Advanced ECG heart age estimation applicable to both sinus and non-sinus rhythm associates with cardiovascular risk, cardiovascular morbidity, and survival

Background: An explainable advanced electrocardiography (A–ECG) heart age gap is the difference between A–ECG heart age and chronological age. This gap is an estimate of accelerated cardiovascular ageing expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A–ECG heart age measures require discernible P waves on the ECG. Aims: To develop and prognostically validate a revised, explainable A–ECG heart age gap without incorporating P–wave measures. Methods: An A–ECG heart age without P–wave measures (non–P) was derived from the 10–second 12–lead ECG in a derivation cohort using multivariable regression using an existing Bayesian 5–minute 12–lead A–ECG heart age as reference. The non–P heart age was externally validated in a separate cohort of patients referred for cardiovascular magnetic resonance imaging by describing its association with heart failure hospitalization or death using Cox regression, and its association with comorbidities. Results: In the derivation cohort (n=2771), A–ECG non–P heart age agreed with the 5–min heart age (R2=0.91, bias 0.0±6.7 years), and increased with increasing co–morbidity. In the validation cohort (n=731, mean age 54±15 years, 43% female, n=139 events over 5.7 [4.8–6.7] years follow–up), increased A–ECG non–P heart age gap (≥10 years) associated with events (hazard ratio [95% confidence interval] 2.04 [1.38–3.00], C–statistic 0.58 [0.54–0.62], and the presence of hypertension, diabetes mellitus, hypercholesterolemia, and heart failure (p≤0.009 for all). Conclusions: An explainable A–ECG non–P heart age gap applicable to both sinus and non–sinus rhythm associates with cardiovascular risk, cardiovascular morbidity, and survival. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### 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: For the derivation cohort, Institutional Review Board (IRB) approvals were obtained from NASA's Johnson Space Center and partner hospitals that fall under IRB exemptions for previously collected and de-identified data. For the validation cohort, approval was obtained from the IRB at University of Pittsburgh Medical Center. Written consent was obtained for all participants for both cohorts, and all data was analyzed following de-identification. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Deidentified data of this study can be made available upon reasonable request to the corresponding author.