Aditi Mallick1, Parul U Gandhi2, Hanna K Gaggin3, Nasrien Ibrahim1, James L Januzzi4. 1. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts. 2. Cardiology Division, VA Connecticut Healthcare System, West Haven, and Yale School of Medicine, New Haven, Connecticut. 3. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts. 4. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts. Electronic address: jjanuzzi@mgh.harvard.edu.
Abstract
OBJECTIVES: The goal of this study was to define and assess the significance of worsening heart failure (WHF) in patients with chronic ambulatory heart failure with reduced ejection fraction (HFrEF). BACKGROUND:WHF has been identified as a potentially relevant clinical event in patients with acute heart failure (HF) and is increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists. It remains uncertain how WHF relates to risk for other HF events or how treatment may affect WHF. METHODS: A total of 151 symptomatic patients with chronic HFrEF were randomized to standard of care HF management or a goal to lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations ≤1,000 pg/ml in addition to standard of care. WHF was prospectively defined as: 1) new or progressive symptoms and/or signs of decompensated HF; and 2) unplanned intensification of diuretic therapy. RESULTS: Over a mean follow-up of 10 months, 45 subjects developed WHF. At baseline, patients developing incident WHF had higher ejection fraction (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 or received these agents at lower doses (p < 0.04), and also received higher loop diuretic doses (p < 0.001). Occurrence of WHF was strongly associated with subsequent HF hospitalization/cardiovascular death (hazard ratio, landmark analysis: 18.8; 95% confidence interval: 5.7 to 62.5; p < 0.001). NT-proBNP-guided care reduced the incidence of WHF in adjusted analyses (hazard ratio: 0.52; p = 0.06) and improved event-free survival (log-rank test p = 0.04). CONCLUSIONS: In chronic HFrEF, WHF was associated with substantial risk for morbidity and mortality. NT-proBNP-guided care reduced risk for WHF.
RCT Entities:
OBJECTIVES: The goal of this study was to define and assess the significance of worsening heart failure (WHF) in patients with chronic ambulatory heart failure with reduced ejection fraction (HFrEF). BACKGROUND:WHF has been identified as a potentially relevant clinical event in patients with acute heart failure (HF) and is increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists. It remains uncertain how WHF relates to risk for other HF events or how treatment may affect WHF. METHODS: A total of 151 symptomatic patients with chronic HFrEF were randomized to standard of care HF management or a goal to lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations ≤1,000 pg/ml in addition to standard of care. WHF was prospectively defined as: 1) new or progressive symptoms and/or signs of decompensated HF; and 2) unplanned intensification of diuretic therapy. RESULTS: Over a mean follow-up of 10 months, 45 subjects developed WHF. At baseline, patients developing incident WHF had higher ejection fraction (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 or received these agents at lower doses (p < 0.04), and also received higher loop diuretic doses (p < 0.001). Occurrence of WHF was strongly associated with subsequent HF hospitalization/cardiovascular death (hazard ratio, landmark analysis: 18.8; 95% confidence interval: 5.7 to 62.5; p < 0.001). NT-proBNP-guided care reduced the incidence of WHF in adjusted analyses (hazard ratio: 0.52; p = 0.06) and improved event-free survival (log-rank test p = 0.04). CONCLUSIONS: In chronic HFrEF, WHF was associated with substantial risk for morbidity and mortality. NT-proBNP-guided care reduced risk for WHF.
Authors: Milton Packer; Javed Butler; Faiez Zannad; Gerasimos Filippatos; Joao Pedro Ferreira; Stuart J Pocock; Peter Carson; Inder Anand; Wolfram Doehner; Markus Haass; Michel Komajda; Alan Miller; Steen Pehrson; John R Teerlink; Sven Schnaidt; Cordula Zeller; Janet M Schnee; Stefan D Anker Journal: Circulation Date: 2021-08-29 Impact factor: 29.690
Authors: Milton Packer; Stefan D Anker; Javed Butler; Gerasimos Filippatos; João Pedro Ferreira; Stuart J Pocock; Peter Carson; Inder Anand; Wolfram Doehner; Markus Haass; Michel Komajda; Alan Miller; Steen Pehrson; John R Teerlink; Martina Brueckmann; Waheed Jamal; Cordula Zeller; Sven Schnaidt; Faiez Zannad Journal: Circulation Date: 2020-10-21 Impact factor: 29.690