Pediatric Cardiology

Dobutamine stress cardiac MRI is safe and feasible in pediatric patients with anomalous aortic origin of a coronary artery (AAOCA).

Dobutamine stress cardiac MRI is safe and feasible in pediatric patients with anomalous aortic origin of a coronary artery (AAOCA). Doan TT, Molossi S, Sachdeva S, Wilkinson JC, Loar RW, Weigand JD, Schlingmann TR, Reaves-O'Neal DL, Pednekar AS, Masand P, Noel CV.Int J Cardiol. 2021 Apr 20:S0167-5273(21)00667-7. doi: 10.1016/j.ijcard.2021.04.031. Online ahead of print.PMID: 33892043 Take home points: Dobutamine stress cardiac MRI (DSCMR) is feasible and safe in pediatric patients with AAOCA, with very low risk of major or minor adverse events Inducible hypoperfusion was present in a small percentage of patients, along with wall motion abnormalities, suggesting that detection of myocardial ischemia with this modality may be helpful in the management of these patients Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch:  Testing to reliably risk stratify patients with AAOCA has not yet been fully elucidated. It is well known that exercise stress testing, stress echo and nuclear perfusion imaging have a low negative predictive valve in detecting myocardial ischemia. This is especially true in patients with anomalous origin of the right coronary artery (AAORCA). This single center study from Texas Children’s Hospital prospectively enrolled all patients < 20 years old with AAOCA. DSCMR and dobutamine administration was performed via the following protocol showed in Figure 1. First pass imaging was added to the protocol due to previous research studies showing reversible ischemia preceding wall motion abnormalities. Dobutamine increases heart rate and contractility, decreases systemic vascular resistance and increases coronary vasodilation which makes it a useful agent to increase oxygen consumption. Atropine was added to achieve the target HR of at least 150 bpm. They also targeted a calculated rate pressure product (RPP) of greater than 20x10^3 bpm*mmHg, which was considered an indirect estimate of high intermediate myocardial oxygen consumption. Inducible hypoperfusion predicts adverse outcomes in adults with ischemic heart disease, so this study was done to assess the feasibility and safety in the pediatric population and to help decision making with their cohort (eg. surgery vs. observation). 221 DSCMRs were completed on 182 patients. 14% had AAOLCA, 9% had intraseptal AAOLCA, and 77% had AAORCA.  Maximum dobutamine dose of 40 mcg/kg/min was given in 94% of studies, and atropine was given in 63%. Sedation was provided in 17% of patients primarily due to younger age. 86% achieved the target RPP. Heart rate did not affect first pass perfusion image quality and only HR > 85% age-predicted maximum reduced cine image quality, which was still adequate in all patients. Intraobserver agreement was very good. No major events (ventricular arrhythmia, MI, cardiac arrest) occurred, and 12.5% had minor events (severe HTN, chest pain, nausea/vomiting, paradoxical bradycardia, rash, anxiety, dizziness, or dyspnea) with none associated with sedation.   Inducible hypoperfusion was detected in 31/221, with 13/31 having wall motion abnormalities. See Table 2. Of the 161 first time DSCMR, 80% had AAORCA, 10% AAOLCA, and 10% intraseptal AAOLCA. Symptoms of exertional chest pain or exertional syncope were associated with inducible hypoperfusion. 13% of AAORCA, 18% AAOLCA, and 44% intraseptal had inducible hypoperfusion (total 27/161). 70% of those underwent successful surgical intervention, 15% were pending, and 15% were medically managed. Post-surgery, only 1 had inducible hypoperfusion on DSCMR that resolved on a follow up study and no patients with a negative DSCMR had any concerning symptoms or events during the time of the study. Figure 4 shows the distribution of regional inducible hypoperfusion seen in AAOLCA and AAORCA. While this study was mostly observational/feasibility, it is important to mention a few caveats. First, it was not clear which patients received surgery, although this may be published elsewhere. Many centers will operate on all patients with AAOLCA regardless of stress testing or MRI, so the utility of DSCMR in this subgroup may be less relevant. Additionally, there was no mention of any patients who had exertional symptoms but a negative DSCMR.  There was no discussion on whether any assessment of the RV could be done on MRI, a known limitation of all stress imaging tests, including MRI, and potentially more important in AAORCA. The authors discuss the lack of an evidence-based target hemodynamic response in the assessment of FPP, so it could be possible that this is not providing the same hemodynamics as exercise or in the pathophysiology of sudden cardiac death. All pediatric and sports cardiologist hope that we can find better testing to risk assess this challenging population, specifically those with AAORCA, where many are diagnosed incidentally and are asymptomatic. This study was not designed to assess negative predictive value so longer term studies will be necessary. Overall though, it is very helpful to know that this test can be done with good quality, and with more centers adding this to the arsenal of testing, hopefully we will have more meaningful data in the future.  

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Left atrial strain and function in pediatric hypertrophic cardiomyopathy.

Left atrial strain and function in pediatric hypertrophic cardiomyopathy. Jhaveri S, Komarlu R, Worley S, Shahbah D, Gurumoorthi M, Zahka K.J Am Soc Echocardiogr. 2021 Apr 26:S0894-7317(21)00431-4. doi: 10.1016/j.echo.2021.04.014. PMID: 33915246 Take home points: Left atrial (LA) strain and dysfunction are markers of diastolic dysfunction, associated with poor exercise capacity in hypertrophic cardiomyopathy patients. Children with phenotype positive hypertrophic cardiomyopathy have reduced LA function, measurable by both volumetric and strain analysis. LA conduit function, LA reservoir function and LA reservoir strain were lower in Phenotype positive hypertrophic cardiomyopathy than in Genotype positive and phenotype negative patients. Children with phenotypic HCM have lower left atrial strain values. Altered LA mechanics are associated with poor exercise capacity. Lower LA conduit function is associated with worsened aerobic capacity in pediatric HCM.         Commentary from Dr. Manoj Gupta (New York, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch Introduction Literature on the assessment of diastolic dysfunction in pediatric HCM has focused primarily on the use of tissue Doppler indices, left atrial (LA) size, and inflow patterns. Research in adult HCM has shown that LAS values are independently associated with adverse outcomes, including heart failure, worsened exercise capacity, arrhythmias, stroke, and death. Left atrial Parameters Volumetric analysis of the left atrium was performed from apical four-chamber and two chamber views and was indexed to body surface area. LA volume (LAV) was collected at three points in the cardiac cycle as follows: (1) maximum LAV just before mitral valve opens (LAV max), (2) minimal LAV at the end of diastole when the mitral valve closes (LAV min), and (3) LAV just before atrial systole, before the p wave on electrocardiography (LAV pre-A). Reservoir function = LAV max - LAV min/ LAV min Conduit function = LAV max - LAV pre-A/LAV max Booster pump function = LAV pre-A - LAV min/LAV pre-A RESULTS The HCM cohort consisted of 78 subjects with a median age of 16 years (range, 3–25 years), of whom 60 (64%) were male). Phenotypic criteria for HCM were present in 59% patients (P+ group, n = 46) whereas the remaining carried the genotype but lacked phenotypic characteristics (G+P- group, n = 32). (Table 1) Diastolic Parameters The maximal LA volume index (LAVI) was higher in patients with P+ HCM compared with the G+P- and control groups (median, 28 vs 20 vs 19 mL/m2 , respectively; P < .001). Nearly one third of the P+ group (32% [n = 14]) had LAVI > 34 mL/m2 , which is the adult cutoff for LA dilation. Higher LAVI was associated with higher NTproBNP (r = 0.43; 95% CI, 0.05–0.71; P = .029). DISCUSSION Left atrial strain and volumetric function parameters were significantly lower in patients with phenotypic (P+) HCM compared with those with a positive genotype but without significant hypertrophy (G+P-). On the basis of these results and known literature, it can be concluded that children with HCM have impaired reservoir and conduit function, similar to their adult counterparts. However, given that they have preserved contractile pump function in childhood years, it can be speculated that changes in their atrial contractile function probably take place as they age. CONCLUSION Altered atrial mechanics, as measured by volumetric and strain analysis, are present even in the pediatric population with phenotypic HCM.

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Delivery room oxygen physiology and respiratory interventions for newborns with cyanotic congenital heart disease.

Delivery room oxygen physiology and respiratory interventions for newborns with cyanotic congenital heart disease. Thomas AR, Ma AL, Weinberg DD, Huber M, Ades A, Rychik J, Foglia EE. J Perinatol. 2021 Mar 23. doi: 10.1038/s41372-021-01029-2. PMID: 33758390     Take-Home Points: In a single-center retrospective study of neonates born with cyanotic congenital heart disease, a comparison was made of the trends of oxygen saturations for the first ten minutes after birth between three physiologies – single ventricle physiology with critical aortic obstruction, single or double ventricle physiology with pulmonary outflow obstruction, and those with transposition of great arteries physiology (TGA) Infants with TGA physiology had lower pulse oximetry levels at all recorded time points (up to 10 min) when compared to those with ductal dependent systemic and pulmonary circulation. Infants with TGA physiology received supplemental oxygen therapy and respiratory interventions more frequently than the other groups. Majority of the infants had stable cardiovascular status with initially recorded heart rates of more than 100 beats per minute.     Commentary from Dr. Venu Amula (Salt Lake City, UT, USA), section editor of Pediatric & Fetal Cardiology Journal Watch:  Newborns with cyanotic congenital heart disease differ from normal neonates concerning oxygen saturations(SpO2). Their transition from fetal to neonatal physiology at birth is also different, and reference oxygen saturation trajectories and respiratory interventions needed have not been well established. In this study by AR Thomas et al., the authors characterize and trend SpO2 values at birth in neonates with cyanotic congenital heart disease. They also report the frequency and intensity of delivery room respiratory interventions in neonates during the birth transition. This single-center, retrospective study of all infants born at > or = 32 weeks GA with a prenatal diagnosis of cyanotic congenital heart disease at a quaternary pediatric care center with a Level IV neonatal care nursery. Based on fetal echocardiogram – the infants were grouped into three categories – those with single ventricle physiology with critical aortic obstruction (SV-CAO )leading to ductal dependent systemic circulation, those with critical pulmonary outflow obstruction ( CPO) with either single ventricle or two ventricles but ductal dependent pulmonary flow and the third group with transposition physiology (TGA) where the systemic and pulmonary circulations are in parallel. At birth for all infants, the standardized institution neonatal resuscitation guidelines were followed with anticipated goal saturations of 75-85% for neonates given their cyanotic heart lesion. The saturations were measured on the right hand to obtain preductal measurements. Interventions were indicated to maintain saturations in the goal range and provide supplemental oxygen therapy, continuous positive airway pressure, positive pressure ventilation, and endotracheal intubation. Delivery room interventions and minute-to-minute SpO2 values were compared across and between three diagnostic groups using standard statistical tests. Of 208 infants ≥32 weeks gestation with eligible prenatally diagnosed cardiac lesions born during the study period, 196 infants were included in the analyses of oxygen saturation and respiratory intervention data. The TGA group had lower pulse SpO2 values at each time point. Comparing each group separately to TGA showed significant differences in SpO2 values at each minute (all p < 0.01 for CPO v TGA and all p < 0.02 for SV-CAO v TGA). No significant differences were found in pairwise comparison of the SV-CAO group to CPO group (p > 0.05) in SpO2 values at each minute after birth. Infants with TGA physiology received supplemental oxygen and non-invasive respiratory interventions more frequently than the infants in the SV-CAO and the CPO groups (Table 3). Significantly more infants with TGA physiology underwent endotracheal intubation in the resuscitation suite (53%) and occurred at a median of 24 (IQR 18–35) minutes after birth.         This study attempts to analyze the trends of target oxygen saturation in children with cyanotic congenital heart disease immediately after birth. These infants represent a heterogeneous group of neonates, and even within the same physiology group, the spectrum of disease dictates the target oxygen saturation achieved. The interventions were performed to achieve the goal target oxygen saturations of 75-85% - and represent the current practice in most institutions, although the optimal saturations are not well known. The goal is to accept some degree of hypoxia to maintain adequate systemic perfusion. Though the study represents a single-center practice, this information is valuable to guide physicians in providing resuscitation to babies with known cyanotic heart disease. Smoothed conditional curves of the 25th, 50th, and 75th percentiles for pre-ductal SpO2 values for minutes 3–10 after birth were plotted for each diagnostic group and for comparison, the 25th, 50th, and 75th percentile values for SpO2 at each minute reported for infants without CCHD by Dawson et al.(1)             Dawson JA, Kamlin COF, Vento M, Wong C, Cole TJ, Donath SM, et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics. 2010;125:e1340–7.

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Comparison of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot.

Goldstein BH, Petit CJ, Qureshi AM, McCracken CE, Kelleman MS, Nicholson GT, Law MA, Meadows JJ, Zampi JD, Shahanavaz S, Mascio CE, Chai PJ, Romano JC, Batlivala SP, Maskatia SA, Asztalos IB, Kamsheh AM, Healan SJ, Smith JD, Ligon RA, Pettus JA, Juma S, Raulston JEB, Hock KM, Pajk AL, Eilers LF, Khan HQ, Merritt TC, Canter M, Juergensen S, Rinderknecht FA, Bauser-Heaton H, Glatz AC. J Am Coll Cardiol. 2021 Mar 2;77(8):1093-1106. doi: 10.1016/j.jacc.2020.12.048. PMID: 33632484 Take-Home Points: In children with symptomatic Tetralogy of Fallot, needing neonatal intervention, a comparison made between those managed with staged repair (SR) vs. primary repair (PR) showed balanced results. Upon adjusting for patient factors, early mortality risk was higher in the PR group; however, the overall risk of death did not differ between treatment groups. Lesser neonatal morbidity was reported in the SR group. In contrast, the overall cumulative morbidity burden (combining the initial palliation and complete repair in the SR group) favored the primary repair group. Reintervention risk was higher in the SR group, but late reintervention risk (>3 months) and reintervention burden following definitive repair did not differ between groups. Both strategies have potential benefits, and hence an individualized case-based approach is warranted based on patient, procedural and institutional factors. Commentary from Dr. Venu Amula (Salt Lake City, UT, USA), section editor of Pediatric & Fetal Cardiology Journal Watch:  Tetralogy of Fallot (TOF) is a congenital heart disease with a spectrum of cyanosis based on the degree of right ventricular outflow tract obstruction. Neonates can be symptomatic early, with cyanosis needing an intervention. Early intervention in symptomatic neonates can be palliative – both surgical and transcatheter procedures to provide additional pulmonary blood flow, or some may consider primary repair of the intracardiac defect. In this study by Goldstein et al., the investigators seek to compare the two treatment strategies of staged repair (SP) ( initial palliation [IP] followed by complete repair [CP])  and Primary repair (PR). The authors performed a retrospective cohort study using a multicenter collaborative with good sample size and practice variability to compare outcomes adjusted for patient-level differences and reduce confounding by indication. Study subjects included all neonates with tetralogy of Fallot who underwent an initial intervention  < or = 30 days at the nine centers of the Congenital Cardiac Research Collaborative. The indication of intervention was cyanosis, ductal dependent pulmonary blood flow, or hyper cyanotic episodes. Cases with discontinuous pulmonary arteries, TOF associated with Atrioventricular canal, Absent Pulmonary Valve, and Major Aortopulmonary Collaterals were excluded. The index procedure ( Initial Palliation or Primary Repair ) was the exposure, with the primary outcome being death or heart transplantation. Secondary outcomes included in-hospital mortality, procedural and hospital complications, reinterventions, and other measures of morbidity. The five variables most likely associated with treatment strategy ( SR vs. PR) – center, preintervention mechanical ventilation, prematurity, DiGeorge syndrome, and presence of antegrade blood flow were used in a logistic regression model to estimate propensity scores. Inverse probability of treatment weighting using propensity scores was used to adjust for potential confounders between groups. The effect of treatment strategy on dichotomous outcomes was evaluated by logistic regression weighted by propensity score. Time-dependent outcomes were analyzed with survival analysis. The overall study cohort consisted of 572 patients, 230 treated with primary repair and 345 with initial palliation.     Adjusted comparison of the primary outcome of death ( none got transplanted in this cohort)  showed no difference in the overall hazard of death (HR: 0.82; 95% CI: 0.49 to 1.38; p = 0.459), although early mortality hazard (<4 months post-intervention) was lower in the SR group (HR: 0.5; 95% CI: 0.25 to 0.97; p =0.041). Propensity score-adjusted differences in continuous secondary outcomes of neonatal morbidities, including procedural complications, duration of mechanical ventilation and inotrope use, procedural support times (CPB, cross-clamp, anesthesia), and ICU LOS, remained lower in the SR group at the index procedure. As was the case in the observed data, the adjusted cumulative burden of the SR strategy was associated with greater exposure to procedural, ICU, and post-procedural secondary outcomes than in the PR group. Adjusted differences in the outcomes of in-hospital mortality and complications showed that the risk of in-hospital mortality was lower in the SR group at the index procedure (OR: 0.37; 95% CI: 0.15 to 0.88; p = 0.025) and again at definitive repair (OR: 0.25; 95% CI: 0.09 to 0.69; p = 0.008), but when the entirety of the SR strategy was compared with PR, there was no difference in the risk of in-hospital mortality between groups (OR: 0.57; 95% CI: 0.26 to 1.24; p = 0.16). Similarly, although components of the SR pathway demonstrated lower rates of complications, there were no differences in the rate of procedural complications (OR: 0.84;95%CI:0.6to1.19; p = 0.33) or hospital complications (OR: 1.13; 95% CI: 0.79 to 1.61; p =0.51) between the treatment groups when the cumulative therapeutic pathways were compared.   The authors tried to address the vital issue of comparing staged repair vs. primary repair in the setting of symptomatic neonates with tetralogy of Fallot. While a well-designed  Randomized Controlled Trial would make the treatment groups well balanced to make an unbiased comparison of two treatment strategies – the large sample size from a research collaborative gave the authors unique opportunity to apply statistical methodology to adjust patient differences and provide a meaningful comparison of outcomes.  Given that early mortality, neonatal morbidity, and procedural complications were lower in the SR group, whereas cumulative morbidity and reinterventions favored the PR group, the authors conclude that an individualized, case-based approach to the initial interventional strategy is warranted.

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Increases in oxygen saturation following discharge from Fontan palliation – an indicator of resolution of pulmonary arteriovenous malformations?

Increases in oxygen saturation following discharge from Fontan palliation - an indicator of resolution of pulmonary arteriovenous malformations? Van Galder H, Schaal AM, Feng M, Pan AY, Frommelt MA, Ginde S, Spearman AD. Cardiol Young. 2021 Mar 11:1-7. doi: 10.1017/S1047951121000913. PMID: 33691814   Take Home Points:   Pulmonary arteriovenous malformations in single ventricle congenital heart disease are poorly understood. Pulmonary arteriovenous malformations are variably diagnosed prior to Fontan palliation; however, all study groups had increased oxygen saturations after Fontan discharge, potentially indicating resolution of pulmonary arteriovenous malformations in all groups. The prevalence of pulmonary arteriovenous malformations pre-Fontan is likely underestimated.   Commentary from Dr. Manoj Gupta (New York, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch   Introduction: In single ventricle patients, intrapulmonary shunting through pulmonary arteriovenous malformations may develop, worsen, or regress after Fontan palliation and can variably impact oxygen saturation. The prevalence of pulmonary arteriovenous malformations in single ventricle CHD is variably reported – ranging from 15 to 100% depending on the specific cohort, diagnostic criteria, and follow-up duration.   The primary objective of this study was to determine whether pulmonary arteriovenous malformations are diagnosed more frequently before Fontan palliation in patients with heterotaxy syndrome compared to matched non-heterotaxy patients. Secondarily the authors sought to compare oxygen saturation changes after Fontan discharge as a clinical marker of resolution of pulmonary arteriovenous malformations.   Diagnosis of pulmonary arteriovenous malformations pre-Fontan was obtained by contrast echocardiogram using agitated saline (“bubble study”) or during cardiac catheterization. Severity of shunting was classified as negative (no bubbles entering the single ventricle), mild (occasional or few bubbles filling of the single ventricle), moderate (moderate filling of the single ventricle), or severe (complete opacification of the single ventricle)   Results   A total of 124 patients with single ventricle CHD and previous Fontan palliation were included in this study with 62 heterotaxy patients and 62 non-heterotaxy hypoplastic left heart syndrome controls. Of the 62 heterotaxy patients, 14 (22.6%) had an interrupted inferior cava vein.   Patients with heterotaxy and interrupted inferior cava vein were more likely to have a documented diagnosis of pulmonary arteriovenous malformations in their medical record prior to Fontan palliation (85.7%) compared to patients with heterotaxy and intact inferior caval vein (20.8%) and non-heterotaxy control (24.2%) (p < 0.01).  Using a linear mixed model, there was no difference in Pre-Fontan oxygen saturations among the three groups (heterotaxy: intact inferior caval vein 82.0 (78.0, 85.0)%, interrupted inferior caval vein 80.5 (77.0, 85.0)%; non-heterotaxy control 82.0 (79.0, 85.0)%   At Fontan discharge, the non-heterotaxy control group (90.0 (86.0, 94.0)%) increased their oxygen saturations more than both heterotaxy sub-groups (intact inferior caval vein 87.0 (83.0, 92.0)%, p < 0.01; interrupted inferior caval vein 84.0 (82.0, 86.0)%, p < 0.01), but there was no difference in oxygen saturation between the two heterotaxy sub-groups (p = 0.18).   At 3, 6, and 12 months post-Fontan, there was no difference in oxygen saturation among the three groups at each time point.   Discussion   In this study, patients with heterotaxy syndrome and non-heterotaxy hypoplastic left heart syndrome had variable diagnostic rates of pulmonary arteriovenous malformations pre-Fontan, yet all study groups had increases in oxygen saturation after Fontan discharge. This data indicate that pulmonary arteriovenous malformations are present prior to Fontan palliation and resolve after Fontan palliation for patients with and without heterotaxy syndrome. The specific patient factors that increase susceptibility to pulmonary arteriovenous malformations remain unknown. Despite a lack of consensus on the prevalence and optimal diagnostic criteria for pulmonary arteriovenous malformations, studies have repeatedly used increased oxygen saturations after Fontan discharge as a surrogate for resolution of pulmonary arteriovenous malformations.   In conclusion, our data indicate that pulmonary arteriovenous malformations are variably diagnosed prior to Fontan palliation. It remains unclear, though, if there are true differences in susceptibility to pulmonary arteriovenous malformations because patients with and without heterotaxy syndrome have increases in oxygen saturations throughout the first year after Fontan discharge. A quantitative, systematic approach to diagnosis and follow-up pulmonary arteriovenous malformations is needed to better understand pulmonary microvascular remodeling in single ventricle CHD.

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Higher efficacy of infliximab than immunoglobulin on Kawasaki disease, a meta-analysis

Higher efficacy of infliximab than immunoglobulin on Kawasaki disease, a meta-analysis. Li X, Tang Y, Ding Y, Chen Y, Hou M, Sun L, Qian G, Qin L, Lv H. Eur J Pharmacol. 2021 Feb 27;899:173985. doi: 10.1016/j.ejphar.2021.173985. Online ahead of print. PMID: 33652059   Take Home Points: Infliximab was more effective than the control group, with the total summary odds ratio (OR) of 0.34 (95% confidence interval (CI): 0.19–0.62). The treatment resistance of the infliximab group was lower than the IVIG group (0.36 [95% CI: 0.14–0.92]) when infliximab was combined with IVIG as the initial treatment. Infliximab treatment for IVIG resistant KD was more effective than the IVIG group (0.28 [95% CI: 0.12–0.66]). Infliximab improved clinical course in IVIG resistant KD patients. Infliximab treatment did not reduce the incidence of coronary artery lesions and did not show any significant increase in the incidence of adverse events. Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch:   Introduction Kawasaki disease (KD) is a systemic immune vasculitis disease affecting the small and medium arteries. Coronary artery lesions (CALs) are one of the most severe complications in KD patients. A high dose of intravenous immunoglobulin (IVIG) is the mainstream treatment of KD. However, about 10–20% of KD patients show resistance to IVIG treatment. A good number of studies in recent days have shown that infliximab could be an effective treatment for IVIG-resistant KD. This is a meta-analysis for the comprehensive evaluation of infliximab’s efficacy and safety as initial therapy for patients with KD and IVIG resistant KD by including both prospective and high-quality retrospective studies. Eight studies were included in this meta-analysis study. These studies covered 713 patients, with 327 cases in the infliximab treated group and 386 in the control group.     Effective of infliximab on KD The total summary OR was 0.34 (95% CI: 0.19 to 0.62) with low heterogeneity (I2 = 30.1%), which showed that infliximab was more effective than the control group. The summary OR of infliximab treatment of IVIG resistant group was 0.28 (95% CI: 0.12 to 0.66), with low heterogeneity (I2 = 0). The results revealed that infliximab treatment was as effective as the initial treatment of KD as well as for IVIG resistant KD.   Coronary artery lesions (CAL) Six studies reported the CALs complication. The summary OR of infliximab treatment on the IVIG resistant group was 0.88 (95% CI: 0.48 to 1.62), with low heterogeneity (I2 = 0). The summary OR was 0.64 (95% CI: 0.23 to 1.74) for infliximab as initial treatment group, with low heterogeneity (I2 = 0), the summary OR of infliximab as treatment of IVIG resistant group was 1.06 (95% CI: 0.49 to 2.28), with low heterogeneity (I2 = 7.9)   Adverse events (AEs) Six studies reported the AEs. Analysis revealed that the incidence of AEs between both groups was not significant. The summary OR was 0.71 (95% CI: 0.44 to 1.16), with low heterogeneity (I2 = 45.3%   Infusion reaction Infusion reaction was regarded as fever with or without chill requiring transient interruption of infusion. The results showed that the infusion reaction incidence in the infliximab group was significantly lower compared to the IVIG group. The summary OR was 0.11 (95% CI: 0.03 to 0.43), with low heterogeneity (I2 = 0).   Other adverse events Patients treated with infliximab had a prevalence of transient hepatomegaly of 19% (6/31) versus 1.5% (1/68) in patients who never received infliximab, with an odds ratio of 16.1 (95% CI, 1.8 to 140.3; P = 0 0.004).   A: Comparison of treatment effectiveness between the infliximab group and control group   B: Comparing the treatment effectiveness of infliximab between prospective and retrospective studies, in the retreatment group.     Discussion The meta-analysis demonstrated that infliximab, a TNF-α blocker is useful either as a first-line treatment in KD or as a treatment for IVIG resistant KD. This analysis has shown that infliximab is potently effective in reducing fever; however, it failed to reduce CALs. Infliximab might also increase the risk of TB and hepatitis when infection occurred. Nevertheless, physicians need to confirm the absence of TB lesions before the use of infliximab. It is highly recommended that pediatricians consider early use of infliximab in cases with refractory KD due to its safety and efficacy.   Conclusion When infliximab combined with IVIG had been used in the primal treatment of patients with KD, it could reduce the rate of resistance compared with conventional IVIG therapy. However, there was no advantage of reducing the incidence of the coronary artery lesions. Infliximab can improve treatment efficiency in treating children resistant to IVIG. There was no increase in adverse events in the treatment of infliximab. Infliximab might reduce the infusion reaction of IVIG. When patients with IVIG contraindicated or exhibited IVIG resistance, infliximab might be useful.   

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The mid-term outcome of Fontan conversion compared with primary total cavopulmonary connection

The mid-term outcome of Fontan conversion compared with primary total cavopulmonary connection. Kato A, Sato J, Yoshii K, Yoshida S, Nishikawa H, Ohashi N, Sakurai T, Sakurai H, Hata T, Yoshikawa T. J Cardiol. 2021 Feb 26:S0914-5087(21)00042-3. doi: 10.1016/j.jjcc.2021.02.005. PMID: 33648806   Take Home Points: The indication of Fontan conversion (FC) from atriopulmonary connection (APC) to total cavopulmonary connection (TCPC) is unclear. Fontan conversion is a safe and feasible procedure to bring APC patients back onto the same track of primary TCPC patients in terms of hemodynamics as well as arrhythmia. The antiarrhythmic procedure should be carefully chosen because sinus node dysfunction can frequently occur and FC itself would reduce the risk of arrhythmia.     Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch:   Introduction The Fontan procedure, which is the treatment of choice for patients with functionally univentricular hearts, has been modified by the Bjork, lateral tunnel, and extracardiac total cavopulmonary connection (TCPC) procedures since the introduction of its initial version—the atriopulmonary connection (APC)—by Fontan et al. in the 1970s.   Fontan conversion, which entails connecting the inferior vena cava to the pulmonary artery using an artificial conduit, combined with arrhythmia surgery has been introduced. Possible benefits of prophylactic Fontan conversion in asymptomatic APC patients are improving cardiac output as well as preventing new onset of atrial tachyarrhythmia. On the other hand, the long-term hemodynamic outcome of patients after Fontan conversion compared with that of patients after primary TCPC is unknown. In this study, the sought to compare the midterm outcomes after prophylactic and therapeutic Fontan conversion with those after primary TCPC.   A total of 54 consecutive patients undergoing either Fontan conversion (n = 30) or primary TCPC (n = 24), followed by cardiac catheterization for postoperative hemodynamic evaluation at over 18 years of age between July 2005 and April 2019, were included in the study The included 52 patients were divided into three groups: p-FC, consisting of 15 asymptomatic APC patients who underwent prophylactic Fontan conversion; t-FC, consisting of 13 symptomatic APC patients who received therapeutic Fontan conversion [including arrhythmia (n = 11), heart failure (n = 1), and protein-losing enteropathy (n = 1)]; and p-TCPC, consisting of 24 patients who underwent primary TCPC.   Tricuspid atresia turned out to be the most frequent diagnosis in patients receiving Fontan conversion procedure and the majority of patients in the t-FC (69%) and p-FC (93%) groups were found to have a dominant left ventricle (p = 0.71).   The initial Fontan procedure was performed at the ages of 7.5 (2.3–18.7), 4.7 (1.4– 10.1), and 6.7 (2.9–26.3) years in the t-FC, p-FC, and p-TCPC groups, respectively. The patients in the t-FC and p-FC groups underwent Fontan conversion at 24.4 (14.1–37.7) and 20.3 (8.0–25.6) years of age, respectively.   Overall outcome     Arrhythmia Before Fontan conversion, nine cases of atrial tachycardia (69%), one case of ventricular tachycardia (8%), and one case of sick sinus syndrome (SSS; 8%) were found in the t-FC group, all of which were managed with concomitant antiarrhythmic surgery.   Overview of the patients who underwent therapeutic Fontan conversion (t-FC). The second row indicates pre-operative rhythm (the dotted boxes); the third row indicates anti-arrhythmic surgeries performed at the time of the Fontan conversion (the bold boxes); the fourth and fifth rows indicate cardiac rhythm and devices required post-operatively, respectively. APC, aortopulmonary connection; AT, atrial tachycardia; AVB, atrioventricular block; CRT-P, cardiac resynchronization therapy pacing; JR, junctional rhythm; RA, right atrium; SSS, sick sinus syndrome; VT, ventricular tachycardia.   Hemodynamics No difference in central venous pressure, aortic pressure, and cardiac index was observed across the three groups. Similarly, the levels of brain natriuretic protein (BNP)—which were found to be 34.3 (9.7–93.5), 10.4 (4.9–59.2), and 21.7 (4.9–365.5) in the t-FC, p-FC, and p-TCPC groups, respectively—exhibited no significant difference (p = 0.22).     Discussion Fontan conversion with the Maze procedure has emerged as a tertiary prevention strategy for those with previous APCs and tachyarrhythmia. The present study revealed that this procedure is both prophylactically and therapeutically feasible and effective and that it can yield the same outcomes in conventional APC patients as those observed with the contemporary primary extracardiac TCPC patients.   Tachyarrhythmia in patients with univentricular hearts is known to be a predictor of worse outcomes, especially in APC patients. Thus, antiarrhythmic interventions, such as the Maze procedure, combined with Fontan conversion, are likely to change the deleterious clinical course in these patients. In this cohort, arrhythmia was very well controlled following Fontan conversion that nearly half of the patients in the t-FC group experienced no recurrence without antiarrhythmic medications. Moreover, no newly developed case of tachyarrhythmia was observed in the p-FC group, suggesting the strategy, Fontan conversion +/- antiarrhythmic procedure, can exert both primary and secondary preventative effects against atrial tachyarrhythmias. Aggressive prophylactic Maze procedure appeared to be more harmful than beneficial in our study since three patients (20%) developed sinus node dysfunction postoperatively.   The strategy utilized in this study turned out to have limited efficacy in the prevention of thromboembolism, as 11% of the patients developed a thromboembolic event following Fontan conversion. Although whether antiplatelet therapy or anticoagulation is more effective has yet to be elucidated, lifelong thromboprophylaxis seems essential even after the TCPC procedure or Fontan conversion is performed —probably more in older age.   Conclusions Fontan conversion is a safe and feasible procedure that helps APC patients keep up with primary TCPC patients with respect to hemodynamics and arrhythmia. It is recommended that this procedure be performed before patients become symptomatic. However, the Maze procedure should be limited to those with a history of significant arrhythmia, as it can frequently result in sinus node dysfunction, whereas Fontan conversion itself could lower the risk of arrhythmia.   

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Angiotensin-converting enzyme inhibition and pre-superior cavopulmonary connection haemodynamics in infants with single-ventricle physiology

Angiotensin-converting enzyme inhibition and pre-superior cavopulmonary connection haemodynamics in infants with single-ventricle physiology. Al Balushi A, Averin K, Hsu DT, Mackie AS. Cardiol Young. 2021 Feb 16:1-5. doi: 10.1017/S1047951121000305. PMID: 33588974   Take Home Points: ACE inhibitors did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to Superior Cavo-pulmonary connection (Glenn) palliation. The pathophysiology of pulmonary vascular remodeling in these infants is complex, and this study suggests that enalapril plays no role in that process in this population.     Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: Introduction: Angiotensin-converting enzyme inhibitors have been used in pediatric heart failure associated with left-to-right shunts or chronic valvular regurgitation because they reduce systemic vascular resistance and left-to-right shunt. Amongst single-ventricle patients, ACEi have been shown to decrease ventricular filling pressure in older children with Fontan physiology while pulmonary hypertension therapies aimed at modulating the pulmonary vascular resistance in this patient population have yielded mixed results. Adults with chronic heart failure treated with ACEi have been shown to have lower PA pressure with short term use.   Material and methods: Using the Pediatric Heart Network Infant Single Ventricle trial (ISV trial) dataset, the original ISV trial showed that enalapril in the first year of life was not associated with improved somatic growth, ventricular function, or heart failure severity, but the ISV trial did not explore the impact of ACEi on measures of pulmonary vascular health. The authors hypothesized that infants enrolled in the ISV trial who received enalapril would have lower mean PA pressure compared to those who received placebo.   The study enrolled infants at 10 centers in the United States of America and Canada from August 2003, to May 2007. Inclusion criteria were infants with single ventricle physiology between 1 week and 45 days of age with stable systemic and pulmonary blood flow in whom a superior Cavo pulmonary connection (SCPC) was planned.   The primary outcome of this analysis was: Invasively measured mean PA pressure at the time of the pre-SCPC catheterization. If the mean PA pressure was not recorded in the catheterization dataset, a pulmonary venous wedge pressure was taken as a representative of mean PA pressure if < 18 mmHg. Transpulmonary gradient and pulmonary-to-systemic blood flow ratio recorded during pre-SCPC catheterization and oxygen saturation post-SCPC (7 days after surgery) were secondary outcomes. The initial enalapril dose prescribed in the ISV trial was 0.1 mg/kg/day. The dose was up titrated as tolerated over a period of 2 weeks to the target dose of 0.4 mg/kg/day, given in two divided doses per day. Patients on enalapril were grouped into low- and high dose, based on a cut-off of 0.3 mg/kg/day.   Within the ISV trial, 179 of 230 patients underwent pre-SCPC cardiac catheterization and were included in the current analysis. There were 94 patients (53%) in the placebo group and 85 (47%) in the enalapril group. Baseline patient characteristics were similar between the two groups.  Results are provided as n (%) unless otherwise specified.DKS = Damus–Kaye–Stansel. PAB = pulmonary artery band. SD = standard deviation. *No direct measurement of pulmonary artery pressure and pulmonary vein wedge pressure > 18 mmHg   Hemodynamic outcomes The primary analysis showed no difference in the mean PA pressure between the enalapril and placebo groups (13.1 ± 2.9 versus 13.7 ± 3.4 mmHg, p = 0.31).     Secondary outcome variables also did not differ between study groups. There was no difference in the enalapril versus placebo groups for any of the outcome measures according to the morphology of the ventricle.     Pre-specified subgroup analysis was also performed according to the type of shunt. In infants who had a Sano shunt (Table 4), the mean PA pressure was 13.0 ± 2.5 in the enalapril group versus 14.0 ± 3.6 in the placebo group (p = 0.25). In the Sano shunt patients, the post-SCPC oxygen saturation was 84 ± 4% in the enalapril group versus 82 ± 5% in the placebo group (p = 0.007). In infants who received an aortopulmonary shunt, the mean PA pressure was 14.0 ± 3.2 in the enalapril group versus 14.0 ± 3.4 in the placebo group (p = 0.75), and post-SCPC oxygen saturation was similar in the enalapril and placebo groups (83 ± 6 versus 82 ± 6, respectively, p = 0.96).     Impact of high-dose enalapril: The mean PA pressure was 13.2 ± 3.6 in the high-dose enalapril group (0.3–0.4 mg/kg/day) versus 13.2 ± 3.5 in the low-dose group (0.1–0.2 mg/kg/day) (p = 0.98).   Conclusion: ACE inhibitors did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to Glenn palliation.   

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High ECG Risk-Scores Predict Late Gadolinium Enhancement on Magnetic Resonance Imaging in HCM in the Young

High ECG Risk-Scores Predict Late Gadolinium Enhancement on Magnetic Resonance Imaging in HCM in the Young. Österberg AW, Östman-Smith I, Jablonowski R, Carlsson M, Green H, Gunnarsson C, Liuba P, Fernlund E. Pediatr Cardiol. 2021 Jan 30. doi: 10.1007/s00246-020-02506-9. PMID: 33515326   Take Home Points: An ECG risk-score has been described that predicts high risk of subsequent cardiac arrest in young patients with hypertrophic cardiomyopathy (HCM). We assessed whether an ECG risk-score could be used as an indicator of myocardial fibrosis. 12-lead ECG was used for calculating the ECG risk-score (grading 0–14p). High-risk ECG (risk-score>5p) occurred only in the HCM group. In low-risk ECG-score patients (0–2p), median percent of myocardium showing LGE were zero percent, in intermediate-risk (3–5p) were 5.4% and in high-risk (6–14p) were 10.9% ECG-score>2p had a sensitivity and specificity of 79% and 84% to detect positive LGE on CMR. ECG risk-score>2 p could be used as a cut-off for screening of myocardial fibrosis.     Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and the leading cause of sudden cardiac death in the young. Several studies by cardiac magnetic resonance (CMR) in HCM patients have shown the gradual and progressive changes of the myocardium with findings of disturbed myocardial perfusion and perfusion defects in the surroundings of fibrotic areas. Myocardial fibrosis as measured by CMR has been proposed as a risk-factor for cardiac events. CMR with late gadolinium enhancement (LGE) is gold standard for evaluating fibrosis in HCM.   Study Details: The study groups consisted of 42 individuals: 26 HCM patients, seven individuals at risk of HCM (genotype-positive, phenotype-negative and first-degree relatives) and nine healthy volunteers, including four athletes (physical activity>10 h/week), without heredity for cardiac disease. The 14 gene standard panel for HCM in the HCM group was positive in 16 patients but the genetic mutations were unknown in 10 patients. It was possible to calculate the ECG risk-scores in all study participants (n=42). High-risk ECG-scores (6–14 p) were found in 35% of the HCM patients (9/26) but in none of the individuals at risk of HCM, nor in healthy volunteers.   LGE could be evaluated in all individuals (n=42). All LGE-positive individuals were in the HCM group. In the HCM group 54% of the individuals (14/26) had positive LGE, with median ECG risk-score of 8p [4–11p]. Among the HCM patients with a high-risk ECG-score, 89% had positive LGE (8/9). The one exception, the patient with negative LGE and a high-risk ECG-score, had HCM due to a PRKAG2 mutation and not a sarcomeric mutation.   Three HCM patients had a very low-risk ECG (0–2p): One HCM patient had a 2.3% LGE of LVM but a completely normal ECG, one HCM patient had an ECG risk-score of 1 point and 4%LGE of LVM and one HCM patient had 2 points and 2.1% LGE of LVM. The individual with normal ECG and 2.3% LGE of LVM was diagnosed with mild HCM two years before the CMR, had a known genetic predisposition with MYBPC3 where the ultrasound showed IVS and PW measurements at 14 mm. Three individuals had an intermediate-range ECG risk-score (3–5p): One HCM patient (14 years) had a score of 3 points and 13.5% LGE of LVM, one HCM patient (30 years) had 4 points and 20.3% LGE of LVM and one patient (13 years) had 5 points and 5.4% LGE of LVM.   The positive and negative predictive value (PPV and NPV) of an ECG risk-score>2 points as a screening test for LGE shows a PPV of 79% [CI 56–91%] and NPV of 84% [CI 66–94%] for LGE being present in patients.   In the HCM group 62% (13/21) had a perfusion defect (PD). The median ECG risk-score in HCM patients with a perfusion defect was 5p [1–9p] and in HCM patients without a perfusion defect 0p [0–1p], p=0.001. All individuals positive for perfusion defect were in the HCM group. An ECG risk-score>2 points was associated with positive PD present on CMR.   Discussion This study showed that conventional 12-lead ECG analyzed by the ECG risk-score method according to Östman-Smith et al. has high specificity and sensitivity for indicating myocardial fibrosis as well as perfusion defects on CMR. Thus, ECG risk-score>2p is an inexpensive and easily available method as a screening for HCM patients with likely myocardial fibrosis and/or perfusion defects. An ECG risk-score>2 points in our study predicted myocardial fibrosis on CMR by late gadolinium enhancement with a specificity of 84% and a sensitivity of 79%. An ECG risk-score>2 points also predicted myocardial perfusion defect with high sensitivity and specificity.   These findings indicate that the ECG risk score could be used as a screening tool for HCM patients for predicting who is at risk of having myocardial fibrosis and need urgent further risk stratification investigations.   Implications for the Future: This study shows the ability of the ECG risk-score in predicting fibrosis and perfusion defects on CMR. Further and larger studies are needed to validate if ECG risk-score and LGE on CMR have independent prognostic value in the clinical follow-up of HCM in the young. Conclusion: Conventional 12-lead ECG analyzed and categorized by the ECG risk-score may predict myocardial fibrosis and perfusion defects as measured by CMR in HCM in the young. An ECG risk-score>2 points could be used as a cut-off for screening of myocardial fibrosis and/or perfusion defects with high sensitivity and specificity. None of the genotype positive, phenotype-negative individuals at risk for HCM demonstrated LGE or perfusion defects on CMR or a high ECG risk-score, nor did the healthy volunteers.   

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Comparison Between Currently Recommended Long-Term Medical Management of Coronary Artery Aneurysms After Kawasaki Disease and Actual Reported Management in the Last Two Decades

Comparison Between Currently Recommended Long-Term Medical Management of Coronary Artery Aneurysms After Kawasaki Disease and Actual Reported Management in the Last Two Decades. Osborne J, Friedman K, Runeckles K, Choueiter NF, Giglia TM, Dallaire F, Newburger JW, Low T, Mathew M, Mackie AS, Dahdah N, Yetman AT, Harahsheh AS, Raghuveer G, Norozi K, Burns JC, Jain S, Mondal T, Portman MA, Szmuszkovicz JR, Crean A, McCrindle BW; International Kawasaki Disease Registry Pediatr Cardiol. 2021 Jan 13. doi: 10.1007/s00246-020-02529-2. PMID: 33439285   Take Home Points: This is an observational registry study. In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) risk stratification was added for long-term management. Generally, past practice was consistent with the latest AHA guidelines. However, the important exception was that 35% of patients with persistent giant coronary artery aneurysms were not on anticoagulants. Physician education could improve guideline compliance and patient outcomes.   Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: Introduction: Kawasaki disease (KD) is a self-limiting, systemic vasculitis of unclear etiology that mostly occurs in children. Coronary artery aneurysms form in approximately 25% of untreated patients and in approximately 4% of patients treated within 10 days of the onset of illness. The long-term consequences of KD may include myocardial infarction and death. In 2017, the American Heart Association (AHA) updated the approach to risk stratification and long-term management of KD patients (https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000484). This manuscript compared the Kawasaki disease management practice from 1999 to 2016 with the most recent AHA 2017 recommendations for thromboprophylaxis and medical therapy based on the new risk stratification. The study included the eligible patients from registry who were diagnosed with Kawasaki disease under the age of eighteen years from 1999 to 2016 and had coronary artery aneurysms (Defined as at least one coronary artery diameter with a maximum z-score ≥ 2.5 at any point in their initial work up and subsequent follow -up). Figure 1: Risk level (RL) classification of coronary artery aneurysms per the 2017 AHA guidelines using maximum z-score, luminal dimension, and amount of regression. Risk Level 1: No involvement Risk Level 2: Dilation only     Results: Prevalence of medication use by risk levels (RL) was explored across 3 eras (1999–2004, 2005–2010, and 2011–2016). Acetylsalicylic Acid (ASA): Use of ASA/aspirin ranged from 88 to 96% for RLs for which use was “indicated” (RLs 3.1, 4.1, 4.2, 5.1, 5.2, and 5.3); this represents patients with coronary artery aneurysms of any size that have not regressed to normal luminal dimensions or dilation only (z-score <2.5)   Systemic anticoagulation is only “recommended” for patients for RL 5.1 (persistent large/giant coronary artery aneurysms). Despite this, only 65% of patients in RL 5.1 were receiving anticoagulation and there was no trend toward increased usage over the different year groups.   Dual antiplatelet therapy (ASA and clopidogrel) was in use at 16% of patient visits for RL 5.2 where use was “reasonably indicated.” For visits for RLs 5.3 and 5.4, dual antiplatelet therapy was used for 11% and 9%, respectively (“not indicated”).   There was an increase in ASA use for RL 3.2 from 54% in 1999–2004 to 73% in 2011–2016 and there was increased single antiplatelet (ASA only) use from 43% in 1999–2004 to 67% in 2011–2017. Conclusions and Implications for Clinical Practice:   The management of patients with Kawasaki disease and coronary artery aneurysms from 1999 to 2016 was generally similar to 2017 AHA Kawasaki disease guidelines.   Physician education could improve guideline compliance and patient outcomes, and knowledge translation efforts are needed to further optimize practice in anticoagulation KD patients. Additionally, more research is needed to advance future recommendations, particularly for statins, beta-blockers, and direct oral anticoagulants.   

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Long-term experience with the one-and-a-half ventricle repair for simple and complex congenital heart defects

Long-term experience with the one-and-a-half ventricle repair for simple and complex congenital heart defects. Cabrelle G, Castaldi B, Vedovelli L, Gregori D, Vida VL, Padalino MA. Eur J Cardiothorac Surg. 2021 Jan 4;59(1):244-252. doi: 10.1093/ejcts/ezaa289. PMID: 32888295   Take Home Points: Long-term (median 13 years) results in patients with a single RV and a 1 ½ ventricle repair are good in this relatively small group. There was no significant difference in survival or freedom from adverse events between simple and complex patients. When planned, a 1.5V repair may be beneficial in a very specific subset of patients and possibly lead to better outcomes than single ventricle (Fontan) palliation?   Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: One and a half ventricle (1 ½ V) repair has been proposed for those with borderline/small right ventricles with hypothetical advantages over single ventricle palliation/Fontan such as ability to increase cardiac output and adapt to exercise, maintain pulsatile pulmonary blood flow, and low venous pressure in the IVC. This single center study retrospectively evaluated 29 patients who underwent 1 ½ V staged or primary repair between 1994-2018. Inclusion criteria were hypoplastic tricuspid valve (z-score < -3) and hypoplastic RV (< 2/3 predicted normal volume). Patients were divided into simple (CHD confined to right heart lesions) and complex anatomy (including other than right heart lesions and more challenging surgical repair). Echo data, cath data (PVR), and metabolic stress test data were followed. See table 2.   Median follow up was 12.5 years. Specific surgical details were discussed in the results section. Most common post-operative complications included pericardial and pleural effusions and arrhythmias. There were 3 late deaths with 2 considered non-cardiac related. 6 required a cardiac cath after a median time of 2.8 years, most commonly to address branch pulmonary artery stenosis. 3 patients required subsequent re-operation; 1 underwent transplant and the other 2 underwent biventricular conversion due to interval RV growth. Survival at 25 years was 89%; all had normal kidney and liver function (based on lab tests). Median O2 sat was 98%. Freedom from any late adverse event was 57% (16/28) and freedom from reoperation or re-intervention was 82.1% (23/28) and 78.6% (22/28) respectively. The complex patients had a much more significant initial post-operative course as would be expected. None of the “late” deaths occurred in the first year of follow up. 5 patients had neurological AEs which possibly contributed the most to the late AE rate, but the paper does not define this well. See tables 3 and 4. Comparison between the complex and simple group found no significant differences in survival, freedom from AE, or freedom from reintervention. See figure 1. Only 10 patients had MRIs and only 12 patients had metabolic stress testing. Mean VO2 was higher than compared to a control group of Fontan patients (33 +/- 5 vs. 24 +/- 1.6 ml/kg/min).   This surgical center planned for 1.5V repair after birth and show overall good results, with a few patients even being able to undergo biventricular conversion. No patients had PLE or chronic liver congestion, known complications of the Fontan. Important limitations include low total number of patients, lack of MRI data, and limited stress test data. When planned, a 1.5V repair may be beneficial in a very specific subset of patients and possibly lead to better outcomes than single ventricle (Fontan) palliation.            

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Six-Year Neurodevelopmental Outcomes for Children With Single-Ventricle Physiology

Six-Year Neurodevelopmental Outcomes for Children With Single-Ventricle Physiology. Sananes R, Goldberg CS, Newburger JW, Hu C, Trachtenberg F, Gaynor JW, Mahle WT, Miller T, Uzark K, Mussatto KA, Pizarro C, Jacobs JP, Cnota J, Atz AM, Lai WW, Burns KM, Milazzo A, Votava-Smith J, Brosig CL; PHN investigators. Pediatrics. 2021 Feb;147(2):e2020014589. doi: 10.1542/peds.2020-014589. Epub 2021 Jan 13. PMID: 33441486   Take Home Points: There is an increase in externalizing behavioral problems and decreased adaptive skills in school age children with HLHS. Many children with HLHS who have low adaptive skills at 6 years of age will not be identified by screening at earlier ages. Serial neurodevelopmental evaluations will be necessary to diagnose deficits as these single ventricle patients get older and advance in school.   Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: Neurodevelopmental deficits are one of the most common long term issues that face children with HLHS. Early identification could theoretically allow for implementation of therapies that could improve long-term educational and behavioral outcomes. This extension study to the Single Ventricle Reconstruction (SVR) Trial studied the original cohort who had a 14-month mental development index (MDI) and psychomotor development index (PDI) via annual developmental (ASQ) and behavioral (externalizing and internalizing)/adaptive assessments (BASC-2) based on parental questionnaires from ages 3-6. The ASQ measures the child’s development in communication, gross motor, fine motor, problem solving and personal social skills, and the BASC-2 measures adaptive skills and problem behaviors in the community and home settings. Adaptive functioning refers to how a child copes with demands of everyday life and their personal independence. Scores were compared to population norms and classified as at least average (< 1 SD), at risk (< 1-2 SC) and impaired (< 2 SD). 249 patients completed the assessments.   The greatest change in proportion of children at being at risk or impaired occurred between ages 3 and 4, but this was largely due to a lower rate of reported problem behaviors at age 3 than the population norms. However, by age 6, many more had externalizing behavior challenges (e.g. hyperactivity, aggression, and rule breaking). There was not an increase in internalizing behaviors or differences compared to population norms. The most significant deviations were noted on the adaptive skills portion of BASC-2, with most differences occurring between ages 5 and 6. At age 3, 87% were age-appropriate, but by age 6, this dropped to only 71%. 22% (vs. 14% expected) were classified as at risk and 7% (vs. 2%) as impaired. See figure 1 and table 2. The authors note that this finding may not be a regression, but rather the parents now having increased opportunities for social comparison now that the children are in school and begin to act more independently. Parent ratings of deficits in problem solving skills and communication were strongly related to future poor adaptive skills, with ~44% of children at risk/impaired on the 14 month MDI and ~ 36% of children at risk/impaired on the 14 month PDI having impaired adaptive skills at age 6. As a “half glass full” observation, the authors highlight that a significant proportion (77-85%) who do not show early impairments remain unimpaired at age 6.   Limitations of the study were that only parental assessments were made, a selection bias was possibly present given that participants had fewer risk factors for impaired neurodevelopment and higher socioeconomic status than non-participants, and the inability to measure impact of access to early intervention services on outcome scores. A follow up study at 10-12 years is already underway to allow for further understanding of a relationship with later school age outcomes and standardized testing.       

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Low-dose prostaglandin E1 is safe and effective for critical congenital heart disease: is it time to revisit the dosing guidelines?

Low-dose prostaglandin E1 is safe and effective for critical congenital heart disease: is it time to revisit the dosing guidelines? Daniel Vari 1, Wendi Xiao 2, Shashank Behere 3, Ellen Spurrier 3, Takeshi Tsuda 3, Jeanne M Baffa 3 Cardiol Young. 2021 Jan;31(1):63-70. doi: 10.1017/S1047951120003297. Epub 2020 Nov 3. PMID: 33140712; DOI: 10.1017/S1047951120003297   Take Home Points: Prostaglandin E1 at an initial and maintenance dose of 0.01 μg/kg/minute was sufficient to maintain ductal patency in 83% in this study, instead of the standard starting dose of prostaglandin E1 is 0.05 μg/kg/minute. Starting low-dose prostaglandin E1 at 0.01 μg/kg/minute is a safe and effective therapy for critical CHD. Patients with pulmonary obstruction were more likely to require higher doses than patients with systemic obstruction. Postnatally diagnosed patients with systemic obstruction are also at a higher risk of dose escalation than prenatally diagnosed infants. The incidence of respiratory depression requiring mechanical ventilation was low and was mostly seen in premature infants.      Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: Of the 153 eligible patients, 127 (83%) were started and maintained on a prostaglandin E1 dose of 0.01 μg/kg/minute until the end- point. Of the 26 patients who had their doses increased, the final dose was less than 0.05 μg/kg/minute in 15, 0.05 μg/kg/minute in five, and greater than 0.05 μg/kg/minute in two patients. 15 patients had their dose increased due to both echocardiographic findings and clinical factors suggesting ductal constriction. In systemic obstruction patients, these factors included blood pressure gradients, pulse abnormalities between upper and lower extremities, and elevated serum lactate levels. In pulmonary obstruction and inadequate mixing patients, the primary clinical factor driving dose increase was hypoxemia. In six patients, there was an echocardiographic finding of ductal constriction without corresponding clinical signs.   Of the 137 patients analyzed for respiratory depression, 38 (28%) had documented respiratory depression at a dose of 0.01μg/kg/ minute. In 10 of these patients, the respiratory depression was transient and did not merit initiation of respiratory support although four were started on caffeine. Fourteen patients (10%) were started on nasal cannula or high-flow nasal cannula, three patients (2%) were placed on continuous positive airway pressure, and 11 patients (8%) were mechanically ventilated via endotracheal intubation as a result of respiratory depression. Premature infants were more likely to experience respiratory depression (12/18, 67%) than term infants (26/117, 22%, p < 0.001). Mechanical ventilation was also more frequent in premature infants (6/18, 33%) than in term infants (5/117, 4%, p = 0.001).   

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