Risk Stratification of Cancer Therapy-Related Cardiac Dysfunction Using AI-Enhanced Electrocardiography

NCT07515859 | Completed

• 1 other identifier: 4-2025-0326
• Study Type: observational
• Target: 31,486
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the use of AI-enhanced electrocardiogram (ECG) for risk stratification of cancer therapy-related cardiac dysfunction (CTRCD) before the initiation of cancer therapy. The study includes patients treated with anthracyclines, HER2 inhibitors, or immune checkpoint inhibitors (ICIs) at Severance Hospital between May 2006 and November 2022, who underwent an ECG within 90 days prior to chemotherapy. The primary goal is to evaluate whether AI-ECG can accurately predict the risk of CTRCD and compare its performance to existing risk stratification models. In addition, we aim to assess whether the variation in AI-ECG scores between pre- and post-chemotherapy assessments could serve as a predictor of CTRCD. Eligible participants are adults without prior heart failure, cardiomyopathy, or myocarditis, and with baseline left ventricular ejection fraction (LVEF) ≥40%. For trajectory analysis, only patients with an additional ECG within 90 days after chemotherapy are included. The primary outcome is the development of CTRCD within 12 months after the last treatment cycle (and no more than 24 months after the first). The secondary outcomes are severe CTRCD (LVEF \<40%) and all-cause mortality. This study aims to validate the clinical utility of AI-enhanced ECG as a simple, accessible, and cost-effective tool for predicting CTRCD across diverse cancer treatment regimens, including newer immunotherapies.

Conditions

Heart Failure; Left Ventricular Dysfunction; Cancer Therapy-Related Cardiac Dysfunction

Keywords

Cardiotoxicity; Electrocardiography; Chemotherapy; AI-ECG; CTRCD; Risk Stratification; Cardio-Oncology

Outcome Measures

Primary Outcomes (1)

• Incidence of cancer therapy-related cardiac dysfunction (CTRCD)

  CTRCD defined as ≥10%p drop in left ventricular ejection fraction (LVEF) from baseline to 40% to 49.9% OR \<10%p drop to 40-49.9% with a reduction in GLS by \>15% OR new LVEF reduction to \<40% from baseline LVEF, OR hospitalization for heart failure or diagnosis of cardiomyopathy defined by ICD codes,, diagnosed within 12 months after the last treatment cycle and no more than 24 months after the first cycle cardiotoxic cancer therapy. LVEF is assessed by either echocardiography or MUGA (Multi-gated acquisition nuclear imaging) scan.

  From initiation of first chemotherapy up to 24 months.

Secondary Outcomes (1)

• All-cause mortality

  From initiation of first chemotherapy up to 24 months.

Study Arms (2)

High baseline AI-ECG risk for CTRCD

Patients classified as high risk for CTRCD based on baseline AI-ECG LVSD prediction probability before initiation of cancer therapy.

Other: No intervention (retrospective observational study)

Low baseline AI-ECG risk for CTRCD

Patients classified as low risk for CTRCD based on baseline AI-ECG LVSD prediction probability before initiation of cancer therapy.

Other: No intervention (retrospective observational study)

Interventions

No intervention (retrospective observational study) OTHER

This is a retrospective observational study using existing clinical data. No intervention or diagnostic procedure is applied to participants.

High baseline AI-ECG risk for CTRCD; Low baseline AI-ECG risk for CTRCD

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who were prescribed anthracycline, HER2 inhibitor, or ICI agents and have ECG prescription within 90 days before their first chemotherapy treatment at Severance hospital from May 2006 to November 2022.

You may qualify if:

• Patients prescribed anthracycline (doxorubicin, daunorubicin, epirubicin, aclarubicin, idarubicin), HER2 inhibitor (trastuzumab, emtansine, tucatinib, trastuzumab deruxtecan, pertuzumab), or immune checkpoint inhibitors (ipilimumab, nivolumab, atezolizumab, pembrolizumab, durvalumab, avelumab)
• ECG performed within 90 days prior to the first chemotherapy treatment
• Age ≥ 19 years
• For trajectory analysis: patients with an additional ECG within 90 days after the first chemotherapy

You may not qualify if:

• Age \< 19 years
• History of heart failure, cardiomyopathy, or myocarditis (confirmed by ICD codes)
• Prior exposure to anthracycline, HER2 inhibitor, or immune checkpoint inhibitor therapy
• Baseline left ventricular ejection fraction (LVEF) \< 40% on echocardiography within 1 year prior to chemotherapy

Sponsors & Collaborators

• Yonsei University: lead
• VUNO Inc.: collaborator
• Korea Health Industry Development Institute: collaborator

Study Sites (1)

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Related Publications (8)

• Stein-Merlob AF, Rothberg MV, Ribas A, Yang EH. Cardiotoxicities of novel cancer immunotherapies. Heart. 2021 Nov;107(21):1694-1703. doi: 10.1136/heartjnl-2020-318083. Epub 2021 Mar 15.

  PMID: 33722826 BACKGROUND

• Lee SH, Cho I, You SC, Cha MJ, Chang JS, Kim WD, Go KY, Kim DY, Seo J, Shim CY, Hong GR, Kang SM, Ha JW, Rha SY, Kim HS. Cancer Therapy-Related Cardiac Dysfunction in Patients Treated with a Combination of an Immune Checkpoint Inhibitor and Doxorubicin. Cancers (Basel). 2022 May 7;14(9):2320. doi: 10.3390/cancers14092320.

  PMID: 35565449 BACKGROUND

• Scalia IG, Farina JM, Pietri MP, Sarkis P, Javadi N, Bismee NN, Viggiano T, Tagle-Cornell C, Koepke L, Kenyon C, Novais B, Tiseer Abbas M, Tamarappoo BK, Lester SJ, Banerjee I, Ibrahim R, Larsen C, Lee KS, Arsanjani R, Ayoub C. Artificial Intelligence for Identification of Patients with Increased Risk of Severe Cancer Therapy-Related Cardiac Dysfunction Following Anthracycline Therapy. Am J Med. 2025 Nov;138(11):1561-1568.e1. doi: 10.1016/j.amjmed.2025.06.035. Epub 2025 Jun 25.

  PMID: 40578470 BACKGROUND

• Choi HM, Kim J, Park J, Park JB, Kim HK, Choi HJ, Yoon YE, Cho GY, Cho Y, Hwang IC. AI derived ECG global longitudinal strain compared to echocardiographic measurements. Sci Rep. 2024 Nov 2;14(1):26458. doi: 10.1038/s41598-024-78268-8.

  PMID: 39488646 BACKGROUND

• Mihos CG, Liu JE, Anderson KM, Pernetz MA, O'Driscoll JM, Aurigemma GP, Ujueta F, Wessly P; American Heart Association Council on Peripheral Vascular Disease; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Speckle-Tracking Strain Echocardiography for the Assessment of Left Ventricular Structure and Function: A Scientific Statement From the American Heart Association. Circulation. 2025 Sep 9;152(10):e96-e109. doi: 10.1161/CIR.0000000000001354. Epub 2025 Aug 6.

  PMID: 40765507 BACKGROUND

• Gomes C,Geels J,Debray TPA,Malekzadeh A,Asselbergs FW,Linschoten M

  BACKGROUND

• Oikonomou EK, Kokkinidis DG, Kampaktsis PN, Amir EA, Marwick TH, Gupta D, Thavendiranathan P. Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis. JAMA Cardiol. 2019 Oct 1;4(10):1007-1018. doi: 10.1001/jamacardio.2019.2952.

  PMID: 31433450 BACKGROUND

• Haj-Yehia E, Michel L, Mincu RI, Rassaf T, Totzeck M. Prevention of cancer-therapy related cardiac dysfunction. Curr Heart Fail Rep. 2025 Feb 19;22(1):9. doi: 10.1007/s11897-025-00697-x.

  PMID: 39969700 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Ventricular Dysfunction, Left; Cardiotoxicity

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 7, 2026
• Study Start: May 1, 2006
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)