Citations

Introduction: Recently, an artificial intelligence (AI) algorithm was validated for identifying ECG signatures of atrial fibrillation (AF) risk during normal sinus rhythm. Traditionally, socioeconomically disadvantaged populations are less likely to receive novel or guideline-recommended treatments, and have high chronic disease burden, including cardiovascular diseases. There have also been concerns about new technologies creating a digital divide, worsening existing health disparities. Hypothesis: An AI algorithm will detect AF risk unequally across patients with different levels of social determinants of health (SDOH). Methods: The initial prospective, non-randomized, interventional study leveraged EHR and digital technologies to prospectively enroll 1004 patients with a broad range of AI-ECG risks of AF, who received continuous cardiac rhythm monitoring for up to 30 days. The Area Deprivation Index (ADI) was used as a composite measure of SDOH which is comprised of indicators spanning four domains: income, education, employment, and house quality. 904 intervention patients linked to the ADI data were matched to 904 real-world control patients derived from eligible but unenrolled patients. Those with ADI under 33% were defined as having better SODH; and patients with ADI above 33% were defined as having worse SODH. Results: Median age was 74 years and 38% were women. After matching, the intervention and control arms were balanced in all baseline characteristics, including HF, HTN, diabetes, stroke, CAD and ADI. A hazard ratio of 3.11 (P<0.001) was computed when comparing intervention to control for primary AF diagnosis outcome. In patients with worse SDOH, the intervention increased AF detection from 2.6% to 8.8% (HR 3.63 [2.09, 6.32]); in the better SDOH, the intervention increased AF detection from 3.9% to 9.3% (2.41 [1.23, 4.74]). Conclusions: An AI-guided AF screening program increased the detection of AF in both patients with better or worse SDOH. The current study validates the use of AI in historically disadvantaged populations displaying the possibility for broad implementation with decreased possibility of perpetuating disparities.

Introduction: Hyperkalemia has been associated with increased mortality in cardiac intensive care unit (CICU) patients. An artificial intelligence (AI) augmented electrocardiogram (ECG) can predict hyperkalemia, and other AI-ECG algorithms have predicted mortality in CICU patients. Hypothesis: We hypothesized that the AI-ECG hyperkalemia algorithm could stratify mortality risk beyond the serum potassium measurement. Methods: We included 11 234 unique Mayo Clinic CICU patients admitted from 2007 to 2018 who had both a 12 lead ECG and blood potassium (K) level obtained at admission with K>=5 mEq/L defining hyperkalemia. ECGs underwent AI evaluation for probability of hyperkalemia (probability >=0.5 defined as positive). Hospital mortality was analyzed using logistic regression and survival to one year was estimated using Kaplan-Meier and Cox analysis. Results: The mean age was 70 years, 37.8% were females, and 92.4% were white. Chronic kidney disease was present in 20%. The mean K value was 4.2 mEq/L, and 13% (n=1460) had hyperkalemia. AI-ECG predicted hyperkalemia in 34% (n=3820). In-hospital mortality was higher in patients with laboratory and/or AI-ECG hyperkalemia, and these patients had lower survival out to 1 year. Mortality was lowest in patients with normal K and negative AI-ECG and highest in patients with both laboratory-confirmed hyperkalemia and AI-ECG predicted hyperkalemia. Patients with isolated laboratory hyperkalemia (false-negative AI-ECG) had higher mortality than those with isolated AI-ECG hyperkalemia (false-positive AI-ECG). Conclusions: AI-ECG probability of hyperkalemia, even with a normal laboratory K, was associated with higher short-term and long-term mortality in CICU patients. The laboratory K value and AI-ECG probability of hyperkalemia are complementary risk factors. The AI algorithm can detect prognostically important ECG abnormalities which may reflect the effects of K levels on the myocardium.

Introduction: Accurate pre-procedure localization of the premature ventricular contractions (PVCs) is critical in preparing for the ablation. So far, no tools exist for artificial intelligence guided PVC-localization. Hypothesis: Trained deep learning model will be able to predict the site of origin (SOO) of PVCs using 12 lead electrocardiogram (ECG). Methods: We analyzed 707 ECG-ablation pairs from 2403 patients who had at least one ECG flagged for PVCs in the 6 months prior to their procedure. First, we used a cohort of 100,000 ECGs without PVCs and 10,000 ECGs with PVCs to train a convolutional neural network (CNN) to isolate the ECG segments with PVCs in them from a 12-lead ECG (Figure 1). We then trained two models, one utilizing a 10-second 12-lead ECG, and the other with just the isolated PVC beats as input. The models were trained using the Keras framework with TensorFlow (Google). Results: The mean age of the patients in the cohort was 61.2 ± 15.0 years. 66.3 percent of patients underwent left ventricle ablation, 54.6 percent had outflow ablation, and 55.3 percent had ablation of sites with leftward axis (septal location for midline and left ventricle PVCs). The model trained on 10-second ECGs yielded validation and test AUCs of 0.941 and 0.931 for outflow, 0.898 and 0.891 for ventricle, and 0.863 and 0.846 for leftward axis (Figure 1A). The model trained on isolated segments containing PVC beats yielded validation and test AUCs of 0.966 and 0.957 for outflow, 0.879 and 0.907 for ventricle, and 0.846 and 0.829 for SOO for leftward axis (Figure 1B). Conclusions: We have trained an accurate convolutional neural network that can predict SOO using the surface ECG. Further fine-tuning would be needed to refine the model and develop prediction of specific sites.

Introduction: Left ventricular diastolic function and filling pressure (FP) can be assessed by echocardiography and cardiac catheterization. Recently, a novel artificial intelligence (AI)-enabled ECG has proven to be effective in identifying increased FP determined by echocardiographic assessment of diastolic function. Aims: We aimed to compare a prognostic value of AI-ECG determination of FP compared to echocardiography and catheterization. Methods: This study included 4,213 patients who had a transthoracic echocardiogram and ECG within 30 days before hemodynamic cardiac catheterization. Increased FP was defined as pulmonary artery wedge pressure >15 mmHg by catheterization and grade 2 or 3 diastolic dysfunction by echocardiography based on diastolic function guidelines. Increased FP by ECG was identified using previously developed AI-ECG. AI-ECG performance was evaluated using the area under the curve (AUC) of the receiver operating curve. We assessed the risk of all-cause mortality using Kaplan-Meier estimate and multivariable Cox proportional-hazards models. Results: AI-ECG had AUCs of 0.8 and 0.7 for predicting increased FP determined by echocardiography and catheterization, respectively. Death was observed in 2,776 (34%) patients over a median follow-up of 7.7 years (IQR 7.1, 8.3). Survival of patients with normal and increased FP by AI-ECG, Echocardiography, and catheterization are shown in Figure 1a. Concordant diagnoses of normal and increased FP by AI-ECG and catheterization or echocardiography had the highest and lowest survival rates, respectively. When FP by AI-ECG was discordant, survival was better predicted by AI-ECG compared to echocardiography and catheterization (Figure 1b). Conclusion: AI-ECG for FP has a potential to discriminate prognosis further compared to FP determined by echocardiography or catheterization.

Background: Early diagnosis of heart failure with reduced ejection fraction (HFrEF) can lead to reduced healthcare costs and improved outcomes. In this study, we evaluated the economic effectiveness of an AI algorithm for detecting low ejection fraction using 12-lead ECG data. Aims: The primary aim was to estimate the health economic impact of the AI-ECG algorithm intervention to detect low ejection fraction. Methods: The study population consisted of 113,719 individuals without a prior history of HFrEF who visited a multistate health system between 2010-2018 with 12-lead ECG data and an echocardiogram within 1 year. The AI-ECG algorithm was run retrospectively, and projected costs were estimated assuming each patient incurred the average cost based on their age group and AI-detected heart failure stage. Hospitalization costs were estimated using Medicare reimbursement rates, and economic benefits from increased survival were estimated using a willingness to pay of $50,000 per quality-adjusted life year (QALY) gained. Results: At the optimal model threshold, the total cost savings per patient (including benefits from QALYs gained) for the AI-ECG algorithm vs. standard-of-care on the overall study population were projected to be $79.11 (95% CI: [$53.77, $104.44]) and $124.93 (95% CI: [$83.99, $165.88]) for the 2 and 4 year periods, respectively. For patients over 50 years old, the projected total cost savings were $85.56 (95% CI: [$56.35, $114.78]) and $135.28 (95% CI: [$88.18, $182.38]) per patient for the 2 and 4 year periods, respectively. See Figure. Conclusions: The AI-ECG algorithm to detect low ejection fraction is a cost-effective early screening tool for HFrEF.

Background: Depression is prevalent in almost half of patients with cardiovascular disease (CVD) and is associated with CVD and mortality. We used an artificial intelligence algorithm using ECG that predicts physiological age (ECG-Age) that has been linked to increased total and CVD mortality and CVD risk factors. We hypothesized that depressive symptoms would be associated with physiologic aging, as measured by AI-ECG Methods: A previously validated algorithm was applied to determine ECG-Age to 105,732 consecutive ECGs of individuals age ≥18 who sought care at Mayo Clinic between June 2019 and January 2022 and filled the Patient Health Questionnaire-9 (PHQ-9) within a month of ECG. PHQ-9 ascertains severity and frequency of depressive symptoms with values from 0 - 27 and were categorized as (None≤4, Mild 5-9, Moderate 10-14, Moderately severe 15-19 and Severe ≥20). Delta-Age was defined as ECG-Age minus chronological age and accelerated aging was defined as a Delta-Age >1SD above the mean. Logistic regression analyses associated PHQ-9 scores with positive Delta-Age while adjusting for CVD risk factors Results: Mean chronological age was 57±17 yr and mean ECG-Age 58±14 yr (R2 0.85, P < 0.0001), Delta-Age 0.71±9.40 yr, 58% women, average PHQ-9 5±6, 61% had none, 20% mild, 10 % moderate, 5%moderately severe and 4% had severe depressive symptoms. Delta-Age was 2.10 years higher in those with depressive symptoms, reflecting accelerated aging. Compared to those with no depressive symptoms, those with severe symptoms were 1.5 times more likely to have Delta-Age >1SD (OR 1.52 CI 95%1.73-1.33), independently of CV risk factors and the Charlson comorbidity index. Figure. There is significant attenuation of the association once accounting for age, sex and CVD risk factors Conclusions: Depressive symptoms are associated with physiologic aging, highlighting the role of depression in physiologic aging and the potential of preventive strategies in patients with depression and CVD

Introduction: The effect of obesity on physiologic aging has not been completely established. We previously developed an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm that predicts age and determines that the difference between AI-ECG age and chronological age (Age-Gap) may reflect accelerated aging, as it is associated with increased total and cardiovascular (CV) mortality. Hypothesis: Obesity is associated with an increased Age-Gap reflecting morbidity and accelerated aging. Methods: We included adults undergoing a wellness evaluation including, body fat percentage (BF%) determination by air displacement plethysmography (Bod-Pod®) and a 12-lead ECG within 2 years. We excluded those with coronary artery disease, congestive heart failure, stroke or being underweight defined as having a BMI<18.5 kg/m2. Logistic regression models tested the association between obesity by BMI (≥30 kg/m2) or BF% quartiles (≥35% for men and ≥25 in women) and being older by AI-ECG. Results: We included 1295 subjects (70% women), mean chronological age 46.7 ± 13.1 years. Mean Age-gap positive difference compared to those with BMI<25 was 1.39, 2.06 and 2.83 for those with BMI 25-29.9, 30-34.9, and >35 respectively (p<0.05). In the BF% group, Age-gap difference compared to those in the 1st quartile was 0.008, 0.37 and 1.52 for those in the 2nd, 3rd, and 4th quartile (p<0.05). Those>3 years older by ECG were more likely to have obesity by BMI and BF%, see figure. Conclusions: Obesity, either by BMI or BF%, is associated with increased physiologic age as measured by AI-ECG, highlighting the importance of obesity as a health threat.

Abstract Aims ECG abnormalities are often the first signs of arrhythmogenic right ventricular cardiomyopathy (ARVC) and we hypothesized that an artificial intelligence (AI)-enhanced ECG could help identify patients with ARVC and serve as a valuable disease-detection tool. Methods and results We created a convolutional neural network to detect ARVC using a 12-lead ECG. All patients with ARVC who met the 2010 task force criteria and had disease-causative genetic variants were included. All case ECGs were randomly assigned in an 8:1:1 ratio into training, validation, and testing groups. The case ECGs were age- and sex-matched with control ECGs at our institution in a 1:100 ratio. Seventy-seven patients (51% male; mean age 47.2 ± 19.9), including 56 patients with PKP2, 7 with DSG2, 6 with DSC2, 6 with DSP, and 2 with JUP were included. The model was trained using 61 case ECGs and 5009 control ECGs; validated with 7 case ECGs and 678 control ECGs and tested in 22 case ECGs and 1256 control ECGs. The sensitivity, specificity, positive and negative predictive values of the model were 77.3, 62.9, 3.32, and 99.4%, respectively. The area under the curve for rhythm ECG and median beat ECG was 0.75 and 0.76, respectively. Conclusion Our study found that the model performed well in excluding ARVC and supports the concept that the AI ECG can serve as a biomarker for ARVC if a larger cohort were available for network training. A multicentre study including patients with ARVC from other centres would be the next step in refining, testing, and validating this algorithm.

High dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) is a standard therapy for patients with plasma cell disorders (PCD). A barrier to improving candidate selection for auto HCT is appraisal of risk for transplant related complications. Electrocardiography (ECG) is a standard pre-HCT test to evaluate the potential for arrhythmia and structural heart disease. We hypothesized that an artificial intelligence (AI) based interpretation of ECG waveform data (AI-ECG) could enhance risk prediction for cardiac-specific and other outcomes following auto HCT for patients with PCD. To test this hypothesis, we used several AI-ECG tools developed using a deep-learning based approach that were trained to predict comorbidity (Attia et al, Lancet 2019 & Grogan et al, Mayo Clin Proc 2021). Model outputs include a scaled prediction value indicating increasing risk for atrial fibrillation/flutter (AF), reduced ejection fraction (EF), or cardiac amyloidosis. We evaluated this tool in 9,225 ECGs obtained from 849 patients (median 6 ECGs/patient, inter-quartile range: 3-12) who underwent first or subsequent auto HCT at Memorial Sloan Kettering Cancer Center between 2016-2022 and who had a diagnosis of multiple myeloma (N = 810), amyloidosis (N = 37), or other PCD (N = 2). The endpoints were to determine whether baseline AI-ECG prediction of AF risk correlated with peri-transplant AF events, and to explore whether model outputs correlated with survival and other cardiac clinical outcomes. The mean age of patients was 61.0 years (range 23.7 - 81.2) and median follow up was 2.7 years post auto HCT. Contributing cardiovascular risk factors included a prior history of AF (N = 101, 11.9%), coronary or cerebrovascular disease (N = 95, 11.2%), and diabetes mellitus (N = 98, 11.5%). Reduced dose melphalan (&lt; 200 mg/m 2) was administered in 26%. The HCT-comorbidity index (HCT-CI) was high risk (≥3) in 52.7%. The one-year overall survival and progression-free survival in the whole cohort was 94% (95% confidence interval (95% CI): 92 - 95%) and 86% (84 - 89%), respectively. Among patients not in AF at pre HCT evaluation, the 90-day cumulative incidence of AF was 5.6% (4.2 - 7.3%). In univariable competing risk regression, baseline pre HCT AI-ECG appraisal of AF risk was strongly correlated with incidence AF in patients who were in sinus rhythm before HCT (hazard ratio (HR): 25.1, 95% CI: 11.7 - 53.7, p &lt; 0.001). In a multivariable model adjusting for patient age and HCT-CI, AI-ECG AF predicted risk remained associated with incidence of post HCT AF (HR: 13.4, 95% CI: 5.9 - 30.4, p &lt; 0.001). Considering a decision threshold identified during original model training, AI-ECG predicted AF events with an accuracy of 75% (Mcnemar's p &lt; 2 x 10 -16). The precision, recall, and F1-score were 0.94, 0.77, and 0.85, respectively. AI-ECG predicted age correlated highly with actual patient age (Spearman rho = 0.59, p &lt; 2 x 10 -16). Amyloid risk scores were highly correlated with a known clinical history of amyloidosis (median 0.45 versus 0.05, Wilcoxon rank-sum p &lt; 0.001). Patients with EF &lt; 50% had greater prediction scores for cardiomyopathy compared to patients with normal EF (median 0.23 versus 0.01, Wilcoxon rank-sum p &lt;0.001). In univariable analysis, increasing AI-ECG predicted age (HR 1.02, CI: 1.003 - 1.04, p = 0.02) and predicted AF risk score (HR: 3.2, CI: 1.4 - 7.2, p = 0.006) were associated with risk for death, whereas predicted amyloid score and predicted low EF were not associated with decreased survival. In multivariable analysis of all patients that considered patient age, hematopoietic comorbidity index, and remission status at HCT, increasing predicted AF score trended towards association with increased risk for death (HR: 2.3, 95%CI: 1.0 - 5.5, p = 0.059). Predicted AF score correlated highly with the HCT-CI and patient age. Finally, we examined whether risk prediction for low EF correlated with peri-HCT fluid overload (FO) defined by absolute weight gain. The incidence of ≥ 10% weight gain (grade 2 FO) and ≥ 20% weight gain (grade 3 FO) at 180 days post HCT was 7.4% (95% CI: 5.8%, 9.3%) and 1.0% (95% CI: 0.5%, 1.8%), respectively. Predicted low EF was not associated with development of either grade 2 or grade 3 FO in this population. In summary, AI-ECG predicts episodes of AF in patients undergoing auto HCT for PCD and may augment transplant risk appraisal when considered in conjunction with other measures of comorbidity.