HFpEF Diagnosis: A Challenge in CKD with Current Algorithms

Background: Chronic kidney disease (CKD) is associated with a high burden of cardiovascular remodeling and increased risk of heart failure with preserved ejection fraction (HFpEF). However, the interpretation of natriuretic peptide-based HFpEF diagnostic remains challenging in CKD populations, where structural cardiac abnormalities and elevated NT-proBNP levels frequently coexist. Methods: We conducted a cross-sectional study including ambulatory patients with CKD stages G3–G4 and NYHA II dyspnea. Clinical, metabolic, vascular, and echocardiographic assessments were performed. HFpEF was assessed using a modified HFA-PEFF-based approach derived from the ESC-recommended diagnostic algorithm. We evaluated the impact of NT-proBNP thresholds on HFpEF classification and explored the relationship between NT-proBNP, echocardiographic diastolic dysfunction, and structural cardiac abnormalities. Results: The cohort displayed a high cardiometabolic burden (74.9%), and structural cardiac abnormalities were highly prevalent. Using a modified HFA-PEFF diagnostic algorithm, HFpEF was identified in 52.9% of patients. However, when the biomarker domain was excluded, 86.7% of patients remained within the intermediate-probability range. In an exploratory analysis, a cutoff of 700 pg/mL was identified as the cohort-adapted threshold with the best diagnostic balance and identified 19.8% patients as having HFpEF. Conclusions: Patients with CKD G3–G4 exhibited substantial structural and functional cardiovascular abnormalities despite no prior diagnosis of heart failure. HFpEF classification varied according to the NT-proBNP threshold applied, while NT-proBNP demonstrated limited discriminatory performance for echocardiographic diastolic dysfunction. These findings support the need for more refined and CKD-sensitive approaches for HFpEF characterization in this population.