Artificial Intelligence in Cardiac Amyloidosis: A Systematic Review and Meta-Analysis of Diagnostic Accuracy Across Imaging and Non-Imaging Modalities

Introduction Cardiac amyloidosis (CA) is an underdiagnosed infiltrative cardiomyopathy associated with poor outcomes if not detected early. Artificial intelligence (AI) has emerged as a promising adjunct to conventional diagnostics, leveraging imaging and non-imaging data to improve recognition of CA. However, evidence on the comparative diagnostic performance of AI across modalities remains fragmented. This meta-analysis aimed to synthesize and quantify the diagnostic performance of AI models in CA across multiple modalities. Methods A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2025. Only published observational studies applying AI to the diagnosis of CA were included. Data were extracted on patient demographics, AI algorithms, modalities, and diagnostic performance metrics. Risk of bias was assessed using QUADAS-2, and certainty of evidence was graded using GRADE. Random-effects meta-analysis (REML) was performed to pool accuracy, precision, recall, F1-score, and area under the curve (AUC). Results From 115 screened studies, 25 observational studies met the inclusion criteria, encompassing a total of 589,877 patients with a male predominance (372,458 males, 63.2%; 221,818 females, 36.6%). A wide range of AI algorithms were applied, most notably convolutional neural networks (CNNs), which accounted for 526,879 patients, followed by 3D-ResNet architectures (56,872 patients), hybrid segmentation-classification networks (3,747), and smaller studies employing random forests (636), Res-CRNN (89), and traditional machine learning approaches (769). Data modalities included ECG (341,989 patients), echocardiography (>70,000 patients across multiple cohorts), scintigraphy (~24,000 patients), cardiac MRI (~900 patients), CT (299 patients), and blood tests (261 patients). Pooled diagnostic performance across all modalities demonstrated an overall accuracy of 84.0% (95% CI: 74.6-93.5), precision of 85.8% (95% CI: 79.6-92.0), recall (sensitivity) of 89.6% (95% CI: 85.7-93.4), and an F1-score of 87.2% (95% CI: 81.8-92.6). Area under the curve (AUC) analysis revealed modality-specific variation, with scintigraphy achieving the highest pooled AUC (99.7%), followed by MRI (96.8%), echocardiography (94.3%), blood tests (95.0%), CT (98.0%), and ECG (88.5%). Subgroup analysis confirmed significant differences between modalities (p < 0.001), with MRI and scintigraphy showing consistent high performance and low-to-moderate heterogeneity, while echocardiography displayed moderate accuracy but marked variability, and ECG demonstrated the lowest and most heterogeneous results. Conclusion AI demonstrates strong potential for improving CA diagnosis, with MRI and scintigraphy providing the most reliable performance, echocardiography offering an accessible but heterogeneous option, and ECG models remaining least consistent. While promising, future prospective multicenter studies are needed to validate AI models, improve subtype discrimination, and optimize multimodal integration for real-world clinical use.