Abstract 17028: “Worsening Heart Failure” in Chronic Heart Failure With Reduced Ejection Fraction: Definition, Characteristics, and Effects of NT-proBNP Guided Therapy
Introduction: Worsening heart failure (WHF) has been identified as a potentially relevant clinical event in patients with HF syndromes and increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists, nor is it known how WHF relates to risk for other events or how HF therapies may impact it.
Hypothesis: Using the definition of WHF in the ProBNP Outpatient Tailored Chronic HF (PROTECT) study, we sought to characterize WHF.
Methods: PROTECT was a randomized trial of 151 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF), comparing standard of care HF management with or without a goal to lower amino-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations <1000 pg/mL. WHF was defined as 1) new or progressive symptoms/signs of decompensated HF, 2) resulting in unplanned intensification of diuretic therapy.
Results: Over mean follow-up of 10 months, 45 subjects developed WHF, the majority of whom had one or two WHF episodes. At baseline, patients destined to develop WHF had higher EF (31% vs. 25%, p=0.03), were more likely to have jugular venous distension and edema (p<0.02), were less likely to receive angiotensin converting enzyme inhibitors (ACEi), and more likely to receive lower ACEi doses (p<0.04); patients destined for WHF also received higher baseline loop diuretic doses (p<0.001) and had higher concentrations of several HF biomarkers including NT-proBNP, ST2, highly sensitive troponin, and galectin-3 (p <0.001). While numerous baseline factors were univariate predictors of WHF, only ST2 concentrations (p<0.001) and EF (p=0.03) at baseline were independently predictive of future WHF. Occurrence of WHF was strongly associated with subsequent HF hospitalization/CV death (56% vs 6%; p <0.001). Relative to therapies, ACEi use and dose were inversely associated with WHF (p<0.05), while loop diuretic dose was directly associated (P =0.006). Allocation to NT-proBNP-guided care independently predicted fewer WHF in adjusted analyses (HR=0.52, p=0.06) and improved time to first WHF event (log rank p=0.04).
Conclusion: In chronic HFrEF, WHF is associated with substantial risk for morbidity and mortality. NT-proBNP guided care reduced risk for this important and deleterious outcome.
Author Disclosures: A. Mallick: None. P.U. Gandhi: None. H.K. Gaggin: Research Grant; Modest; Roche Diagnostics. Consultant/Advisory Board; Modest; Critical Diagnostics, Roche Diagnostics, American Regent, Boston Heart Diagnostics. J.L. Januzzi: Research Grant; Significant; Singulex, Thermo Fisher, Prevencio, Siemens. Other Research Support; Modest; Amgen. Other Research Support; Significant; Novartis, Boeringer Ingelheim. Consultant/Advisory Board; Modest; Critical Diagnostics, Sphingotec. Consultant/Advisory Board; Significant; Roche, Novartis.
- © 2015 by American Heart Association, Inc.