Outcomes of atrioventricular septal defects with and without down syndrome: analysis of the national inpatient database.

BACKGROUND: Controversial data exist about the impact of Down syndrome on outcomes after surgical repair of atrioventricular septal defect. AIMS: (A) assess trends and outcomes of atrioventricular septal defect with and without Down syndrome and (B) determine risk factors associated with adverse outcomes after atrioventricular septal defect repair. METHODS: We queried The National Inpatient Sample using International Classification of Disease codes for patients with atrioventricular septal defect < 1 year of age from 2000 to 2018. Patients' characteristics, co-morbidities, mortality, and healthcare utilisation were evaluated by comparing those with versus without Down syndrome. RESULTS: In total, 2,318,706 patients with CHD were examined; of them, 61,101 (2.6%) had atrioventricular septal defect. The incidence of hospitalisation in infants with atrioventricular septal defect ranged from 4.5 to 7.5% of all infants hospitalised with CHD per year. A total of 33,453 (54.7%) patients were associated with Down syndrome. Double outlet right ventricle, coarctation of the aorta, and tetralogy of Fallot were the most commonly associated with CHD in 6.9, 5.7, and 4.3% of patients, respectively. Overall atrioventricular septal defect mortality was 6.3%. Multivariate analysis revealed that prematurity, low birth weight, pulmonary hypertension, and heart block were associated with mortality. Down syndrome was associated with a higher incidence of pulmonary hypertension (4.3 versus 2.8%, p < 0.001), less arrhythmia (6.6 versus 11.2%, p < 0.001), shorter duration for mechanical ventilation, shorter hospital stay, and less perioperative mortality (2.4 versus 11.1%, p < 0.001). CONCLUSION: Trends in atrioventricular septal defect hospitalisation had been stable over time. Perioperative mortality in atrioventricular septal defect was associated with prematurity, low birth weight, pulmonary hypertension, heart block, acute kidney injury, and septicaemia. Down syndrome was present in more than half of atrioventricular septal defect patients and was associated with a higher incidence of pulmonary hypertension but less arrhythmia, lower mortality, shorter hospital stay, and less resource utilisation.

Antenatal occlusion of a ductal arteriosus aneurysm: a potential postnatal surgical emergency. Case report and literature review.

Symptomatic presentation of ductal arteriosus aneurysm is usually a consequence of associated complications, including thromboembolism, infection, and compression of adjacent structures. In this case report, we present a thrombosed ductal aneurysm that developed antenatally with further postnatal progression of the thrombus and complete occlusion of the left pulmonary artery. Urgent surgical thrombectomy was successful and the post-operative course was uneventful.

Factors affecting cerebrovascular reactivity to CO2 in premature infants.

Background Hypercarbia increases cerebral blood flow secondary to cerebral vasodilatation, while hypocarbia can lead to vasoconstriction with a subsequent decrease in cerebral blood flow. The aim of this study was to examine CO2 cerebral vasoreactivity in a cohort of premature infants and to identify factors which influence this reactivity. Methods We prospectively studied a cohort of hemodynamically stable premature infants [birth weight (BW) <1500 g and gestational age (GA) ≤34 weeks]. Subjects underwent two studies, one in the first 72 h and the second after 1 week of life. Infants were continuously monitored via a physiology station that included transcutaneous CO2 (tcPCO2) monitor, near-infrared spectroscopy (NIRS), arterial pulse oximetry and heart rate. The total hemoglobin (Hb-T) signal of NIRS was used as an indicator of cerebral blood volume (CBV). Correlation between tcPCO2 and Hb-T was performed in each 1-h period using Pearson's correlation. Factors affecting the CO2 cerebrovascular reactivity were examined using bivariate and linear regression analyses. Results A total of 3847 1-h epochs were obtained from 140 studies of 72 premature infants. tcPCO2 correlated positively with Hb-T in 42% of epochs. In regression analysis, factors associated with increased percentage of positive correlation epochs were male sex and younger postmenstrual age (PMA; ß = 0.176, 0.169 and P-value = 0.036, 0.047 respectively). Factors associated with increased strength of positive correlation were mechanical ventilation and increased average tcPCO2 (ß = 0.198, 0.220 and P-value = 0.024, 0.011 respectively). Conclusion Increased prematurity, male sex, mechanical ventilation and hypercarbia are associated with stronger PCO2 cerebrovascular reactivity in premature infants. This association may explain their role in the pathogenesis of brain injury.

Fetal and Postnatal Echocardiographic Diagnosis of Ebstein Anomaly of the Mitral Valve.

Ebstein anomaly of mitral valve (MV) is an extremely rare congenital heart disease. In the current report, we present a case of Ebstein of MV that was diagnosed prenatally. Fetal echocardiogram showed that the posterior leaflet of MV was tethered to the lateral wall of left ventricle (LV) with downward displacement into LV cavity. Postnatal transthoracic and transesophageal echocardiograms confirmed the diagnosis with apical displacement of the level of coaptation MV into the LV cavity. To the best of our knowledge, fetal diagnosis of Ebstein anomaly of MV has not yet been reported in the medical literature.

Hypoplastic Left Heart Syndrome with Congenital Complete Heart Block.

Congenital complete atrioventricular block (CCAVB) is a rare condition with an incidence of 1 of 20,000 live births. Hypoplastic left heart syndrome (HLHS) occurs more frequently than CCAVB and occurs in 1 of 5000 live births. HLHS in association with CCAVB is exceedingly rare. In this report, we describe a rare case of HLHS and CCAVB diagnosed in utero. Postnatal diagnosis, management and outcome are presented as well as review of the medical literature.

Chronic Low Dose Prostaglandin and Neonatal Heart Block.

Long-term prostaglandin use is commonly associated with side effects such as cortical proliferation of the bones, hypertrophic pyloric stenosis, and soft tissue swelling of the extremities. We report a neonate with critical coarctation of the aorta, who developed second and third degree atrioventricular blocks associated with prolonged prostaglandin E1 (PGE1) infusion. Interestingly, these conduction blocks only occurred at low PGE1 dose. The rhythm disturbances resolved promptly with the discontinuation of PGE1 following surgical repair.

Transcutaneous Carbon Dioxide Monitoring with Reduced-Temperature Probes in Very Low Birth Weight Infants.

Background Obtaining blood gases in very low birth weight (VLBW) infants is an invasive procedure. Studies using transcutaneous carbon dioxide (tcPCO2) have reported variable skin complications with high-temperature probes. No enough data available on tcPCO2 monitoring using reduced-temperature probes (41°C). Objective The objective of this study was to assess reliability and safety of tcPCO2 monitoring at reduced-temperature probe in VLBW infants. Design and Methods A prospective study was conducted on VLBW infants. tcPCO2 was monitored for 12 hours. Default skin probe temperature was adjusted at 41°C. Blood gases were done as clinically indicated. Arterial partial pressure of CO2 (PaCO2) as well as capillary CO2 were compared with simultaneous tcPCO2. Results A total of 124 data points were identified from 50 patients (gestational age [GA] = 28.1 ± 2.4 weeks and birth weight [BW] = 1,035 ± 291 g). Patients were supported with continuous positive airway pressure (40%), noninvasive positive pressure ventilation (16%), mechanical ventilation (18%), and high-frequency oscillation ventilation (24%). PaCO2 was measured using either capillary (58%) or arterial (42%) samples. Mean CO2 did not differ between tcPCO2 (51.3 ± 16) and PaCO2 (49.1 ± 13.7) mm Hg. tcPCO2 showed positive correlation with partial pressure of CO2 (r = 0.6, p < 0.001). This correlation continued to be significant after controlling for GA, postmenstrual age, type of sample, and pH. No skin complications were reported. Conclusion tcPCO2 monitoring using a temperature of 41°C is feasible and reliable in VLBW infants.

Brain Maturity and Variation of Oxygen Extraction in Premature Infants.

Objectives The ability of the premature brain to extract and use oxygen has not been studied adequately. This study aimed to determine factors that influence fractional tissue oxygen extraction (FTOE) of the brain in premature infants using near-infrared spectroscopy (NIRS) and pulse oximetry. Study Design We prospectively studied FTOE in very low birth weight (BW) infants (< 1,500 g and ≤ 34 weeks' gestation). Factors affecting FTOE and its variability were examined using bivariate and linear regression models. FTOE variability was measured on two scales: short scales (3-20 seconds) and long scales (20-150 seconds). Results We examined 147 simultaneous NIRS and pulse oximetry recordings that were collected from 72 premature infants (gestational age [GA] = 28 weeks and BW = 1,036 g). In regression models, average FTOE correlated negatively with hemoglobin (Hb) and increased significantly in patients with severe intraventricular hemorrhage/periventricular leukomalacia. Both FTOE short- and long-scale variabilities correlated negatively with GA and positively with postnatal age (PNA). Moreover, FTOE long-scale variability was significantly reduced in infants supported with invasive ventilation. Conclusions In premature infants, cerebral oxygen extraction increased with reduced Hb and severe brain injury. Variability in oxygen extraction showed differential changes with GA and PNAs and was affected by invasive ventilation.

Neonatal outcomes in preterm infants with severe congenital heart disease: a national cohort analysis.

Background: Prematurity and congenital heart disease (CHD) are the leading causes of neonatal mortality and morbidity. Limited data are available about the outcomes of premature infants with severe CHD. Methods: We queried The National Inpatient Database using ICD-10 codes for premature patients (<37 weeks) with severe CHD from 2016 to 2020. Severe CHDs were grouped into three categories: A. left-sided lesions with impaired systemic output, B. Cyanotic CHD, and C. Shunt lesions with pulmonary overcirculation. Patients with isolated atrial or ventricular septal defects and patent ductus arteriosus were excluded. We also excluded patients with chromosomal abnormalities and major congenital anomalies. Patients' demographics, clinical characteristics, and outcomes were evaluated by comparing premature infants with vs. without CHD adjusting for gestational age (GA), birth weight, and gender. Results: A total of 27710 (1.5%) out of 1,798,245 premature infants had severe CHD. This included 27%, 58%, and 15% in groups A, B, and C respectively. The incidence of severe CHD was highest between 25 and 28 weeks of gestation and decreased significantly with increasing GA up to 36 weeks (p < 0.001). Premature infants with severe CHD had a significantly higher incidence of neonatal morbidities including necrotizing enterocolitis (NEC) [OR = 4.88 (4.51-5.27)], interventricular hemorrhage [OR = 6.22 (5.57-6.95)], periventricular leukomalacia [OR = 3.21 (2.84-3.64)] and bronchopulmonary dysplasia [OR = 8.26 (7.50-10.06) compared to preterm infants of similar GA without CHD. Shunt lesions had the highest incidence of NEC (8.5%) compared to 5.3% in cyanotic CHD and 3.7% in left-sided lesions (p < 0.001). Mortality was significantly higher in premature infants with CHD compared to control [11.6% vs. 2.5%, p < 0.001]. Shunt lesions had significantly higher mortality (11.0%) compared to those with left-sided lesions (8.3%) and cyanotic CHD (6.4%), p < 0.001. Conclusion: Premature infants with severe CHD are at high risk of neonatal morbidity and mortality. Morbidity remains increased across all GA groups and in all CHD categories. This significant risk of adverse outcomes is important to acknowledge when managing this patient population and when counseling their families. Future research is needed to examine the impact of specific rather than categorized congenital heart defects on neonatal outcomes.

Longitudinal Changes in Ventricular Mechanics in Adolescents After the Fontan Operation.

BACKGROUND: Ventricular dysfunction is a significant clinical challenge in the long-term follow-up of patients with single-ventricle (SV) physiology. Ventricular function and myocardial mechanics can be studied using speckle-tracking echocardiography, which provides information on myocardial deformation. Limited information is available on serial changes in SV myocardial mechanics after the Fontan operation. The aim of this study was to describe serial changes in myocardial mechanics in children after the Fontan operation and the relationship of these changes with myocardial fibrosis markers as obtained by cardiac magnetic resonance and exercise performance parameters. METHODS: The authors hypothesized that ventricular mechanics decline in patients with SVs over time and are associated with increased myocardial fibrosis and reduced exercise performance. A single-center retrospective cohort study including adolescents after the Fontan operation was conducted. Ventricular strain and torsion were assessed using speckle-tracking echocardiography. Cardiac magnetic resonance and cardiopulmonary exercise testing data closest to the latest echocardiographic examinations were performed. The most recent follow-up echocardiographic and cardiac magnetic resonance data were compared with those from sex- and age-matched control subjects and with individual patients' early post-Fontan data. RESULTS: Fifty patients with SVs (31 left ventricle, 13 right ventricle [RV], and six codominant) were included. Median time at follow-up echocardiography from the time of Fontan was 12.8 years (interquartile range [IQR], 10.6 to 16.6 years). Compared with early post-Fontan echocardiography, follow-up assessment showed reduced global longitudinal strain (-17.5% [IQR, -14.5% to -19.5%] vs -19.8% [IQR, -16.0% to -21.7%], P = .01], circumferential strain (-15.7% [IQR, -11.4% to -18.7%] vs -18.9% [IQR, -15.2% to -25.0%], P = .009), and torsion (1.28°/cm [IQR, 0.51°/cm to 1.74°/cm] vs 1.72°/cm [IQR, 0.92°/cm to 2.34°/cm], P = .02), with decreased apical rotation but no significant change in basal rotation. Single RVs had lower torsion compared with single left ventricles (1.04°/cm [IQR, 0.12°/cm to 2.20°/cm] vs 1.25°/cm [IQR, 0.25°/cm to 2.51°/cm], P = .01). T1 values were higher in patients with SV compared with control subjects (1,009 ± 36 vs 958 ± 40 msec, P = .004) and in those with single RVs compared with single left ventricles (1,023 ± 19 vs 1,006 ± 17 msec, P = .02). T1 was correlated with circumferential strain (r = 0.59, P = .04) and inversely correlated with O2 saturation (r = -0.67, P < .001) and torsion (r = -0.71, P = .02). Peak oxygen consumption was correlated with torsion (r = 0.52, P = .001) and untwist rates (r = 0.23, P = .03). CONCLUSIONS: After the Fontan procedures, there is a progressive decrease in myocardial deformation parameters. The progressive decrease in SV torsion is related to a decrease in apical rotation, which is more pronounced in single RVs. Decreased torsion is associated with increased markers of myocardial fibrosis and lower maximal exercise capacity. Torsional mechanics may be an important parameter to monitor after Fontan palliation, but further prognostic information is required.

Prenatal Diagnosis of Vascular Ring: Evaluation of Fetal Diagnosis and Postnatal Outcomes.

BACKGROUND: The impact of fetal echocardiography on the diagnosis and outcomes of vascular ring has not been well examined. We hypothesized that prenatal detection of vascular ring has improved over time and that prenatal diagnosis of vascular ring is associated with earlier intervention and favorable outcomes. METHODS: This is a single-center, retrospective study of the evolution and outcomes of prenatal diagnosis of vascular ring from 2000 to 2020. We compared clinical presentation, timing of surgical intervention, and outcomes between the prenatally and postnatally diagnosed cases during the same study period. RESULTS: A total of 170 patients were included: 50 with prenatal and 120 with postnatal diagnosis of vascular ring. Prenatal diagnoses included 42 patients (84%) with right aortic arch (RAA), aberrant left subclavian artery (ALSCA), and a left-sided ductus arteriosus and eight (16%) patients with double aortic arch (DAA). The postnatal cohort consisted mainly of 90 patients (75%) with DAA and 22 (18%) with RAA-ALSCA. None of the postnatally diagnosed cases had undergone a fetal echocardiogram. Numbers (percentage) of prenatally diagnosed cases of vascular ring compared with the postnatal cases improved from 4/31 (13%), to 10/29 (34%), to 14/25 (56%), and to 22/35 (69%), respectively, during 2000-2005, 2005-10, 2010-15, and 2015-20 (P = .032). Vascular ring was an isolated abnormality in 84% and 85% of the prenatal and postnatal cohorts, respectively. Compared with the prenatal cohort, postnatally diagnosed patients with an isolated vascular ring were more frequently symptomatic (66% vs 48%, P < .03) and underwent cross-sectional imaging (69% vs 44%, P = .009) and surgery more frequently (79% vs 48%, P = .003). Surgery was performed at a later patient age (18 [2-147] months vs 4.8 [0.5-42] months, P = .01) and was more often associated with residual symptoms (27/81 [33%] vs 1/20 [5%], P = .01) in the postnatal cohort than in the prenatal cohort. CONCLUSIONS: The diagnosis of vascular ring by fetal echocardiography has improved over time. A significantly higher incidence of RAA-ALSCA in the prenatal compared with the postnatal cohort suggests that patients with this form of vascular ring often do not present to medical attention with significant symptoms postnatally. Prenatal diagnosis of vascular ring was associated with a lower incidence of symptoms, less frequent use of cross-sectional imaging, earlier age at surgical intervention, and lower likelihood of residual symptoms.

Analyzing Continuous Physiologic Data to Find Hemodynamic Signatures Associated With New Brain Injury After Congenital Heart Surgery.

Continuous data capture technology is becoming more common. Establishing analytic approaches for continuous data could aid in understanding the relationship between physiology and clinical outcomes. OBJECTIVES: Our objective was to design a retrospective analysis for continuous physiologic measurements and their relationship with new brain injury over time after cardiac surgery. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study in the Cardiac Critical Care Unit at the Hospital for Sick Children in patients after repair of transposition of the great arteries (TGA) or single ventricle (SV) lesions. MAIN OUTCOMES AND MEASURES: Continuously acquired physiologic measurements for up to 72 hours after cardiac surgery were analyzed for association with new brain injury by MRI. Distributions of heart rate (HR), systolic blood pressure (BP), and oxygen saturation (Spo2) for SV and TGA were analyzed graphically and with descriptive statistics over postoperative time for data-driven variable selection. Mixed-effects regression analyses characterized relationships between HR, BP, and Spo2 and new brain injury over time while accounting for variation between patients, measurement heterogeneity, and missingness. RESULTS: Seventy-seven patients (60 TGA; 17 SV) were included. New brain injury was seen in 26 (34%). In SV patients, with and without new brain injury, respectively, in the first 24 hours after cardiac surgery, the median (interquartile range) HR was 172.0 beats/min (bpm) (169.7-176.0 bpm) versus 159.6 bpm (145.0-167.0 bpm); systolic BP 74.8 (67.9-78.5 mm Hg) versus 68.9 mm Hg (61.6-70.9 mm Hg). Higher postoperative HR (parameter estimate, 19.4; 95% CI, 7.8-31; p = 0.003 and BP, 8.6; 1.3-15.8; p = 0.024) were associated with new brain injury in SV patients. The strength of this relationship decreased with time. CONCLUSIONS AND RELEVANCE: Retrospective analysis of continuous physiologic measurements can provide insight into changes in postoperative physiology over time and their relationship with new brain injury. This technique could be applied to assess relationships between physiologic data and many patient interventions or outcomes.

Neonatal Myocardial Infarction in Association With Gestational Diabetes.

Fetal and neonatal hypertrophic cardiomyopathy is a complication of gestational diabetes and usually follows a benign course. In this report, we present a rare case of a newborn of a diabetic mother with severe ventricular hypertrophy who developed myocardial infarction confirmed by elevated cardiac enzymes, electrocardiographic changes, and subendocardial ischemia on cardiac magnetic resonance imaging. Follow-up revealed complete functional myocardial recovery with normalisation of ventricular systolic and diastolic functions on serial echocardiograms.

The Many Faces of Neonatal Ductus Arteriosus Aneurysms: Multimodality Imaging with an Emphasis on CT and MRI Appearance.

Neonatal ductus arteriosus aneurysm (DAA) is a rare abnormality that is typically diagnosed at fetal third trimester or early postnatal echocardiography. While echocardiography is usually adequate for diagnosis and clinical decision-making, cross-sectional imaging, including CT or cardiac MRI, may be necessary to clarify the diagnosis or delineate associated complications. Severe complications include thromboembolism, infection, compression of adjacent structures, airway erosion, and aneurysm rupture. This imaging essay reviews the pathophysiology and depicts the spectrum of cross-sectional imaging appearances of neonatal DAAs. Most neonatal DAAs will spontaneously regress and can be managed conservatively. Keywords: CT, MRI, Cardiac, Aneurysms, Congenital Supplemental material is available for this article. ©RSNA, 2021.

Myocardial Fibrosis in Pediatric Patients With Ebstein's Anomaly.

BACKGROUND: Left ventricular dysfunction in Ebstein's anomaly (EA) is associated with higher mortality. The health of the left ventricular myocardium in children and adolescents with EA has not been investigated in detail. METHODS: Patients with unrepaired EA who had undergone cardiac magnetic resonance imaging including T1 mapping were retrospectively reviewed. Patients were compared with age- and sex-matched controls. EA severity index was calculated using volumetric measurements at end diastole ([right atrial+atrialized right ventricular volumes]/[functional right ventricular+left atrial+left ventricular volumes]). Global circumferential and radial strain and as well as strain rate were examined using cardiac magnetic resonance feature tracking. RESULTS: Twelve EA patients and an equal number of controls were included. Functional and atrialized right ventricular end-diastolic volumes were 84±15 and 21±13 mL/m2, respectively. Late gadolinium enhancement, confined to the right ventricle, was found in 2 patients (16%). Left ventricular native T1 values and extracellular volume fractions were higher in patients compared with controls (1026±47 versus 956±40 ms, P=0.0004 and 28.5±3.4% versus 22.5±2.6%, P<0.001, respectively). Native T1 times correlated inversely with patients' age, body surface area, and O2 saturations (r=-0.63, -0.62, and -0.91, respectively; P=0.02, P=0.02, and P<0.0001, respectively). EA severity index ranged between 0.15 and 0.94 and correlated with T1 values (r=0.76, P=0.003). Native T1 correlated with global circumferential strain (r=0.58, P=0.04) but not ejection fraction (EF). EA patients had reduced maximum oxygen uptake (Vo2max). Vo2max correlated inversely with T1 values (r=-0.79, P=0.01). CONCLUSIONS: Children and adolescents with EA experience an abnormal degree of diffuse myocardial fibrosis. Its association with O2 saturation points toward a role of hypoxemia in the pathogenesis of fibrosis. Larger and prospective studies are needed to evaluate the value of T1 mapping for risk stratification and monitoring in EA.

Changes in cerebral tissue oxygenation and fractional oxygen extraction with gestational age and postnatal maturation in preterm infants.

OBJECTIVE: This study examined the correlation of cerebral tissue oxygen saturation (SctO2) and cerebral tissue fractional oxygen extraction (cFTOE) with gestational age (GA) and postnatal age over the first 28 days of life. STUDY DESIGN: Preterm infants with birth weight (BW) <1500 g were monitored with near-infrared spectroscopy (NIRS) during the first 28 days of life. SctO2 and cFTOE measurements were analyzed using a linear mixed model. RESULTS: A total of 70 preterm infants were included. Mean SctO2 decreased with increasing GA; SctO2 was 76.4% and 74.6% in the first 24 h for infants 24 and 28-week GA, respectively. For infants born at 24 and 28 it decreased to 52.9% and 58.4% at 28 days of life, respectively. cFTOE increased with increasing GA and postnatal age. CONCLUSIONS: There is an inverse relationship between SctO2 and gestational age and postnatal age but a direct relationship between cFTOE with GA and postnatal age.

Amino Acid and Phospholipid Metabolism as an Indicator of Inflammation and Subtle Cardiomyopathy in Patients with Marfan Syndrome.

Patients with Marfan syndrome (MFS) have an increased risk of aortic aneurysm formation, dissection and development of a subtle cardiomyopathy. We analyzed amino acid and lipid metabolic pathways in MFS patients, seeking biomarker patterns as potential monitoring tools of cardiovascular risk with deterioration of myocardial function. We assessed myocardial function in 24 adult MFS patients and compared traditional laboratory values and mass spectrometry-based amino acid, phospholipid and acylcarnitine metabolomes in patients with those in healthy controls. Analytes for which values differed between patients and controls were subjected to regression analysis. A high proportion of patients had signs of impaired diastolic function and elevated serum levels of NT-proBNP. Patients had lower serum levels of taurine, histidine and PCaeC42:3 than controls. The evidence of diastolic dysfunction, aortic root dimensions and history of aortic root surgery correlated with NT-proBNP and taurine levels. Alterations in serum levels of metabolism derived analytes link MFS pathophysiology with inflammation, oxidative stress and incipient cardiomyopathy.

Anomalous Origin of Left Coronary Artery From Right Pulmonary Artery in Association With Scimitar Syndrome.

This paper reports a unique case of anomalous origin of the left coronary artery from the right pulmonary artery associated with scimitar syndrome. The presence of pulmonary hypertension may have contributed to maintain coronary perfusion, which likely prevented early significant coronary steal. This study reports the clinical course, diagnosis challenges, and management strategy. (Level of Difficulty: Intermediate.).

Complicated ventricular arrhythmia and hematologic myeloproliferative disorder in RIT1-associated Noonan syndrome: Expanding the phenotype and review of the literature.

BACKGROUND: Noonan syndrome is an autosomal dominant disorder secondary to RASopathies, which are caused by germ-line mutations in genes encoding components of the RAS mitogen-activated protein kinase pathway. RIT1 (OMIM *609591) was recently reported as a disease gene for Noonan syndrome. METHODS AND RESULTS: We present a patient with RIT1-associated Noonan syndrome, who in addition to the congenital heart defect, had monocytosis, myeloproliferative disorder, and accelerated idioventricular rhythm that was associated with severe hemodynamic instability. Noonan syndrome was suspected given the severe pulmonary stenosis, persistent monocytosis, and "left-shifted" complete blood counts without any evidence of an infectious process. Genetic testing revealed that the patient had a heterozygous c.221 C>G (pAla74Gly) mutation in the RIT1. CONCLUSION: We report a case of neonatal Noonan syndrome associated with RIT1 mutation. The clinical suspicion for Noonan syndrome was based only on the congenital heart defect, persistent monocytosis, and myeloproliferative process as the child lacked all other hallmarks characteristics of Noonan syndrome. However, the patient had an unusually malignant ventricular dysrhythmia that lead to his demise. The case highlights the fact that despite its heterogeneous presentation, RIT1-associated Noonan syndrome can be extremely severe with poor outcome.

Negative Impact of Obesity on Ventricular Size and Function and Exercise Performance in Children and Adolescents With Repaired Tetralogy of Fallot.

BACKGROUND: Up to 25% of children with congenital heart disease are obese, which may have negative physiologic consequences for patients with repaired tetralogy of Fallot (rTOF). METHODS: Patients with rTOF who underwent cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise testing from 2007 to 2018 were reviewed. Complex rTOF patients were excluded. Obese patients (body mass index [BMI] ≥ 95th percentile) were compared with normal-weight patients (BMI < 85th percentile). CMR data were indexed to actual body surface area (aBSA), height, and BSA assuming ideal body weight (iBSA). RESULTS: We compared 32 obese patients matched with 64 normal-weight patients. Obese vs normal-weight patients had significantly lower right (RV; median 45% [interquartile range 42%-48%] vs 52% [47%-55%]; P < 0.0001) and left (LV; 52% [47%-56%] vs 56% [54%-60%]; P < 0.0001) ventricular ejection fractions (EFs). There were no statistically significant differences regarding aBSA-indexed volumes of the RV or LV at either end-diastole (EDV) or end-systole (ESV). However, when indexed to either height or iBSA, obese patients had significantly greater RVEDV and LVEDV, greater LV mass, and higher RV and LV stroke volumes. Obese patients had lower peak oxygen consumption and oxygen consumption at anaerobic threshold. These results did not change after adjusting for degree of pulmonary regurgitation. CONCLUSIONS: Obesity is associated with increased biventricular size, decreased biventricular EFs, and impaired exercise performance after rTOF. These data suggest a potential role for cardiac rehabilitation for weight management and to optimize fitness.