BACKGROUND: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations. METHODS: This prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419). FINDINGS: Of the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR<18 brpm showed a marked ICD benefit on mortality (adjusted HR 0.529 (95% CI 0.376-0.746); p = 0.0003), no treatment effect was demonstrated in 655 patients with NRR≥18 brpm (adjusted HR 0.981 (95% CI 0.669-1.438); p = 0.9202). INTERPRETATION: In the EU-CERT-ICD trial, patients with NRR≥18 brpm showed limited benefit from primary prophylactic ICD implantation. Those with NRR<18 brpm benefitted substantially. FUNDING: European Community's 7th Framework Programme FP7/2007-2013 (602299).

2nd Department of Cardiology Attikon University Hospital Athens Greece

Department of Cardiology and Pneumology Heart Center University Medical Center Göttingen Göttingen Germany

Department of Cardiology Medical University of Lodz Hospital Lodz Poland

Department of Cardiology Semmelweis University Heart Center Budapest Hungary

Department of Internal Medicine and Cardiology Medical Faculty Masaryk University Brno Czech Republic

Department of Medical Statistics University Medical Center Göttingen Göttingen Germany

DZHK partner site Göttingen Göttingen Germany

German Center for Cardiovascular Research partner site Munich Heart Alliance Munich Germany

Heart and Lung Institute Imperial College London London United Kingdom

Interdisciplinary Sleep Medicine Center Charité Universitätsmedizin Berlin Germany

Klinikum rechts der Isar Medizinische Klinik und Poliklinik 1 Technical University of Munich Munich Germany

Medical Research Center Oulu University Hospital and University of Oulu Oulu Finland

Medizinische Klinik und Poliklinik 1 Munich University Clinic Munich Germany

University Hospital for Internal Medicine 3 Medical University Innsbruck Innsbruck Austria

University Hospital University of Basel Basel Switzerland

University Hospitals of Leuven Leuven Belgium

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