Myocarditis in children 2024, new themes and continued questions.

PURPOSE OF REVIEW: While pediatric myocarditis incidence has increased since the coronavirus disease 2019 (COVID-19) pandemic, there remain questions regarding diagnosis, risk stratification, and optimal therapy. This review highlights recent publications and continued unanswered questions related to myocarditis in children. RECENT FINDINGS: Emergence from the COVID-19 era has allowed more accurate description of the incidence and prognosis of myocarditis adjacent to COVID-19 infection and vaccine administration as well that of multi-system inflammatory disease in children (MIS-C). As cardiac magnetic resonance technology has shown increased availability and evidence in pediatric myocarditis, it is important to understand conclusions from adult imaging studies and define the use of this imaging biomarker in children. Precision medicine has begun to allow real-time molecular evaluations to help diagnose and risk-stratify cardiovascular diseases, with emerging evidence of these modalities in myocarditis. SUMMARY: Recent information regarding COVID-19 associated myocarditis, cardiac magnetic resonance, and molecular biomarkers may help clinicians caring for children with myocarditis and identify needs for future investigations.

Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy.

BACKGROUND: Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials. METHODS AND RESULTS: Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (P<0.0001). Rate of increase in indexed left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (P=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups. CONCLUSIONS: Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.

Design and implementation of multicenter pediatric and congenital studies with cardiovascular magnetic resonance: Big data in smaller bodies.

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.

Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant.

BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Mitral Valve Abnormalities Associated with Single-Ventricle Palliation, Cardiac Death or Transplant in Fetuses with Postnatally Confirmed Coarctation of the Aorta.

Predicting if a fetus with borderline left heart structures and coarctation of the aorta (CoA) will require single ventricle palliation (SVP) is challenging, partly due to the limitations of fetal echocardiography in defining valvar abnormalities. Fetal echocardiographic findings predictive of SVP, particularly in relation to the mitral valve (MV), are not well defined. We performed a retrospective review of fetuses with postnatally confirmed CoA from 2010 to 2020. Fetuses with complex congenital heart disease or unequivocal hypoplastic left heart syndrome were excluded. Data were compared between those who underwent biventricular repair (BVR) versus SVP, cardiac death or orthotopic heart transplant (OHT) to determine differences in fetal echocardiograms. Of 67 fetuses with 131 total echocardiograms, 62 (93%) underwent BVR and 5 (7%) experienced SVP, cardiac death or OHT. Fetuses with confirmed CoA who experienced SVP, cardiac death, or OHT, had fetal MV z-scores that were 2.03 lower, on average, than those who underwent BVR (z-score = - 3.98 vs. - 1.94, 95% CI - 2.93, - 1.13). The incidences of MV anomalies and left to right flow across the foramen ovale were higher in the SVP, cardiac death and OHT group. SVP, cardiac death or OHT in fetuses with confirmed CoA were associated with severe fetal MV hypoplasia, MV anomalies and left to right flow across the foramen ovale. These findings may help guide prenatal counseling about the likelihood of SVP, cardiac death or OHT in fetuses with CoA and borderline left heart structures.

Regional 4D Cardiac Magnetic Resonance Strain Predicts Cardiomyopathy Progression in Duchenne Muscular Dystrophy.

Background: Cardiomyopathy (CMP) is the leading cause of death in Duchenne muscular dystrophy (DMD). Characterization of disease trajectory can be challenging, especially in the early stage of CMP where onset and clinical progression may vary. Traditional metrics from cardiovascular magnetic resonance (CMR) imaging such as LVEF (left ventricular ejection fraction) and LGE (late gadolinium enhancement) are often insufficient for assessing disease trajectory. We hypothesized that strain patterns from a novel 4D (3D+time) CMR regional strain analysis method can be used to predict the rate of DMD CMP progression. Methods: We compiled 115 short-axis cine CMR image stacks for n=40 pediatric DMD patients (13.6±4.2 years) imaged yearly for 3 consecutive visits and computed regional strain metrics using custom-built feature tracking software. We measured regional strain parameters by determining the relative change in the localized 4D endocardial surface mesh using end diastole as the initial reference frame. Results: We first separated patients into two cohorts based on their initial CMR: LVEF≥55% (n=28, normal cohort) and LVEF<55% (n=12, abnormal cohort). Using LVEF decrease measured two years following the initial scan, we further subclassified these cohorts into slow (ΔLVEF%≤5) or fast (ΔLVEF%>5) progression groups for both the normal cohort (n=12, slow; n=15, fast) and the abnormal cohort (n=8, slow; n=4, fast). There was no statistical difference between the slow and fast progression groups in standard biomarkers such as LVEF, age, or LGE status. However, basal circumferential strain (Ecc) late diastolic strain rate and basal surface area strain (Ea) late diastolic strain rate magnitude were significantly decreased in fast progressors in both normal and abnormal cohorts (p<0.01, p=0.04 and p<0.01, p=0.02, respectively). Peak Ea and Ecc magnitudes were also decreased in fast progressors, though these only reached statistical significance in the normal cohort (p<0.01, p=0.24 and p<0.01, p=0.18, respectively). Conclusion: Regional strain metrics from 4D CMR can be used to differentiate between slow or fast CMP progression in a longitudinal DMD cohort. These results demonstrate that 4D CMR strain is useful for early identification of CMP progression in patients with DMD. Clinical Perspective: Cardiomyopathy is the number one cause of death in Duchenne muscular dystrophy, but the onset and progression of the disease are variable and heterogeneous. In this study, we used a novel 4D cardiovascular magnetic resonance regional strain analysis method to evaluate 40 pediatric Duchenne patients over three consecutive annual visits. From our analysis, we found that peak systolic strain and late diastolic strain rate were early indicators of cardiomyopathy progression. This method offers promise for early detection and monitoring, potentially improving patient outcomes through timely intervention and management.

Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial.

Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. Objective: To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM. Design, Setting, and Participants: The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular [LV] wall thickness [LVWT] to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022. Interventions: Treatment with placebo or valsartan (80 mg/d for children weighing <35 kg, 160 mg/d for children weighing ≥35 kg, or 320 mg/d for adults aged ≥18 years). Main Outcomes and Measures: The primary outcome was a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial [LA] volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels). Results: This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female [44%] and 10 male [56%]) were randomized to valsartan and 16 (9 female [56%] and 7 male [44%]) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean change in composite z score compared with placebo: -0.01 [95% CI, -0.29 to 0.26]; P = .92). Overall, 2-year phenotypic progression was modest, with only a mild increase in LA volume detected (increased by 3.5 mL/m2 [95% CI, 1.4-6.0 mL/m2]; P = .002). Nine participants (26%) had increased LVWT, including 6 (18%) who developed clinically overt HCM. Baseline LA volume index (LAVI; 35 vs 28 mL/m2; P = .01) and average interventricular septum thickness (8.5 vs 7.0 mm; P = .009) were higher in participants who developed HCM. Conclusions and Relevance: In this exploratory cohort, valsartan was not proven to slow progression of subclinical HCM. Minimal changes in markers of cardiac remodeling were observed, although nearly one-fifth of patients developed clinically overt HCM. Transition to disease was associated with greater baseline interventricular septum thickness and LAVI. These findings highlight the importance of following sarcomere variant carriers longitudinally and the critical need to improve understanding of factors that drive disease penetrance and progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01912534.

Mitral valve abnormalities associated with single-ventricle palliation, cardiac death or transplant in fetuses with postnatally confirmed coarctation of the aorta.

Introduction: Predicting if a fetus with borderline left heart structures and coarctation of the aorta (CoA) will require single ventricle palliation (SVP) is challenging, partly due to the limitations of fetal echocardiography in defining valvar abnormalities. Fetal echocardiographic findings predictive of SVP, particularly in relation to the mitral valve (MV), are not well defined. Methods: We performed a retrospective review of fetuses with postnatally confirmed CoA from 2010 to 2020. Fetuses with complex congenital heart disease or unequivocal hypoplastic left heart syndrome were excluded. Data were compared between those who underwent biventricular repair (BVR) vs. SVP cardiac death or orthotopic heart transplant (OHT) to determine differences in fetal echocardiograms. Results: Of 67 fetuses with 131 total echocardiograms, 62 (93%) underwent BVR and 5 (7%) experienced SVP, cardiac death or OHT. Fetuses with confirmed CoA who experienced SVP cardiac death, or OHT, had fetal MV z-scores that were 2.06 lower, on average, than those who underwent BVR (z-score = -3.98 vs. -1.92, 95% CI: -2.96, -1.16). The incidences of MV anomalies and left to right flow across the foramen ovale were higher in the SVP cardiac death and OHT group. Conclusion: SVP, cardiac death or OHT in fetuses with confirmed CoA were associated with fetal MV hypoplasia, MV anomalies and left to right flow across the foramen ovale. These findings may help guide prenatal counseling about the likelihood of SVP, cardiac death or OHT in fetuses with CoA and borderline left heart structures.

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.

Cardiovascular Measures of All-Cause Mortality in Duchenne Muscular Dystrophy.

BACKGROUND: Cardiopulmonary failure is the leading cause of death in Duchenne muscular dystrophy (DMD). Research into DMD-specific cardiovascular therapies is ongoing, but there are no Food and Drug Administration-approved cardiac end points. To adequately power a therapeutic trial, appropriate end points must be chosen and the rate of change for these end points reported. The objective of this study was to evaluate rate of change for cardiac magnetic resonance and blood biomarkers and to determine which measures associate with all-cause mortality in DMD. METHODS: Seventy-eight DMD subjects underwent 211 cardiac magnetic resonance studies analyzed for left ventricular (LV) ejection fraction, indexed LV end diastolic and systolic volumes, circumferential strain, late gadolinium enhancement presence and severity (global severity score, and full width half maximum), native T1 mapping, T2 mapping, and extracellular volume. Blood samples were analyzed for BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), and troponin I. Cox proportional hazard regression modeling was performed with all-cause mortality as the outcome. RESULTS: Fifteen subjects (19%) died. LV ejection fraction, indexed end systolic volumes, global severity score, and full width half maximum worsened at 1 and 2 years while circumferential strain and indexed LV end diastolic volumes worsened at 2 years. LV ejection fraction, indexed LV end diastolic and systolic volumes, late gadolinium enhancement full width half maximum, and circumferential strain associated with all-cause mortality (P<0.05). NT-proBNP was the only blood biomarker that associated with all-cause mortality (P<0.05). CONCLUSIONS: LV ejection fraction, indexed LV volumes, circumferential strain, late gadolinium enhancement full width half maximum, and NT-proBNP are associated with all-cause mortality in DMD and may be the best end points for use in cardiovascular therapeutic trials. We also report change over time of cardiac magnetic resonance and blood biomarkers.

Myocardial Strain during Surveillance Screening Is Associated with Future Cardiac Dysfunction among Survivors of Childhood, Adolescent and Young Adult-Onset Cancer.

Cardiovascular disease is a leading contributor to mortality among childhood, adolescent and young adult (C-AYA) cancer survivors. While serial cardiovascular screening is recommended in this population, optimal screening strategies, including the use of echocardiography-based myocardial strain, are not fully defined. Our objective was to determine the relationship between longitudinal and circumferential strain (LS, CS) and fractional shortening (FS) among survivors. This single-center cohort study retrospectively measured LS and CS among C-AYAs treated with anthracycline/anthracenedione chemotherapy. The trajectory of LS and CS values over time were examined among two groups of survivors: those who experienced a reduction of >5 fractional shortening (FS) units from pre-treatment to the most recent echocardiogram, and those who did not. Using mixed modeling, LS and CS were used to estimate FS longitudinally. A receiver operator characteristic curve was generated to determine the ability of our model to correctly predict an FS ≤ 27%. A total of 189 survivors with a median age of 14 years at diagnosis were included. Among the two survivor groups, the trajectory of LS and CS differed approximately five years from cancer diagnosis. A statistically significant inverse relationship was demonstrated between FS and LS -0.129, p = 0.039, as well as FS and CS -0.413, p < 0.001. The area under the curve for an FS ≤ 27% was 91%. Among C-AYAs, myocardial strain measurements may improve the identification of individuals with cardiotoxicity, thereby allowing earlier intervention.

Multimodality Cardiac Imaging in COVID.

Infection with SARS-CoV-2, the virus that causes COVID, is associated with numerous potential secondary complications. Global efforts have been dedicated to understanding the myriad potential cardiovascular sequelae which may occur during acute infection, convalescence, or recovery. Because patients often present with nonspecific symptoms and laboratory findings, cardiac imaging has emerged as an important tool for the discrimination of pulmonary and cardiovascular complications of this disease. The clinician investigating a potential COVID-related complication must account not only for the relative utility of various cardiac imaging modalities but also for the risk of infectious exposure to staff and other patients. Extraordinary clinical and scholarly efforts have brought the international medical community closer to a consensus on the appropriate indications for diagnostic cardiac imaging during this protracted pandemic. In this review, we summarize the existing literature and reference major societal guidelines to provide an overview of the indications and utility of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging for the diagnosis of cardiovascular complications of COVID.

Association of cardiovascular magnetic resonance diastolic indices with arrhythmia in repaired Tetralogy of Fallot.

BACKGROUND: Patients with repaired Tetralogy of Fallot (rTOF) experience a high burden of long-term morbidity, particularly arrhythmias. Cardiovascular magnetic resonance (CMR) is routinely used to assess ventricular characteristics but the relationship between CMR diastolic function and arrhythmia has not been evaluated. We hypothesized in rTOF, left ventricular (LV) diastolic dysfunction on CMR would correlate with arrhythmias and mortality. METHODS: Adolescents and adults with rTOF who underwent CMR were compared to healthy controls (n = 58). Standard ventricular parameters were assessed and manual planimetry was performed to generate filling curves and indices of diastolic function. Chart review was performed to collect outcomes. Univariate and multivariable logistic regression was performed to identify outcome associations. RESULTS: One-hundred sixty-seven subjects with rTOF (mean age 32 years) and 58 healthy control subjects underwent CMR. Patients with rTOF had decreased LV volumes and increased right ventricular (RV) volumes, lower RV ejection fraction (RVEF), lower peak ejection rate (PER), peak filling rate (PFR) and PFR indexed to end-diastolic volume (PFR/EDV) compared to healthy controls. Eighty-three subjects with rTOF had arrhythmia (63 atrial, 47 ventricular) and 11 died. Left atrial (LA) volumes, time to peak filling rate (tPFR), and PFR/EDV were associated with arrhythmia on univariate analysis. PER/EDV was associated with ventricular (Odds ratio, OR 0.43 [0.24-0.80], p = 0.007) and total arrhythmia (OR 0.56 [0.37-0.92], p = 0.021) burden. A multivariable predictive model including diastolic covariates showed improved prediction for arrhythmia compared to clinical and conventional CMR measures (area under curve (AUC) 0.749 v. 0.685 for overall arrhythmia). PFR/EDV was decreased and tPFR was increased in rTOF subjects with mortality as compared to those without mortality. CONCLUSIONS: Subjects with rTOF have abnormal LV diastolic function compared to healthy controls. Indices of LV diastolic function were associated with arrhythmia and mortality. CMR diastolic indices may be helpful in risk stratification for arrhythmia.

Localized strain characterization of cardiomyopathy in Duchenne muscular dystrophy using novel 4D kinematic analysis of cine cardiovascular magnetic resonance.

BACKGROUND: Cardiomyopathy (CMP) is the most common cause of mortality in Duchenne muscular dystrophy (DMD), though the age of onset and clinical progression vary. We applied a novel 4D (3D + time) strain analysis method using cine cardiovascular magnetic resonance (CMR) imaging data to determine if localized strain metrics derived from 4D image analysis would be sensitive and specific for characterizing DMD CMP. METHODS: We analyzed short-axis cine CMR image stacks from 43 DMD patients (median age: 12.23 yrs [10.6-16.5]; [interquartile range]) and 25 male healthy controls (median age: 16.2 yrs [13.3-20.7]). A subset of 25 male DMD patients age-matched to the controls (median age: 15.7 yrs [14.0-17.8]) was used for comparative metrics. CMR images were compiled into 4D sequences for feature-tracking strain analysis using custom-built software. Unpaired t-test and receiver operator characteristic area under the curve (AUC) analysis were used to determine statistical significance. Spearman's rho was used to determine correlation. RESULTS: DMD patients had a range of CMP severity: 15 (35% of total) had left ventricular ejection fraction (LVEF) > 55% with no findings of myocardial late gadolinium enhancement (LGE), 15 (35%) had findings of LGE with LVEF > 55% and 13 (30%) had LGE with LVEF < 55%. The magnitude of the peak basal circumferential strain, basal radial strain, and basal surface area strain were all significantly decreased in DMD patients relative to healthy controls (p < 0.001) with AUC values of 0.80, 0.89, and 0.84 respectively for peak strain and 0.96, 0.91, and 0.98 respectively for systolic strain rate. Peak basal radial strain, basal radial systolic strain rate, and basal circumferential systolic strain rate magnitude values were also significantly decreased in mild CMP (No LGE, LVEF > 55%) compared to a healthy control group (p < 0.001 for all). Surface area strain significantly correlated with LVEF and extracellular volume (ECV) respectively in the basal (rho = - 0.45, 0.40), mid (rho = - 0.46, 0.46), and apical (rho = - 0.42, 0.47) regions. CONCLUSION: Strain analysis of 3D cine CMR images in DMD CMP patients generates localized kinematic parameters that strongly differentiate disease from control and correlate with LVEF and ECV.

Association of Bulboventricular Foramen Size and Need for Early Intervention in Infants with Tricuspid Atresia or Double-Inlet Left Ventricle with Normally Related Great Arteries.

BACKGROUND: The association of bulboventricular foramen (BVF) size and systemic outflow adequacy has been studied in patients with tricuspid atresia (TA) or double-inlet left ventricle (DILV) with transposed great arteries. The aim of this study was to determine the relationship between initial BVF size and risk for progressive pulmonary outflow obstruction requiring intervention to increase pulmonary blood flow in patients with TA or DILV with normally related great arteries. METHODS: Patients with TA or DILV with normally related great arteries were identified by retrospective chart review at a single center from 2005 to 2021. Patients were stratified by indexed BVF area (iBVFA) to determine the relationship of iBVFA size and the need for intervention before the Glenn operation to establish supplemental pulmonary blood flow with either a Blalock-Taussig-Thomas shunt (BTTS) or patent ductus arteriosus (PDA) stent. Patients were followed through the time of their Glenn operations. Logistic regression analysis was performed to determine optimal iBVFA cut points. RESULTS: Thirty-seven patients with TA or DILV with normally related great arteries were included. Sixteen had iBVFA < 1 cm2/m2, with all 16 (100%) requiring either a BTTS or PDA stent to increase pulmonary blood flow before the Glenn operation. Seventeen had iBVFAs of 1 to 2 cm2/m2, with 10 (59%) requiring either a BTTS or PDA stent. Nine of those 10 demonstrated flow acceleration across the BVF and/or pulmonary outflow tract. Four had iBVFA > 2 cm2/m2, with only one patient (25%) requiring a BTTS. Among our cohort, an iBVFA of <1.8 cm2/m2 provided sensitivity of 96% with good positive and negative predictive values (81% and 80%, respectively) for requiring intervention with a BTTS or PDA stent before the Glenn operation. CONCLUSIONS: An iBVFA of ≤1.8 cm2/m2 on initial postnatal echocardiography is associated with the development of subpulmonary obstruction requiring intervention with a BTTS or PDA stent before the Glenn operation, with the highest risk noted in those with iBVFA of ≤1 cm2/m2. Factors such as BVF flow acceleration or pulmonary outflow tract narrowing should also be considered in the decision to augment pulmonary blood flow.

Spirometry correlates with physical activity in patients with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness and respiratory decline. To date, studies have focused on respiratory decline and loss of ambulation as a metric of loss of skeletal muscle strength. However, new functional measures can assess skeletal muscle disease regardless of ambulatory status. The relationship between these tests and concurrent lung function is currently unexplored. OBJECTIVE: To assess the correlation between spirometry measurements and functional muscle assessments such as accelerometry and quantitative muscle testing (QMT). METHODS: Enrolled patients with DMD underwent accelerometry and QMT at study clinic visits. Any pulmonary function testing within 6 months of visit was obtained from the electronic medical record. The Spearman correlation coefficient was used to assess the relationship between spirometry and functional muscle testing. RESULTS: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1 ) demonstrated the strongest correlation with accelerometry. Both FVC and FEV1 showed a similar relationship to accelerometry when activity was divided into intensity categories, with low intensity and moderate-to-vigorous activity categories showing the strongest correlation. Maximal expiratory pressure (MEP) and FVC showed the most robust correlations with total QMT (p < 0.001 and p < 0.01, respectively). CONCLUSION: Lung function, specifically FVC percent predicted and FEV1 %p, shows a good correlation with upper and lower extremity skeletal muscle functional testing such as accelerometry and QMT.

Myocardial strain imaging in Duchenne muscular dystrophy.

Cardiomyopathy (CM) is the leading cause of death for individuals with Duchenne muscular dystrophy (DMD). While DMD CM progresses rapidly and fatally for some in teenage years, others can live relatively symptom-free into their thirties or forties. Because CM progression is variable, there is a critical need for biomarkers to detect early onset and rapid progression. Despite recent advances in imaging and analysis, there are still no reliable methods to detect the onset or progression rate of DMD CM. Cardiac strain imaging is a promising technique that has proven valuable in DMD CM assessment, though much more work has been done in adult CM patients. In this review, we address the role of strain imaging in DMD, the mechanical and functional parameters used for clinical assessment, and discuss the gaps where emerging imaging techniques could help better characterize CM progression in DMD. Prominent among these emerging techniques are strain assessment from 3D imaging and development of deep learning algorithms for automated strain assessment. Improved techniques in tracking the progression of CM may help to bridge a crucial gap in optimizing clinical treatment for this devastating disease and pave the way for future research and innovation through the definition of robust imaging biomarkers and clinical trial endpoints.

Novel Cardiac Imaging Risk Score for Mortality Prediction in Duchenne Muscular Dystrophy.

Cardiovascular disease is the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD), but there is significant cardiomyopathy phenotypic variability. Some patients demonstrate rapidly progressive disease and die at a young age while others survive into the fourth decade. Criteria to identify DMD subjects at greatest risk for early mortality could allow for increased monitoring and more intensive therapy. A risk score was created describing the onset and progression of left ventricular dysfunction and late gadolinium enhancement in subjects with DMD. DMD subjects prospectively enrolled in ongoing observational studies (which included cardiac magnetic resonance [CMR]) were used to validate the risk score. A total of 69 subjects had calculable scores. During the study period, 12 (17%) died from complications of DMD. The median risk score was 3 (IQR [2,5]; range [0,9]). The overall risk score applied at the most recent imaging age was associated with mortality at a median age of 17 years (IQR [16,20]) (HR 2.028, p < 0.001). There were no deaths in subjects with a score of less than two. Scores were stable over time. An imaging-based risk score allows risk stratification of subjects with DMD. This can be quickly calculated during a clinic visit to identify subjects at greatest risk of early death.

Prenatally diagnosed coronary artery abnormalities in hypoplastic left heart syndrome are associated with a higher probability of heart transplantation.

OBJECTIVE: Coronary artery abnormalities (CA) occur in patients with hypoplastic left heart syndrome (HLHS) and may be associated with higher mortality and heart transplantation (HT). We aimed to determine whether fetuses with HLHS and prenatal CA have a higher risk of death or HT. METHODS: We performed a retrospective review of fetal echocardiograms with HLHS from 2011 to 2018. We excluded fetuses with ventricular septal defects, elective termination, death in utero, planned postnatal non-intervention, or absent follow-up data. Presence or absence of CA was determined by review of serial fetal echocardiograms. Survival analysis was used to evaluate the relationship between prenatal CA and death or HT. RESULTS: Of 86 patients with fetal HLHS, 11 had prenatal diagnosis of CA. Of these, six required HT and five died (one after undergoing HT); only one remains alive without HT. Of those without prenatal CA (n = 75), 25 died and 7 underwent HT. Patients with prenatal diagnosis of HLHS and CA had a significantly increased likelihood of death or HT (p-value <0.05). CONCLUSION: Prenatal diagnosis of CA in our cohort of patients with HLHS was associated with increased risk of death or HT. These data have significance for prenatal counseling and postnatal management.