A combined anatomic and electrophysiologic substrate based approach for sudden cardiac death risk stratification

• Type of Material: Article
• Authors: Faisal Merchant, Emory University; Hui Zheng, Massachusetts General Hospital; Thomas Bigger, Columbia University; Richard Steinman, Columbia University; Takanori Ikeda, Toho University; Roberto F. E. Pedretti, IRCCS Fondazione Salvatore Maugeri; Jorge A. Salerno-Uriarte, University of Insubria; Catherine Klersy, University of Pavia; Paul S. Chan, St Luke's Mid America Heart Institute; Cheryl Bartone, Christ Hospital; Stefan H. Hohnloser, Goethe University Frankfurt; Jeremy N. Ruskin, Massachusetts General Hospital; Antonis A. Armoundas, Massachusetts General Hospital
• Language: English
• Date: 2013-10-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Mosby, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ahj.2013.06.023
• Title of Journal or Parent Work: American Heart Journal
• ISSN: 0002-8703
• Volume: 166
• Issue: 4
• Start Page: 744
• End Page: 752
• Grant/Funding Information: The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers).; This work was conducted with support from Harvard Catalyst; Dr. Chan was supported by Grant Number K23HL102224 from the National Heart, Lung, And Blood Institute.; Dr. Armoundas was supported by a Scientist Development Grant (#0635127N) and by NIA grant 1R21AG035128.; This work was also supported by a Fellowship and a Science Award from the Center for Integration of Medicine and Innovative Technology (CIMIT), the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke and the Cardiovascular Research Society.
• Keywords: Cardiac & Cardiovascular Systems; CORONARY-ARTERY-DISEASE; Science & Technology; ARRHYTHMIA VULNERABILITY; LEFT-VENTRICULAR DYSFUNCTION; Cardiovascular System & Cardiology; EJECTION FRACTION; T-WAVE ALTERNANS; PREDICTIVE-VALUE; Life Sciences & Biomedicine; NONISCHEMIC DILATED CARDIOMYOPATHY; CONGESTIVE-HEART-FAILURE; ACUTE MYOCARDIAL-INFARCTION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background Although left ventricular ejection fraction (LVEF) is the primary determinant for sudden cardiac death (SCD) risk stratification, in isolation, LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker strategy would provide more robust SCD risk stratification than LVEF alone. Methods We collected patient-level data (n = 3355) from 6 studies assessing the prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of the group was used for derivation (n = 2242) and one-third for validation (n = 1113). The discriminative capacity of the multivariable model was assessed using the area under the receiver-operating characteristic curve (c-index). The primary endpoint was SCD at 24 months. Results In the derivation cohort, 59 patients experienced SCD by 24 months. Stepwise selection suggested that a model based on 3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD risk prediction. In the derivation cohort, the c-index of the model was 0.817, which was significantly better than LVEF used as a single variable (0.637, P <.001). In the validation cohort, 36 patients experienced SCD by 24 months. The c-index of the model for predicting the primary endpoint was again significantly better than LVEF alone (0.774 vs 0.671, P =.020). Conclusions A multivariable model based on presence of coronary artery disease, LVEF and MTWA status provides significantly more robust SCD risk prediction than LVEF as a single risk marker. These findings suggest that multi-marker strategies based on different aspects of the electro-anatomic substrate may be capable of improving primary prevention implantable cardioverter-defibrillator treatment algorithms.