Egbe, Alexander

Introduction/Background: Despite numerous medical advances, 30% of patients with Fontan circulation require heart transplantation by 21. Current risk stratification relies on clinical metrics that lack strong correlations to patient outcomes, leading to a high waitlist mortality. Hypothesis: Integration of physics-based hemodynamic modeling with interpretable machine learning will improve prediction of patient outcomes (listing for heart transplant and/or cardiac death) by quantifying physiologic mechanisms inaccessible through clinical measures alone. Goals/Aims: 1. Develop a lumped-parameter mechanistic model (LPMM) of Fontan circulation 2. Identify patient clusters and predictors of patient outcomes 3. Validate model-informed classifiers against clinical-only approaches Methods/Approach: A LPMM incorporating ventricular sarcomere mechanics, atrial hemodynamics, and vascular viscoelastic effects was optimized to cardiac catheterization and echocardiography data from 51 patients (age 25±8 years). Thirty-eight parameters (ventricular inotropy, atrial stiffness, pulmonary elastance, etc.) were calibrated via surrogate optimization, minimizing least-squares error versus 11 clinical targets. Partial least-squares regression with leave-one-out cross-validation compared clinical-only versus model-informed classifiers of outcomes. Results/Data: The LPMM achieved 2% mean error across hemodynamic targets, with CVP and pulmonary pressures matching clinical measurements within 1%. Model-derived minimum atrial pressure (4.46±1.78 vs 2.68±0.87 mmHg, p<0.05) outperformed all clinical variables in discriminating patient outcomes. Integration of LPMM parameters increased AUROC from 0.67 to 0.78 for patient outcome prediction. Conclusions: Physics-based modeling identifies ventricular passive stiffness, atrial end-diastolic volume, and minimum atrial pressure, along with patient age (a clinical value) as critical determinants of Fontan failure. Combined mechanistic-machine learning approaches enable phenotype-specific risk stratification, supporting earlier referral for advanced therapies. This methodology establishes a framework for precision management of complex congenital circulations.

Background: Patients with Fontan palliation have reduced aerobic capacity because of impaired cardiac, pulmonary, and skeletal muscle function. However, the assessment of aerobic capacity in this population still relies on comparisons with people without cardiovascular disease, rather than comparison with the expected aerobic capacity of other Fontan patients. The purpose of this study was to determine the expected aerobic capacity of adults with Fontan palliation. Method: Adults with Fontan palliation who underwent cardiopulmonary exercise test at Mayo Clinic (2003-2023) were stratified into quartiles based on the predicted peak VO 2 . We assessed the correlates of predicted peak VO 2 , and the relationship between predicted peak VO 2 quartiles and cardiovascular outcomes (death/transplant). Results: Of 323 patients (age 29±9 years; 177 [55%] men), the median peak VO2 was 19.1 (15.2 - 23.9) ml/kg/min, and this corresponds to a predicted peak VO 2 of 51% (range 19 -88; interquartile range 41 - 62). The correlates of higher predicted peak VO 2 were smaller body mass index, higher systemic saturation, and lower Fontan pressures. The top, 2 nd ,3 rd , and bottom quartile of predicted peak VO 2 corresponds to predicted peak VO 2 of 63-88%, 51-62%, 41-50%, and 19-40%, respectively. Using the top quartile as the reference, the 3 rd quartile (HR 1.13, 95% CI 1.03-1.28, p=0.02), and 4 th quartile were associated with a higher risk of death/transplant (HR 1.32, 95% CI 1.16-1.69, p<0.001). Conclusions: The results of the current study would help calibrate the interpretation of exercise test data in adults with Fontan palliation and improve risk stratification in this population.

Background: Pulmonary hypertension (PH) and secondary right ventricle dysfunction is present in 20% of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. Method: Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure >20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. Results: Of 99 COA patients that underwent RHC, 57 (58%) had PH. Of the patients with PH, 14 (25%) had isolated precapillary PH while 43 (75%) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95% CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95% CI 0921-0.98 per 1%), and atrial fibrillation (adjusted OR 2.18, 95% CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95% CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95% CI 1.02-1.08 per 1 mmHg). Conclusions: PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.

AbstractBackgroundThe improved life expectancy observed in patients living with human immunodeficiency virus (HIV) infection has made age‐related cardiovascular complications, including arrhythmias, a growing health concern.HypothesisWe describe the temporal trends in frequency of various arrhythmias and assess impact of arrhythmias on hospitalized HIV patients using the Nationwide Inpatient Sample (NIS).MethodsData on HIV‐related hospitalizations from 2005 to 2014 were obtained from the NIS database using International Classification of Diseases, 9th Revision (ICD‐9) codes. Data was further subclassified into hospitalizations with associated arrhythmias and those without. Baseline demographics and comorbidities were determined. Outcomes including in‐hospital mortality, cost of care, and length of stay were extracted. SAS 9.4 (SAS Institute Inc., Cary, NC) was utilized for analysis. A multivariable analysis was performed to identify predictors of arrhythmias among hospitalized HIV patients.ResultsAmong 2 370 751 HIV‐related hospitalizations identified, the overall frequency of any arrhythmia was 3.01%. Atrial fibrillation (AF) was the most frequent arrhythmia (2110 per 100 000). The overall frequency of arrhythmias increased over time by 108%, primarily due to a 132% increase in AF. Arrhythmias are more frequent among older males, lowest income quartile, and nonelective admissions. Patients with arrhythmias had a higher in‐hospital mortality rate (9.6%). In‐hospital mortality among patients with arrhythmias decreased over time by 43.8%. The cost of care and length of stay associated with arrhythmia‐related hospitalizations were mostly unchanged.ConclusionsArrhythmias are associated with significant morbidity and mortality in hospitalized HIV patients. AF is the most frequent arrhythmia in hospitalized HIV patients.

Background: The improved life expectancy observed in patients living with Human Immunodeficiency Virus (HIV) infection has made age-related cardiovascular complications, including arrhythmias, a growing health concern. We describe the temporal trends in frequency of various arrhythmias and assess impact of arrhythmias on hospitalized HIV patients using the Nationwide Inpatient Sample (NIS) Methods and Results: Data on HIV-related hospitalizations from 2005 to 2014 were obtained from the NIS using International Classification of Diseases, 9th Revision (ICD-9) codes. Data was further subclassified into hospitalizations with associated arrhythmias and those without arrhythmia. Baseline demographics and comorbidities were determined. Outcomes including in-hospital mortality, cost of care, and length of stay were extracted. SAS 9.4 (SAS Institute Inc., Cary, North Carolina) was utilized for analysis. A multivariable analysis was performed to identify predictors of arrhythmias among hospitalized HIV patients. Among 2,370,751 HIV-related hospitalizations identified, the overall frequency of any arrhythmia was 3.01%. Atrial fibrillation (AF) was the most frequent arrhythmia (2110 per 100,000). The overall frequency of arrhythmias has increased over time by 108%, primarily due to a 132% increase in AF. Arrhythmias are more frequent among older males, lowest income quartile and non-elective admissions. Patients with arrhythmias had a higher in-hospital mortality rate (9.6%). In-hospital mortality among patients with arrhythmias has decreased over time by 43.8%. The cost of care and length of stay associated with arrhythmia-related hospitalizations were mostly unchanged. Conclusions: Arrhythmias are associated with significant morbidity and mortality in hospitalized HIV patients. AF is the most frequent arrhythmia in hospitalized HIV patients.