Diagnostic And Prognostic Implications of Heart Failure With Preserved Ejection Fraction Scoring Systems

Background The phenotypically heterogeneous syndrome of heart failure with preserved ejection fraction (HFpEF) is challenging to diagnose. The HFA-PEFF and H2FPEF scores were developed to guide HFpEF diagnosis but have not been directly compared. We evaluated the generalizability and prognostic implications of the two scores in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) and PDE-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF (RELAX) trial participants and matched controls from Atherosclerosis Risk in Community (ARIC) study. Methods Participants from TOPCAT, RELAX, and ARIC studies were categorized as having low, intermediate, and high likelihood of HFpEF based on the respective scores. Diagnostic performance was evaluated using age, sex, and race matched controls, free of cardiovascular disease from ARIC study. Multivariable-adjusted Cox regression was used to assess the prognostic value of the scores. Results The median HFA-PEFF score in TOPCAT, RELAX and ARIC was 5.0 (IQR:5.0-6.0), 4.0 (IQR:2.0-4.0) and 3 (IQR:2.0-4.0), respectively. The median H2FPEF score in the three populations was 5.0 (IQR:4.0-7.0), 6.0 (IQR:4.0-7.0), and 2.5 (IQR:2.0-4.0), respectively. High HFA-PEFF scores were seen in 75.8%, 20.4%, and 16.5% of in the three populations, respectively. High H2FPEF scores were seen in 42.3%, 55.3%, and 1.9% of the three populations, respectively. Application of HFA-PEFF score categories to patients categorized using H2FPEF score led to 84.2% of TOPCAT, and 50.5% of RELAX participants being reclassified (Figure 1A,B). Using low HFA-PEFF and H2FPEF scores, HFpEF can be ruled-out with high sensitivity (99.5% and 99.9%, respectively) and high negative predictive value (95.7% and 98.5%, respectively). A high HFA-PEFF and H2FPEF score can rule-in HFpEF with good specificity (83.5% and 98.1%, respectively) and positive predictive value (80.6% and 95.5%, respectively). Among TOPCAT participants, the hazard for adverse cardiovascular events per point increase in HFA-PEFF and H2FPEF score was 1.32 (95% CI: 1.03-1.69) and 1.03 (95% CI: 0.91-1.17), respectively (Figure 1 C,D). Conclusion The HFA-PEFF and the H2FPEF scores are reliable diagnostic tools for HFpEF. The scores also provide prognostic value for the risk stratification of HFpEF patients.