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      Development and validation of echocardiography-based machine-learning models to predict mortality

      research-article
      a , b , c , d , e , f , b , c , b , d , f , f , d , g , d , g , h , i , j , b , d , b , d ,
      eBioMedicine
      Elsevier
      Echocardiography, Machine learning, Deep learning, Mortality, Heart failure, Prognostic models, Functional status, Echo, Echocardiography, ML, Machine learning, HF, Heart failure, HFrEF, Heart failure with reduced ejection fraction, HFpEF, Heart failure with preserved ejection fraction, KCCQ, Kansas city cardiomyopathy questionnaire, AUROC, Area under the receiver-operating curve, PLAX, Parasternal long axis, Alberta HEART, Alberta Heart Failure Etiology and Analysis Research Team, MAGGIC, Meta-Analysis global group in chronic heart failure, CSS, Clinical summary score, OSS, Overall summary score, DNN, Deep neural networks, CNN, Convolution neural networks, IVS, Interventricular septal, LV, Left ventricular, LVIDs, Left ventricular internal dimension end-systolic, LVIDd, Left ventricular internal dimension end-diastolic, PWTDI, Pulsed-wave tissue Doppler imaging, ROC, Receiver operating characteristics, AUPRC, Area under the precision–recall curve, SHAP, SHapley additive exPlanations

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          Summary

          Background

          Echocardiography (echo) based machine learning (ML) models may be useful in identifying patients at high-risk of all-cause mortality.

          Methods

          We developed ML models (ResNet deep learning using echo videos and CatBoost gradient boosting using echo measurements) to predict 1-year, 3-year, and 5-year mortality. Models were trained on the Mackay dataset, Taiwan (6083 echos, 3626 patients) and validated in the Alberta HEART dataset, Canada (997 echos, 595 patients). We examined the performance of the models overall, and in subgroups (healthy controls, at risk of heart failure (HF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)). We compared the models' performance to the MAGGIC risk score, and examined the correlation between the models’ predicted probability of death and baseline quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ).

          Findings

          Mortality rates at 1-, 3- and 5-years were 14.9%, 28.6%, and 42.5% in the Mackay cohort, and 3.0%, 10.3%, and 18.7%, in the Alberta HEART cohort. The ResNet and CatBoost models achieved area under the receiver-operating curve (AUROC) between 85% and 92% in internal validation. In external validation, the AUROCs for the ResNet (82%, 82%, and 78%) were significantly better than CatBoost (78%, 73%, and 75%), for 1-, 3- and 5-year mortality prediction respectively, with better or comparable performance to the MAGGIC score. ResNet models predicted higher probability of death in the HFpEF and HFrEF (30%–50%) subgroups than in controls and at risk patients (5%–20%). The predicted probabilities of death correlated with KCCQ scores (all p < 0.05).

          Interpretation

          Echo-based ML models to predict mortality had good internal and external validity, were generalizable, correlated with patients’ quality of life, and are comparable to an established HF risk score. These models can be leveraged for automated risk stratification at point-of-care.

          Funding

          Funding for Alberta HEART was provided by an doi 10.13039/501100000145, Alberta Innovates - Health Solutions; Interdisciplinary Team Grant no. doi 10.13039/501100003179, AHFMR; ITG 200801018. P.K. holds a doi 10.13039/501100000024, Canadian Institutes of Health Research; (CIHR) Sex and Gender Science Chair and a Heart & Stroke Foundation Chair in Cardiovascular Research. A.V. and V.S. received funding from the Mitacs Globalink Research Internship.

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          Most cited references32

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          2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

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            Heart Disease and Stroke Statistics—2020 Update

            Circulation
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              Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies.

              Using a large international database from multiple cohort studies, the aim is to create a generalizable easily used risk score for mortality in patients with heart failure (HF). The MAGGIC meta-analysis includes individual data on 39 372 patients with HF, both reduced and preserved left-ventricular ejection fraction (EF), from 30 cohort studies, six of which were clinical trials. 40.2% of patients died during a median follow-up of 2.5 years. Using multivariable piecewise Poisson regression methods with stepwise variable selection, a final model included 13 highly significant independent predictors of mortality in the following order of predictive strength: age, lower EF, NYHA class, serum creatinine, diabetes, not prescribed beta-blocker, lower systolic BP, lower body mass, time since diagnosis, current smoker, chronic obstructive pulmonary disease, male gender, and not prescribed ACE-inhibitor or angiotensin-receptor blockers. In preserved EF, age was more predictive and systolic BP was less predictive of mortality than in reduced EF. Conversion into an easy-to-use integer risk score identified a very marked gradient in risk, with 3-year mortality rates of 10 and 70% in the bottom quintile and top decile of risk, respectively. In patients with HF of both reduced and preserved EF, the influences of readily available predictors of mortality can be quantified in an integer score accessible by an easy-to-use website www.heartfailurerisk.org. The score has the potential for widespread implementation in a clinical setting.
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                Author and article information

                Contributors
                Journal
                eBioMedicine
                EBioMedicine
                eBioMedicine
                Elsevier
                2352-3964
                28 February 2023
                April 2023
                28 February 2023
                : 90
                : 104479
                Affiliations
                [a ]Bits Pilani KK Birla Goa Campus, Goa, India
                [b ]Canadian VIGOUR Centre, University of Alberta, Alberta, Canada
                [c ]Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada
                [d ]Faculty of Medicine & Dentistry, University of Alberta, Alberta, Canada
                [e ]Aligarh Muslim University, Uttar Pradesh, India
                [f ]US2.ai, Singapore
                [g ]Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada
                [h ]Saw Swee Hock School of Public Health, National University of Singapore & National University Health System, Singapore
                [i ]Duke-NUS Medical School, Singapore
                [j ]MacKay Memorial Hospital, Taipei City, Taiwan
                Author notes
                []Corresponding author. University of Alberta, Centre for Pharmacy and Health Research, 4-120 Katz Group, Edmonton, T6G2E1, Alberta, Canada. pkaul@ 123456ualberta.ca
                Article
                S2352-3964(23)00044-0 104479
                10.1016/j.ebiom.2023.104479
                10006431
                36857967
                422195fa-2994-4655-a225-a9d83581b275
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 3 October 2022
                : 1 February 2023
                : 1 February 2023
                Categories
                Articles

                echocardiography,machine learning,deep learning,mortality,heart failure,prognostic models,functional status,echo, echocardiography,ml, machine learning,hf, heart failure,hfref, heart failure with reduced ejection fraction,hfpef, heart failure with preserved ejection fraction,kccq, kansas city cardiomyopathy questionnaire,auroc, area under the receiver-operating curve,plax, parasternal long axis,alberta heart, alberta heart failure etiology and analysis research team,maggic, meta-analysis global group in chronic heart failure,css, clinical summary score,oss, overall summary score,dnn, deep neural networks,cnn, convolution neural networks,ivs, interventricular septal,lv, left ventricular,lvids, left ventricular internal dimension end-systolic,lvidd, left ventricular internal dimension end-diastolic,pwtdi, pulsed-wave tissue doppler imaging,roc, receiver operating characteristics,auprc, area under the precision–recall curve,shap, shapley additive explanations

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