Echocardiographic phenogrouping by machine learning for risk stratification in the general population

There is a need for better phenotypic characterization of the asymptomatic stages of cardiac maladaptation. We tested the hypothesis that an unsupervised clustering analysis utilizing echocardiographic indexes reflecting left heart structure and function could identify phenotypically distinct groups of asymptomatic individuals in the general population.

We prospectively studied 1407 community-dwelling individuals (mean age, 51.2 years; 51.1% women), in whom we performed clinical and echocardiographic examination at baseline and collected cardiac events on average 8.8 years later. Cardiac phenotypes that were correlated at r > 0.8 were filtered, leaving 21 echocardiographic features, and systolic blood pressure for phenogrouping. We employed hierarchical and Gaussian mixture model-based clustering. Cox regression was used to demonstrate the clinical validity of constructed phenogroups. Unsupervised clustering analyses classified study participants into three distinct phenogroups that differed markedly in echocardiographic indexes. Indeed, cluster 3 had the worst left ventricular (LV) diastolic function (i.e. lowest e' velocity and left atrial (LA) reservoir strain, highest E/e', and LA volume index) and LV remodelling. The phenogroups were also different in cardiovascular risk factor profiles. We observed increase in the risk for incidence of adverse events across phenogroups. In the third phenogroup, the multivariable adjusted risk was significantly higher than the average population risk for major cardiovascular events (51%, P = 0.0028).

Unsupervised learning algorithms integrating routinely measured cardiac imaging and haemodynamic data can provide a clinically meaningful classification of cardiac health in asymptomatic individuals. This approach might facilitate early detection of cardiac maladaptation and improve risk stratification.