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Objective: To develop and validate a novel, machine learning-derived model to predict the risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM)., Research Design and Methods: Using data from 8,756 patients free at baseline of HF, with <10% missing data, and enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we used random survival forest (RSF) methods, a nonparametric decision tree machine learning approach, to identify predictors of incident HF. The RSF model was externally validated in a cohort of individuals with T2DM using the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)., Results: Over a median follow-up of 4.9 years, 319 patients (3.6%) developed incident HF. The RSF models demonstrated better discrimination than the best performing Cox-based method (C-index 0.77 [95% CI 0.75-0.80] vs. 0.73 [0.70-0.76] respectively) and had acceptable calibration (Hosmer-Lemeshow statistic χ 2 = 9.63, P = 0.29) in the internal validation data set. From the identified predictors, an integer-based risk score for 5-year HF incidence was created: the WATCH-DM (Weight [BMI], Age, hyperTension, Creatinine, HDL-C, Diabetes control [fasting plasma glucose], QRS Duration, MI, and CABG) risk score. Each 1-unit increment in the risk score was associated with a 24% higher relative risk of HF within 5 years. The cumulative 5-year incidence of HF increased in a graded fashion from 1.1% in quintile 1 (WATCH-DM score ≤7) to 17.4% in quintile 5 (WATCH-DM score ≥14). In the external validation cohort, the RSF-based risk prediction model and the WATCH-DM risk score performed well with good discrimination (C-index = 0.74 and 0.70, respectively), acceptable calibration ( P ≥0.20 for both), and broad risk stratification (5-year HF risk range from 2.5 to 18.7% across quintiles 1-5)., Conclusions: We developed and validated a novel, machine learning-derived risk score that integrates readily available clinical, laboratory, and electrocardiographic variables to predict the risk of HF among outpatients with T2DM., (© 2019 by the American Diabetes Association.)

Aims To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycaemia and in combination with natriuretic peptides (NPs). Methods and results Adults with diabetes/pre-diabetes free of HF at baseline from four cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning-[WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C-index) and calibration by the Greenwood-Nam-D'Agostino (GND) statistic. Improvement in model performance with the addition of NP levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5 years. The WATCH-DM(ml) and WATCH-DM(i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycaemia (C-indices = 0.80 and 0.71, respectively), with no evidence of miscalibration (GND P =0.10). The C-index of elevated NP levels alone for predicting incident HF among individuals with dysglycaemia was significantly higher among participants with low/intermediate (<13) vs. high (=13)WATCH-DM(i) scores [0.71 (95% confidence interval 0.68-0.74) vs. 0.64 (95% confidence interval 0.61-0.66)]. When NP levels were combined with the WATCH-DM(i) score, HF risk discrimination improvement and NRI varied across the spectrum of risk with greater improvement observed at low/intermediate risk [WATCH-DM(i)<13] vs. high risk [WATCH-DM(i) =13] (C-index = 0.73 vs. 0.71; NRI = 0.45 vs. 0.17). Conclusion TheWATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycaemia. The addition of NP levels is associated with greater improvement in the HF risk prediction performance among individuals with low/intermediate risk than those with high risk. [ABSTRACT FROM AUTHOR]

Aim: To identify distinct phenotypic subgroups in a highly-dimensional, mixed-data cohort of individuals with heart failure (HF) with preserved ejection fraction (HFpEF) using unsupervised clustering analysis.Methods and Results: The study included all Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) participants from the Americas (n = 1767). In the subset of participants with available echocardiographic data (derivation cohort, n = 654), we characterized three mutually exclusive phenogroups of HFpEF participants using penalized finite mixture model-based clustering analysis on 61 mixed-data phenotypic variables. Phenogroup 1 had higher burden of co-morbidities, natriuretic peptides, and abnormalities in left ventricular structure and function; phenogroup 2 had lower prevalence of cardiovascular and non-cardiac co-morbidities but higher burden of diastolic dysfunction; and phenogroup 3 had lower natriuretic peptide levels, intermediate co-morbidity burden, and the most favourable diastolic function profile. In adjusted Cox models, participants in phenogroup 1 (vs. phenogroup 3) had significantly higher risk for all adverse clinical events including the primary composite endpoint, all-cause mortality, and HF hospitalization. Phenogroup 2 (vs. phenogroup 3) was significantly associated with higher risk of HF hospitalization but a lower risk of atherosclerotic event (myocardial infarction, stroke, or cardiovascular death), and comparable risk of mortality. Similar patterns of association were also observed in the non-echocardiographic TOPCAT cohort (internal validation cohort, n = 1113) and an external cohort of patients with HFpEF [Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial cohort, n = 198], with the highest risk of adverse outcome noted in phenogroup 1 participants.Conclusions: Machine learning-based cluster analysis can identify phenogroups of patients with HFpEF with distinct clinical characteristics and long-term outcomes. [ABSTRACT FROM AUTHOR]