Agarwal, Richa

Background: Pulmonary hypertension (PH) is a life-threatening disease affecting up to 1% of the global population. Diagnosis can be challenging and is often delayed due to the need for advanced imaging and invasive procedures. The use of artificial intelligence applied to ECGs (ECG-AI) has been shown to detect subtle patterns in voltage-time data and may be a valuable tool for the early detection of PH. Hypothesis and Purpose: To evaluate the performance of a previously trained, ECG-AI algorithm to detect PH (ECG-AI PH) using real-world data (RWD) collected in a multicenter, validation study. A joint primary hypothesis required sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) to exceed the null values of 76%, 70%, 10% and 90%. Study Design and Methods: This retrospective validation study was conducted at 5 geographically diverse U.S. health systems. Adult subjects were eligible for inclusion if they had a 12-lead ECG paired with an echocardiogram (Echo) in which tricuspid regurgitation velocity (TRV) was recorded, following presentation with dyspnea. Patients were classified according to echocardiographic criteria as either PH (PH+, TRV >3.4 m/s) or controls (PH-, TRV ≤2.8 m/s) to simulate the real-world use of ECG-AI, where a positive result could lead to a follow-up Echo. The study database was locked before processing the digital ECGs with ECG-AI PH. Performance was also estimated in a subset of subjects that later had a right heart catheterization using mPAP ≥ 20mmHg as the definition of PH. Results: A total of 14281 subjects (53% female, 63% aged 50+ years) met the inclusion criteria, including 3019 PH+ cases and 11262 PH- controls (Figure). Sn and Sp were 84.0% (95% CI: 82.6%, 85.3%) and 71.7% (95% CI: 70.9%, 72.6%), respectively. The positive and negative predictive values were 18.9% (95% CI: 18.4%, 19.4%) and 98.3% (95% CI: 98.1%, 98.4%), respectively, at 7.3% prevalence. Each endpoint met pre-defined performance criteria. In the subset of 1683 subjects with a follow up RHC, performance remained robust (Sn 85% (1155/1358); Sp 46% (151/325)). Conclusion: While ECG-AI PH was first developed as an investigational tool to detect PH, continued development as software as a medical device for clinical use demonstrated that the algorithm retained strong performance to detect PH in diverse, non-overlapping clinical settings and patient populations.