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Journal of Clinical and
            Translational Research                                                AI and LLMs in iPSC cardiac research




            Table 1. Comparative evaluation of AI and LLM studies in cardiovascular and biomedical research
            Study         Methodological approach  Model system  Key finding            Notable limitation
            1. Liu et al. 37  CNN on echocardiograms  Human echo datasets Outperformed cardiologists in detecting  Reduced accuracy on
                                                            HCM                         underrepresented ethnicities
            2. Panahiazar et al. 38  Random forest and EHR  Retrospective EHR  Predicted heart failure six months in   No external validation across
                                                            advance                     systems
            3. Olawade et al. 15  Narrative review of AI in   AI in general  Reviewed current AI trends in cardiology,  Lacked specific model validation
                          cardiology in general             highlighting LLMs’ potential in   or benchmarking
                                                            diagnostics and clinical support
            4.  Tolu-Akinnawo   Systematic literature review AI in non-invasive   Improved cardiac image analysis   Applied heterogeneous
              et al. 16                      cardiac imaging  accuracy, including LLM support in   validation metrics across
                                                            annotation and automation.  studies.
            5.  Kasartzian and   Review      ML/AI for cardiac risk  Outperformed traditional risk calculators  Limited real-world
              Tsiampalis 17                  prediction     in CVD risk assessment.     implementation
            6. Leivaditis et al. 18  Review  AI in cardiac surgery  LLMs supported surgical planning and   Need for data standardization
                                                            patient stratification      and a regulatory framework
            7. Salihu et al. 24  Pilot study  ChatGPT for heart   ChatGPT enhanced team communication  Limited by a small sample size
                                             team decision making in evaluating severe arctic stenosis cases  and a qualitative nature
            8. Ahmed et al. 25  Opinion peace  ChatGPT in   Outlined the potential of ChatGPT to   No empirical data or case
                                             cardiothoracic surgery improve pre-/post-operation patient   application
                                                            communication
            9. Clark 27   Perspective        ChatGPT in     Proposed integration of LLMs in   Remained conceptual, no
                                             cardiac surgery and   education and procedural support  implementation data.
                                             transplantation
            10. Chen et al. 21  Model development  Multi-role ChatGPT   ChatGPT can assist in clinical   Dependent on prompt
                                             framework      summarization and medical data   engineering
                                                            structuring
            11. Iqbal et al. 20  Umbrella review  LLM in healthcare   Strong potential for clinical   Unresolved hallucination and
                                             (focus on ChatGPT)  communication, patient interaction, and  bias mitigation
                                                            record summarization
            12. Pan et al. 39  Computational-expert   LLM human   LLMs boost disease detection accuracy   Required clinical validation to
                          hybrid pipeline    integration in EHR  when augmented with clinical oversight  avoid misclassification
            Abbreviations: AI: Artificial intelligence; CNN: Convolutional neural network; CVD: Cardiovascular disease; EHRs: Electronic health records;
            HCM: Hypertrophic cardiomyopathy; LLMs: Large language models; ML: Machine learning.

            and more personalized, from literature scans to clinical   regression  or  rule-based  natural  language  processing
            predictions. The AI-enhanced approach offers deeper   (NLP) in tasks, such as myocardial infarction identification
            insights, minimizes human bias, and brings research closer   from clinical notes or gene-phenotype linkage in iPSC-
            to real-world applications with unmatched precision.   derived  platforms.  For  instance,  BioGPT  outperformed
            Clinically, these integrated tools  support  the refinement   MetaMap and cTAKES in semantic accuracy when
            of maturation protocols and enhance patient-specific   classifying drug-induced arrhythmia mechanisms from
            therapeutic planning. By mapping mitochondrial density   biomedical abstracts. The comparative evaluation of LLMs
            and electrophysiological maturity across iPSC-CM cohorts,   in cardiovascular applications is discussed in Section 3.8.
            LLMs can identify underdeveloped grafts that are unsuitable
            for  transplantation,  ensuring  safety  and efficacy.  This   3.2. Predictive modeling and diagnostics for iPSC-
            integration of cellular bioenergetics with computational   CMs disease modeling and early intervention
            modeling  supports  strategies  for  biologically  aligned   LLMs are transforming the landscape of predictive
            and data-driven cardiac regeneration. This integration   and  diagnostic  cardiology  by  integrating  patient-level,
            provides a framework for advancing translational insight   biomolecular, and physiological datasets (Table  2). In
            and supporting clinical standardization of regenerative   the context of iPSC-CMs, LLMs can forecast disease
            therapies.                                         phenotypes by analyzing genomic instability, ion
              Comparative studies have begun to show the superiority   channel  transcriptomics,  and  electrophysiological
            of  transformer-based  models  over  traditional  logistic   aberrancies associated with arrhythmogenic and dilated


            Volume 11 Issue 5 (2025)                        8                          doi: 10.36922/JCTR025230026
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