Sanjiv J. Shah

Yiming Li, Sanjiv J. Shah, Donna Arnett et al.

Hypertension is the leading global cause of cardiovascular disease and premature death. Distinct hypertension subtypes may vary in their prognoses and require different treatments. An individual's risk for hypertension is determined by genetic and environmental factors as well as their interactions. In this work, we studied 911 African Americans and 1,171 European Americans in the Hypertension Genetic Epidemiology Network (HyperGEN) cohort. We built hypertension subtype classification models using both environmental variables and sets of genetic features selected based on different criteria. The fitted prediction models provided insights into the genetic landscape of hypertension subtypes, which may aid personalized diagnosis and treatment of hypertension in the future.

Yuan Luo, Chengsheng Mao, Yiben Yang et al.

Hypertension is a heterogeneous syndrome in need of improved subtyping using phenotypic and genetic measurements so that patients in different subtypes share similar pathophysiologic mechanisms and respond more uniformly to targeted treatments. Existing machine learning approaches often face challenges in integrating phenotype and genotype information and presenting to clinicians an interpretable model. We aim to provide informed patient stratification by introducing Hybrid Non-negative Matrix Factorization (HNMF) on phenotype and genotype matrices. HNMF simultaneously approximates the phenotypic and genetic matrices using different appropriate loss functions, and generates patient subtypes, phenotypic groups and genetic groups. Unlike previous methods, HNMF approximates phenotypic matrix under Frobenius loss, and genetic matrix under Kullback-Leibler (KL) loss. We propose an alternating projected gradient method to solve the approximation problem. Simulation shows HNMF converges fast and accurately to the true factor matrices. On real-world clinical dataset, we used the patient factor matrix as features to predict main cardiac mechanistic outcomes. We compared HNMF with six different models using phenotype or genotype features alone, with or without NMF, or using joint NMF with only one type of loss. HNMF significantly outperforms all comparison models. HNMF also reveals intuitive phenotype-genotype interactions that characterize cardiac abnormalities.

Jeffrey Zhang, Sravani Gajjala, Pulkit Agrawal et al.

Automated cardiac image interpretation has the potential to transform clinical practice in multiple ways including enabling low-cost serial assessment of cardiac function in the primary care and rural setting. We hypothesized that advances in computer vision could enable building a fully automated, scalable analysis pipeline for echocardiogram (echo) interpretation. Our approach entailed: 1) preprocessing; 2) convolutional neural networks (CNN) for view identification, image segmentation, and phasing of the cardiac cycle; 3) quantification of chamber volumes and left ventricular mass; 4) particle tracking to compute longitudinal strain; and 5) targeted disease detection. CNNs accurately identified views (e.g. 99% for apical 4-chamber) and segmented individual cardiac chambers. Cardiac structure measurements agreed with study report values (e.g. mean absolute deviations (MAD) of 7.7 mL/kg/m2 for left ventricular diastolic volume index, 2918 studies). We computed automated ejection fraction and longitudinal strain measurements (within 2 cohorts), which agreed with commercial software-derived values [for ejection fraction, MAD=5.3%, N=3101 studies; for strain, MAD=1.5% (n=197) and 1.6% (n=110)], and demonstrated applicability to serial monitoring of breast cancer patients for trastuzumab cardiotoxicity. Overall, we found that, compared to manual measurements, automated measurements had superior performance across seven internal consistency metrics with an average increase in the Spearman correlation coefficient of 0.05 (p=0.02). Finally, we developed disease detection algorithms for hypertrophic cardiomyopathy and cardiac amyloidosis, with C-statistics of 0.93 and 0.84, respectively. Our pipeline lays the groundwork for using automated interpretation to support point-of-care handheld cardiac ultrasound and large-scale analysis of the millions of echos archived within healthcare systems.