Early-Onset Late Gadolinium Enhancement is a Prognostic Factor for Duchenne Cardiomyopathy.

Dilated cardiomyopathy (DCM) is an inevitable complication of Duchenne muscular dystrophy (DMD). Late gadolinium enhancement (LGE) demonstrated by cardiac MRI occurs in DMD-related DCM, indicating myocyte death and remodeling. We conducted a retrospective chart review identifying DMD patients in our center between January 2009 and July 2013. Subjects were cohorted by presence of LGE before age 14. We excluded patients in whom we could not determine LGE status prior to age 14. We reviewed comprehensive clinical data. Of the 41 subjects with complete data, 15 demonstrated LGE before age 14 ("early LGE") and 26 had no LGE by age 14 ("controls"). Those with early LGE exhibited a more rapid decline in LV fractional shortening (p = 0.028). Patients with early LGE were younger at age of initiation of ACE inhibition (p = 0.025), mineralocorticoid receptor antagonism (p = 0.0024), and beta-blockade (p = 0.0017), suggesting aggressive clinical management in response to abnormal MRI findings. There were no significant differences in LV dilation between the two groups (p = 0.1547). Early LGE was not associated with obesity (p = 0.32), age at loss of ambulation (p = 0.31), or heart rate (p-value > 0.8). Early onset of myocardial fibrosis as indicated by LGE on cardiac MRI is associated with earlier progression of cardiomyopathic changes despite earlier medication therapy. Identifying this risk factor, observed in 34% of our cohort during preadolescence, may guide medical therapy and early counseling about cardiomyopathy progression. We advocate for obtaining at least one MRI in patients with DMD prior to age 14 to risk stratify patients.

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy.

Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53-75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Cardiac Function in Children and Young Adults Treated with MEK Inhibitors: A Retrospective Cohort Study.

MEK inhibitors (MEKi) have shown efficacy in pediatric low-grade glioma as well as plexiform neurofibroma. MEKi have been associated with acute cardiac dysfunction in adults. Cardiac consequences in children are unknown. We performed a single center retrospective cohort study evaluating cardiac function by echocardiography (echo) in children and young adults < 21 years receiving MEKi between October 2013 and May 2018. Blinded assessment of left ventricular function by fractional shortening (FS) and ejection fraction (EF) was performed on all available echocardiograms performed before, during, and following therapy, as well as after re-initiation of therapy. Twenty-six patients underwent MEKi therapy with echo follow-up during the study period. Twenty-four of these had complete echo data. Median follow-up was 12 months. Borderline EF (EF 53-57.9%) occurred in 12 (50%) patients; and 3 (12.5%) progressed to abnormal EF (EF < 53%). Cardiac dysfunction, when it occurred, was mild (lowest documented EF was 45%, and lowest FS was 24.4%). EF abnormalities typically fluctuated during therapy, resolved off therapy, and recurred with MEKi re-initiation. No clinical or demographic differences were detected between those who maintained normal cardiac function and those who developed borderline or overt cardiac dysfunction. Symptomatic heart failure did not occur. In this cohort of children and young adults, MEKi use was associated with a high (50%) incidence of borderline or mildly decreased left ventricular function. There was no evidence of permanent cardiac dysfunction. Further evaluation in larger prospective trials is needed.

The clinical impact of donor-specific antibodies on antibody-mediated rejection and long-term prognosis after heart transplantation.

PURPOSE OF REVIEW: Outcomes after cardiac transplantation have improved over past decades, but long-term graft survival remains limited in part because of uncertainty regarding clinical implications of donor-specific antibodies (DSAs). The purpose of this review is to consolidate recent advances in knowledge on the topic of DSA and their potential to impact long-term prognosis after heart transplantation. RECENT FINDINGS: The presence of persistent DSA increases the risk of poor outcome after heart transplantation, including development of antibody-mediated rejection (AMR), graft failure, cardiac allograft vasculopathy, and mortality. Importantly, different DSA vary in clinical significance. DSA capable of activating the complement cascade portend a higher risk of developing AMR. human leukocyte antigen class I and class II antigens are expressed differently within the heart, and so, clinical manifestations of class I and class II DSA vary accordingly. Further, compared with class I, class II DSA carry an increased risk of graft loss and mortality. When comparing preexisting DSA with formation of de-novo DSA, de-novo DSA are associated with worse outcome. SUMMARY: DSAs are generally associated worse long-term prognosis after heart transplantation but vary in their clinical significance. Recognition of specific risk profiles is essential for guiding posttransplant antibody management.

Outcomes of Berlin Heart EXCOR® pediatric ventricular assist device support in patients with restrictive and hypertrophic cardiomyopathy.

The outcomes of pediatric ventricular assist device support in patients with diastolic heart failure have not been well described. This study reviews the North American experience with Berlin Heart EXCOR® ventricular assist device implants in children with such physiology. The Berlin Heart clinical database was reviewed. Patients with primary diastolic dysfunction are included in this study. Twenty pediatric patients with restrictive cardiomyopathy (n = 13), hypertrophic cardiomyopathy (n = 3), or congenital heart disease with restrictive physiology (n = 4) who were supported with EXCOR® were identified. Of these, nine (45%) were successfully bridged to transplant, one (5%) weaned from support, and 10 (50%) died after support was withdrawn. Of patients under age 3 years (n = 13), 38.5% survived, whereas those aged 3 or older (n = 7) had 71.4% survival (P = .35). Biventricular assist device (BiVAD) patients experienced a 27.3% survival, vs 77.8% for patients with left ventricular assist device only (P = .07). Primary causes of death included stroke, infection, acidosis, multisystem organ failure, and bleeding. Pediatric patients with diastolic heart failure comprise a high-risk population for mechanical circulatory support. However, half of patients with this physiology have been successfully supported to explant with EXCOR® . The trends toward higher mortality for younger patients and those receiving BiVAD support warrant consideration.

Exercise capacity following pediatric heart transplantation: A systematic review.

Pediatric HTs account for 13% of all HTs with >60% of recipients surviving at least 10 years post-HT. The purpose of this systematic review is to synthesize the literature on exercise capacity of pediatric HT recipients to improve understanding of the mechanisms that may explain the decreased exercise capacity. Six databases were searched for studies that compared the exercise capacity of HT recipients ≤21 years old with a control group or normative data. Sixteen studies were included. Pediatric HT recipients, as compared to controls or normative data, exhibit significantly higher resting HR, and at peak exercise exhibit significantly decreased HR, VO2 , power, work, minute ventilation, and exercise duration. Peak VO2 appears to improve within the first 2.5 years post-HT; peak work remains constant; and there is inconclusive evidence that peak HR, HR recovery, and HR reserve improve with time since HT. These results are discussed in the context of the mechanisms that may explain the impaired exercise capacity of pediatric HT recipients, including chronotropic incompetence, graft dysfunction, side effects of immunosuppression therapy, and deconditioning. In addition, the limited literature on rehabilitation after pediatric HT is summarized.

Left Ventricular Tonic Contraction as a Novel Biomarker of Cardiomyopathy in Duchenne Muscular Dystrophy.

Dilated cardiomyopathy (DCM) inevitably afflicts patients with Duchenne muscular dystrophy (DMD) as a consequence of cell death induced by unguarded calcium influx into cardiomyocytes. This mechanism may also inhibit muscle relaxation in early stages of cardiomyopathy. ACE inhibition (ACEi) is known to delay the onset and slow the progression of DCM in DMD. The objective of this study is to use echocardiography to assess for preclinical cardiac changes consistent with intracellular calcium dysregulation before the onset of overt ventricular dysfunction, and to evaluate how prophylactic ACEi may alter these pre-cardiomyopathic changes in the pediatric DMD population. We examined 263 echocardiograms from 70 pediatric patients with DMD. We defined abnormal tonic contraction (TC) as left ventricular internal dimension in diastole (LVIDd) Z-score < -1.5. In our cohort, we found that TC is detectable as early as 8 years of age, and most commonly affects patients between 11 and 15 years. This effect was independent of LV mass and systolic function. Prophylactic ACEi decreased the incidence of TC (p = 0.007) and preserved cardiac function (p < 0.0001). Left ventricular TC often precedes DCM in DMD, most commonly affecting the 11- to 15-year-old age range. TC is not related to ventricular hypertrophy, but rather may be a clinical correlate of the "calcium hypothesis" of DMD pathophysiology. LV TC is thus a promising biomarker for early detection of cardiomyopathy in DMD. ACEi prophylaxis suppresses LV TC and delays the development of DCM in DMD.

Left bronchial compression and pulmonary hypertension related to anomalous right pulmonary artery.

Anomalous origin of a pulmonary artery from the ascending aorta is a congenital defect that can be complicated by pulmonary arterial hypertension, typically due to vascular disease if the anomaly is left uncorrected past 6 months of age. We describe a unique case of severe pulmonary arterial hypertension with this defect in a 1-month-old infant unexpectedly caused instead by bronchial compression from her dilated left pulmonary artery.

Extracorporeal membrane oxygenation support after pediatric orthotopic heart transplantation.

Mechanical circulatory support has been used for more than 30 yr to allow the heart to recover from ischemia and injury. There are limited pediatric data, however, on the efficacy of ECMO in the setting of post-transplantation support for primary graft dysfunction or rejection. Data from all patients at our university-affiliated, tertiary care children's hospital who underwent OHT between 1998 and 2010 and required subsequent ECMO support were analyzed. The primary outcome measure was survival to hospital discharge. Two hundred and three pediatric patients underwent OHT between 1998 and 2010 at our institution. Twenty-nine of these patients experienced post-transplantation cardiac failure requiring ECMO support, 18 of whom survived to hospital discharge (62%). Survival in the rejection and allograft vasculopathy group was 75%, and survival in patients with primary graft failure was 53% after ECMO support (p = 0.273). Patient survival to hospital discharge was not associated with ischemic time or duration of ECMO. ECMO provides hemodynamic support in the setting of cardiac failure and can be used successfully after pediatric OHT for primary graft dysfunction or rejection.

Unguarded mitral orifice associated with hypoplastic left heart syndrome.

In the spectrum of mitral valve anomalies, unguarded mitral orifice is an exceedingly rare malformation, with only four cases described in the current literature. All previously reported cases have been associated with discordant atrioventricular connections. We describe the first known case of unguarded mitral valve orifice, in the setting of atrioventricular concordance, in a newborn with hypoplastic left heart syndrome.

Cardiovascular Follow-up of Patients Treated for MIS-C.

OBJECTIVES: To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C). METHODS: Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram. RESULTS: Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups. CONCLUSIONS: The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children.

Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals. Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C. Design, Setting, and Participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions. Exposures: COVID-19 vaccination after MIS-C diagnosis. Main Outcomes and Measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables. Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C. Conclusions and Relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

Drug Treatment of Heart Failure in Children: Gaps and Opportunities.

Medical therapy for pediatric heart failure is based on a detailed mechanistic understanding of the underlying causes, which are diverse and unlike those encountered in most adult patients. Diuresis and improved perfusion are the immediate goals of care in the child with acute decompensated heart failure. Conversion to maintenance oral therapy for heart failure is based on the results of landmark studies in adults, as well as recent pediatric clinical trials and heart failure guidelines. There will continue to be an important role for newer drugs, some of which are in active trials in adults, and some of which are already approved for use in children. The need to plan for clinical trials in children during drug development for heart failure is emphasized.

Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is a rare yet serious complication of obstructive sleep apnea (OSA). Echocardiographic screening for PH is recommended in children with severe OSA, but the health care burden of universal screening is high. We sought to determine the prevalence of PH on echocardiogram among children with severe OSA and identify variables associated with a positive PH screen. METHODS: Retrospective study of 318 children with severe OSA (obstructive apnea-hypopnea index ≥ 10 events/h) and echocardiogram within 1 year of polysomnogram. PH-positive echocardiogram was defined by peak tricuspid regurgitation velocity ≥ 2.5 m/s and/or 2 or more right-heart abnormalities suggestive of elevated pulmonary artery pressure. Patient characteristics and polysomnogram data were compared to identify factors associated with PH. RESULTS: Twenty-six children (8.2%; 95% confidence interval [CI] 5.4-11.8%) had echocardiographic evidence of PH. There was no difference in age, sex, body mass index, obstructive apnea-hypopnea index, or oxygenation indices between patients with and without PH. Sleep-related hypoventilation (end-tidal CO2 > 50 mmHg for > 25% of total sleep time) was present in 25% of children with PH compared with 6.3% of children without PH (adjusted prevalence ratio = 2.73; 95% CI 1.18-6.35). Forty-six percent of children (12/26) with PH had Down syndrome vs 14% (41/292) without PH (adjusted prevalence ratio = 3.11; 95% CI 1.46-6.65). CONCLUSIONS: There was a relatively high prevalence of PH on echocardiogram in our cohort of children with severe OSA. The findings of increased PH prevalence among children with sleep-related hypoventilation or Down syndrome may help inform the development of targeted screening recommendations for specific pediatric OSA populations. CITATION: Maloney MA, Davidson Ward SL, Su JA, et al. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1629-1637.

Postoperative Serum Troponin Trends in Infants Undergoing Cardiac Surgery.

Troponin-I (TN-I) levels are elevated following pediatric cardiac surgery with speculation that particular patterns may have prognostic significance. There is lack of procedure-specific data regarding postoperative TN-I levels in infants undergoing cardiac surgery. We hypothesized that TN-I elevation varies with type of surgery and persistent elevation predicts poor prognosis. We prospectively measured serial TN-I levels (preoperatively, 4, 8, 12, 24, and 48 hours postoperatively) in 90 infants (age < 1 year) undergoing cardiac surgery: off cardiopulmonary bypass (CPB) (n = 15), on CPB (n = 43), and on CPB with ventricular incision (CPB with ventricular incision; n = 32). All patients had undetectable baseline TN-I levels. The area under the curve of TN-I levels over the 48-hour period was significantly different among the surgical groups (P < 0.002), and highest in patients with CPB with ventricular incision. Generally, TN-I levels peaked by 4 hours after surgery and returned to near-normal levels within 48 hours. A persistent TN-I rise beyond 8 hours after surgery was a strong predictor of postoperative hypoperfusion injury (defined as a composite endpoint of end-organ injury resulting from inadequate perfusion, odds ratio 21.5; P = 0.001) and mortality (30% in those with persistently high TN-I, compared with 3.5% in the remaining patients; P < 0.001), independent of patient age, anatomy and/or complexity of surgery, and level of postoperative support. Our data provide benchmark values for TN-I levels following cardiac surgery in infants. Extent of TN-I elevation correlates with type of surgery. Persistent TN-I elevation beyond 8 hours after surgery is strongly associated with postoperative hypoperfusion injury and mortality.

Prenatal exposure to methyldopa leading to hypertensive crisis and cardiac failure in a neonate.

A 2-week-old infant with normal intracardiac anatomy presented to the emergency department in a hypertensive crisis with acute cardiac failure. Despite extensive evaluation, no underlying disease was found. The patient's hypertension and cardiac dysfunction resolved after 1 week of supportive care in the PICU, and she was discharged within 2 weeks of presentation. The patient's history revealed transplacental exposure to the α-adrenergic agonist methyldopa for 10 weeks before delivery. Her age at presentation and the self-limited nature of cardiac sequelae with complete resolution of cardiac dysfunction suggest withdrawal effects from this exposure. Whereas the rebound hypertensive effects of α-adrenergic agonists are well established in the adult population, this report shows an unusual adverse outcome of in utero exposure to methyldopa.