Early Diagnosis of Heart Failure Using NT-proBNP Levels in Primary Care

leads to better clinical outcomes compared to the usual referral pathway. Patients are randomized 1:1 to early cardiology evaluation (within 7 days of NT-proBNP result) versus standard PC-driven referral. This approach seeks to bridge the gap between suspicion and diagnosis, allowing for timely initiation or optimization of therapy when appropriate.

The study will be conducted in collaboration with the Córdoba-Guadalquivir Primary Care District. A training session has been held with primary care providers, and informed consent materials have been distributed throughout the district.

The primary outcome is a composite hierarchical endpoint, assessed using a win ratio approach. The components of this outcome include cardiovascular mortality, all-cause mortality, number of HF hospitalizations, number of urgent visits due to HF, number of GDMT drugs initiated (when indicated), number of GDMT drugs up-titrated (when indicated), and proportional change in log-transformed NT-proBNP at 12 months. The win ratio methodology allows for an ordered comparison of outcomes, giving greater weight to more severe events (e.g., death) while preserving statistical efficiency in detecting clinical benefit across multiple domains.

This design aligns with real-world priorities: reducing hard endpoints (mortality, hospitalization), improving evidence-based pharmacologic management, and optimizing biomarker control. It also recognizes the heterogeneity in HF diagnosis and severity among patients presenting to PC with unexplained dyspnea or fatigue.

The trial includes stratified secondary analyses in patients with and without confirmed HF, in those with HFpEF vs HFrEF phenotypes, and by sex, to explore differential responses to early intervention and inform future implementation strategies. All patients are followed for 12 months, with data collected from both cardiology and primary care visits. The target sample size of 304 participants provides adequate power to detect a clinically meaningful win ratio based on prior observational and interventional data. This total includes 152 patients per arm (early cardiology intervention vs. standard care), with a 1:1 allocation ratio

The study has received approval from the local ethics committee (reference number 6145). All participants are required to provide written informed consent before enrolling in the study, and are informed of their right to withdraw from the study at any time without giving any impact on their standard medical care. Participant confidentially is strictly maintained and all data are securely stored in compliance with data protection regulations. The study results will be disseminated through scientific publications and conference presentations.

Inclusion criteria

• Age ≥ 18 years.
• Signs and symptoms related to heart failure (HF).
• Patients assessed in primary care.
• No prior diagnosis of HF.
• NT-proBNP levels > 300 pg/mL.

Exclusion criteria

• Patients diagnosed with a chronic disease with persistently elevated NT-proBNP levels, assessed by Cardiology, in whom heart failure (HF) has been ruled out in the previous year (mainly by echocardiography).
• Chronic kidney disease on hemodialysis.
• Patients with a life expectancy of less than 1 year due to severe comorbidities such as advanced-stage cancer.
• Patients enrolled in other clinical trials.
• Inability of the patient to understand the clinical trial and to provide informed consent.