• Axel Bauer, Mathias Klemm, Konstantinos D Rizas, Wolfgang Hamm, Lukas von Stülpnagel, Michael Dommasch, Alexander Steger, Andrezej Lubinski, Panagiota Flevari, Markus Harden, Tim Friede, Stefan Kääb, Bela Merkely, Christian Sticherling, Rik Willems, Heikki Huikuri, Marek Malik, Georg Schmidt, Markus Zabel, and EU-CERT-ICD investigators.
• Medizinische Klinik und Poliklinik I, Munich University Clinic, Munich, Germany; University Hospital for Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria; German Center for Cardiovascular Research partner site, Munich Heart Alliance, Munich, Germany. Electronic address: axel.bauer@i-med.ac.at.
• Lancet. 2019 Oct 12; 394 (10206): 1344-1351.

BackgroundA small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality.MethodsWe did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality.FindingsBetween May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0-3·3] in the ICD group and 1·2 years [0·8-2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41-0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13-0·47] for the ICD group vs the control group; p<0·0001) than in those with periodic repolarisation dynamics less than 7·5 deg (n=1166; adjusted HR 0·69 [95% CI 0·47-1·00]; p=0·0492; pinteraction=0·0056). The number needed to treat was 18·3 (95% CI 10·6-4895·3) in patients with periodic repolarisation dynamics less than 7·5 deg and 3·1 (2·6-4·8) in those with periodic repolarisation dynamics of 7·5 deg or higher.InterpretationPeriodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation.FundingThe European Community's 7th Framework Programme.Copyright © 2019 Elsevier Ltd. All rights reserved.

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