Risk Factors for Recurrent Heart Failure Events in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II)

Risk Factors for Recurrent Heart Failure. Background: This study was designed to identify risk factors for recurrent heart failure (HF) events in patients with ischemic left ventricular dysfunction enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II). Methods and Results: The Prentice, Williams, and Peterson (PWP) statistical model was utilized to identify and compare risk factors for 1 or ≥2 HF hospitalizations among 1,218 patients with ischemic left ventricular dysfunction enrolled in the MADIT‐II trial. Risk factors for a first HF hospitalization included treatment with an ICD (HR = 1.31; P = 0.05), New York Heart Association class >II (HR = 1.95; P < 0.001), female gender (HR = 1.38; P = 0.05), atrial fibrillation (HR = 1.90; P = 0.001), QRS >120 ms (HR = 1.41; P = 0.01), diabetes mellitus (HR = 1.51; P = 0.003), heart rate ≥80 (HR = 1.35; P = 0.04), diuretic therapy (HR = 1.82; P < 0.001), and the presence of prerenal azotemia (defined as blood urea nitrogen:creatinine >20; HR = 1.45; P = 0.01). In contrast, prerenal azotemia was the only risk factor that was independently associated with a significant increase in the risk of ≥2 HF hospitalizations (HR = 1.52; P = 0.027). The occurrence of 1 HF event after enrolment was associated with a 2.8‐fold (P < 0.001) increase in the risk of death, whereas after the occurrence of a second event there was a 6.7‐fold (P < 0.001) increase in the risk of subsequent mortality. Conclusions: In MADIT‐II, prerenal azotemia was the only significant and independent risk factor for HF progression after a first event, and recurrent HF was the most powerful predictor of mortality. These findings stress the importance of identifying risk factors for HF progression among patients who receive an ICD for primary prevention. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1217‐1223, November 2010)