B-type natriuretic peptide levels predict long-term mortality in a large cohort of adults with congenital heart disease.

B-type natriuretic peptide levels predict long-term mortality in a large cohort of adults with congenital heart disease.

Yumita Y, Xu Z, Diller GP, Kempny A, Rafiq I, Montanaro C, Li W, Gu H, Dimopoulos K, Niwa K, Gatzoulis MA, Brida M.Eur Heart J. 2024 Jun 14;45(23):2066-2075. doi: 10.1093/eurheartj/ehae254.PMID: 38743452

Dr. Yonatan Buber

Commentary from Dr. Yonatan Buber (Seattle, USA), section editor of ACHD Journal Watch:

Introduction: 

This study investigates the assumption that baseline BNP and trends in BNP levels over time can be predictive of all cause mortality in the general adult congenital heart disease patient population, regardless of the underlying defect. 

Study Design: 

This study was a retrospective cohort study between 2006 and 2019 that analyzed the prognostic role of B-type natriuretic peptide (BNP) and its serial measurements in a large group of ACHD patients. The study included 3392 consecutive, clinically stable ACHD patients under periodic long-term follow-up at the Royal Brompton Hospital in London. Data on patient demographics, primary diagnosis, previous interventions, clinical characteristics, laboratory parameters, echocardiographic findings, and cardiopulmonary exercise testing results was collected from dedicated electronic health records. Researchers categorized patients based on disease complexity (simple, moderate, and complex) and specific morphologic and hemodynamic features. The primary endpoint was all-cause mortality.

Key Finding

  • Both baseline BNP levels and temporal changes in BNP (ΔBNP) were strongly associated with all-cause mortality in ACHD patients. This association held true regardless of the specific CHD diagnosis, disease complexity, anatomical or hemodynamic features, and systolic ventricular function
  • Patients with higher baseline BNP levels had a significantly higher risk of death. Those in the highest quartile of baseline BNP (>107 ng/L) had a hazard ratio (HR) of 5.77 for mortality compared to those in lower quartiles.
  • Similarly, patients who experienced significant increases in BNP levels over time (ΔBNP) also had a higher risk of mortality. Those in the highest quartile of ΔBNP (>35 ng/L) had an HR of 3.6 for mortality compared to those in lower quartiles.
  • While baseline BNP levels correlated with the New York Heart Association functional class, ΔBNP did not show a significant correlation with changes in NYHA class. This suggests that ΔBNP may be a more sensitive indicator of clinical deterioration than NYHA functional class, potentially identifying patients at risk before a change in NYHA class becomes apparent
  • Both baseline BNP and ΔBNP were significantly associated with systemic ventricular dysfunction. This highlights the potential value of BNP as a surrogate marker for global heart function, especially in ACHD patients where echocardiographic assessment of ventricular function can be challenging.

Implications for Clinical Practice

  • These findings strongly support the use of BNP as a routine tool in the surveillance of ACHD patients. The authors recommend:
  • Establishing a baseline BNP level for all ACHD patients, even those with simple CHD lesions. This allows for comparisons over time and can help identify those who may develop late complications.
  • Performing serial BNP measurements in ACHD patients, especially those with higher baseline BNP levels or those considered to be at higher risk for heart failure.
  • Considering earlier interventions, such as adjusting heart failure medications, scheduling earlier hemodynamic interventions, or referral for advanced heart failure assessment (including transplantation)

Study Strengths and Limitations

  • Large sample size, comprehensive data collection, and long follow-up period
  • Single-center design: The study was conducted at a single tertiary ACHD center, potentially limiting the generalizability of findings. External validation in other settings is needed.
  • Retrospective nature
  • Potential selection bias: The study only included patients who had BNP measurements, which may have skewed the sample toward more complex patients with heart failure.

Take-home Points:

1. Baseline BNP levels and temporal changes in BNP levels are significantly associated with all-cause mortality in adults with congenital heart disease. This association is independent of the underlying CHD diagnosis, disease complexity, specific anatomical and hemodynamic features, and systolic ventricular function. Patients in the highest quartile for baseline BNP levels (>107 ng/L) had a significantly increased risk of death. Likewise, patients in the highest quartile for temporal BNP change (>35 ng/L) also had a significantly increased risk of death.

2. Serial BNP measurements are a valuable tool for identifying ACHD patients at risk of clinical deterioration and adverse outcomes. This finding highlights the importance of monitoring BNP levels over time, rather than relying on a single measurement.

3. BNP is an easy-to-obtain, inexpensive, and reproducible marker that can be readily incorporated into the routine, lifelong surveillance of ACHD patients. The widespread availability of BNP testing makes it a practical tool for monitoring ACHD patients in a variety of clinical settings.

Conclusion:

Baseline BNP and temporal BNP changes are both significantly associated with all-cause mortality in ACHD independent of congenital heart disease diagnosis, complexity, anatomic/hemodynamic features, and/or systolic systemic ventricular function. B-type natriuretic peptide levels represent an easy to obtain and inexpensive marker conveying prognostic information and should be used for the routine surveillance of patients with ACHD.