Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth.

Tissue hypoxia increases erythropoietin production and release of immature erythrocytes that can be measured using nucleated red blood cell counts (nRBC). We hypothesized that hypoxia due to congenital heart disease (CHD) is chronic and is better tolerated than hypoxia due to respiratory disease (RD), which is an acute stress in newborns leading to higher nRBC. This study assesses the utility of nRBC as a marker to differentiate hypoxia due to CHD vs RD in term neonates. This was a single-center, retrospective study of term neonates with cyanosis from 2015 to 2022. Neonates < 37 weeks of gestation, with hypoxic-ischemic encephalopathy, and those with other causes of cyanosis were excluded. The patients were divided into 2 groups: cyanotic CHD and cyanotic RD. Clinical and laboratory data done within 12 h and 24-36 h after birth were collected. Data are represented as median and Interquartile range. Of 189 patients with cyanosis, 80 had CHD and 109 had RD. The absolute nRBC count at ≤ 12 h of age was lower in the CHD (360 cells/mm3) compared to RD group (2340 cells/mm3) despite the CHD group having significantly lower baseline saturations. A value of 1070 cells/mm3 was highly sensitive and specific for differentiating CHD from RD. The positive predictive value for this cut-off value of 1070 cells/mm3 was 0.94 and the negative predictive value was 0.89. The absolute nRBC is a simple screening test and is available worldwide. A nRBC < 1070 cells/mm3 in cyanotic newborns should hasten the search for CHD etiology with the possible need for prostaglandin therapy.

Effect of Preoperative Volume Overload on Left Ventricular Function Recovery After Ventricular Septal Defect Repair.

Significant left-to-right shunt across a ventricular septal defect (VSD) may lead to left ventricle (LV) volume overload and dilation. The acute loss of LV preload after repair of VSD may contribute to postoperative LV systolic dysfunction. The primary aim of the study is to assess the effect of presence of preoperative LV dilation on LV systolic function recovery after VSD repair. We evaluated the LV systolic function by measuring LV longitudinal strain and ejection fraction (EF) before surgery (time point 1) and at 5 time points after VSD repair (time point 2: 0 to 2 weeks, time point 3: 2 to 6 weeks, time point 4: 6 weeks to 4 months, time point 5: 4 to 12 months, and time point 6: >12 months). A total of 120 patients were included in the study cohort. A total of 84 patients (70%) had LV dilation (group 1) and 36 patients (30%) had normal LV size on preoperative echocardiogram (group 2). Median age (interquartile range 25% to 75%) at surgery was 5.5 months (4 to 10) and 7 months (5 to 44.5) in groups 1 and 2 respectively (p = 0.03). Mean LV EF and strain were not significantly different among the 2 groups at time point 1. At time point 2, both mean EF and strain were significantly lower in group 1 compared with group 2 (p <0.05). At time point 3, mean EF was not significantly different among the two groups, while mean LV strain was significantly lower in group 1 (p = 0.044). At time points 4, 5 and 6, mean EF and strain were not significantly different between the two groups. In conclusion, presence of preoperative LV dilation is associated with a more pronounced LV systolic dysfunction in the early postoperative period only. The LV systolic function recovers back to the baseline after the first year following the repair. These are very reassuring prognostic findings.

Cardiac Fibroma with Asymptomatic Ventricular Arrhythmia in an Adolescent with Gorlin's Syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS), also referred to as Gorlin's syndrome, is an autosomal dominant inherited condition that predisposes affected individuals to various tumors such as cardiac fibromas. Though technically benign, cardiac fibromas may result in malignant arrhythmias and sudden death. The pertinent literature pertaining to pediatric cases of cardiac fibromas and their clinical features were reviewed. We present the case of an asymptomatic teenage with de novo NBCCS who was diagnosed with both NBCCS and cardiac fibroma later in life. The patient was noted to have clinically significant ventricular arrhythmias that were eliminated with tumor resection. There are no established best practice guidelines for the management of cardiac fibromas in patients with NBCCS. Given the risk of sudden arrhythmic death, the presence of ventricular arrhythmias should prompt strong consideration of tumor resection.

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.

Efficacy of Biomarkers in Identifying Abnormal Echocardiogram in Multisystem Inflammatory Syndrome in Children.

Cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) is common and contributes to significant morbidity and mortality. We evaluated the efficacy of cardiac biomarkers in detection of an abnormal echocardiogram in MIS-C patients. A retrospective chart review of children ≤18 years diagnosed with MIS-C at our hospital was performed. Sensitivity and specificity of high-sensitivity troponin I (hs-TnI) and B-type natriuretic peptide (BNP) were estimated for an abnormal echocardiogram. Of the 83 patients with MIS-C, 33 (39.8%) had an abnormal echocardiogram. While BNP was more sensitive, hs-TnI >50 ng/L was more specific for detecting an abnormal echocardiogram. Compared with children who had normal hs-TnI levels (<17 ng/L), those with hs-TnI >50 ng/L were more likely to have an echocardiographic abnormality (relative risk: 4.9; 95% CI, 2.9-10.9). Children with abnormal BNP and/or troponin (especially greater than 3-fold the upper limit of normal) would benefit from an urgent echocardiogram in the emergency department.

Vitamin D and morbidity in children with Multisystem inflammatory syndrome related to Covid-19.

Background: Multisystem inflammatory syndrome (MIS-C) is a clinical presentation reported in children related to Coronavirus-19 infection who present with a toxic shock like syndrome. Vitamin D deficiency has been postulated to play a role with severity of coronavirus infection in adult patients and other viral respiratory infections. Objective: This study aims to investigate if severe vitamin D deficiency was associated with increased disease severity and cardiac involvement in MIS-C. Methods: This is a retrospective and single center study. We included hospitalized patients less than 18 years of age with diagnosis of MIS-C between March and July 2020. Severe vitamin D deficiency was defined as 25-OH vitamin D level < 10 ng/ml within 48 h of admission. The composite outcome severe disease included patients requiring inotropes, mechanical ventilation, and extracorporeal membrane oxygenation. Results: Of the 31 patients with MIS-C, 45% were male and 58% were African American. The median age was 8 (1-13) years. Ten patients had severe vitamin D deficiency with a mean level of 7.2 ng/ml. Ninety percent of patients with severe vitamin D deficiency had severe disease (P < 0.001). Patients with severe vitamin D deficiency had an increased risk of cardiac involvement (P < 0.001). Conclusions: We describe a potential association between severe vitamin D deficiency and severe disease in children presenting with MIS-C. Severe vitamin D deficiency predisposes patients for cardiovascular involvement and may play a critical role in the host immune response to COVID-19 infection. Future prospective studies at the basic science and clinical level should be pursued to better delineate this association.

Anthracycline Treatment and Left Atrial Function in Children: A Real-Time 3-Dimensional Echocardiographic Study.

Anthracycline (AC) therapy is associated with left ventricular (LV) dysfunction. Left atrial (LA) size and function are used to assess LV diastolic function in heart failure in adults. Data on LA size and function following AC therapy in children is limited. We hypothesized that LA size and function will be abnormal in children following AC chemotherapy. This retrospective review included patients who received AC for pediatric cancers. Controls had normal echocardiograms performed for evaluation of chest pain, murmur, or syncope. Real-time three-dimensional echocardiography was performed to evaluate LA reservoir, conduit, and booster pump function parameters. In addition to LA volume data, LV shortening fraction, spectral and tissue Doppler variables assessing diastolic function as well as myocardial performance index was obtained. Groups with and without AC therapy were compared by student t-test and chi-square test. We evaluated 136 patients, 55 (40.4%) had received AC. There was no significant difference between the groups in LV shortening fraction, diastolic as well as global function indices. LA reservoir and conduit function parameters were significantly lower in AC group compared to controls. The booster function parameters showed variable results. It is intriguing that AC-treated children have smaller LA reservoir and abnormal booster function. We speculate that these findings may reflect early changes in LA compliance associated with AC exposure. Assessment of LA volumes and function as prognostic markers of AC-induced cardiotoxicity in children is warranted.

Echocardiographic Indicators Associated with Adverse Clinical Course and Cardiac Sequelae in Multisystem Inflammatory Syndrome in Children with Coronavirus Disease 2019.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 causes significant cardiovascular involvement, which can be a determinant of clinical course and outcome. The aim of this study was to investigate whether echocardiographic measures of ventricular function were independently associated with adverse clinical course and cardiac sequelae in patients with MIS-C. METHODS: In a longitudinal observational study of 54 patients with MIS-C (mean age, 6.8 ± 4.4 years; 46% male; 56% African American), measures of ventricular function and morphometry at initial presentation, predischarge, and at a median of 3- and 10-week follow-up were retrospectively analyzed and were compared with those in 108 age- and gender-matched normal control subjects. The magnitude of strain is expressed as an absolute value. Risk stratification for adverse clinical course and outcomes were analyzed among the tertiles of clinical and echocardiographic data using analysis of variance and univariate and multivariate regression. RESULTS: Median left ventricular apical four-chamber peak longitudinal strain (LVA4LS) and left ventricular global longitudinal strain (LVGLS) at initial presentation were significantly decreased in patients with MIS-C compared with the normal cohort (16.2% and 15.1% vs 22.3% and 22.0%, respectively, P < .01). Patients in the lowest LVA4LS tertile (<13%) had significantly higher C-reactive protein and high-sensitivity troponin, need for intensive care, and need for mechanical life support as well as longer hospital length of stay compared with those in the highest tertile (>18.5%; P < .01). Initial LVA4LS and LVGLS were normal in 13 of 54 and 10 of 39 patients, respectively. There was no mortality. In multivariate regression, only LVA4LS was associated with both the need for intensive care and length of stay. At median 10-week follow-up to date, seven of 36 patients (19%) and six of 25 patients (24%) had abnormal LVA4LS and LVGLS, respectively. Initial LVA4LS < 16.2% indicated abnormal LVA4LS at follow-up with 100% sensitivity. CONCLUSION: Impaired LVGLS and LVA4LS at initial presentation independently indicate a higher risk for adverse acute clinical course and persistent subclinical left ventricular dysfunction at 10-week follow-up, suggesting that they could be applied to identify higher risk children with MIS-C.

Spontaneous closure of muscular ventricular septal defect by growth of right ventricular muscle bundles: a rare mechanism.

We present a case of an 18-year-old male with large anterior muscular ventricular septal defect. Assessment by echocardiography showed that the defect has completely closed by the growth of muscle bundles that formed a pouch-like structure on the right ventricular side. This unusual mechanism of closure has been reported in one prior case report. In our report, we present images obtained by three-dimensional echocardiography.

16 Years of Cardiac Resynchronization Pacing Among Congenital Heart Disease Patients: Direct Contractility (dP/dt-max) Screening When the Guidelines Do Not Apply.

OBJECTIVES: The purpose of this study was to use direct cardiac resynchronization therapy (CRT)-paced contractility (dP/dt-max) response as a pre-implantation evaluation among patients with congenital heart disease (CHD) and follow clinical parameters and contractility indexes after CRT implantation. BACKGROUND: Patients with CHD often develop early heart failure with few therapeutic options, leading to heart transplantation (HT). Unfortunately, guidelines for CRT do not apply, and function evaluations by cardiac ultrasound are often inaccurate among CHD anatomies. Therefore, which CHD patients would benefit from CRT remains an enigma. METHODS: From 1999 to 2015, 103 CHD patients with New York Heart Association (NYHA) functional class II to IV were listed for HT; 40 patients on optimal medical therapy were referred for paced contractility response cardiac catheterization before CRT consideration. If dP/dt-max improved ≥15% from baseline, these "responders" were given the option of CRT with continued follow-up after implantation. RESULTS: Of 40 patients studied, 26 (65%) (age 22 ± 8.2 years; 9 of 26 [35%] single or systemic right ventricle; 17 of 26 [65%] with pacemakers) met criteria for possible hemodynamic benefit and underwent CRT implantation. All 26 patients improved in NYHA functional classification: 5 of 26 patients (19%) were later relisted for HT (4 to 144 months, mean 55 months) after CRT implantation, whereas 21 of 26 (81%) continued with improved NYHA functional class (12 to 112 months, mean 44 months) later. A repeat dP/dt-max study following long-term CRT showed stable function or continued contractility improvement. CONCLUSIONS: Heart failure is common among CHD patients, and therapies are limited. CRT guidelines do not address clinical and anatomic issues of CHD. Short-term paced contractility response testing identifies those CHD patients who are likely to respond to CRT regardless of anatomy.

Innocent Heart Murmurs from the Perspective of the Pediatrician.

Innocent heart murmurs are quite common in children and adolescents. These murmurs are physiologic in nature and are not associated with any structural heart disease. Not only does the idea of having a child with a murmur bring unnecessary unrest to families, but the child also often goes through numerous tests that could be avoided. It is critical to obtain a detailed history and perform a thorough physical examination to diagnose these innocent murmurs. This article reviews the different types of innocent murmurs, their characteristics, how they can be differentiated on the physical examination, and most importantly, how they can be differentiated from pathologic murmurs, which require referral to a pediatric cardiologist and additional testing. [Pediatr Ann. 2016;45(8):e306-e309.].

Comparative Chronic Valve and Venous Effects of Lumenless versus Stylet-Delivered Pacing Leads in Patients with and Without Congenital Heart.

BACKGROUND: Standard, 5-7-Fr diameter pacing leads (PLs) can adversely affect atrioventricular valve (AVV) and venous (superior vena cava [SVC], innominate [INN]) integrities. Although chronic pacing/sensing performances have been reported on the steroid-eluting, lumenless, 4.1-Fr PL (Model 3830, Medtronic Inc., Minneapolis, MN, USA), comparative valve and venous effects are largely unknown. METHODS: Patients (n = 134) were divided into two PL groups: Group 1 (n = 65, Model 3830) and Group 2 (n = 69, various 5-7 Fr models) and followed up to 9 years postimplant. Patient demographics, clinical findings, valve function, and venous dimensions were reviewed. Statistical significance was defined as P < 0.05. RESULTS: Patient implant age (mean 16.4 years vs 17.3 years), presence of congenital heart defect (CHD), and preexisting valve issues were comparable between groups. New or worsening valve insufficiency occurred in 12% of Group 1 patients (mean follow-up 4.3 ± 2.8 years) and 27% of Group 2 patients (mean follow-up 6.2 ± 3.5 years; P < 0.05). Significant SVC or INN narrowing was found in 11 % of Group 1 and 24% of Group 2 patients (P = 0.0004). All Group 1 patients <12 years of age showed normal while 50% of those from Group 2 exhibited stunted SVC or INN growth (P < 0.05). CONCLUSION: The lumenless, 4.1-Fr diameter PL offers improved clinical benefits, better AVV integrity, and venous development compared with larger 5-7-Fr diameter PL and should be considered especially in younger patients with/without CHD.

Vasoactive-inotropic score after pediatric heart transplant: a marker of adverse outcome.

VIS, a quantitative index of pressor support, has been shown to be a predictor of morbidity and mortality in infants younger than six months who underwent CPB. Data on its prognostic utility following pediatric OHT are lacking. This study compared clinical outcomes in children with differential VIS after pediatric OHT. A retrospective cohort study of 51 consecutive heart transplants from 2004 to 2011 was performed at a pediatric tertiary care facility. Peak VIS was computed within initial 24 and 48 h after OHT and was weighted for peak dose and administration of any or all of six pressors. Patients with peak VIS ≥ 15 constituted high VIS group. Children who persistently required a higher magnitude of pressor support for the first 48 h after OHT, as reflected by high peak VIS, had significantly longer ICU stay (30.2 vs. 15.9 days, p = 0.01), pressor (11.4 vs. 6.8 days, p = 0.02) and ventilatory durations (12.4 vs. 5.9 days, p = 0.05), and higher rates of short-term morbidities. Patients with longer CPB (213 vs. 153 min, p = 0.005) time have higher peak VIS. High peak VIS at 48 h is an effective, yet simple clinical marker for adverse outcomes in pediatric OHT recipients.