Biomarker-Guided Therapy for Worsening Heart Failure

Study Questions:

What is the significance of worsening heart failure (WHF) in ambulatory patients with systolic dysfunction?


The study cohort was comprised of 151 symptomatic patients with chronic systolic HF who were randomized to standard of care HF management or a goal to lower N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations ≥1000 pg/ml in addition to standard of care. The investigators defined WHF as: 1) new or progressive symptoms and/or signs of decompensated HF, and 2) unplanned intensification of diuretic therapy. The primary endpoint of the study was total cardiovascular (CV) events (including WHF) over a 1-year period. The total burden of WHF was considered as a function of treatment allocation, with logistic regression expressing reduction in total WHF events in odds ratios (ORs) and 95% confidence intervals (CIs). They then utilized Cox proportional hazards analysis to evaluate the effects of NT-proBNP–guided therapy on the occurrence of WHF. Finally, they constructed Kaplan-Meier curves to evaluate the effects of NT-proBNP versus standard of care management relative to the time-to-first WHF event and compared the two by using the log-rank test.


The study investigators found that 45 subjects developed WHF over a mean follow-up of 10 months. At baseline, patients developing incident WHF had higher ejection fraction (31% vs. 25%; p = 0.03), were more likely to have jugular venous distention (51% vs. 29%, p=0.01) and peripheral edema (49% vs. 24%, p < 0.02), were less likely to receive angiotensin-converting enzyme inhibitors or received these agents at lower doses (p < 0.03), and also received higher loop diuretic doses (60 mg vs. 40 mg, p < 0.001). Occurrence of WHF was strongly associated with subsequent HF hospitalization/CV death (hazard ratio, landmark analysis: 18.8; 95% CI, 5.7-62.5; p < 0.001). NT-proBNP–guided care reduced the incidence of WHF (hazard ratio, 0.52; 95% CI, 0.28-0.96; p = 0.04) and improved event-free survival (log-rank test p = 0.03).


The authors concluded that WHF was associated with substantial risk for morbidity and mortality in patients with systolic HF. They opined that NT-proBNP–guided care reduced risk for WHF.


The findings of this study are important because they suggest that biomarker-guided therapy can reduce the risk of worsening HF. More data are required to determine how comorbidities, particularly underlying renal function, affect such an approach and whether indeed this approach is cost-effective. The alternative is to use a package of biomarkers including tissue Doppler to reduce risk of WHF.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Angiotensin-Converting Enzyme Inhibitors, Biological Markers, Disease-Free Survival, Diuretics, Edema, Geriatrics, Heart Failure, Heart Failure, Systolic, Natriuretic Peptide, Brain, Peptide Fragments, Standard of Care

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