A Phenotyping of Diastolic Function by Machine Learning Improves Prediction of Clinical Outcomes in Heart Failure

Background: Discriminating between different patterns of diastolic dysfunction in heart failure (HF) is still challenging. We tested the hypothesis that an unsupervised machine learning algorithm would detect heterogeneity in diastolic function and improve risk stratification compared with recommended consensus criteria. Methods: This study included 279 consecutive patients aged 24-97 years old with clinically stable HF referred for echocardiographic assessment, in whom diastolic variables were measured according to the current guidelines. Cluster analysis was undertaken to identify homogeneous groups of patients with similar profiles of the variables. Sequential Cox models were used to compare cluster-based classification with guidelines-based classification for predicting clinical outcomes. The primary endpoint was hospitalization for worsening HF. Results: The analysis identified three clusters with distinct properties of diastolic function that shared similarities with guidelines-based classification. The clusters were associated with brain natriuretic peptide level (p < 0.001), hemoglobin concentration (p = 0.017) and estimated glomerular filtration rate (p = 0.001). During a mean follow-up period of 2.6 ± 2.0 years, 62 patients (22%) experienced the primary endpoint. Cluster-based classification predicted events with a hazard ratio 1.68 (p = 0.019) that was independent from and incremental to the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score for HF, and from left ventricular end-diastolic volume and global longitudinal strain, whereas guidelines-based classification did not retain its independent prognostic value (hazard ratio = 1.25, p = 0.202). Conclusion: Machine learning can identify patterns of diastolic function that better stratify the risk for decompensation than the current consensus recommendations in HF. Integrating this data-driven phenotyping may help in refining prognostication and optimizing treatment.