Competing Risks in Patients with Primary Prevention Implantable Cardioverters Defibrillators: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) Study

Background Global electrical heterogeneity (GEH) is associated with sudden cardiac death in the general population. Objective To investigate whether GEH is associated with sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) leading to appropriate implantable cardioverter-defibrillator (ICD) therapies in systolic heart failure (HF) patients with primary prevention ICDs. Methods We conducted a multicenter retrospective cohort study. GEH was measured by spatial ventricular gradient (SVG) direction and magnitude, QRS-T angle, and sum absolute QRST integral (SAIQRST) on pre-implant 12-lead ECGs. Survival analysis using cause-specific hazard functions compared the strength of associations with two competing outcomes: sustained VT/VF leading to appropriate ICD therapies and all-cause death without appropriate ICD therapies. Results We analyzed data from 2,668 patients (age 63±12y; 23% female; 78% white; 43% nonischemic cardiomyopathy (NICM); left ventricular ejection fraction 28±11% from 6 academic medical centers). After adjustment for demographic, clinical, device, and traditional ECG characteristics, SVG elevation (Hazard Ratio (HR) per 1 standard deviation (SD) 1.14 (95% CI 1.04-1.25); P =0.004), SVG azimuth (HR 1.12(1.01-1.24); P =0.039); SVG magnitude (HR per 1 SD 0.75 (0.66-0.85); P <0.0001), and QRS-T angle (HR per 1 SD 1.21 (95% CI 1.08-1.36); P =0.001) were associated with appropriate ICD therapies. The SVG azimuth was also associated with a lower competing risk of death ( P difference =0.007): HR 0.91(0.82-1.02); P =0.095. SAIQRST had different associations in ischemic [HR 1.29(1.04-1.60)] and NICM [HR 0.78(0.62-0.96); P interaction =0.022]. Conclusion In patients with primary prevention ICDs, GEH is independently associated with appropriate ICD therapies. The SVG vector points in distinctly different directions in patients with two competing outcomes. Clinical Trial Registration URL:[www.clinicaltrials.gov][1] Unique identifier: [NCT03210883][2]. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial URL:[www.clinicaltrials.gov][1] Unique identifier: [NCT03210883][2] ### Clinical Protocols ### Funding Statement This study was funded through the AHA Grant-In-Aid #17GRNT33670428 (LGT) and partially HL118277 (LGT). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The multicenter study has been approved by the OHSU Institutional Review Board (IRB). In addition, each participating center obtained local IRB approval prior to participating. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data will be available through the National Heart, Lung, and Blood Institute Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) after the publication of this manuscript (planning submission). The open-source MATLAB (MathWorks, Natick, MA, USA) code for ECG analysis is provided at and . Statistical analysis code is provided at . * CM : cardiomyopathy LVEF : left ventricular ejection fraction SCD : sudden cardiac death ICD : implantable cardioverter-defibrillator NYHA : New York Heart Association HF : heart failure ICM : ischemic/infarct-related cardiomyopathy NICM : nonischemic cardiomyopathy GEH : global electrical heterogeneity SVG : spatial ventricular gradient CRT-D : cardiac resynchronization therapy defibrillator PVC : premature ventricular complex SAIQRST : sum absolute QRST integral VMQTi : QT integral on vector magnitude signal NID : number of intervals to detect [1]: http://www.clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03210883&atom=%2Fmedrxiv%2Fearly%2F2020%2F12%2F29%2F2020.12.16.20248369.atom