Operationalizing AI-Enabled Cardiovascular Biomarkers: A Clinician-Centered Framework for Validation, Governance, and Workflow Integration

Abstract

Abstract Cardiovascular biomarkers are increasingly extracted or interpreted using artificial intelligence (AI) applied to electrocardiograms, imaging, laboratory measurements, electronic health records, wearable devices, and longitudinal data. Predictive performance alone, however, does not establish that a measurement is valid, that a model is transportable and calibrated, or that acting on its output improves care. Existing resources provide essential but complementary foundations: the US Food and Drug Administration–National Institutes of Health (FDA-NIH) BEST (Biomarkers, EndpointS, and other Tools) resource standardizes biomarker terminology; the V3 and V3+ frameworks address verification, analytical validation, clinical validation, and usability of digitally measured signals; prediction-model and trustworthy-AI guidance addresses reporting, risk of bias, early clinical evaluation, and deployability; and regulatory qualification pathways evaluate evidence within a defined context of use. A remaining practical challenge is translating these complementary requirements into accountable clinical action within cardiovascular workflows. This viewpoint proposes a clinician-centered operational framework organized around validation, governance, and workflow integration. For each pillar, it identifies accountable actors, required steps, documented outputs, and escalation or stop rules. Validation establishes whether the input measurement and model are fit for the intended population and decision. Governance assigns institutional authorization, clinical ownership, version control, monitoring, and authority to restrict, pause, or withdraw the intervention. Workflow integration specifies who receives the output, what confirmatory action follows, how disagreement is handled, and how decisions are documented. A worked example of an AI-enabled electrocardiographic screening output for possible left ventricular systolic dysfunction illustrates the pathway from local evaluation to echocardiographic confirmation and lifecycle monitoring. The framework does not replace established validation or regulatory standards; it operationalizes them as a clinician-centered and institutionally accountable pathway from validated signal to governed, patient-facing action.