Artificial Intelligence-Enabled Electrocardiogram Improves the Diagnosis and Prediction of Mortality in Patients With Pulmonary Hypertension.

Background: Pulmonary hypertension is a disabling and life-threatening cardiovascular disease. Early detection of elevated pulmonary artery pressure (ePAP) is needed for prompt diagnosis and treatment to avoid detrimental consequences of pulmonary hypertension. Objectives: This study sought to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify patients with ePAP and related prognostic implications. Methods: From a hospital-based ECG database, the authors extracted the first pairs of ECG and transthoracic echocardiography taken within 2 weeks of each other from 41,097 patients to develop an AI model for detecting ePAP (PAP > 50 mm Hg by transthoracic echocardiography). The model was evaluated on independent data sets, including an external cohort of patients from Japan. Results: Tests of 10-fold cross-validation neural-network deep learning showed that the area under the receiver-operating characteristic curve of the AI model was 0.88 (sensitivity 81.0%; specificity 79.6%) for detecting ePAP. The diagnostic performance was consistent across age, sex, and various comorbidities (diagnostic odds ratio >8 for most factors examined). At 6-year follow-up, the patients predicted by the AI model to have ePAP were independently associated with higher cardiovascular mortality (HR: 3.69). Similar diagnostic performance and prediction for cardiovascular mortality could be replicated in the external cohort. Conclusions: The ECG-based AI model identified patients with ePAP and predicted their future risk for cardiovascular mortality. This model could serve as a useful clinical test to identify patients with pulmonary hypertension so that treatment can be initiated early to improve their survival prognosis.

A Single-Cell Network-Based Drug Repositioning Strategy for Post-COVID-19 Pulmonary Fibrosis.

Post-COVID-19 pulmonary fibrosis (PCPF) is a long-term complication that appears in some COVID-19 survivors. However, there are currently limited options for treating PCPF patients. To address this problem, we investigated COVID-19 patients' transcriptome at single-cell resolution and combined biological network analyses to repurpose the drugs treating PCPF. We revealed a novel gene signature of PCPF. The signature is functionally associated with the viral infection and lung fibrosis. Further, the signature has good performance in diagnosing and assessing pulmonary fibrosis. Next, we applied a network-based drug repurposing method to explore novel treatments for PCPF. By quantifying the proximity between the drug targets and the signature in the interactome, we identified several potential candidates and provided a drug list ranked by their proximity. Taken together, we revealed a novel gene expression signature as a theragnostic biomarker for PCPF by integrating different computational approaches. Moreover, we showed that network-based proximity could be used as a framework to repurpose drugs for PCPF.