Comprehensive cardiac magnetic resonance T1, T2, and extracellular volume mapping to define Duchenne cardiomyopathy.

BACKGROUND: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Cardiac magnetic resonance (CMR) parametric mapping sequences offer insights into disease pathophysiology. We propose a novel approach by leveraging T2 mapping in conjunction with T1 and extracellular volume (ECV) mapping to perform a virtual myocardial biopsy. While previous work has attempted to describe myocardial changes in DMD, our inclusion of T2 mapping enables comprehensive categorization of myocardial tissue characteristics of fibrosis, edema, and fat to better understand the pathological composition of the myocardium with disease progression. METHODS: DMD patients (n = 49; median: 12 years-old) underwent CMR, including T1, T2, and ECV. Categories were defined as normal, isolated high T1 (normal ECV, high T1, normal T2), fibrosis (high ECV, normal or high T1, normal T2), edema (normal or high ECV, normal or high T1, high T2), fat (normal ECV, low T1, high T2) or fibrofatty (high ECV, low T1, high T2). RESULTS: Median left ventricular ejection fraction (LVEF) was 59% with 27% having LVEF < 55%. Those with normal LVEF and no late gadolinium enhancement (37%) were younger in age (10.5 ± 2.6 vs. 15.0 ± 4.3 years-old, p < 0.001). Native T1 was elevated in at least one slice in 82% of patients. Those with high T2 at any slice (27%) were older (p = 0.005) and had lower LVEF (p = 0.005) compared with subjects with normal T2 (73%). The most common myocardial characterization was fibrosis (43%) followed by isolated high T1 (24%). Of the 13 with high T2, ten were categorized as edema, two as fibrofatty, and one as fat. CONCLUSION: CMR parametric mapping sequences offer insights into Duchenne cardiomyopathy pathophysiology, which should drive development of therapeutic interventions aimed at these targets. Myocardial fibrosis is common in DMD. Patients with elevated T2 were older and had lower LVEF. Though fat infiltration was present, the majority of subjects with elevated T2 met criteria for myocardial edema.

Machine Learning to Predict Interstage Mortality Following Single Ventricle Palliation: A NPC-QIC Database Analysis.

There is high risk of mortality between stage I and stage II palliation of single ventricle heart disease. This study aimed to leverage advanced machine learning algorithms to optimize risk-prediction models and identify features most predictive of interstage mortality. This study utilized retrospective data from the National Pediatric Cardiology Quality Improvement Collaborative and included all patients who underwent stage I palliation and survived to hospital discharge (2008-2019). Multiple machine learning models were evaluated, including logistic regression, random forest, gradient boosting trees, extreme gradient boost trees, and light gradient boosting machines. A total of 3267 patients were included with 208 (6.4%) interstage deaths. Machine learning models were trained on 180 clinical features. Digoxin use at discharge was the most influential factor resulting in a lower risk of interstage mortality (p < 0.0001). Stage I surgery with Blalock-Taussig-Thomas shunt portended higher risk than Sano conduit (7.8% vs 4.4%, p = 0.0002). Non-modifiable risk factors identified with increased risk of interstage mortality included female sex, lower gestational age, and lower birth weight. Post-operative risk factors included the requirement of unplanned catheterization and more severe atrioventricular valve insufficiency at discharge. Light gradient boosting machines demonstrated the best performance with an area under the receiver operative characteristic curve of 0.642. Advanced machine learning algorithms highlight a number of modifiable and non-modifiable risk factors for interstage mortality following stage I palliation. However, model performance remains modest, suggesting the presence of unmeasured confounders that contribute to interstage risk.

Sedated Echocardiograms Better Characterize Branch Pulmonary Arteries Following Bidirectional Glenn Palliation with Minimal Risk of Adverse Events.

Patients post-bidirectional Glenn (BDG) operation are at risk of left and right pulmonary artery (LPA and RPA) hypoplasia. Transthoracic echocardiograms (TTE) in active children can miss essential elements of anatomy. Procedural sedation improves image quality but increases risk of adverse events. We hypothesized that echocardiograms performed with sedation in patients post-BDG would improve visualization of branch pulmonary arteries with minimal adverse events. Patients post-BDG between 2007-2016 were identified. Exclusion criteria were > 12 months of age, absence of complete TTE before discharge, death before discharge, conversion to shunt physiology, and prolonged post-operative course > 7 weeks. Of 254 post-BDG patients, 153 met inclusion/exclusion criteria. TTE reports were reviewed for visualization of LPA/RPA and hypoplasia of LPA/RPA. Blinded assessment of image quality was performed (scale of 1[poor] to 5[excellent]). Pertinent clinical data were recorded. Pearson's chi-squared and Wilcoxon Rank Sum tests used for statistical analysis. The median age at surgery and hospital stay were 4.8 months and 10 days. Twenty-three patients underwent sedated TTE (15%). Sedated TTE significantly improved visualization of the RPA (100% vs 82%, p = 0.029) and LPA, though this did not reach statistical significance (100% vs 91%, p = 0.129). Sedated TTEs has significantly better image quality (median of 4 vs 3, p < 0.001). There were no serious adverse events due to sedation. Sedated TTE early post-BDG is safe, improves visualization of the RPA and LPA, and improves overall image quality. Routine sedated TTE in these patients should be considered. Implications for long-term outcome need to be further analyzed.

Recovery of Pulmonary Function after Allogeneic Hematopoietic Cell Transplantation in Children is Associated with Improved Survival.

Abnormal pulmonary function is prevalent in survivors of allogeneic hematopoietic cell transplantation (HCT). Post-transplantation recovery of pulmonary function, and its effect on survival, in children are not known. This retrospective cohort study of 308 children followed for 10 years after HCT at a single institution included 2 groups of patients. Group 1 comprised 188 patients with 3 or more pulmonary function test (PFT) results, of which at least 1 was abnormal, and group 2 comprised 120 patients with 3 or more PFTs, all of which were normal. Pulmonary function normalized post-transplantation in 51 patients (27%) in group 1. Obstructive lung disease, restrictive lung disease, mixed lung disease, and normal pattern were seen in 43%, 25%, 5%, and 27% of patients, respectively, at a median of 5 years (range, 0.5 to 11.9 years) post-transplantation. Lung volumes recovered better than spirometric indices. Pulmonary complications were seen in 80 patients (43%) in group 1. Patients who recovered pulmonary function had better overall survival (P = .006), which did not differ significantly from that in patients in group 2 with normal lung function post-transplantation (P = .80). After adjusting for duration of follow-up, pulmonary complications (P = .01), and lower pretransplantation forced vital capacity z-scores (P = .01) were associated with poor recovery. T cell depletion (P < .001), lower pretransplantation forced expired volume in 1 second z-scores (P = .006), and chronic graft-versus-host disease (P < .001) increased the risk for pulmonary complications. Nonrecovery of lung function with pulmonary complications (P = .03), acute graft-versus-host disease (P = .004), and mechanical ventilation (P < .001) were risk factors for nonrelapse mortality. Normalization of pulmonary function is possible in long-term survivors of allogeneic HCT. Strategies to decrease the risk of pulmonary complications may improve outcomes.

Pre-hematopoietic stem cell transplant lung function and pulmonary complications in children.

RATIONALE: Pulmonary complications are a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. OBJECTIVES: The relationship between pretransplant pulmonary function tests (PFTs) and development of post-transplant pulmonary complications in children was studied. METHODS: This is a retrospective single institution cohort study of 410 patients who underwent pretransplant PFT and were monitored to 10 years posttransplant. MEASUREMENTS AND MAIN RESULTS: Pulmonary complications were observed in 174 (42%) patients. Children with pulmonary complications had significantly lower forced expiratory flow at 25-75% of vital capacity (P = 0.02) derived using conventional predicted equations for age, and the Global Lung Initiative-2012 predicted equations (P = 0.01). T-cell depletion (P = 0.001), acute grade 3-4 graft-versus-host disease (P = 0.008), and chronic graft-versus-host disease (P = 0.01) increased risk for pulmonary complications. Patients who had pulmonary complications had a 2.8-fold increased risk of mortality (P < 0.0001). The cumulative incidence of death due to pulmonary complications was significantly higher in children who had low lung volumes, FRC less than 50% (P = 0.005), TLC less than 50% (P = 0.0002), residual volume less than 50% (P = 0.007), and T-cell depletion (P = 0.01). Lower FEV1 (P = 0.0005), FVC (P = 0.0005), TLC (P < 0.0001), residual volume less than 50% (P = 0.01), and restrictive lung disease (P = 0.01) predicted worse overall survival. CONCLUSIONS: Abnormal pretransplant PFT significantly increased risk after transplant. These patients may benefit from modified transplant strategies to reduce morbidity and mortality.