Exercise-Induced Electrocardiography Changes in Pulmonary Arterial Hypertension.

Cardiopulmonary exercise testing (CPET) is an important tool in assessing the functional status of patients with pulmonary arterial hypertension (PAH). During CPET, continuous electrocardiography (ECG) is used as a marker of exercise-induced ischemia or arrhythmia. We hypothesize that ECG changes with exercise may be an early indicator of clinical worsening in PAH and could predict adverse outcomes. Clinical, hemodynamic, and CPET data of 155 children and young adult patients with PAH who underwent CPET between 2012 and 2019 in our pulmonary hypertension (PH) center were included in this retrospective analysis. ECGs were analyzed for ST depressions and T-wave inversions, along with coincident hemodynamic data. These data were correlated with adverse outcomes divided into 2 categories: severe worsening (death or receiving lung transplant) and mild to moderate worsening (PAH medication escalation, hospitalization, shunt creation, or listing for lung transplant). The median age was 19 years (range 7 to 40 years), 69% were female, and the average follow-up time was 5 years (range 1 to 8 years). A total of 63 patients (41%) had at least 1 adverse outcome. A total of 39 patients (25%) demonstrated significant ST-T-wave changes with exercise. Patients with ST-T-wave changes were 20% more likely to die or need lung transplant than those without. The multiple linear regression found that ST-T-wave changes were a predictor of elevated mean pulmonary arterial pressure (mPAP) found on catheterization (R = 0.489, p = 0.003), although not of pulmonary vascular resistance index (R = -0.112, p = 0.484). An mPAP of 55 mm Hg was the most sensitive and specific point in identifying when ST-T-wave changes with exercise begin to appear. In conclusion, ST-T-wave changes on exercise ECG are significantly associated with adverse outcomes in PH in a medium-term follow-up study, and the presence of ST-T-wave changes correlates with higher mPAP. These ECG changes with exercise may be used as early indicators of clinical worsening in PH and predictors of adverse outcomes.

Elevated cardiac biomarkers and outcomes in children and adolescents with acute COVID-19.

Cardiac involvement associated with multi-system inflammatory syndrome in children has been extensively reported, but the prevalence of cardiac involvement in children with SARS-CoV-2 infection in the absence of inflammatory syndrome has not been well described. In this retrospective, single centre, cohort study, we describe the cardiac involvement found in this population and report on outcomes of patients with and without elevated cardiac biomarkers. Those with multi-system inflammatory syndrome in children, cardiomyopathy, or complex CHD were excluded. Inclusion criteriaz were met by 80 patients during the initial peak of the pandemic at our institution. High-sensitivity troponin T and/or N-terminal pro-brain type natriuretic peptide were measured in 27/80 (34%) patients and abnormalities were present in 5/27 (19%), all of whom had underlying comorbidities. Advanced respiratory support was required in all patients with elevated cardiac biomarkers. Electrocardiographic abnormalities were identified in 14/38 (37%) studies. Echocardiograms were performed on 7/80 patients, and none demonstrated left ventricular dysfunction. Larger studies to determine the true extent of cardiac involvement in children with COVID-19 would be useful to guide recommendations for standard workup and management.

Lack of Age-Appropriate Reference Intervals Causing Potentially Missed Alerts in Clinical Reports of Dyslipidemia.

This study shows that only 12.5% of laboratory reports (2/16) included age-appropriate pediatric reference ranges for all lipid and lipoproteins. The use of erroneous reference range(s) could lead to missed alerts of dyslipidemia in up to 97.3% (total cholesterol), 93.6% (high-density lipoprotein cholesterol), 94.8% (low-density lipoprotein cholesterol), and 87.8% (triglycerides) of youth in the population-based National Health and Nutrition Examination Survey cohort. These findings highlight the potential missed opportunities for reinforcing lifestyle counseling for dyslipidemia in addition to obesity in youth.

Impact of Coronavirus Disease 2019 (COVID-19) on Patients With Congenital Heart Disease Across the Lifespan: The Experience of an Academic Congenital Heart Disease Center in New York City.

Background We sought to assess the impact and predictors of coronavirus disease 2019 (COVID-19) infection and severity in a cohort of patients with congenital heart disease (CHD) at a large CHD center in New York City. Methods and Results We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID-19 between March 1, 2020 and July 1, 2020. The primary end point was moderate/severe response to COVID-19 infection defined as (1) death during COVID-19 infection; or (2) need for hospitalization and/or respiratory support secondary to COVID-19 infection. Among 53 COVID-19-positive patients with CHD, 10 (19%) were <18 years of age (median age 34 years of age). Thirty-one (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair. Eight (15%) had a genetic syndrome, 6 (11%) had pulmonary hypertension, and 9 (17%) were obese. Among adults, 18 (41%) were physiologic class C or D. For the entire cohort, 9 (17%) had a moderate/severe infection, including 3 deaths (6%). After correcting for multiple comparisons, the presence of a genetic syndrome (odds ratio [OR], 35.82; P=0.0002), and in adults, physiological Stage C or D (OR, 19.38; P=0.002) were significantly associated with moderate/severe infection. Conclusions At our CHD center, the number of symptomatic patients with COVID-19 was relatively low. Patients with CHD with a genetic syndrome and adults at advanced physiological stage were at highest risk for moderate/severe infection.

Cardiac workup and monitoring in hospitalised children with COVID- 19.

Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.

Extreme hypertriglyceridemia: Genetic diversity, pancreatitis, pregnancy, and prevalence.

BACKGROUND: Triglyceride (TG) concentrations >2000 mg/dL are extremely elevated and increase the risk of pancreatitis. OBJECTIVES: We characterized five cases and two kindreds and ascertained prevalence in a reference laboratory population. METHODS: Plasma lipids and DNA sequences of LPL, GPIHBP1, APOA5, APOC2, and LMF1 were determined in cases and two kindreds. Hypertriglyceridemia prevalence was assessed in 440,240 subjects. RESULTS: Case 1 (female, age 28 years) had TG concentrations >2000 mg/dL and pancreatitis since infancy. She responded to diet and medium-chain triglycerides, but not medications. During two pregnancies, she required plasma exchange for TG control. She was a compound heterozygote for a p.G236Gfs*15 deletion and a p.G215E missense mutation at LPL, as was one sister with hypertriglyceridemia and pancreatitis during pregnancy. Her father was heterozygous for the deletion and had hypertriglyceridemia and recurrent pancreatitis. Other family members had either the missense mutation or the deletion, and had hypertriglyceridemia but no pancreatitis. In kindred 2, three preschool children had severe hypertriglyceridemia and were homozygous for a GPIHBP1 p.T108R missense mutation. Case 5 (male, age 43 years) presented with pancreatitis and TG levels >5000 mg/dL and had heterozygous GPIHBP1 p.G175R and APOC2 intron 2-4G>C mutations. On diet, fenofibrate, fish oil, and atorvastatin, his TG concentration was 2526 mg/dL, but normalized to <100 mg/dL with added pioglitazone. In our population study, 60 subjects (0.014%) of 440,240 had TG concentrations >2000 mg/dL, and 66.7% were diabetic and had elevated insulin levels. CONCLUSIONS: Extreme hypertriglyceridemia is rare (0.014%); and during pregnancy, it may require plasma exchange.

Usefulness of High-Dose Oral Flecainide for Termination of Recent-Onset Atrial Fibrillation in Children.

A high dose of oral flecainide has been used for acute termination of atrial fibrillation (AF) and atrial flutter or intra-atrial re-entry tachycardia (AFL-IART) in adults. The use of flecainide for these conditions in children has not been well described. We describe our institutional experience on acute termination of AF or AFL-IART in children with a single high dose of oral flecainide in a hospital setting. All patients who received a single high dose of oral flecainide from 2009 to 2016 who were <21 years of age were included. Patients were treated only if AF or AFL-IART was less than 24 hours of duration. The dose was 300 mg for patients >70 kg, 200 mg for patients 40 to 70 kg, and 5 mg/kg for patients <40 kg. Charts were reviewed to determine demographic information, flecainide dose, termination of arrhythmia, and time to termination. There were 22 patients identified. The median age was 16 years (range 4.6 to 20.3) with a median weight of 75 kg (range 19 to 112). There were 13 patients with AF (11 with a normal heart, 85%) and 9 patients with AFL-IART (1 with a normal heart, 11%) (p <0.05). The median dose of flecainide given was 3.6 mg/kg (range 2.7 to 6.1) or 136 mg/m2 (range 90 to 171). AF in all patients (13/13, 100%) and AFL-IART in 5 of 9 patients (55%) terminated acutely (p <0.05). All patients with normal heart (12/12, 100%) and 6 of the 10 patients (60%) with heart disease have their arrhythmia terminated acutely (p <0.05). The only patients whose tachycardia did not terminate were 4 patients with IART and heart disease. The arrhythmia terminated in a median time of 60 minutes (range 30 to 120). There were no adverse events or proarrhythmia encountered. In conclusion, a single high dose of oral flecainide successfully terminated AF of less than 24 hours' duration in all pediatric patients without side effects. This approach is less effective for AFL-IART in patients with heart disease.

Percutaneous Coronary Intervention With Bioresorbable Scaffolds in a Young Child.

Importance: Although much less frequent than in adults, coronary artery disease requiring revascularization may develop in children because of homozygous familial hypercholesterolemia or other underlying conditions. Percutaneous coronary intervention (PCI) with a bioresorbable scaffold (BRS) may have advantages over metallic coronary stents in this population. Objective: To present a case of the successful treatment of unstable, multivessel coronary artery disease in a child with PCI with BRS implantation. This case highlights the limitations of conventional metal stents and the potential benefits of using BRSs in children. Design, Setting, and Participants: This is a case report from an academic tertiary care institution of a 3-year-old boy with homozygous familial hypercholesterolemia and unstable coronary artery disease requiring revascularization. We also briefly review the related literature. Interventions/Exposures: Intravascular imaging-guided PCI of the proximal right coronary artery and the left main and proximal left circumflex arteries was performed with BRSs. Main Outcomes and Measures: The primary outcomes were acute procedural success and survival to liver transplant (3 months after PCI). Results: Following BRS implantation, the patient recovered and remained free of cardiovascular symptoms 3 months after PCI. He subsequently underwent an orthotopic liver transplant for definitive treatment of homozygous familial hypercholesterolemia but died of noncardiac complications. A postmortem examination, including a histological assessment, revealed both BRSs to be patent with nonobstructive neointimal hyperplasia. Conclusions and Relevance: To our knowledge, this is the first report of PCI with BRSs in a child. This represents an application of a BRS with potentially important implications for the future treatment of coronary artery disease in children and warrants further study.

Hypoplastic Left Heart Syndrome: Exploring a Paradigm Shift in Favor of Surgery.

We hypothesized that enthusiasm for surgery increased for infants with hypoplastic left heart syndrome (HLHS) at Columbia University Medical Center (CUMC) between 1995 and 2012. We sought to identify factors that engendered this paradigm shift. Confidential surveys were distributed to providers at CUMC in 1995 and 2012 to measure enthusiasm for surgical intervention for HLHS. Surgical preference scores are presented as median [interquartile range]. Surveys were completed by 99/176 providers (56 % response rate) in 1995 and 153/267 (57 %) in 2012. The median surgical preference score for infants with HLHS increased from 35 [25-45] in 1995 to 45 [35-50] in 2012, P < 0.001. 53 %, 95 % CI [42, 64] of respondents recommended surgical intervention for a ward of the court in 1995 compared to 81 % [73, 89] in 2012, P < 0.001. In 2012, 64 % [53, 75] of respondents were more likely to recommend surgery than 10 years prior. The percentage of respondents who saw good outcomes following three-stage repair increased from 49 % [38, 60] in 1995 to 84 % [78, 90] in 2012, P < 0.001. The majority believed that parents should have the option of comfort care, 91 % [85, 97] in 1995 and 85 % [79, 91] in 2012, P = 0.06. In both eras, prematurity and additional surgical problems dissuaded providers from recommending surgical intervention. Despite the fact that most providers have seen good outcomes and now recommend surgery for infants with HLHS, the majority of providers still believe that the option of comfort care should be available to families.

Long-Term Effects of In Utero Antiretroviral Exposure: Systolic and Diastolic Function in HIV-Exposed Uninfected Youth.

The aim of this study was to evaluate the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children. A prospective, multisite cohort study in HEU children was conducted by the Pediatric HIV/AIDS Cohort Study (PHACS). Echocardiographic measures of LV systolic and diastolic function and cardiac structure were obtained from HEU subjects aged ≥6 years enrolled in the PHACS Surveillance Monitoring of ART Toxicities study. Echocardiographic Z-scores were calculated using normative data from an established reference cohort. We used adjusted linear regression models to compare Z-scores for echocardiographic measures from HEU children exposed in utero to HAART with those exposed to non-HAART, adjusting for demographic and maternal health characteristics. One hundred seventy-four HEU subjects with echocardiograms and maternal ARV information were included (mean age 10.9 years; 48% male, 56% black non-Hispanic). Among 156 HEU youth with any ARV exposure, we observed no differences in Z-scores for LV systolic function measures between youth exposed in utero to HAART (39%) and HAART-unexposed youth in either unadjusted or adjusted models. In adjusted models, those exposed to HAART had significantly lower mitral late diastolic inflow velocities (adjusted mean Z-score = 0.00 vs. 0.52, p = .04) and significantly higher adjusted mean LV mass-to-volume ratio Z-scores (adjusted mean Z-score = 0.47 vs. 0.11, p = .03) than HAART-unexposed youth. Uninfected children with perinatal exposure to HAART had no difference in LV systolic function. However, small but significant differences in LV diastolic function and cardiac structure were observed, suggesting that continued monitoring for cardiac outcomes is warranted in this population.

Heterotaxy syndrome and intestinal rotational anomalies: Impact of the Ladd procedure.

BACKGROUND: Children with heterotaxy syndrome and intestinal rotational anomalies (IRA) are at risk for midgut volvulus and ischemia. Controversy exists regarding risks and benefits of prophylactic Ladd procedures. The purpose of this study is to assess the impact of Ladd procedures on adverse events for children with heterotaxy and IRA. METHODS: A retrospective cohort study using the Pediatric Health Information System (PHIS) database was performed. All children with heterotaxy and IRA admitted at age ≤ 30 days and discharged between 1/1/2004 and 1/1/2011 were included with a minimum 2-year follow-up period. The primary outcome was major morbidity, defined as a composite variable for intestinal obstruction/volvulus, ischemia, or resection, or inhospital mortality. Univariable and multivariable analyses were performed. RESULTS: There were 325 patients who met the inclusion criteria, including 92 (28%) patients with single ventricles. Mean gestational age was 38.0 ± 2.1 weeks and birth weight was 3.1 ± 0.6 kg. Ladd procedure was performed during initial hospitalization on 188 (58%) children. In multivariable analyses, Ladd procedure on initial hospitalization was associated with a 2.2 times increased odds of adverse events on subsequent admissions (95% CI 1.3-4.0, p = 0.007). CONCLUSIONS: Ladd procedure is associated with increased odds of adverse events for children with heterotaxy and IRA.

Defining the electrocardiogram in the neonate with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe form of congenital heart disease characterized by underdevelopment of the left heart. There has been no previously defined "classic" ECG pattern in a large homogenous population of patients with HLHS. We performed a retrospective review of ECGs from neonates with HLHS from 2001 to 2011 with electrocardiograms available prior to surgical intervention. Eighty-nine neonates met the inclusion criteria and were compared to a control population. HLHS patients had a longer PR interval 108 ± 18 versus 98 ± 11 ms (p < 0.05), a wider QRS complex 84 ± 17 versus 54 ± 5 ms (p < 0.05), lower voltage S waves in V1 2.0 ± 3.3 versus 5.8 ± 4.6 mm (p < 0.001) or absent S waves in V1 52 versus 4 % (p < 0.001) and lower voltage R waves in V6 7.8 ± 4.8 versus 9.3 ± 4.2 mm (p < 0.05). Patients with HLHS were more likely to have absent Q waves in the lateral precordial leads 78 versus 0 % (p < 0.001) and inferior leads 20 versus 1 % (p < 0.001) and an abnormal frontal plane QRS axis 26 versus 11 % (p < 0.05). HLHS patients were more likely to have a preexcited appearance 11 versus 0 % (p = 0.001). Despite these findings, 20 % of patients with HLHS had a normal ECG. Compared to age-matched controls, patients with HLHS were more likely to exhibit a longer PR interval, a wider QRS complex, decreased left-sided forces, an absence of septal Q waves in the inferior and lateral leads, an abnormal frontal plane QRS axis and a preexcited appearance.

Treatment of tetralogy of Fallot hypoxic spell with intranasal fentanyl.

We present the case of a 3-month-old girl who had unrepaired Tetralogy of Fallot who presented to the emergency department with an acute hypoxic episode. The patient was hyperpneic and cyanotic, with an initial oxygen saturation of 56%. She did not respond to knee-to-chest positioning. A single dose of intranasal fentanyl was administered with subsequent resolution of her symptoms and improvement of her oxygen saturation to 78% within 10 minutes. To our knowledge, this is the first report of the successful treatment of a hypoxic episode of Tetralogy of Fallot using intranasal fentanyl.

Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus.

BACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy. METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period. CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.

Usefulness of transtelephonic monitoring in epicardial pacemaker systems.

BACKGROUND: Transtelephonic monitoring (TTM) of pediatric patients with cardiac pacemakers (PMs) has been shown to have high sensitivity and specificity in identifying PM malfunction. The objective of this study is to determine if there is a difference in the rate of abnormal TTM findings in transvenous versus epicardial PM systems. METHODS: Our TTM database was reviewed. Patients younger than 21 years of age enrolled for TTM between 1990 and 2010 were included. The abnormal TTM recordings (not including elective replacement indicator) were identified. Logistic regression was used for statistical analysis. Note that P < 0.05 was considered significant. RESULTS: We identified 186 patients. There were 75 (40%) epicardial systems. The mean age at TTM enrollment was 6.8 ± 5.9 years (2 months-20.2 years). There were 41 (22%) patients with abnormal TTM findings. The abnormalities were found in 23/75 (31%) epicardial and 18/111 (16%) transvenous systems (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.13-4.62, P = 0.02). When controlling for age and presence of heart disease the OR for abnormal transmission in epicardial systems compared with transvenous was 2.1 (95% CI: 1.03-4.43, P = 0.04). Patients with epicardial systems were more likely to have capture abnormalities on TTM than transvenous systems (OR: 6.1, 95% CI: 1.9-19.5, P = 0.002). CONCLUSION: Pediatric patients with epicardial PM systems are more likely to have abnormal TTM test (particularly capture problems) than patients with transvenous systems regardless of age or presence of heart disease. Consequently, patients with epicardial PM systems should be followed closely with TTM.

Nitric oxide-associated pulmonary edema in children with pulmonary venous hypertension.

Nitric oxide (NO)-associated pulmonary edema is rarely reported in children; in adults, it is often associated with left-sided heart failure. We report a case series of children with NO-associated pulmonary edema, which was defined as new multilobar alveolar infiltrates and worsening hypoxemia within 24 h of initiation or escalation of NO and radiologic or clinical improvement after NO discontinuation. We identified six patients (0.4-4 years old) with ten episodes of NO-associated pulmonary edema. Diagnoses included atrioventricular canal defect with mitral valve disease (n = 2), pulmonary atresia and major aorta-pulmonary collateral arteries (n = 2), total anomalous pulmonary venous return (n = 1), and pulmonary veno-occlusive disease (n = 1). All patients had evidence of pulmonary venous hypertension, and two had mitral valve disease resulting in clinical evidence of left-sided heart failure. Pulmonary edema improved or resolved within 24 h of discontinuing NO. At cardiac catheterization, mean left atrial pressure was <15 mmHg in three of three patients (none with mitral valve disease), whereas pulmonary artery occlusion pressure was >15 mmHg in two of five patients. In conclusion, we describe six young children with NO-associated pulmonary edema and pulmonary venous hypertension. Only two of these children had left-sided heart failure: Left atrial pressure as well as pulmonary artery occlusion pressure may not be helpful in identifying children at risk for NO-associated pulmonary edema.

Congenital cutaneous hemangioma causing cardiac failure: a case report and review of the literature.

We present a case of a large congenital hemangioma (CH) on the neck causing cardiac failure and thrombocytopenia in a female neonate. A trial of medical therapy with corticosteroids and propranolol was attempted, but the patient ultimately underwent definitive treatment with embolization and surgical resection with a positive outcome. A review of the English language literature revealed 16 previously reported cases of CHs complicated by congestive heart failure. This series supports known demographic features of CHs, including a lack of gender discrepancy and a predilection to affect the head and neck. These CHs are rarely diagnosed in utero; most patients present with a mass at birth. Cardiac failure is identified prenatally or in the first days of life. A mild to moderate thrombocytopenia and coagulopathy, which is likely transient and distinct from classic Kasabach-Merritt phenomenon, accompanies many of these cases. There is a 30% associated mortality rate. Both medical and interventional treatment modalities have been reported. Steroids are the most commonly used medication, but without any clear benefit. We hypothesize that, based on its possible mechanisms of action,propranolol may be a more effective treatment for CHs requiring treatment. As surgical intervention may be necessary, we recommend a multidisciplinary approach to treating patients with problematic CHs.

CM-AVM syndrome in a neonate: case report and treatment with a novel flow reduction strategy.

Mutations in the RASA-1 gene underlie several related disorders of vasculogenesis. Capillary malformation-arteriovenous malformation (CM-AVM) is one such entity and was recently encountered in a neonate who demonstrated its clinical and radiologic features. A single mutation in the RASA-1 gene was detected.A novel flow reduction strategy was employed to a large AVM affecting the patient's upper limb. The imaging findings, surgical procedure and patient's improved post-operative state are described.