Background Four hypertension-mediated left ventricular hypertrophy (LVH) phenotypes have been reported using cardiac magnetic resonance (CMR): normal LV, LV remodeling, eccentric and concentric LVH, with varying prognostic implications. The electrocardiogram (ECG) is routinely used to detect LVH, however its capacity to differentiate between LVH phenotypes is unknown. This study aimed to classify hypertension-mediated LVH from the ECG using machine learning (ML) and test for associations of ECG-predicted phenotypes with incident cardiovascular outcomes. Methods ECG biomarkers were extracted from the 12-lead ECG of 20,439 hypertensives in UK Biobank (UKB). Classification models integrating ECG and clinical variables were built using logistic regression, support vector machine (SVM) and random forest. The models were trained in 80% of participants, and the remaining 20% formed the test set. External validation was sought in 877 hypertensives from Study of Health in Pomerania (SHIP). In the UKB test set, we tested for associations between ECG-predicted LVH phenotypes and incident major adverse cardiovascular events (MACE) and heart failure. Results Among UKB participants 19,408 had normal LV, 758 LV remodeling, 181 eccentric and 92 concentric LVH. Classification performance of the three models was comparable, with SVM having a slightly superior performance (accuracy 0.79 ,sensitivity 0.59, specificity 0.87, AUC 0.69) and similar results observed in SHIP. There was superior prediction of eccentric LVH in both cohorts. In the UKB test set, ECG-predicted eccentric LVH was associated with heart failure (HR 3.42, CI 1.06-9.86). Conclusions ECG-based ML classifiers represent a potentially accessible screening strategy for early detection of hypertension-mediated LVH phenotypes.

SEP provides consultancy to and owns stock of Cardiovascular Imaging Inc, Calgary, Alberta, Canada.

HN was supported by the British Heart Foundation Pat Merriman Clinical Research Training Fellowship (FS/20/22/34640). JR acknowledges fellowship RYC2021-031413-I from the European Union ??NextGenerationEU/PRTR?? and MCIN/AEI/10.13039/501100011033. NA acknowledges support from Medical Research Council for his Clinician Scientist Fellowship (MR/X020924/1). SEP acknowledges the British Heart Foundation for funding the manual analysis to create a cardiovascular magnetic resonance imaging reference standard for the UK Biobank imaging resource in 5000 CMR scans (www.bhf.org.uk;PG/14/89/31194). SEP and PBM acknowledge support from the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at Barts (NIHR202330). SEP, KL and ER have received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No 825903 (euCanSHare project). KL has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreements No 101080430 (AI4HF project) and No. 101057849 (DataTools4Heart project). The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net (CMR) (http://www.medizin.uni-greifswald. de/icm) of the University Medicine Greifswald, which is supported by the German Federal Ministry of Education and Research (BMBF, grant number: 01ZZ96030 and 01ZZ0701) and the Federal State of Mecklenburg-West Pomerania. MRI scans in SHIP-2 and SHIP-TREND-0 have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. This study was carried out in collaboration with the German Centre for Cardiovascular Research (DZHK), which is supported by the German Federal Ministry of Education and Research (BMBF).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study complies with the Declaration of Helsinki; the work was covered by the ethical approval for UK Biobank studies from the NHS National Research Ethics Service on 17th June 2011 (Ref 11/NW/0382) and extended on 18 June 2021 (Ref 21/NW/0157) with written informed consent obtained from all participants. The work related to Study of Health in Pomerania is via application reference number SHIP/2023/31/D. The study is covered by the overall ethical approval for SHIP studies approved by the Ethics Committee at the University Medicine Greifswald, Germany.

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