Dear Editor,
I read with interest the recent study evaluating outcomes in patients with HFpEF: ‘Worse Long-Term Outcomes in New-Onset HFpEF vs HFrEF and HFmrEF: Findings from the Stockholm PREFERS Study’.1 The authors report worse prognosis in this group; however, several aspects of the diagnostic framework and its interpretation warrant further consideration.
First, the definition of HFpEF relied on an E/e′ threshold >8, which falls within the indeterminate range and does not reliably indicate elevated filling pressures.2 This raises concerns regarding the inclusion of patients without clear evidence of haemodynamic congestion.
Second, the NT-proBNP thresholds used (>125 ng/L in outpatients and >300 ng/L in hospitalized patients) are non-specific for rule in HF and may reflect comorbidity burden rather than true heart failure, particularly in an elderly population with a high prevalence of atrial fibrillation and other systemic conditions.3
Taken together, the combination of a non-specific biomarker threshold and an echocardiographic parameter within the grey zone raises concerns about the robustness of the HFpEF diagnosis in this cohort.
Although multivariable adjustment was performed, it remains difficult to disentangle the effect of HFpEF itself from the overall clinical profile of these patients, given the close interplay between age, comorbidities, and the HFpEF definition. Even after adjustment, the observed association may therefore reflect the underlying clinical phenotype rather than a distinct disease effect.
This issue has been increasingly recognized, as current HFpEF definitions may include heterogeneous populations without consistent demonstration of elevated filling pressures or exclusion of alternative cardiac causes of symptoms.4
A more cautious interpretation of HFpEF as a diagnostic category would strengthen the clinical implications of the study.
Sincerely,
Maria Giulia Bellicini
Cardiology Institute; Spedali Civili di Brescia, Brescia, Italy
Declarations
Disclosure of Interest
The author declare no disclosure of interest for this contribution.
Data Availability
No data were generated or analysed for this manuscript.
Funding
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References
- 1. Persson H, Winderud A, Hage C, Corovic Cabrera C, Löfström U, Lyngå P, et al. (April 9, 2026) Worse long-term outcomes in new-onset HFpEF vs HFrEF and HFmrEF: findings from the Stockholm PREFERS study. ESC Heart Fail, 10.1093/eschf/xvag105 [DOI] [PMC free article] [PubMed] [Google Scholar]
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Data Availability Statement
No data were generated or analysed for this manuscript.