Predicting Long-Term Mortality after Acute Coronary Syndrome Using Machine Learning Techniques and Hematological Markers.

INTRODUCTION: Hematological indices including red cell distribution width and neutrophil to lymphocyte ratio are proven to be associated with outcomes of acute coronary syndrome. The usefulness of machine learning techniques in predicting mortality after acute coronary syndrome based on such features has not been studied before. OBJECTIVE: We aim to create an alternative risk assessment tool, which is based on easily obtainable features, including hematological indices and inflammation markers. PATIENTS AND METHODS: We obtained the study data from the electronic medical records of 5053 patients hospitalized with acute coronary syndrome during a 5-year period. The time of follow-up ranged from 12 to 72 months. A machine learning classifier was trained to predict death during hospitalization and within 180 and 365 days from admission. Our method was compared with the Global Registry of Acute Coronary Events (GRACE) Score 2.0 on a test dataset. RESULTS: For in-hospital mortality, our model achieved a c-statistic of 0.89 while the GRACE score 2.0 achieved 0.90. For six-month mortality, the results of our model and the GRACE score on the test set were 0.77 and 0.73, respectively. Red cell distribution width (HR 1.23; 95% CL 1.16-1.30; P < 0.001) and neutrophil to lymphocyte ratio (HR 1.08; 95% CL 1.05-1.10; P < 0.001) showed independent association with all-cause mortality in multivariable Cox regression. CONCLUSIONS: Hematological markers, such as neutrophil count and red cell distribution width have a strong association with all-cause mortality after acute coronary syndrome. A machine-learned model which uses the abovementioned parameters can provide long-term predictions of accuracy comparable or superior to well-validated risk scores.Peer Reviewe

Clinical applications of artificial intelligence in cardiology on the verge of the decade

Artificial intelligence (AI) has been hailed as the fourth industrial revolution and its influence on people’s lives is increasing. The research on AI applications in medicine is progressing rapidly. This revolution shows promise for more precise diagnoses, streamlined workflows, increased accessibility to healthcare services and new insights into ever-growing population-wide datasets. While some applications have already found their way into contemporary patient care, we are still in the early days of the AI-era in medicine. Despite the popularity of these new technologies, many practitioners lack an understanding of AI methods, their benefits, and pitfalls. This review aims to provide information about the general concepts of machine learning (ML) with special focus on the applications of such techniques in cardiovascular medicine. It also sets out the current trends in research related to medical applications of AI. Along with new possibilities, new threats arise — acknowledging and understanding them is as important as understanding the ML methodology itself. Therefore, attention is also paid to the current opinions and guidelines regarding the validation and safety of AI-powered tools

Machine-learned models using hematological inflammation markers in the prediction of short-term acute coronary syndrome outcomes.

BACKGROUND: Increased systemic and local inflammation play a vital role in the pathophysiology of acute coronary syndrome. This study aimed to assess the usefulness of selected machine learning methods and hematological markers of inflammation in predicting short-term outcomes of acute coronary syndrome (ACS). METHODS: We analyzed the predictive importance of laboratory and clinical features in 6769 hospitalizations of patients with ACS. Two binary classifications were considered: significant coronary lesion (SCL) or lack of SCL, and in-hospital death or survival. SCL was observed in 73% of patients. In-hospital mortality was observed in 1.4% of patients and it was higher in the case of patients with SCL. Ensembles of decision trees and decision rule models were trained to predict these classifications. RESULTS: The best performing model for in-hospital mortality was based on the dominance-based rough set approach and the full set of laboratory as well as clinical features. This model achieved 81 ± 2.4% sensitivity and 81.1 ± 0.5% specificity in the detection of in-hospital mortality. The models trained for SCL performed considerably worse. The best performing model for detecting SCL achieved 56.9 ± 0.2% sensitivity and 66.9 ± 0.2% specificity. Dominance rough set approach classifier operating on the full set of clinical and laboratory features identifies presence or absence of diabetes, systolic and diastolic blood pressure and prothrombin time as having the highest confirmation measures (best predictive value) in the detection of in-hospital mortality. When we used the limited set of variables, neutrophil count, age, systolic and diastolic pressure and heart rate (taken at admission) achieved the high feature importance scores (provided by the gradient boosted trees classifier) as well as the positive confirmation measures (provided by the dominance-based rough set approach classifier). CONCLUSIONS: Machine learned models can rely on the association between the elevated inflammatory markers and the short-term ACS outcomes to provide accurate predictions. Moreover, such models can help assess the usefulness of laboratory and clinical features in predicting the in-hospital mortality of ACS patients

Time and event-specific deep learning for personalized risk assessment after cardiac perfusion imaging

Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range [IQR]: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval [CI]: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making

Unsupervised learning to characterize patients with known coronary artery disease undergoing myocardial perfusion imaging

PURPOSE Patients with known coronary artery disease (CAD) comprise a heterogenous population with varied clinical and imaging characteristics. Unsupervised machine learning can identify new risk phenotypes in an unbiased fashion. We use cluster analysis to risk-stratify patients with known CAD undergoing single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS From 37,298 patients in the REFINE SPECT registry, we identified 9221 patients with known coronary artery disease. Unsupervised machine learning was performed using clinical (23), acquisition (17), and image analysis (24) parameters from 4774 patients (internal cohort) and validated with 4447 patients (external cohort). Risk stratification for all-cause mortality was compared to stress total perfusion deficit (< 5%, 5-10%, ≥10%). RESULTS Three clusters were identified, with patients in Cluster 3 having a higher body mass index, more diabetes mellitus and hypertension, and less likely to be male, have dyslipidemia, or undergo exercise stress imaging (p < 0.001 for all). In the external cohort, during median follow-up of 2.6 [0.14, 3.3] years, all-cause mortality occurred in 312 patients (7%). Cluster analysis provided better risk stratification for all-cause mortality (Cluster 3: hazard ratio (HR) 5.9, 95% confidence interval (CI) 4.0, 8.6, p < 0.001; Cluster 2: HR 3.3, 95% CI 2.5, 4.5, p < 0.001; Cluster 1, reference) compared to stress total perfusion deficit (≥10%: HR 1.9, 95% CI 1.5, 2.5 p < 0.001; < 5%: reference). CONCLUSIONS Our unsupervised cluster analysis in patients with known CAD undergoing SPECT MPI identified three distinct phenotypic clusters and predicted all-cause mortality better than ischemia alone

Clinical phenotypes among patients with normal cardiac perfusion using unsupervised learning:a retrospective observational study

BACKGROUND: Myocardial perfusion imaging (MPI) is one of the most common cardiac scans and is used for diagnosis of coronary artery disease and assessment of cardiovascular risk. However, the large majority of MPI patients have normal results. We evaluated whether unsupervised machine learning could identify unique phenotypes among patients with normal scans and whether those phenotypes were associated with risk of death or myocardial infarction.METHODS: Patients from a large international multicenter MPI registry (10 sites) with normal perfusion by expert visual interpretation were included in this cohort analysis. The training population included 9849 patients, and external testing population 12,528 patients. Unsupervised cluster analysis was performed, with separate training and external testing cohorts, to identify clusters, with four distinct phenotypes. We evaluated the clinical and imaging features of clusters and their associations with death or myocardial infarction.FINDINGS: Patients in Clusters 1 and 2 almost exclusively underwent exercise stress, while patients in Clusters 3 and 4 mostly required pharmacologic stress. In external testing, the risk for Cluster 4 patients (20.2% of population, unadjusted hazard ratio [HR] 6.17, 95% confidence interval [CI] 4.64-8.20) was higher than the risk associated with pharmacologic stress (HR 3.03, 95% CI 2.53-3.63), or previous myocardial infarction (HR 1.82, 95% CI 1.40-2.36).INTERPRETATION: Unsupervised learning identified four distinct phenotypes of patients with normal perfusion scans, with a significant proportion of patients at very high risk of myocardial infarction or death. Our results suggest a potential role for patient phenotyping to improve risk stratification of patients with normal imaging results.FUNDING: This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R35HL161195 to PS]. The REFINE SPECT database was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R01HL089765 to PS]. MCW was supported by the British Heart Foundation [FS/ICRF/20/26002].</p

Deep learning-enabled coronary CT angiography for plaque and stenosis quantification and cardiac risk prediction: an international multicentre study

BACKGROUND: Atherosclerotic plaque quantification from coronary CT angiography (CCTA) enables accurate assessment of coronary artery disease burden and prognosis. We sought to develop and validate a deep learning system for CCTA-derived measures of plaque volume and stenosis severity. METHODS: This international, multicentre study included nine cohorts of patients undergoing CCTA at 11 sites, who were assigned into training and test sets. Data were retrospectively collected on patients with a wide range of clinical presentations of coronary artery disease who underwent CCTA between Nov 18, 2010, and Jan 25, 2019. A novel deep learning convolutional neural network was trained to segment coronary plaque in 921 patients (5045 lesions). The deep learning network was then applied to an independent test set, which included an external validation cohort of 175 patients (1081 lesions) and 50 patients (84 lesions) assessed by intravascular ultrasound within 1 month of CCTA. We evaluated the prognostic value of deep learning-based plaque measurements for fatal or non-fatal myocardial infarction (our primary outcome) in 1611 patients from the prospective SCOT-HEART trial, assessed as dichotomous variables using multivariable Cox regression analysis, with adjustment for the ASSIGN clinical risk score. FINDINGS: In the overall test set, there was excellent or good agreement, respectively, between deep learning and expert reader measurements of total plaque volume (intraclass correlation coefficient [ICC] 0·964) and percent diameter stenosis (ICC 0·879; both p<0·0001). When compared with intravascular ultrasound, there was excellent agreement for deep learning total plaque volume (ICC 0·949) and minimal luminal area (ICC 0·904). The mean per-patient deep learning plaque analysis time was 5·65 s (SD 1·87) versus 25·66 min (6·79) taken by experts. Over a median follow-up of 4·7 years (IQR 4·0–5·7), myocardial infarction occurred in 41 (2·5%) of 1611 patients from the SCOT-HEART trial. A deep learning-based total plaque volume of 238·5 mm(3) or higher was associated with an increased risk of myocardial infarction (hazard ratio [HR] 5·36, 95% CI 1·70–16·86; p=0·0042) after adjustment for the presence of deep learning-based obstructive stenosis (HR 2·49, 1·07–5·50; p=0·0089) and the ASSIGN clinical risk score (HR 1·01, 0·99–1·04; p=0·35). INTERPRETATION: Our novel, externally validated deep learning system provides rapid measurements of plaque volume and stenosis severity from CCTA that agree closely with expert readers and intravascular ultrasound, and could have prognostic value for future myocardial infarction

Predicting Long-Term Mortality after Acute Coronary Syndrome Using Machine Learning Techniques and Hematological Markers

Introduction. Hematological indices including red cell distribution width and neutrophil to lymphocyte ratio are proven to be associated with outcomes of acute coronary syndrome. The usefulness of machine learning techniques in predicting mortality after acute coronary syndrome based on such features has not been studied before. Objective. We aim to create an alternative risk assessment tool, which is based on easily obtainable features, including hematological indices and inflammation markers. Patients and Methods. We obtained the study data from the electronic medical records of 5053 patients hospitalized with acute coronary syndrome during a 5-year period. The time of follow-up ranged from 12 to 72 months. A machine learning classifier was trained to predict death during hospitalization and within 180 and 365 days from admission. Our method was compared with the Global Registry of Acute Coronary Events (GRACE) Score 2.0 on a test dataset. Results. For in-hospital mortality, our model achieved a c-statistic of 0.89 while the GRACE score 2.0 achieved 0.90. For six-month mortality, the results of our model and the GRACE score on the test set were 0.77 and 0.73, respectively. Red cell distribution width (HR 1.23; 95% CL 1.16-1.30; P<0.001) and neutrophil to lymphocyte ratio (HR 1.08; 95% CL 1.05-1.10; P<0.001) showed independent association with all-cause mortality in multivariable Cox regression. Conclusions. Hematological markers, such as neutrophil count and red cell distribution width have a strong association with all-cause mortality after acute coronary syndrome. A machine-learned model which uses the abovementioned parameters can provide long-term predictions of accuracy comparable or superior to well-validated risk scores