Subspecialty Health Care Utilization in Pediatric Patients With Muscular Dystrophy in the United States.

Background and Objectives: Standards of care exist to optimize outcomes in Duchenne and Becker muscular dystrophy (DBMD), caused by alterations in the DMD gene; however, there are limited data regarding health care access in these patients. This study aims to characterize outpatient subspecialty care utilization in pediatric patients with DBMD. Methods: This retrospective cohort study used administrative claims data from IBM MarketScan Medicaid and Commercial Claims and Encounters Research Databases (2013-2018). Male patients 1-18 years with an ICD-9/10 diagnosis code for hereditary progressive muscular dystrophy between January 1, 2013, and December 31, 2017, were included. Participants were stratified into 3 age cohorts: 1-6 years, 7-12 years, and 13-18 years. The primary outcome was rate of annual neurology visits. Secondary outcomes included annual follow-up rates in other subspecialties and proportion of days covered (PDC) by corticosteroids. Results: A total of 1,386 patients met inclusion-347 (25.0%) age 1-6 years, 502 (36.2%) age 7-12 years, and 537 (38.7%) age 13-18 years. Heart failure, respiratory failure, and technology dependence increased with age (p for all<0.05). The rate of neurology visits per person-year was 0.36 and did not differ by age. Corticosteroid use was low; 30% of person-years (1452/4829) had a PDC ≥20%. Medicaid insurance was independently associated with a lower likelihood of annual neurology follow-up (OR 0.23; 95% CI 0.18-0.28). Discussion: The rate of annual neurology follow-up and corticosteroid use in patients with DBMD is low. Medicaid insurance status was independently associated with a decreased likelihood of neurology follow-up, while age was not, suggesting that factors other than disease severity influence neurology care access. Identifying barriers to regular follow-up is critical in improving outcomes for patients with DBMD.

Hypertension: An Important But Reversible Cause of Systolic Dysfunction in a Cohort of Pediatric Patients.

Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. We aimed to describe the presentation and outcomes of pediatric CDHTN and identify clinical features associated with resolution of dysfunction. A single-center retrospective cohort study of patients ≤ 21 years with CDHTN from January 2005-September 2020 was performed. Patients with systolic dysfunction without another cause, blood pressure > 95th percentile, and physician judgment that dysfunction was secondary to hypertension were included. Demographics, clinical characteristics, echocardiographic findings, and outcomes were examined using Fisher's exact and Mann-Whitney U tests. Multiple correspondence analysis was used to explore the relationship of resolution of dysfunction to clinical features. Thirty-four patients were analyzed at a median age of 10.9 (IQR 0.3-16.9) years. Patients were divided into groups < 1 year (n = 12) and ≥ 1 year (n = 22). Causes of hypertension were varied by age, with renovascular disease most common in infants (42%) and medical renal disease most common in older patients (77%). Echocardiography demonstrated mild LV dilation (median LV end-diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.4). Most patients (81%) had resolution of dysfunction, particularly infants (92%). One patient died and one patient was listed for heart transplant. None required mechanical circulatory support (MCS). No clinical features were statistically associated with resolution of dysfunction. Hypertension is an important but reversible cause of systolic dysfunction in children. Patients are likely to recover with low mortality and low utilization of MCS or transplantation. Further studies are needed to confirm features associated with resolution of dysfunction.

A Comparison of Muscle Recruitment Across Three Straight-Legged, Hinge-Pattern Resistance Training Exercises.

Hinge exercises are critical to building a balanced resistance training program in concert with 'knee-dominant' (e.g., squat, lunge) exercises. Biomechanical differences between various straight-legged hinge (SLH) exercises may alter muscle activation. For example, a Romanian deadlift (RDL) is a closed-chain SLH, while a reverse hyperextension (RH) is open-chain. Likewise, the RDL offers resistance via gravity while the cable pull-through (CP) offers redirected-resistance through a pulley. A deeper understanding of the potential impact of these biomechanical differences between these exercises may improve their application to specific goals. Participants completed repetition-maximum (RM) testing on the RDL, RH, and CP. On a follow-up visit, surface electromyography of the longissimus, multifidus, gluteus maximus, semitendinosus, and biceps femoris, muscles that contribute to lumbar/hip extension, was recorded. After a warm-up, participants completed maximal voluntary isometric contractions (MVICs) in each muscle. They then completed five repetitions of the RDL, RH, and CP at 50% of estimated one RM. Testing order was randomized. A one-way, repeated-measures ANOVA test was used in each muscle to compare activation (%MVIC) across the three exercises. Shifting from a gravity-(RDL) to a redirected-resistance (CP) SLH significantly decreased activation in the longissimus (-11.0%), multifidus (-14.1%), biceps femoris (-13.1%), and semitendinosus (-6.8%). Alternately, changing from a closed-(RDL) to an open-chain (RH) SLH significantly increased activation in the gluteus maximus (+19.5%), biceps femoris (+27.9%), and semitendinosus (+18.2). Alterations in the execution of a SLH can change muscle activation in lumbar/hip extensors.

Temporal trends in primary payers in pediatric heart transplant and association with long-term survival.

BACKGROUND: Pediatric heart transplantation (HT) is resource intensive. In adults, there has been an increase in the proportion of HTs funded by public insurance, with post-HT outcomes inferior to those funded by private sources. Trends in the funding of pediatric HT and outcomes in children have not been described. METHODS: We queried the United Network for Organ Sharing (UNOS) database for children (<18 years) listed for and undergoing HT between 2004 and 2021. We identified the primary payer at listing, HT, 1 year, and 1-5 years following HT. Trends were analyzed using generalized logit models. Multivariable-extended Cox regression models were used to test the relationship between insurance type at the time of transplant and time to death or re-transplant. RESULTS: There were 6382 pediatric patients who underwent transplants and had either public or private insurance at the time of transplant. The percentage of patients with public insurance at the time of HT increased over time. Public insurance at the time of HT was associated with an increased risk of death or re-transplant beyond 2 months after HT (adjusted HR at 6 months = 1.43, 95% CI: 1.13-1.81, p = .003; adjusted HR at 9 months = 1.67, 95% CI: 1.17-2.37, p = .004). CONCLUSION: There has been a statistically significant trend toward increasing public insurance for children awaiting, at the time of, and after HT. Black patients and those with public insurance at HT have worse long-term outcomes. This study highlights ongoing disparities in pediatric HT and the need to focus efforts on achieving equitable outcomes.

Initial multicenter experience with ventricular assist devices in children and young adults with muscular dystrophy: An ACTION registry analysis.

PURPOSE: Cardiac disease results in significant morbidity and mortality in patients with muscular dystrophy (MD). Single centers have reported their ventricular assist device (VAD) experience in specific MDs and in limited numbers. This study sought to describe the outcomes associated with VAD therapy in an unselected population across multiple centers. METHODS: We examined outcomes of patients with MD and dilated cardiomyopathy implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers from 9/2012 to 9/2020. RESULTS: A total of 19 VADs were implanted in 18 patients across 12 sites. The majority of patients had dystrophinopathy (66%) and the median age at implant was 17.2 years (range 11.7-29.5). Eleven patients were non-ambulatory (61%) and 6 (33%) were on respiratory support pre-VAD. Five (28%) patients were implanted as a bridge to transplant, 4 of whom survived to transplant. Of 13 patients implanted as bridge to decision or destination therapy, 77% were alive at 1 year and 69% at 2 years. The overall frequencies of positive outcome (transplanted or alive on device) at 1 year and 2 years were 84% and 78%, respectively. Two patients suffered a stroke, 2 developed sepsis, 1 required tracheostomy, and 1 experienced severe right heart failure requiring right-sided VAD. CONCLUSIONS: This study demonstrates the potential utility of VAD therapies in patients with muscular dystrophy. Further research is needed to further improve outcomes and better determine which patients may benefit most from VAD therapy in terms of survival and quality of life.

Health Care Use of Cardiac Specialty Care in Children With Muscular Dystrophy in the United States.

Background Duchenne and Becker muscular dystrophy are progressive disorders associated with cardiac mortality. Guidelines recommend routine surveillance; we assess cardiac resource use and identify gaps in care delivery. Methods and Results Male patients, aged 1 to 18 years, with Duchenne and Becker muscular dystrophy between January 2013 and December 2017 were identified in the IBM MarketScan Research Database. The cohort was divided into <10 and 10 to 18 years of age. The primary outcome was rate of annual health care resource per person year. Resource use was assessed for place of service, cardiac testing, and medications. Adjusted incidence rate ratios (IRRs) were estimated using a Poisson regression model. Medication use was measured by proportion of days covered. There were 1386 patients with a median follow-up time of 3.0 years (interquartile range, 1.9-4.7 years). Patients in the 10 to 18 years group had only 0.40 (95% CI, 0.35-0.45) cardiology visits per person year and 0.66 (95% CI, 0.62-0.70) echocardiography/magnetic resonance imaging per person year. Older patients had higher rates of inpatient admissions (IRR, 1.46; 95% CI, 1.03-2.09), outpatient cardiology visits (IRR, 2.0; 95% CI, 1.66-2.40), cardiac imaging (IRR, 1.59; 95% CI, 1.40-1.80), and Holter monitoring (IRR, 3.33; 95% CI, 2.35-4.73). A proportion of days covered >80% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was observed in 13.6% (419/3083) of total person years among patients in the 10 to 18 years group. Conclusions Children 10 to 18 years of age have higher rates of cardiac resource use compared with those <10 years of age. However, rates in both age groups fall short of guidelines. Opportunities exist to identify barriers to resource use and optimize cardiac care for patients with Duchenne and Becker muscular dystrophy.

Diversity of Dystrophin Gene Mutations and Disease Progression in a Contemporary Cohort of Duchenne Muscular Dystrophy.

Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1-6). Subjects with mutations starting at exon positions 40-54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18-∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12-15) in subjects with mutations that started between exons 55-79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.

Current Practices in Treating Cardiomyopathy and Heart Failure in Duchenne Muscular Dystrophy (DMD): Understanding Care Practices in Order to Optimize DMD Heart Failure Through ACTION.

Cardiac disease has emerged as a leading cause of mortality in Duchenne muscular dystrophy in the current era. This survey sought to identify the diagnostic and therapeutic approach to DMD among pediatric cardiologists in Advanced Cardiac Therapies Improving Outcomes Network. Pediatric cardiology providers within ACTION (a multi-center pediatric heart failure learning network) were surveyed regarding their approaches to cardiac care in DMD. Thirty-one providers from 23 centers responded. Cardiac MRI and Holter monitoring are routinely obtained, but the frequency of use and indications for ordering these tests varied widely. Angiotensin converting enzyme inhibitor and aldosterone antagonist are generally initiated prior to onset of systolic dysfunction, while the indications for initiating beta-blocker therapy vary more widely. Seventeen (55%) providers report their center has placed an implantable cardioverter defibrillator in at least 1 DMD patient, while 11 providers (35%) would not place an ICD for primary prevention in a DMD patient. Twenty-three providers (74%) would consider placement of a ventricular assist device (VAD) as destination therapy (n = 23, 74%) and three providers (10%) would consider a VAD only as bridge to transplant. Five providers (16%) would not consider VAD at their institution. Cardiac diagnostic and therapeutic approaches vary among ACTION centers, with notable variation present regarding the use of advanced therapies (ICD and VAD). The network is currently working to harmonize medical practices and optimize clinical care in an era of rapidly evolving outcomes and cardiac/skeletal muscle therapies.

Impact of Age on Emergency Resource Utilization and Outcomes in Pediatric and Young Adult Patients Supported with a Ventricular Assist Device.

There are minimal data describing outcomes in ambulatory pediatric and young adult ventricular assist device (VAD)-supported patient populations. We performed a retrospective analysis of encounter-level data from 2006 to 2017 Nationwide Emergency Department Sample (NEDS) to compare emergency department (ED) resource utilization and outcomes for pediatric (≤18 years, n = 494) to young adult (19-29 years, n = 2,074) VAD-supported patient encounters. Pediatric encounters were more likely to have a history of congenital heart disease (11.3% vs. 4.8%). However, Pediatric encounters had lower admission/transfer rates (37.8% vs. 57.8%) and median charges ($3,334 (IQR $1,473-$19,818) vs. $13,673 ($3,331-$45,884)) (all p < 0.05). Multivariable logistic regression modeling revealed that age itself was not a predictor of admission, instead high acuity primary diagnoses and medical complexity were: (adjusted odds ratio; 95% confidence intervals): cardiac (3.0; 1.6-5.4), infection (3.4; 1.7-6.5), bleeding (3.9; 1.7-8.8), device complication (7.2; 2.7-18.9), and ≥1 chronic comorbidity (4.1; 2.5-6.7). In this largest study to date describing ED resource use and outcomes for pediatric and young adult VAD-supported patients, we found that, rather than age, high acuity presentations and comorbidities were primary drivers of clinical outcomes. Thus, reducing morbidity in this population should target comorbidities and early recognition of VAD-related complications.

Mental health disorders and emergency resource use and outcomes in ventricular assist device supported patients.

There are limited data describing the prevalence of mental health disorders (MHDOs) in patients with ventricular assist devices (VADs), or associations between MHDOs and resource use or outcomes. We used the Nationwide Emergency Department Sample administrative database to analyze 44,041 ED encounters for VAD-supported adults from 2010 to 2017, to assess the relationship between MHDOs and outcomes in this population. MHDO diagnoses were present for 23% of encounters, and were associated with higher charges and rates of admission, but lower mortality.

Severe multisystem organ dysfunction in an adolescent with simultaneous presentation of Addison's and Graves' disease.

OBJECTIVES: To report an unusual case of simultaneous presentation of Addison's and Graves' disease in an adolescent female previously diagnosed with type 1 diabetes (T1D) and Hashimoto's. CASE PRESENTATION: A 15-year-old female with T1D and hypothyroidism presented to the emergency department with altered mental state, fever, and left arm weakness for one day. Clinical work-up revealed coexistent new-onset adrenal insufficiency and hyperthyroidism. Her clinical course was complicated by severe, life-threating multisystem organ dysfunction including neurologic deficits, acute kidney injury, and fluid overload. Thyroidectomy was ultimately performed in the setting of persistent signs of adrenal crises and resulted in rapid clinical improvement. CONCLUSIONS: Endocrinopathy should be included in the differential diagnosis of altered mental status. This case additionally illustrates the challenges of managing adrenal insufficiency in the setting of hyperthyroidism and supports the use of thyroidectomy in this situation.

Implantable Cardioverter Defibrillator Use in Males with Duchenne Muscular Dystrophy and Severe Left Ventricular Dysfunction.

Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF) < 35% and/ or shortening fraction (SF) < 16% on final echocardiogram. SLVD was present in 57/436 (13.1%) patients, of which 12 (21.1%) died during the study period. Of these 12, (mean EF 20.9 ± 6.2% and SF 13.7 ± 7.2%), 8 received GDMT, 5 received steroids, and none received an ICD. ICDs were placed in 9/57 (15.8%) patients with SLVD (mean EF 31.2 ± 8.5% and SF 10.3 ± 4.9%) at a mean age of 20.4 ± 6.3 years; 8/9 received GDMT, 7 received steroids, and all were alive at study end; mean ICD duration was 36.1 ± 26.2 months. Nine ICDs were implanted at six different institutions, associated with two appropriate shocks for ventricular tachycardia in two patients, no inappropriate shocks, and one lead fracture. ICD use may be associated with improved survival and minimal complications in DMD cardiomyopathy with SLVD. However, inconsistent GDMT utilization may be a significant confounder. Future studies should define optimal indications for ICD implantation in patients with DMD cardiomyopathy.

Risk Factors for Cardiac and Non-cardiac Causes of Death in Males with Duchenne Muscular Dystrophy.

As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9-24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger [14.9 (IQR: 11.0-19.1) years] than those dying of cardiac [18 (IQR 15.5-24) years, p = 0.03] and non-cardiac [19 (IQR: 16.5-23) years, p = 0.002] causes. GC use was lower for those dying of cardiac causes compared to those living [2/8 (25%) vs. 304/378 (80.4%), p = 0.001]. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8, p = 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3, p = 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.

Use of advanced heart failure therapies in Duchenne muscular dystrophy.

BACKGROUND: As survival and neuromuscular function in Duchenne Muscular Dystrophy (DMD) improve with glucocorticoid therapy and respiratory advances, the proportion of cardiac deaths is increasing. Little is known about the use and outcomes of advanced heart failure (HF) therapies in this population. METHODS: A retrospective cohort study of 436 males with DMD was performed, from January 1, 2005-January 1, 2018, with the primary outcome being use of advanced HF therapies including: implantable cardioverter defibrillator (ICD), left ventricular assist device (LVAD), and heart transplantation (HTX). RESULTS: Nine subjects had an ICD placed, 2 of whom (22.2%) had appropriate shocks for ventricular tachycardia; 1 and 968 days after implant, and all of whom were alive at last follow-up; median 18 (IQR: 12.5-25.5) months from implant. Four subjects had a LVAD implanted with post-LVAD survival of 75% at 1 year; 2 remaining on support and 1 undergoing HTX. One subject was bridged to HTX with ICD and LVAD and was alive at last follow-up, 53 months after HTX. CONCLUSION: Advanced HF therapies may be used effectively in select subjects with DMD. Further studies are needed to better understand risk stratification for ICD use and optimal candidacy for LVAD implantation and HTX, with hopes of improving cardiac outcomes.

Left Main Coronary Artery Atresia in an Infant With Inclusion-Cell Disease.

A 2-month-old male with dysmorphic facies, neonatal thrombocytopenia, left congenital cataract, and long bone abnormalities became hypotensive with ST depression on induction of anesthesia for congenital cataract repair. Echocardiogram demonstrated decreased left ventricular function (ejection fraction 46%), mild mitral valve regurgitation (MR), and regional wall motion abnormalities. The left coronary artery could not be visualized. Subsequent cardiac catheterization confirmed atresia of the left main coronary artery. The patient underwent cardiac surgery with coronary artery bypass grafting of the left internal mammary artery to the left anterior descending coronary artery. His postoperative course was uncomplicated, his ventricular function normalized, and he was discharged home. Over the next few months, he developed progressive, severe MR refractory to medical management. Repeat cardiac catheterization revealed stenosis of the right proximal coronary artery, raising concern for progressive coronary involvement. In addition to dysmorphic features and failure to thrive, there were profound developmental delays and a finding of vacuolated lymphocytes on blood smear, which led to a diagnosis of mucolipidosis II (Inclusion [I]-cell disease). The patient was referred for mitral valve replacement, which was successful; however, ongoing respiratory issues attributed to the progression of I-cell disease led to a prolonged hospitalization with placement of a tracheostomy. Reports of coronary anomalies in patients with I-cell disease are rare. An association between mucopolysaccharidosis syndromes and coronary artery abnormalities has been established and is supported by this case report, highlighting the importance of considering the potential for coronary artery involvement with I-cell disease and other similar storage diseases.

Emergency department utilization in pediatric heart transplant recipients.

We used the NEDS database (2010) to evaluate ED utilization in PED HT recipients compared to other patient populations with focus on characteristics of ED visits, risk factors for admission, and charges. We analyzed 433 ED visits by PED HT recipients (median age 8 [range: 0-18] years). The most common primary diagnosis category was infectious (n=163, 37.6%), with pneumonia being the most common infectious etiology. When compared to all PED visits, HT visits were more likely to result in hospital admission (32.6% versus 3.9%, P<.001), had greater hospital LOS (median of 3 days [IQR 2-4] versus 2 days [IQR 1-4], P=.001), and accumulated greater total hospital charges (median $26 317 [IQR $11 438-$46 407] versus $12 332 [IQR $7092-$22 583], P<.001). When compared to visits by other SOT recipients, results varied with similar rates of hospital admission for HT, LUNGT, and KT visits and similar LOS for HT and KT visits but differing total hospital charges. Although PED HT recipients account for a small percentage of overall ED visits, they are more likely to be hospitalized and require greater resource utilization compared to the general PED population, but not when compared to other SOT recipients.

Successful surgical palliation of a triple-outlet right ventricle: a rare congenital cardiac malformation.

Most commonly, hearts have either a single arterial trunk or two arterial trunks; however, rare reports exist of a "tritruncal" heart, a heart with three outflow tracts. Here, we present one of the first reports of successful surgical palliation of a triple-outlet right ventricle.

Pediatric versus adult cardiomyopathy and heart failure-related hospitalizations: a value-based analysis.

BACKGROUND: Value-based health care is a proposed driver for reimbursement under the Affordable Care Act, with value broadly defined as outcomes divided by cost. Data on value-based health care in pediatric heart failure are scarce. METHODS AND RESULTS: A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database and Nationwide Inpatient Sample was performed for pediatric and adult cardiomyopathy and heart failure-related hospitalizations. The study included 5,689 pediatric and 473,416 adult hospitalizations. Pediatric cardiomyopathy and heart failure hospitalizations were significantly longer than adult hospitalizations (mean ± SE 16.2 ± 0.7 days vs 6.8 ± 0.1 days; P < .001). Overall mortality was greater for pediatric hospitalizations (7.7% vs 5.6%; P < .001), although it decreased over time for both pediatric and adult hospitalizations. Charges were greater for pediatric hospitalizations, both overall ($116,483 ± $5,735 vs $40,662 ± $1,419; P < .001) and for all years evaluated. CONCLUSIONS: In a value-based model, pediatric cardiomyopathy and heart failure-related hospitalizations are associated with worse outcomes and greater charges than adult hospitalizations. More research is needed to understand the cost effectiveness of pediatric heart failure treatment and to reduce the burden on the health care system.