A Simplified Approach for Diagnosing Heart Failure with Preserved Ejection Fraction by Assessing the Left Atrium and Natriuretic Peptides

Aims Heart failure with preserved ejection fraction (HFpEF) is common but diagnosing it remains cumbersome and complex. Left atrial (LA) enlargement and dysfunction is an important pathologic marker in HFpEF. We evaluated whether LA measures and circulating natriuretic peptides (NPs) could simplify HFpEF diagnosis as a first step. Methods and results A new, first-step diagnostic approach to rule in HFpEF is presented using LA volume indexed for height2 (LAViH2; cut-off >35.5 ml/m2 in sinus rhythm, or >38.6 ml/m2 in atrial fibrillation) and NPs (as per the HFA-PEFF major criterion). The LA/NP approach was derived from 443 patients with suspected of HFpEF (final diagnosis 84% HFpEF, 16% controls without heart failure), and validated in two independent cohorts (503 patients, 90% HFpEF; and 123 patients undergoing (exercise) right heart catheterization, 86% HFpEF). The LA/NP step identified 60% HFpEF patients with 88% specificity and 97% positive predictive value (PPV) (derivation cohort). Sequentially applying the LA/NP step, and if normal followed by either HFA-PEFF or H2FPEF algorithm, reduced intermediate HFpEF likelihood scores compared to starting with the algorithms, decreasing additional diagnostic needs for HFpEF diagnosis by 27% (HFA-PEFF) and 56% (H2FPEF). Validation cohorts confirmed the LA/NP approach (76–80% specificity, 92–97% PPV, and 21–57% reduction in intermediate scores). Replacing LAViH2 with LA reservoir strain showed comparable results. Conclusion A first-step approach using enlarged LA volume and elevated NPs simplifies HFpEF diagnosis. This approach identifies most HFpEF patients with high specificity and substantially reduces the need for additional diagnostics by lowering intermediate HFA-PEFF or H2FPEF scores.