TY - JOUR
T1 - Machine learning to predict the risk of incident heart failure hospitalization among patients with diabetes
T2 - The WATCH-DM risk score
AU - Segar, Matthew W.
AU - Vaduganathan, Muthiah
AU - Patel, Kershaw V.
AU - McGuire, Darren K.
AU - Butler, Javed
AU - Fonarow, Gregg C.
AU - Basit, Mujeeb
AU - Kannan, Vaishnavi
AU - Grodin, Justin L.
AU - Everett, Brendan
AU - Willett, Duwayne
AU - Berry, Jarett
AU - Pandey, Ambarish
N1 - Funding Information:
Funding. The Texas Health Resources Clinical Scholars Program funded this study. M.V. is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health [NIH]/National Center for Advancing Translational Sciences award UL 1TR002541). M.V. participates on clinical end point committees for studies sponsored by the NIH. J.B. has received research support from the NIH, Patient-Centered Outcomes Research Institute, and the European Union. J.L.G. and A.P. are supported by the Texas Health Resources Clinical Scholars Program. Duality of Interest. M.V. serves on advisory boardsforAmgen,AstraZeneca,BayerAG,Baxter Healthcare, and Boehringer Ingelheim and participates on clinical end point committees for studies sponsored by Novartis. D.K.M. reports honoraria for trial leadership from AstraZeneca, Sanofi, Lilly USA, Janssen, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline, and Esperion and honoraria for consulting for AstraZeneca, Sanofi, Lilly USA, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Metavant, and Afimmune. J.B. has served as a consultant for Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, and Vifor. G.C.F. reports consulting for Abbott, Amgen, Bayer, Janssen, Medtronic, and Novar-tis. J.L.G. serves as a consultant for Pfizer. No other potential conflicts of interest relevant to this article were reported. Author Contributions. M.W.S., M.V., and A.P. developed the study concept and design, interpreted data, and critically revised and drafted the manuscript. K.V.P., D.K.M., J.Bu., G.C.F., J.L.G., B.E., and J.Be. contributed to discussion and critically revised and reviewed the manuscript. M.B., V.K., and D.W. performed statistical analyses and reviewed the manuscript. M.W.S. and A.P. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the EPI|Lifestyle Scientific Sessions of the American Heart Association, Houston, TX, 6–8 March 2019, and at the Heart Failure Society of America 23rd Annual Scientific Meeting, Philadelphia, PA, 13–16 September 2019.
Funding Information:
All patients provided written informed consent to participate in ACCORD and ALLHAT, and study protocols were approved by local institutional review boards. Both ACCORD and ALLHAT were supported by the National Heart, Lung, and Blood Institute, and limited anonymized data are available by request to the National Institutes of Health Biologic Specimen and Data Repository Information Coordinating Center.
Publisher Copyright:
© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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 x2 5 9.63, P 5 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 5 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.
AB - 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 x2 5 9.63, P 5 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 5 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.
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U2 - 10.2337/dc19-0587
DO - 10.2337/dc19-0587
M3 - Article
C2 - 31519694
AN - SCOPUS:85075814170
SN - 1935-5548
VL - 42
SP - 2298
EP - 2306
JO - Diabetes Care
JF - Diabetes Care
IS - 12
ER -