Abstract:Large language models (LLMs) have demonstrated remarkable progress in healthcare. However, a significant gap remains regarding LLMs' professionalism in domain-specific clinical practices, limiting their application in real-world diagnostics. In this work, we introduce ZODIAC, an LLM-powered framework with cardiologist-level professionalism designed to engage LLMs in cardiological diagnostics. ZODIAC assists cardiologists by extracting clinically relevant characteristics from patient data, detecting significant arrhythmias, and generating preliminary reports for the review and refinement by cardiologists. To achieve cardiologist-level professionalism, ZODIAC is built on a multi-agent collaboration framework, enabling the processing of patient data across multiple modalities. Each LLM agent is fine-tuned using real-world patient data adjudicated by cardiologists, reinforcing the model's professionalism. ZODIAC undergoes rigorous clinical validation with independent cardiologists, evaluated across eight metrics that measure clinical effectiveness and address security concerns. Results show that ZODIAC outperforms industry-leading models, including OpenAI's GPT-4o, Meta's Llama-3.1-405B, and Google's Gemini-pro, as well as medical-specialist LLMs like Microsoft's BioGPT. ZODIAC demonstrates the transformative potential of specialized LLMs in healthcare by delivering domain-specific solutions that meet the stringent demands of medical practice. Notably, ZODIAC has been successfully integrated into electrocardiography (ECG) devices, exemplifying the growing trend of embedding LLMs into Software-as-Medical-Device (SaMD).