What is the clinical evidence from this study?

Study design: Review. Population: Heart failure with preserved ejection fraction (HFpEF). Intervention: HFpEF probability scores (HFA-PEFF and H2FPEF).

April 7, 2026Open Access

Strengths and limitations of HFpEF probability scores in the era of precision medicine

Key Result

HFpEF probability scores like HFA-PEFF and H2FPEF effectively capture typical presentations but have significant limitations in phenotypes with atrial fibrillation and obesity.

Structured PICO

Population

Patients with heart failure with preserved ejection fraction (HFpEF), particularly those with atrial fibrillation or obesity phenotypes

Intervention

HFpEF probability scores (HFA-PEFF and H2FPEF) and precision medicine approaches

Outcome

Performance, strengths, and limitations of HFpEF probability scales

HFpEF probability scores are valuable but require phenotype-specific interpretation, particularly in patients with obesity or atrial fibrillation, to improve diagnostic accuracy and guide targeted therapies.

Limitations

Current evidence is largely derived from observational and subgroup analyses, lacking large prospective phenotype-specific validation.
Prospective validation studies specifically designed to assess the performance of HFpEF probability scores in AF-dominant phenotypes are limited.
No large prospective studies have systematically evaluated the performance of HFA-PEFF and H2FPEF scores across different body mass index strata.

Abstract

Background: Heart failure with preserved ejection fraction is a heterogeneous syndrome influenced by comorbidities, complicating diagnosis and treatment. Probability-based scales, such as HFA-PEFF and H2FPEF, are commonly used but have limitations in specific phenotypes, including atrial fibrillation and obesity. Methods: A structured literature review was conducted using PubMed, Scopus, Wiley Online Library, and Google Scholar. Keywords included "HFpEF," "HFA-PEFF," "H2FPEF," "atrial fibrillation," "obesity," "probability scores," and "precision medicine." Relevant studies were screened to summarize the performance, strengths, and limitations of HFpEF probability scales and their implications for precision medicine. Results: HFA-PEFF and H2FPEF effectively capture typical HFpEF presentations and can rule out disease with low scores. Limitations arise in phenotypes with AF, which alters natriuretic peptide levels and echocardiographic parameters, and obesity, which impairs NP-based diagnostics. Integration of advanced phenotyping, including left atrial function and BMI-adjusted thresholds, may improve detection. Precision medicine strategies, such as GLP-1 receptor agonists for obesity-related HFpEF or AF ablation, highlight phenotype-specific therapeutic potential. Conclusion: HFpEF probability scores are valuable tools but must be interpreted in the context of individual phenotypes. Precision medicine approaches, combining phenotyping, comorbidity assessment, and targeted therapies, offer improved diagnostic and therapeutic strategies for this heterogeneous population.

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