Science
Our mission is to use FORCE data to improve outcomes for Fontan patients.
Learn more about our published and in progress research below.
Published Studies
High-Performing Fontan Patients
A Fontan Outcome Registry by Cardiac Magnetic Resonance Imaging Study
Tarek Alsaied, MD, MSC, • Runjia Li, MS, • Adam B. Christopher, MD, • Mark A. Fogel, MD, • Timothy C. Slesnick, MD, • Rajesh Krishnamurthy, MD, • Vivek Muthurangu, MD, PHD, • Adam L. Dorfman, MD, • Christopher Z. Lam, MD, • Justin D. Weigand, MD, • Joshua D. Robinson, MD, • Rachael Cordina, MD, • Laura J. Olivieri, MD, • Rahul H. Rathod, MD, • the FORCE Investigators.
BACKGROUND Fontan patients exhibit decreased exercise capacity. However, there is a subset of high-performing Fontan (HPF) patients with excellent exercise capacity.
OBJECTIVES This study aims to: 1) create a Fontan-specific percent predicted peak VO2 tool using exercise data; 2) examine clinical factors associated with HPF patients; and 3) examine late outcomes in HPF patients.
METHODS Patients in the multi-institutional Fontan Outcomes Registry Using CMR Examination above the age of 8 years who had a maximal exercise test were included. An HPF patient was defined as a patient in the upper Fontanspecific percent predicted peak VO2 quartile. Multivariable logistic regression was employed to investigate factors associated with the HPF and Cox regression was used to examine the association between HPF patients and late outcomes (composite of death or listing for cardiac transplant).
RESULTS The study included 813 patients (mean age: 20.2 8.7 years). An HPF patient was associated with left ventricular morphology (OR: 1.50, P . 0.04), mixed morphology (OR: 2.23, P < 0.001), and a higher ejection fraction (OR: 1.31 for 10% increase, P . 0.01). Patients with at least moderate atrioventricular valve regurgitation, protein-losing enteropathy, or who were using psychiatric medications, were less likely to be an HPF patient. After a mean follow-up of 3.7 years, 46 (5.7%) patients developed a composite endpoint. HPF had a lower risk of death or listing for cardiac transplant (HR: 0.06 [95% CI: 0.01–0.25]).
CONCLUSIONS Patients with HPF have more favorable outcomes when compared to patients with lower exercise capacity. This large registry data highlights the role of exercise testing in providing personalized care and surveillance post-Fontan. (JACC Adv. 2024;3:101254) © 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
A Deep Learning Pipeline for Assessing Ventricular Volumes from a Cardiac MRI Registry of Patients with Single Ventricle Physiology
Tina Yao, MRes* • Nicole St. Clair, BSc* • Gabriel F. Miller, MSc • Adam L. Dorfman, MD • Mark A. Fogel, MD •Sunil Ghelani, MD • Rajesh Krishnamurthy, MD • Christopher Z. Lam, MD • Michael Quail, MD •Joshua D. Robinson, MD • David Schidlow, MD, MMus • Timothy C. Slesnick, MD • Justin Weigand, MD • Jennifer A. Steeden, PhD • Rahul H. Rathod, MD, MBA • Vivek Muthurangu, MD(res)
Abstract: An end-to-end deep learning pipeline was developed to provide automatic segmentation and cardiac function metrics for a cardiac MRI registry of patients with single ventricle physiology; the pipeline requires no human input and is the first to segment images in this patient population.
Purpose: To develop an end-to-end deep learning (DL) pipeline for automated ventricular segmentation of cardiac MRI data from a multicenter registry of patients with Fontan circulation (Fontan Outcomes Registry Using CMR Examinations [FORCE])..
Materials and Methods: This retrospective study used 250 cardiac MRI examinations (November 2007–December 2022) from 13 institutions for training, validation, and testing. The pipeline contained three DL models: a classifier to identify short-axis cine stacks and two U-Net 3+ models for image cropping and segmentation. The automated segmentations were evaluated on the test set (n = 50) by using the Dice score. Volumetric and functional metrics derived from DL and ground truth manual segmentations were evaluated on the test set (n = 50) by using the Dice score. Volumetric and functional metrics derived from DL and ground truth manual segmentations were compared using Bland-Altman and intraclass correlation analysis. The pipeline was further qualitatively evaluated on 475 unseen examinations.ntations were compared using Bland-Altman and intraclass correlation analysis. The pipeline was further qualitatively evaluated on 475 unseen examinations.
Results: There were acceptable limits of agreement (LOA) and minimal biases between the ground truth and DL end-diastolic volume (EDV) (bias: −0.6 mL/m2, LOA: −20.6 to 19.5 mL/m2) and end-systolic volume (ESV) (bias: −1.1 mL/m2, LOA: −18.1 to 15.9 mL/m2), with high intraclass correlation coefficients (ICCs > 0.97) and Dice scores (EDV, 0.91 and ESV, 0.86). There was moderate agreement for ventricular mass (bias: −1.9 g/m2, LOA: −17.3 to 13.5 g/m2) and an ICC of 0.94. There was also acceptable agreement for stroke volume (bias: 0.6 mL/m2, LOA: −17.2 to 18.3 mL/m2) and ejection fraction (bias: 0.6%, LOA: −12.2% to 13.4%), with high ICCs (>0.81). The pipeline achieved satisfactory segmentation in 68% of the 475 unseen examinations, while 26% needed minor adjustments, 5% needed major adjustments, 5% needed major adjustments, and in 0.4%, the cropping model failed.5% needed major adjustments, and in 0.4%, the cropping model failed. and in 0.4%, the cropping model failed.
Conclusion: The DL pipeline can provide fast standardized segmentation for patients with single ventricle physiology across multiple centers. This pipeline can be applied to all cardiac MRI examinations in the FORCE registry.
Characterization and Z-score Calculation of Cardiac MRI parameters in patients after the Fontan operation. A Fontan Outcome Registry using CMR Examinations (FORCE) study
Tarek Alsaied • Runjia Li • Adam Christopher • Mark Fogel • Timothy C Slesnick • Rajesh Krishnamurthy • Vivek Muthurangu • Adam L Dorfman • Christopher Z Lam • Justin Weigand • Jong-Hyeon Jeong • Joshua D Robinson • Laura J Olivieri • Rahul H Rathod • FORCE Investigators
Background: Cardiac magnetic resonance (CMR) offers valuable hemodynamic insights post-Fontan, but is limited by the absence of normative single ventricle data. The Fontan Outcomes Registry using CMR Examinations (FORCE) is a large international Fontan-specific CMR registry. This study used FORCE registry data to evaluate expected CMR ventricular size/function and create Fontan-specific z-scores adjusting for ventricular morphology (VM) in healthier Fontan patients.
Methods: "Healthier" Fontan patients were defined as patients free of adverse outcomes, who are New York Heart Association Class I, have mild or less valve disease, and <30% aortopulmonary collateral burden. General linear modeling was performed on 70% of the dataset to create z-scores for volumes and function. Models were tested using the remainder (30%) of the data. The z-scores were compared between children and adults. The z-scores were also compared between "healthier" Fontan and patients with adverse outcomes (death, listing for transplantation or multiorgan disease).
Results: The "healthier" Fontan population included 885 patients (15.0 ± 7.6 years) from 18 institutions with 1,156 CMR examinations. Patients with left ventricle morphology had lower volume, mass and higher ejection fraction (EF) compared to right or mixed (two-ventricles) morphology (p<0.001 for all pairwise comparisons). Gender, BSA and VM were used in z-scores. Of the "healthier" Fontan patients, 647 were children <18 years and 238 were adults. Adults had lower ascending aorta flow (2.9 ± 0.7 vs 3.3 ± 0.8L/min/m2, p<0.001) and ascending aorta flow z-scores (-0.16 ± 1.23 vs 0.05 ± 0.95, 0.02) compared to children. Additionally, there were 1595 patients with adverse outcomes who were older (16.1 ± 9.3 vs 15.0 ± 7.6, p<0.001) and less likely to have LV morphology (35 vs 47%, p<0.001). Patients with adverse outcomes had higher z-scores for ventricular volume and mass and lower z-scores for EF and ascending aorta flow compared to the "healthier" Fontan cohort.
Conclusion: This is the first study to generate CMR z-scores post-Fontan. Importantly the z-scores were generated and tested in "healthier" Fontan patients and both pediatric and adult Fontan patients. These equations may improve CMR-based risk stratification after the Fontan operation.
Cardiac MRI Predictors of Arrhythmic Sudden Cardiac Events in Patients With Fontan Circulation
Natasha K Wolfe • Mary D Schiff • Laura J Olivieri • Adam B Christopher • Mark Fogel • Timothy C Slesnick • Rajesh Krishnamurthy • Vivek Muthurangu • Adam L Dorfman • Christopher Z Lam • Justin Weigand • Joshua D Robinson • Rahul H Rathod • Tarek Alsaied • FORCE Investigators
Background: Among patients with congenital heart disease, those with single ventricles have the highest risk of early mortality. Sudden cardiac death is an important cause of death in this population. Understanding the risk factors for sudden cardiac events (SCE) in Fontan patients could improve prediction and prevention.
Objectives: The goal of this study was to determine the prevalence of SCE and risk factors for SCE in the Fontan population.
Methods: The Fontan Outcomes Registry Using CMR Examinations (FORCE) is an international registry collecting clinical and imaging data on Fontan patients. SCE was defined as: 1) cardiac arrest from a shockable rhythm; 2) need for emergent cardioversion/defibrillation; or 3) documented sustained ventricular tachycardia. Univariate and multivariate Cox proportional hazards regression models estimated hazard ratios for predictors of SCE.
Results: Our sample included 3,132 patients (41% female). The median age at first cardiac magnetic resonance was 14.6 years. SCE was experienced by 3.5% (n = 109) over a median follow-up time of 4.00 years. Of the 109 patients with SCE, 39 (36%) died. On multivariable analysis, NYHA functional class >II (HR: 4.91; P < 0.0001), history of protein-losing enteropathy/plastic bronchitis (HR: 2.37; P = 0.0082), single-ventricle end-diastolic volume index >104 mL/m2 (HR: 3.15; P < 0.0001), and ejection fraction <50% (HR: 1.73; P = 0.0437) were associated with SCE. Kaplan-Meier analysis demonstrated that in patients with none of the above risk factors, the 4-year freedom from SCE was 99.5%.
Conclusions: SCE occurred in 3.5% of the study population, and one-third of patients who experienced SCE died. Mild ventricular dysfunction and dilatation by cardiac magnetic resonance, NYHA functional class, and history of protein-losing enteropathy/plastic bronchitis were associated with SCE.