Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE

Background: Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). Objective: Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies. Methods: We 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. Results: NYHA 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. 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