This prospective observational diagnostic accuracy study evaluates whether large language models (LLMs) - GPT-4o (OpenAI, gpt-4o-2024-11-20) and Claude (Anthropic, claude-sonnet-4-6) - can accurately calculate HEART scores from unstructured Turkish clinical notes and predict 30-day major adverse cardiac events (MACE) in emergency department patients presenting with non-traumatic chest pain.

The study will enroll 600 consecutive adult patients. For each patient, the same anonymized data (free-text anamnesis, ECG report text, troponin value, and age) will be independently processed by both LLMs via separate API calls with deterministic settings (temperature=0, JSON format). A three-expert consensus HEART score - derived through blinded independent scoring by three emergency medicine physicians with majority-vote adjudication - serves as the reference standard for agreement analysis. Actual 30-day MACE (all-cause death, AMI Type 1/2/4b, unplanned revascularization) determined via national health database and telephone follow-up serves as the outcome for diagnostic accuracy analysis.

A secondary documentation-quality sub-study will quantify how spontaneously Turkish emergency anamnesis notes capture HEART score parameters.

AI SYSTEM SPECIFICATIONS AND PROMPT PROTOCOL Two distinct large language models (LLMs) will be evaluated as index tests: OpenAI GPT-4o (model string: gpt-4o-2024-11-20) and Anthropic Claude (model string: claude-sonnet-4-6). To ensure reproducibility and eliminate stochastic variation, both models will be accessed via standardized API calls using deterministic parameters (temperature = 0, max_tokens = 500, and strict JSON response format). The exact system prompt layout will be locked prior to initialization, and its integrity will be verified using a SHA-256 cryptographic hash. The models will evaluate each patient record independently in zero-shot isolation, with no cross-contamination or conversational history retention between runs.

REFERENCE STANDARD CONSENSUS PROTOCOL The reference standard consists of a structured consensus HEART score established by three independent emergency medicine physicians (each possessing >=3 years of clinical experience and specific training on HEART score criteria). The physicians will review the anonymized clinical charts while remaining strictly blinded to the LLM outputs and the final 30-day MACE outcomes. For each of the 5 HEART components (scored 0, 1, or 2), a majority vote (2/3 agreement) will determine the final component score. In the event of complete disagreement across all three reviewers on a specific component, a fourth independent adjudicator will resolve the tie.

INDETERMINATE RESULTS MANAGEMENT

In strict compliance with STARD-AI 2025 guidelines, cases with missing or uninterpretable parameters within the free-text clinical notes will be classified into predefined indeterminate tiers:

1. Complete Cases: 0 indeterminate components (eligible for primary diagnostic accuracy analysis).
2. Partial Indeterminate: Exactly 1 missing component preventing definitive automatic calculation.
3. Full Indeterminate: >=2 missing components. The proportion of indeterminate classifications will be quantified for both LLMs and evaluated alongside the routine documentation quality of the charts.

STATISTICAL ANALYSIS AND AGREEMENT WEIGHTING Statistical power and sample size calculation are based on the Hanley-McNeil methodology for the Area Under the ROC Curve (AUC). To achieve an expected AUC of 0.85 with a non-inferiority margin of 0.05, a power of 80%, and a two-sided alpha of 0.05, the primary complete-case analysis requires 600 evaluable patients. Accounting for an anticipated 15% indeterminate rate, a total enrollment target of 690 patients is set. Inter-rater agreement between each LLM and the expert consensus will be computed using quadratic weighted Cohen's Kappa for the ordinal total HEART score (0-10) and linear weighted Kappa for individual components (0-2). Diagnostic performance metrics (sensitivity, specificity, PPV, NPV) will be calculated at prespecified binary (>=4) and trimodal thresholds with 95% Wilson confidence intervals. Pairwise comparison of AUC values between GPT-4o and Claude will be executed using the DeLong test.

DATA ANONYMIZATION AND PRIVACY To ensure full compliance with local personal data protection legislation (KVKK), all free-text emergency department notes will undergo strict de-identification. Patient names, institutional ID numbers, precise dates, and specific demographic identifiers will be stripped entirely before formatting the data payload for API transmission.

PATIENT AND PUBLIC INVOLVEMENT BEYANI Patient and public involvement was not applicable to this study as it involves the analysis of routinely collected clinical data.

INCLUSION CRITERIA:

• Age >=18 years
• Chief complaint of non-traumatic chest pain at the emergency department
• Written informed consent obtained from the patient or legally authorized representative
• Availability for 30-day follow-up (reachable by telephone and/or actively registered in the e-Nabiz national health database)

EXCLUSION CRITERIA:

• Traumatic chest pain etiology
• ST-elevation myocardial infarction (STEMI) at presentation requiring immediate reperfusion protocol
• Refusal or subsequent withdrawal of informed consent
• Inability to complete the mandatory 30-day follow-up period

WITHDRAWAL CRITERIA:

• Patient or representative requests data withdrawal after initial consent
• Administrative identification of retrospective data entry after enrollment

The study population consists of consecutive adult patients presenting with a chief complaint of non-traumatic chest pain to the emergency department of Marmara University Pendik Training and Research Hospital, a tertiary care academic medical center in Istanbul, Turkey. This target population comprises real-world emergency medicine admissions that require acute coronary syndrome risk stratification and evaluation with the HEART score. It excludes individuals presenting with traumatic pain etiologies or acute ST-elevation myocardial infarction (STEMI) requiring immediate, time-critical reperfusion pathways.

Anonymized individual participant data (including de-identified baseline demographics, clinical presentation characteristics, index test outputs from GPT-4o and Claude, and the reference standard expert consensus HEART scores) will be made publicly available to support academic transparency and replication. Additionally, the complete deterministic system prompt texts (verified with SHA-256 cryptographic hashes) and the complete statistical analysis code will be included as supplementary material.

The anonymized dataset, protocol documents, and analytic code will be made available immediately upon formal publication of the study results.

Data and code will be accessible via an open-access repository on the Open Science Framework (OSF) for researchers and clinicians interested in replication or meta-analysis.