Periodic Repolarization Dynamics Identifies ICD Responders in Nonischemic Cardiomyopathy: A DANISH Substudy
Rune Boas, Nikolay Sappler, Lukas von Stülpnagel, Mathias Klemm, Ulrik Dixen, Jens Jakob Thune, Steen Pehrson, Lars Køber, Jens Cosedis Nielsen, Lars Videbæk, Jens Haarbo, Eva Korup, Niels Eske Bruun, Axel Brandes, Hans Eiskjær, Anna Margrethe Thøgersen, Berit T. Philbert, Jesper Hastrup Svendsen, Jacob Tfelt‐Hansen, Axel Bauer, Konstantinos D. Rizas
Abstract
Background: Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation. Methods: We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00–06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg 2 as an exploratory cut-off value for ICD implantation. Results: A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group ( P =0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio [HR], 1.28 [95% CI, 1.09–1.50] per SD increase; P =0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 [95% CI, 1.25–1.81]; P <0.001) but not in the ICD group (HR, 1.04 [95% CI, 0.83–1.54]; P =0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality ( P =0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg 2 (HR, 0.54 [95% CI, 0.34–0.84]; P =0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg 2 (HR, 1.17 [95% CI, 0.77–1.78]; P =0.46; P for interaction=0.01). Conclusions: Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.