Abstract
BackgroundSudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF).ObjectiveIdentifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies.MethodsWe developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial.ResultsNYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell’s C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE.ConclusionWe developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death.Trial registration numberPARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658.Graphics abstract
Highlights
Sudden death (SD) and pump failure death (PFD) are the predominant modes of death in patients with heart failure and reduced ejection fraction [1]
Very recently, based on the same population, the authors developed the Seattle Proportional Risk Model (SPRM) to predict the proportion of deaths due to SD rather than the absolute risk [13]. It is unclear whether these models still perform well when applied to a contemporary cohort and, as recently demonstrated, the risk of sudden death has declined in parallel with improvements in medical therapy [14]
PARADIGM-HF evaluated the effect of LCZ696 with enalapril in 8399 patients with a left ventricular ejection fraction (LVEF) ≤ 40% and NYHA class II-IV HF, in addition to recommended treatment including an angiotensin converter enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and a beta-blocker and a mineralocorticoid receptor antagonists (MRAs)
Summary
Sudden death (SD) and pump failure death (PFD) are the predominant modes of death in patients with heart failure and reduced ejection fraction [1]. Very recently, based on the same population, the authors developed the Seattle Proportional Risk Model (SPRM) to predict the proportion of deaths due to SD rather than the absolute risk [13]. It is unclear whether these models still perform well when applied to a contemporary cohort and, as recently demonstrated, the risk of sudden death has declined in parallel with improvements in medical therapy [14]. Conclusion We developed and validated models which separately predict SD and PFD in patients with HFrEF These models may help clinicians and patients consider therapies targeted at these modes of death. Trial registration number PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658
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