedly have substantial consequences for identification, classification, and management of HF patients.