Pediatric Cardiology

Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease. Peyvandi S, Xu D, Barkovich AJ, Gano D, Chau V, Reddy VM, Selvanathan T, Guo T, Gaynor JW, Seed M, Miller SP, McQuillen P.J Am Coll Cardiol. 2023 Jan 24;81(3):253-266. doi: 10.1016/j.jacc.2022.10.029.PMID: 36653093 Take home points: Over a 20-year period, patients with complex congenital heart disease (CHD), the prevalence of preoperative white matter injury (WMI) remained stable, but postoperative WMI declined Improved postoperative systolic, mean, and diastolic blood pressure in the first 24 hours postoperatively was the most important clinical risk factor in reducing postoperative WMI Longitudinal studies will be necessary to determine if this will lead to improved neurodevelopmental outcomes Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: As surgical mortality has declined and patients are living longer with even the most complex CHD, the focus has shifted to other morbidities, in particular, neurodevelopmental issues. This includes attention, processing speed, memory, impulsivity, executive function, and decision-making problems amongst others. This has personal and communal impact as there is an association with lower educational attainment and less employment opportunities. Preoperative brain injury (primarily WMI) is likely due to prenatal factors leading to decreased cerebral oxygen delivery, genetic factors, and possibly the time between birth and initial surgery. It has been reported in 10-35% of patients with neonatal complex/cyanotic CHD. Postoperative WMI may be more modifiable. Prevalence of postoperative WMI has ranged from 33-75% of patients. There have been many changes over the years to try to decrease risks, including improved bypass techniques and support times, improved hematocrit, and likely better post-operative ICU care. This study aimed to describe the temporal trends of neonatal brain injury over a 20-year period between 2001-2021 using pre- and post-operative brain MRI, hypothesizing that improved clinical care may decrease the rate of brain injury. Most patients enrolled were diagnosed with d-TGA or single ventricle physiology (SVP) and expected to require neonatal surgery. Pre-operative MRI was performed as soon as a patient was stable enough to be transported to the MRI scanner. Postoperative MRI were done prior to discharge, with an average of 15 days between studies. 270 patients were enrolled prospectively. 246 patients had a preoperative MRI and 220 had a postoperative MRI. The 20-year period was divided into four 5-year epochs. Primary outcome was presence of WMI, and secondary outcomes included other forms of brain injury (eg. Stroke). The absolute frequency of preoperative WMI or stroke did not change over the study period. However, postoperative WMI decreased and was significantly lower in epoch 4 compared to epoch 1 with an overall decline of ~ 18.7% and a prevalence of ~11% in the most recent epoch. See central illustration. Patients with d-TGA and SVP were stratified and risk factors for WMI studied separately. In both groups, there was no difference in timing of surgery, but both groups had longer bypass and cross-clamp times over the study period. See Tables 4 and 5. In the SVP group, systolic, mean, and diastolic blood pressures were significantly higher in Epoch 4; in the d-TGA group, mean and diastolic BPs were higher. See Figure 2. Some changes in inotropic support were noted, primarily increased use of epinephrine and less milrinone. Since the study was observational, causal inference is limited; however, the rates of early postoperative hypotension were significantly lower by epoch 4, suggesting that changes in postoperative care and better cerebral perfusion may have an important impact on preventing WMI. However, this is in contrast to previous data suggesting elevated SVR and low cardiac output with poor outcomes. The balance between optimal cerebral perfusion and preventing low cardiac output can be tenuous in the critically ill infant and may require new strategies. Additionally, the rates of preoperative WMI did not change, so further understanding of this process to help prevent prenatal WMI is necessary. Whether the lower postoperative WMI will be associated with true improvement in neurodevelopmental testing remains to be seen. An accompanying editorial written by Dr. Jane Newburger eloquently places this study in the context of the overall canon of research on ND in CHD. Other studies have not shown improved ND outcomes even with lower postoperative WMI, with other factors (length of stay and socioeconomic status) having a greater impact. Additionally, preoperative WMI may have a greater impact on developmental scores than postoperative WMI. Further longitudinal study and multicenter analysis will be necessary in order to develop evidence-based pathways and interventions to improve ND outcomes.

Initial Experience with Telemedicine for Interstage Monitoring in Infants with Palliated Congenital Heart Disease. Stagg A, Giglia TM, Gardner MM, Offit BF, Fuller KM, Natarajan SS, Hehir DA, Szwast AL, Rome JJ, Ravishankar C, Laskin BL, Preminger TJ.Pediatr Cardiol. 2023 Jan;44(1):196-203. doi: 10.1007/s00246-022-02993-y. Epub 2022 Sep 1.PMID: 36050411 Take home points: The addition of telemedicine visits in lieu of entirely in-person visits for interstage monitoring of single ventricle patients is feasible, safe, prevents unplanned ER visits, and is associated with high levels of satisfaction by both families and clinicians Larger studies as well as adjunct use of remote diagnostic technologies will help determine the full capabilities of TM in this population Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: The interstage period between stage 1 and stage 2 surgical palliation for single ventricle congenital heart disease has historically been considered high risk for morbidity and mortality. The development of home monitoring and dedicated single ventricle teams have been instrumental in improving outcomes. Especially due to the COVID pandemic, telemedicine visits have been more frequently used for routine care, but its efficacy and safety in a higher risk subgroup has not been fully evaluated. This study assessed the use of TM in the interstage period along with the standard home monitoring protocols. In their program called interstage single ventricle monitoring program (ISVMP), weekly visits were performed alternating between the PCP and cardiologist. TM replaced at least one in-person PCP visit and was not used at nights or over the weekend. The TM visit tracked clinical concerns, interim ED visits or hospitalizations, visual assessment of patient color, activity, work of breathing, and respiratory rate, along with documentation of the HR and O2 sat using the home pulse oximeter. The clinician also discussed the daily weights, nutrition, and medications with the primary caregiver. The monthly frequency of ED visits per patient and estimated costs were tracked by comparing the standard ISVMP (Aug 2018-May 2019) with ISVMP + TM (Aug 2019- May 2020). Additional tracking included hospitalizations, identification of clinical concerns, whether TM prevented unnecessary ED visits or expedited in-person visits, and clinician and caregiver satisfaction. 60 TM visits were conducted for 29 patients with a median monitoring time of 199 days. The median number of TM visits/patient was 2 (range 1-5). 98% of visits had a successful audiovisual connection at the first attempt, and the average length of the visit was 20 minutes. In 6 TM visits (6 different patients), significant clinical findings (decreased O2 sats, tachypnea, poor feeding) were identified that led to therapeutic changes that avoided an ED visit (as these findings prior to TM would have been associated with an automatic referral to the ED). Expedited follow-ups were subsequently performed in 3 of the 6 patients. An additional 5 TM visits led to expedited follow-up with one of these patients being hospitalized. There were no missed events or deaths. There was a reduction in median monthly ED visits (see Table 2). 6 hospitalizations occurred in 2 patients who were unable to be seen via TM due to night/weekend events. All visits identified at least one non-urgent issue. 97% of caregivers were satisfied with TM visits, were interested in future TM visits, and only about 17% experienced some technical difficulties that were resolved quickly. Clinicians were also highly satisfied, thought the caregivers were receptive, and the visits effective for patient care. Family/patient education and troubleshooting home equipment problems were markedly improved using TM than from in-person visits. The use of TM greatly expanded during the COVID pandemic but is likely to continue to be a useful resource, even for the highest risk patients. There is a significant saving of time and money from the family’s perspective, and if there is not an increase in patient events or negative effects on outcomes, this should be considered in more centers if medical reimbursement remains. The authors noted that there are significant logistical and staffing needs when using TM, along with the need for technical support and translation services.

German Registry for Cardiac Operations and Interventions in Patients with Congenital Heart Disease: Report 2020—Comprehensive Data from 6 Years of Experience Andreas Beckmann, S. Dittrich, C. Arenz, et al  and German Quality Assurance / Competence Network for Congenital Heart Defects Investigators Thorac Cardiovasc Surg. 2021 Dec;69(S 03):e21-e31. doi: 10.1055/s-0041-1722978. Epub 2021 Feb 26. PMID: 33638137; PMCID: PMC7920329. Take Home Message: Large registries can be successfully maintained and can provide valuable information Registries can form a basis for internal and external quality assurance for participating institutions. Mortality in CHD interventions and surgeries is low. It is highest in neonates with high risk  complex diseases, that require multiple procedures. In Germany, mortality for isolated surgical procedures is minimal and rises to about 12% in high risk, STA5 procedures. Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch Introduction In Germany, the  German Society for Thoracic and Cardiovascular Surgery (DGTHG) and German Society for Pediatric Cardiology and Congenital Heart Defects (DGPK) took the initiative to create a multicenter registry study concerning interventional and surgical therapies in patients with CHD. The nationwide registry started in 2012.  This report presents data from the first 6 years of data entry. Each included patient receives a unique personal identification (PID), valid for life. Based on the PID, any invasive interventional or cardiac surgical procedure can be assigned exactly to each individual patient, even if the treatment is provided in different institutions. This enables longitudinal, procedure-related data acquisition, as well as short-, mid- and long-term evaluations. Risk adjustment models for operations and interventions were implemented in 2014. The risk group classification for operations is performed according to the society of thoracic surgeons (STAT) mortality score while risk group adjustment for interventions is based on the internationally acknowledged Bergersen's score. In addition to procedure-related data, various indicators, including the occurrence of adverse events, in-hospital mortality, and 30-day and 90-day mortality, are evaluated. Major and minor adverse events following surgical procedures are classified according to the society of thoracic surgeons (STS) morbidity classification. Risk adjustment models for operations and interventions were implemented in 2014. The risk group classification for operations is performed according to the internationally recognized society of thoracic surgeons-european association for cardio-thoracic surgery (STAT) mortality score 4 5 while risk group adjustment for interventions is based on the internationally acknowledged Bergersen's score. 6 These classifications cover five categories for surgical and four for interventional procedures. However, it has to be remembered that the two risk scores are not comparable, as they are based on different morbidity expectations and different evaluations of special features and complications. In addition to procedurerelated data, various indicators, including the occurrence of adverse events, in-hospital mortality, and 30day and 90-day mortality, are evaluated. Major and minor adverse events following surgical procedures are classified according to the society of thoracic surgeons (STS) morbidity classification. Results Data and results encompass the period between 2013 to 2018 collected from 20 to 24 departments performing surgical and from 24 to 30 departments carrying out interventional procedures depending on the year. A total number of 35,730 patients was included, leading to 39,875 cases, and 46,700 procedures. The cases could be subdivided into 17,259 interventional, 21,027 surgical cases, and 1,589 with multiple procedures ( hybrid procedures are included under multiple procedures and comprised less than 1% of all procedures). Overall, 4,708 (11.8%) of all cases were performed in neonates, 10,047 (25.2%) in infants,  19,351 (48.5%) in children/adolescents at age of 1 to 18 years, and 5,769 (14.5%) in adults. Mortality by age and type of procedure is shown below: The observed mortality rate was lowest in interventional cases and highest for cases requiring multiple procedures with a range of 6.2 to 10.4%. This can be explained by the fact that in the majority of cases, the combination of more than one surgical and interventional procedure is frequently requires in newborns and infants with complex heart malformations, representing the highest risk groups. Mortality was minimal in procedures performed for isolated defects.  It increased by STAT risk category, as expected, but even in the highest risk category STAT5) the vast majority of patients survived (87.8%). Mortality by defect and stat category is shown in the table below: Similarly, complications were the lowest in interventional cases and highest in the patients who underwent multiple procedures as shown in the figure below: Adverse events followed the same pattern. Over 90% of interventional cases were uncomplicated, surgical cases had some adverse events in about 36% of the cases, while about 56% of cases with multiple interventions had some adverse event. Of those, 8.7% were serious or “catastrophic” Over the registry period, the overall incidence of mortality or adverse events did not change. Conclusion The creation of large registries is possible and can give valuable data. Overall mortality in congenital heart disease in Germany is low. Interventional procedures have significantly lower risk than surgical procedures. It has to be emphasized, however, that interventions and operations must not be understood as competing, but as complementary therapeutic options. Even in patients with the same anatomic diagnosis, the selection criteria for interventional or surgical procedures, may differ considerably. Registry data of course have limitations, as specific patient characteristics cannot be distinguished. Nevertheless, the data obtained is valuable and can provide longitudinal trends overtime, as well important comparative feedback for specific centers.

Longitudinal changes in ventricular size and function are associated with death and transplantation late after the Fontan operation. Ghelani SJ, Lu M, Sleeper LA, Prakash A, Castellanos DA, Clair NS, Powell AJ, Rathod RH. J Cardiovasc Magn Reson. 2022 Nov 14;24(1):56. doi: 10.1186/s12968-022-00884-y.PMID: 36372887 Take home points: Over time, ventricular size increases and function and muscle mass decrease in patients with Fontan circulation as seen on CMR Rapid increase in EDVI > ~ 5 ml/BSA^1.3/year may have a higher risk of adverse outcomes (death or need for heart transplant) Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: Long-term risk stratification in Fontan patients is necessary to identify patients at higher risk of morbidity and late mortality. Routine cardiac MRI (CMR) every 2-3 years is currently recommended, with prior studies showing that increased ventricular dilation, decreased function, and presence of LGE are risk factors for adverse outcomes. This study was designed to assess changes of ventricular size and function over time to help determine if rate of change may be associated with death or need for heart transplant.  This was a single center retrospective analysis of 156 Fontan patients who had at least 2 CMR exams without any catheter or surgical cardiac interventions between the first and last CMR. The authors describe the CMR protocol in the methods section. The median number of CMRs per patient was 3 over a median follow-up time of 10 years. EDVi and ESVi significantly increased, with an annual increase of EDVi by about 1.63 ml/BSA^1.3. Mass index, EF, and mass to volume ratio significantly decreased, with an annual decrease in mass index of 1.7 g/BSA^1.3 and EF by 0.4%/year. See Table 1. 22 patients met the composite outcome of death or transplant and those patients. These patients had a higher initial EDVi and lower mass index and EF on CMR. When assessing for annualized change, they also had higher significant increases in EDVi and ESVi and decreases in mass index, mass to volume ratio, and EF. A mixed regression model showed that only EDVi (4.7 ml/BSA^1.3/year vs. 0.8 ml/BSA^1.3/year), ESVi, and mass to volume ratio were associated with the composite outcome. See Table 3. More patients with a single right ventricle experienced the composite outcome (21% vs. 8%). The estimated annual rate of change was significantly higher for ESVi and lower in EF for the RV dominant group (Table 5).  The authors discuss the various factors that may contribute to ventricular dilation and why RV dominance may be disadvantageous. Limitations included limited generalizability (patients that had interventions or with pacemakers and ICDs were excluded). They also assumed a linear pattern of change; there may be more sudden and larger changes that could be present if there were more interim CMR studies to compare. Since larger changes were associated with worse outcomes, closer follow-up and surveillance in those patients should be considered. 

Thirty-Year Survival After Cardiac Surgery in Children with Williams-Beuren Syndrome (from the Pediatric Cardiac Care Consortium Study). Zinyandu T, Montero AJ, Thomas AS, Sassis L, Kefala-Karli P, Knight J, Kochilas LK.Am J Cardiol. 2023 Jan 15;187:48-53. doi: 10.1016/j.amjcard.2022.10.037. Epub 2022 Nov 29.PMID: 36459747 Take home points: The overall 30-year survival rate for Williams-Beuren syndrome (WBS) and requiring intervention is 90% Survival rate is higher (96%) for those with isolated left or right heart lesions and lower (83.4%) for those with combined disease Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: WBS is an autosomal dominant condition due to a mutation in the 7q11.23 region that includes the elastin gene. Congenital heart disease is seen in up to 90% of patients with the most common lesions including supravalvar aortic stenosis/SVAS (left heart obstructive lesion/LHOL) and pulmonary artery stenosis/PAS (right heart obstructive lesion/RHOL). The majority of patients require surgery and/or transcatheter interventions. The risk of CV events and death is higher during hospitalizations and need for anesthesia and there is also risk of sudden cardiac death thought to be due to congenital coronary abnormalities.  This was a retrospective cohort study of 200 patients with WBS who underwent cardiac interventions between 1982-2009 and enrolled in the Pediatric Cardiac Care Consortium registry. Most patients were male (61.6%) and had combined LHOL/RHOL (49%). Isolated LHOL was seen in 37% and isolated RHOL in 11%, with females more likely to have RHOL. See Table 1. A supplementary table lists all of the various LHOL and RHOL, but the most common were SVAS and PAS. Nearly all patients with isolated LHOL required surgery as the first intervention. About 39% of all patients required a subsequent procedure. Over a median of 23.7 years, and up to 30 years later, 16 deaths were recorded. Figure 2 shows the survival plot after the first CHD intervention. Attrition was highest during the first year of follow up, but the overall 30-year survival rate was 90.1%. Highest mortality was seen in combined LHOL/RHOL which was 83.4%. Adjusted analysis identified the combined LHOL/RHOL group to have a 6.85 times hazard for death.  There was also an era effect with higher mortality in the earlier periods (1982-1992 and 1992-1997) then the latest period (1998-2009). CHD was listed as the most common cause of death (65%), with 31% attributed to ischemic heart disease and 25% due to heart failure or arrhythmias.  This study is the longest follow up for WBS patients and shows overall quite good survival. Limitations include lack of information on possible significant contributing factors to survival that were not included in the PCCC registry, including socioeconomic status, medications, or other procedures. Additionally, there is limited discussion regarding coronary issues, hypertension and renal artery abnormalities, or QTc prolongation, all of which may be associated with cardiac morbidity and mortality in WBS. The article also does not include those patients who did not require interventions. Presumably, this group would have a better survival rate, but whether they would also be at similar risk for sudden cardiac death is not clear. 

Palliation Strategy to Achieve Complete Repair in Symptomatic Neonates with Tetralogy of Fallot. Law MA, Glatz AC, Romano JC, Chai PJ, Mascio CE, Petit CJ, McCracken CE, Kelleman MS, Nicholson GT, Meadows JJ, Zampi JD, Shahanavaz S, Batlivala SP, Pettus J, Pajk AL, Hock KM, Goldstein BH, Qureshi AM; Congenital Cardiac Research Collaborative (CCRC) Investigators.Pediatr Cardiol. 2022 Oct;43(7):1587-1598. doi: 10.1007/s00246-022-02886-0. Epub 2022 Apr 5.PMID: 35381860 Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch. Take home points: Neonates with symptomatic tetralogy of Fallot (sTOF) may undergo palliations with varying physiology, namely systemic to pulmonary artery connections (SPC) or right ventricular outflow tract interventions (RVOTI). A comparison of palliative strategies based on the physiology created is lacking. RVOTI had increased interstage reintervention (HR=2.15). This data supports patient and institution individualized approach to palliation of symptomatic TOF. Introduction Neonates with symptomatic tetralogy of Fallot (sTOF) have cyanosis requiring early complete repair (CR) or palliation to augment pulmonary blood flow. Various palliation options are used, including BTT shunt, Balloon pulmonary valvuloplasty, RVOT stenting, surgical transannular patch, RV-PA conduit without VSD closure, PDA stenting. These palliations create physiologic differences including volume loading of the heart and pulmonary vasculature as well as short- and medium-term risks. Generally, RVOTI allows for pulsatile flow into the pulmonary arteries with maintained systemic diastolic pressure, thereby potentially mitigating the risk of altered abdominal visceral and coronary perfusion seen in patients with systemic aorta to pulmonary artery connections (SPC) due to continuous pulmonary blood flow throughout diastole. Furthermore, RVOT stenting has been associated with increased pulmonary artery growth compared to BTTS in the TOF population. Materials and Methods A multicenter, retrospective cohort study was performed including consecutive neonates (<=30 days) with sTOF who underwent palliation at nine centers of the CCRC between January 1, 2005, and November 30, 2017. Patients with the following diagnosis were excluded: (1) non-confluent branch pulmonary arteries; (2) TOF with atrioventricular canal; (3) TOF with absent pulmonary valve syndrome; (4) TOF with major aortopulmonary collateral arteries who underwent (or intent for) unifocalization, or (5) double outlet RV. Patients were categorized into two palliative groups prior to the complete repair (CR) based on the predominant physiology created by the first palliative procedure: (1) SPC including surgical aorta to pulmonary artery shunts or ductus arteriosus stent; or (2) RVOTI including balloon pulmonary valvuloplasty, RV to pulmonary artery conduit/transannular patch without VSD closure, and RVOT stent. Outcomes The primary outcome was defined as survival to CR by 18 months. Secondary outcomes included overall survival and dichotomous events including procedural/hospital complications and interstage reinterventions (RI), and continuous measures of risk exposure including hospital/ intensive care length of stay, mechanical ventilation duration, inotropic agents, cardiopulmonary bypass (CPB)/ cross-clamp/inhaled anesthetic agent times, and pulmonary artery growth from birth to CR. Baseline demographics of patients undergoing palliation DiGeorge syndrome: Total patients 43 (13.44%), SPC was performed in 28 (11.11%) and RVOTI was performed in 15 (22.06%), p value 0.019 Birthweight < 2.5 kg: Total 96, 68 (27%) underwent SPC, and 28 (41%) were taken for RVOTI, p value 0.023 More patients with branch pulmonary artery stenosis (z score < 2), underwent RVOT intervention. P value 0.007 Results Nine patients’ palliative physiology changed within 60 days following initial palliative intervention. Six patients who underwent an initial balloon pulmonary valvuloplasty required SPC (one ductus arteriosus stent and five BTTS) while three patients changed physiologic palliative strategies from a SPC to RVOTI (one ductus arteriosus stent and two BTTS underwent RVOT patch). Incidence of Complete Repair by 18 Months Under 3 months from IP, CR was more likely in the RVOTI group (HR=2.60; 95% CI=1.12–5.95, p=0.026). After 3 months, there was no difference in the hazard of repair. Neonatal and Overall Exposures and Morbidity Duration of inotropes, ventilation, and CPB times favored RVOTI during the IP, while inotrope duration, CPB and anesthesia time favored RVOTI in the cumulative (IP+CR). No difference was noted in-hospital mortality and complications between the two groups. Reintervention Interstage RI was noted to be more frequent in RVOTI. By 12 months, cumulative pre-repair RI was 39.7% in RVOTI patients compared to 24.8% in SPC patients (HR = 1.73, 95% CI=1.11–2.70, p=0.015, SPC reference), and after adjustment similar findings were noted (HR = 2.15 95%, CI = 1.36, 3.39, p = 0.001). Discussion The management of sTOF is quite variable, with significant institutional variation in the palliative strategies offered to these neonates. This data suggests that an individual treating center’s management strategy specific to individual patient characteristics could be equally effective. This study highlights an important secondary outcome that RI burden after RVOTI is common. Morbidity burden overall is similar between the two strategies. Neonatal morbidities of ventilation time and inotrope use were lower in RVOTI. This decrease is likely driven by a higher frequency of catheterization-based strategy in RVOTI and surgery in SPC. When comparing ductus arteriosus stent to BTTS, intensive care unit length of stay and procedural complications were lower in the ductus arteriosus stent group. Similarly, Stumper et al., described lower length of stay and intensive care unit readmissions when comparing RVOT stent to BTTS. The potential early morbidity benefit comes at a cost of increased RI as seen in this study as well as other studies of catheter-based interventions of ductus arteriosus stent versus BTTS. Conclusion In conclusion, palliative strategy comparing RVOTI to SPC in neonates with sTOF yields similar incidence of CR by 18 months and similar overall survival. While patients with RVOTI have a higher RI burden after IP the overall morbidity burden is generally similar among patients undergoing palliation when grouped based on physiology. This data supports patient and institution individualized approach to palliation of sTOF.

Treating Pediatric Myocarditis with High Dose Steroids and Immunoglobulin. Schauer J, Newland D, Hong B, Albers E, Friedland-Little J, Kemna M, Wagner T, Law Y. Pediatr Cardiol. 2022 Sep 12:1-10. doi: 10.1007/s00246-022-03004-w. PMID: 36097060 Take home points: There is considerable variability in practice among pediatric centers for treatment of myocarditis. Median duration of IV steroids was 7 days (IQR 4–12) followed by an oral taper. Median cumulative dose of IV immunoglobulin (IVIG) was 2 g/kg. Overall transplant free survival was 92.5% with median follow-up of 1 year and by 3 months from diagnosis, 70% of patients regained normal left ventricular function. High dose steroids in conjunction with IVIG to treat acute myocarditis can be safe without significant infections or long-term side effects. Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch. Introduction In the real world, most pediatric myocarditis diagnoses are based on clinical presentation, incorporating echocardiography, electrocardiography and cardiac specific biomarkers. Best practice for treating myocarditis remains controversial. IVIG and steroids are frequently used in other inflammatory diseases in children such as Kawasaki disease as well as for treatment of rejection after cardiac transplantation. Materials and Methods This is a single center retrospective study of children less than 21 years of age diagnosed with myocarditis from January 2004-April 2021 at Seattle Children’s Hospital. Patients with myocarditis are managed or consulted on by the Heart Failure, Transplant, and Mechanical Circulatory Support (HF/TXP/MCS) service. Our standard myocarditis treatment protocol includes 2 g/kg IVIG based on actual body weight given over 48 h and an initial high dose steroid “pulse” that is tapered over 10–12 weeks. (Table 3) Results An initial medical record query for the diagnosis of myocarditis revealed 112 patients. Forty patients ultimately met inclusion criteria. The initial echocardiogram showed severe LV systolic dysfunction (EF < 35%) in 21 patients (54%), moderate LV systolic dysfunction (EF 35–44%) in 6 patients (15%), and mild LV systolic dysfunction (EF 45–55%) in 4 patients (10%). Eight patients (21%) had a normal ejection fraction but with significant left ventricular dyskinesis or hypokinesis on echocardiogram. Median initial LV end-diastolic dimension z score was 0.02 (IQR − 0.87 to 1.79). Twenty-two patients (65%) had at least mild mitral valve regurgitation, and 21 patients (53%) had at least mild tricuspid valve regurgitation on initial echocardiogram. Nine patients (23%) had at least a mild pericardial effusion. Treatment with high dose steroids was initiated within 48 h of admission for 65.8% of patients. Intravenous Immunoglobulin (IVIG) was received by all patients. Thirty-two (80%) patients required inotropic support, the majority of which received milrinone.  Thirty-eight patients (95%) received conventional heart failure therapy (including angiotensin converting enzyme inhibitors (ACE-I) or angiotensin II  receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), digoxin, beta blockers or isosorbide dinitrate/hydralazine) during their inpatient stay. Outcomes Of the cohort, 10 (25%) required mechanical circulatory support (MCS) during their initial hospitalization with extracorporeal membrane oxygenation (ECMO) being the most common form (n=6; median 11 days, range 4–25 days). Three patients were supported with a left ventricular assist device (LVAD). All but one patient was cannulated onto MCS prior to initiation of steroids. The remaining patient was cannulated within 12 h of steroid initiation. Three patients (7.5%) either died or required transplantation. Complications during hospital stay: (Table 6) Follow up Echocardiographic Data The majority of patients showed improvement in left ventricular function over time with 42% (13 out of 31) showing normalization of ejection fraction by 1 week, 65% (22 out of 34) by 1 month, and 70% (14 out of 21) by 1 year. Discussion Under this regimen, transplant free survival in our cohort was 92.5% over a median follow up period of 1 year (IQR 0.5–3), with improvement in multiple echocardiographic indices of myocardial function observed over time. Conclusion Use of high dose steroids with IVIG to treat myocarditis in a contemporary cohort can be safe and was not associated with any apparent propagation of viral infection affecting clinical outcome. The cohort had excellent recovery of ventricular function and survival without transplant (94%). Prospective comparison of a combination of high dose steroids with IVIG versus either therapy alone is needed.

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant. Stanford NT, McAllister J, Gibbons M, Jensen K, Lee H, Rothkopf A, Jackson R, Farr M, Addonizio L, Law S, Lee T, Richmond M, Zuckerman W. Pediatr Transplant. 2022 Nov;26(7):e14370. doi: 10.1111/petr.14370. Epub 2022 Aug 11.PMID: 35950955 Take Home Points: A significant percentage of adult survivors of pediatric OHT are able to achieve the usual societal milestones of full employment, marriage and independence. About 1/3 of adult survivors of pediatric OHT receive a college degree or higher. They report satisfactory QoL, comparable to that of other groups with chronic diseases. The era of transplantation and the type of physician group (adult or pediatric) that follows them does nto have an impact on the overall QoL of adult survivors of HT. Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch Introduction Survival from Pediatric heart transplantation (PHT) has improved over the years, with the median survival estimated at 18-25 years post-transplant for current recipients. Studies on adult recipients of a heart transplant (OHT) show improved quality of life (QoL) compared to prior to transplant. Pediatric recipients however face additional challenges including interruption in normal growth and development, missing school, effects of heart disease and cardiac bypass on the developing brain, and lifelong immunosuppression.  To date, no QoL studies have been performed on adults who received OHT as a child. Methods: Adult patients followed at Columbia Hospital were included if they received a OHT at an age <18 y/o between 1984 and 2007 and have survived at least 10 years post OHT. Patients were asked to complete two surveys: CHONY Pediatric Heart Transplant Life Achievement Survey, which is a simple survey asking about family structure, education, employment and income, and the Quality of Life Index (QLI) cardiac version by Ferrans and Power, which evaluates health and functioning. The results were evaluated by domain, and were subdivided by age at transplantation, current age, indication for transplant and if they are followed by pediatric or adult cardiology. Results: 113 patients were included but only 66 (58%) completed the surveys. Average age at survey was 26.5 years. 62% of respondents were caucasian. 75% of responders were transplanted for cardiomyopathy and only 22% for CHD. 71% were never married and 13.6% had children. 9% did not have a high school degree, while 33% had completed college or a postgraduate degree. 9% were unable to work and 16.7% were unemployed. 34% lived independently and 42% were insured through Medicare/ Medicaid. The overall mean QLI score was 0.75 ± 0.14 (where 0=very dissatisfied and1=very satisfied). The scores in the health/function, socioeconomic, psych/spiritual, and family domains were 0.75 ± 0.16, 0.72 ± 0.15, 0.73 ± 0.18, and 0.81 ± 0.12, respectively. Highest score was in family domain and lowest in socioeconomic domain. Among the subgroups, neonatal transpalntation,  female gender and transplantation for CHD had a weak correlation with better QoL as shown in figure 2, although none of the differences reached statistical significance. QoL was not associated with transplantation era or with type of physician group (adult versus pediatric). Discussion: This study demonstrates that adult survivors of pediatric OHT can achieve satisfactory QoL, especially in the family domain. They can achieve the usual societal milestones, although a significant proportion is unable to work. A similar percentage as the US census achieve a college or higher degree,  although this finding may be biased by the retrospective nature of the study and the population selection.In addition, this population seemed to be less likely to be married and have children that the generla populaiton. The study is limited by its small sample, and by the fact that QoL questionnaires were not obtained in comparable control samples.

Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017) Christina Karazisi, Mikael Dellborg, Karin Mellgren, Kok Wai Giang, Kristofer Skoglund, Peter Eriksson, Zacharias Mandalenakis. Lancet Reg Health Eur. 2022 May 29;18:100407. doi: 10.1016/j.lanepe.2022.100407. eCollection 2022 Jul. PMID: 35663362   Take-Home Points: 1) There is a 23% increased risk of cancer in young and older patients with congenital heart disease when compared to matched controls without congenital heart disease 2) The risk is higher in children and those who were born in later birth cohorts 3) The risk remains elevated after excluding patients with genetic syndromes and transplant recipients Overall Congenital cardiac surgery was not associated with an increased risk of cancer except in children who underwent cardiac surgery during the first year of life       Commentary from Dr. Venu Amula (Salt Lake City, UT, USA), section editor of Pediatric & Fetal Cardiology Karazasi et al. performed an observational case-control study using the Swedish health registry to investigate the risk of cancer in young and older patients with CHD and to evaluate the excess risk of cancer by syndromes, organ transplantation, and cardiac surgery. With the increasing survival of patients with congenital heart disease, they are at risk of acquired cardiovascular conditions and other diseases such as cancer. However, limited studies exist quantifying such a risk in patients with congenital heart disease compared to the general population. The authors of this study used data from the Swedish National Inpatient Register, the Swedish National Outpatient Register, and the Swedish Cause of Death Register. Inclusion criteria included patients born between 1930 and 2017 with a diagnosis of CHD. ICD codes were used for diagnosis. Each patient with CHD was matched by sex and birth year with ten controls without CHD from the general population, identified from the Swedish Total Population Register. Follow-up times for CHD and control populations were estimated from birth until the event (cancer), death, or the end of the study period (31 December 2017), whichever occurred first. Incidence rates were reported as per 10,000 person-years and were estimated as the number of events divided by the total follow-up time of the population. Incidence rate ratio (IRR) was defined as the relative difference between CHD and the control population, with 95% confidence intervals (CI) Cox proportional hazard regression models used to obtain hazard ratios (HR) with 95% CIs. For all models, the control population was considered the reference population. The authors identified 89,542 patients born between 1930 and 2017 who were registered with the diagnosis of CHD and 890,472 controls who were matched by birth year and sex. As noted in the table below, the baseline characteristics were similar in cases and controls. After a median follow-up time of 58.8 years for CHD patients and 61.3 years for controls, 4.5% of patients with CHD and 4.0% of the control population developed cancer. The cancer risk was 23% more in patients with CHD than in controls. The increased risk was maintained after excluding patients with syndromes and organ transplant recipients. When studying the cumulative incidence of cancer according to the birth cohort, the incidence of cancer was significantly higher in the CHD population from the youngest birth cohorts. Figure:   Cumulative incidence of cancer risk by birth cohort: Birth cohorts 1970−1989 and 1990-2017.   This study is of utmost importance and raises several important questions. The reasons for such an increased cancer risk remain elusive, but several are plausible. Genetic predisposition, increased exposure to low ionizing radiation as a part of diagnostic and therapeutic procedures, and early thymectomy with immune dysregulation are possible explanations without any direct evidence incriminating them. The association of higher cancer risk with younger birth cohorts does follow the increased surgical and catheter-based intervention trends in recent periods. Longitudinal studies involving large populations may provide more insight, but in the meanwhile, cardiologists should be aware of this higher risk and engage in heightened surveillance of young patients.  

Assessing the Association Between Pre-operative Feeding and the Development of Oral Feeding Skills in Infants with Single Ventricle Heart Disease: An Analysis of the NPC-QIC Dataset. Sagiv E, Tjoeng YL, Davis M, Keenan E, Fogel J, Fogg K, Slater N, Prochaska-Davis S, Frontier KD, Fridgen J, Chan T.Pediatr Cardiol. 2022 Jun;43(5):1141-1155. doi: 10.1007/s00246-022-02837-9. Epub 2022 Feb 14.PMID: 35157095   Take Home Points: Preoperative oral feeding was not associated with tube-free feeding in the first year of life Preoperative oral feeding was also not associated with increased risk of NEC, but markers of increased severity of illness and more difficult post-operative clinical course were Oral feeding can and should be offered to the appropriate risk patients, but our expectations of outcomes may need to be tempered and defining that patient group may not always be simple Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch:   Patients with HLHS or single ventricular lesions with no or decreased systemic outflow require a patient ductus arteriosus for systemic perfusion. Due to significant diastolic run-off to the pulmonary vasculature, systemic and primarily splanchnic circulation may be compromised, increasing the risk for necrotizing enterocolitis (NEC), and enteral feeding may increase risk. However, there is some data to suggest early feeding may reduce perioperative morbidity, lower length of hospital stay, and improve parental bonding and neurodevelopmental outcomes. Since optimal nutrition leads to better interstage survival and decreased morbidity at the 2nd stage palliation surgery, many patients will have a feeding tube to ensure adequate calories. Previous NPC-QIC data and the Single Ventricle Reconstruction (SVR) trial showed that about ~60% of patients are discharged home with feeding tubes after stage 1 palliation (S1P). Tube free feeding (TFF) is an important goal for parents and tube dependance has a negative effect on neurodevelopment. This study performed a secondary analysis of NPC-QIC phase II registry data and hypothesized that preoperative introduction of oral and enteral feedings would be associated with earlier TFF in the first year of life.   All data was obtained from the registry. The independent variable was preoperative enteral feeding and categorized as oral only, oral with tube feedings, tube feeds only, NPO for clinical reasons, and NPO due to institutional practice. Timing, volume, and reasons for these choices were not available. Dependent variables included TFF at hospital discharge after S1P, at the time of S2P admission, and 1st birthday. Patients were grouped as HLHS and non-HLHS, and secondary factors such as restrictive atrial septum, anomalous pulmonary veins, AV valve regurgitation, arrhythmias, low birth weight, prematurity, genetic syndrome, and non-cardiac anomalies were also assessed with regards to outcomes.   The authors provide a lot of demographic and preoperative characteristics. 944 patients from 57 institutions completed both surgeries and survived to age 1 and were included in the study with regards to TFF. To summarize, 41% were fed orally, 5% oral and tube, 11% tube only, 12% not fed for institutional practice and 30% not fed for a clinical reason. There were some clinical differences between those, with those receiving oral feeds having lower rates of markers suggesting higher severity illness. At hospital discharge after S1P, 57% of patients required tube feeding, and 39% still required tube feeding at the 1st birthday.   When comparing those that achieved TFF with univariate analysis, while the pre-op feeding group had the highest rates of TFF, this was not significantly different compared to those who were not fed for institutional reasons. This was significantly different when compared to those fed via feeding tube or NPO due to clinical reasons. However, on multivariate analysis pre-op feeding was not associated with TFF at one year (OR 1.3, CI 0.8-2). For pre-op feeding variables, the OR was calculated comparing to patients not fed enterally for institutional practice. For feeding mode at discharge, OR was calculated comparing to patients who were discharged without a feeding tube. Need for a feeding tube at S1P discharge though was significantly negatively associated with TFF at one year. Other risk factors for less likelihood to TFF included genetic syndrome, lower GA, need for PA band or AV valve repair, ECMO, and >2 postop complications. See Figure 1     Data from 1740 patients were available to determine the risk of NEC. 229 patients (13.2%) developed NEC, most occurring post-operatively (88%). Patients who received both oral and tube feeding pre-operatively had the highest risk of both pre- and post-op NEC, but when compared to those not fed for institutional practice, there was no significant risk of NEC. PO feeding alone was also not associated with increased risk. However, on multivariate analysis, for pre-op NEC, the group that received both oral and tube feeds did have an increased risk (OR 4.0). However, tube feeding only was not a risk factor. This was a small overall cohort, and the authors discuss reasons why this group may have been unique. But, other risk factors were also present, including pre-op neurologic deficit and PA banding prior to S1P. On the other hand, for post-op NEC, pre-op feeding type was not associated with post-op NEC. Other risk factors were present, most of which were due to higher severity of illness or complicated post-op clinical course. See Figure 2. Notably, those that were NPO preoperatively based on institutional practice did not have a decreased risk of NEC post-operatively.     One of the more difficult decisions in the preoperative and postoperative single ventricle patients is feeding; when to feed, who to feed, how to feed. Due to the sheer amount of data, sometimes the article was at times a bit hard to follow. However, the important take home point is that for the lower risk patient, there is not a significant increase risk of NEC, and with the overall positive benefits of feeding including earlier time to full feeds, lower hospital stay, and psychosocial and neurodevelopmental benefits (even without a statistically significant difference TFF at one year), it is possible that more patients could and should be fed, especially at those institutions who currently do not feed at all. With additional time and data, the hope is that standardized feeding algorithms based on clearly defined risk stratification can be developed for use across institutions.   

Cardiopulmonary Exercise Performance in the Pediatric and Young Adult Population Before and During the COVID-19 Pandemic D. S. Burstein, J. Edelson, S. O’Malley, M. G. McBride, P. Stephens, S. Paridon,and J. A. BrothersPediatr Cardiol. 2022; 43(8): 1832–1837. https://doi-org.online.uchc.edu/10.1542/peds.2021-052567   Take Home Points: Cardiopulmonary exercise performance decreased during the COVID-19 pandemic in children, adolescents and young adults compared to pre-pandemic values. The greatest decrease in exercise performance was among those who were the most aerobically fit pre-pandemic. School structure was not associated with changes in exercise performance. Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch:   Introduction: During the COVID 19 pandemic, schools closed for the last 3 months of the 2019-2020 school year and many schools continued the following school year with online or hybrid instruction.In addition, sports teams cancelled practices and competitions, and public parks were closed to the public. Self-reported survey data and device measured activity showed a decrease in physical activity (PA) and increase in sedentary behaviors (BH) during the pandemic. This study hypothesized that there would be a decrease in exercise performance in children and adolescents after the pandemic, compared to prepandemic values.   Methods This was a retrospective cohort study of all patients aged 6-22 who underwent at least one maximal CPET before the pandemic and one during (June 1, 2020 to May 7, 2021) at CHOP. Patients were excluded if they did not achieve maximal CPET criteria or if their cardiac condition changed during this time period (either started new medication, had dose escalation, interventions or cardiac surgery/ transplantation). A maximal test was defined as achieving a RER > 1.1. Measured variables included VO2max, ventilator anaerobic threshold (VAT), work rate, HR. Pre and pandemic data were compared using two-sampled t test or Wilcoxon matched pair signed rank test for no parametric data distribution.   Results: Total n was 122 patients with a median age of 14 years. The majority were white. 60% were male. The diagnosis was long QT in 30%, hypertrophic cardiomyopathy in 9% anomalous origin of a coronary artery in 11%, Fontan in 4% and other congenital heart disease in 9%. 34% self-reported unchanged level of physical activity, while 43% reported decreased level of PA. There was a clinically insignificant increase in BMI during the pandemic. Aerobic capacity significantly decreased among both females (92% vs. 82% predicted peak VO2, p = 0.047) and males (96% vs. 92% predicted peak VO2, p = 0.008) during the pandemic. Patients who were more physically fit based on a pre-pandemic peak predicted VO2 had a greater decrease in aerobic capacity during the pandemic compared to those who were less fit before the pandemic as shown in the figure below.     School structure (remote versus in person) was not associated with changes in exercise performance There was no significant change in physical working capacity (predicted peak work) during the pandemic.   

Impact of Right Ventricular Pressure Load After Repair of Tetralogy of Fallot. Latus H, Stammermann J, Voges I, Waschulzik B, Gutberlet M, Diller GP, Schranz D, Ewert P, Beerbaum P, Kühne T, Sarikouch S; German Competence Network for Congenital Heart Defects Investigators *.J Am Heart Assoc. 2022 Apr 5;11(7):e022694. doi: 10.1161/JAHA.121.022694. Epub 2022 Mar 18.PMID: 35301850   Take Home Points: In patients with repaired tetralogy of Fallot, higher right ventricular outflow tract gradients were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not reduce the risk for later pulmonary valve replacement. These findings may affect the timing and indication of pulmonary valve replacement procedures in patients after repair of tetralogy of Fallot. Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch.   Introduction Following surgical repair of tetralogy of Fallot (TOF), pulmonary regurgitation (PR) frequently emerges as the predominant residual lesion causing progressive right ventricular (RV) enlargement, functional impairment, and, potentially, sudden cardiac death. Surgical management of patients after TOF repair has therefore shifted toward a pulmonary valve-sparing repair technique with the aim of preserving RV integrity. Subsequently, some degree of residual pulmonary stenosis is typically accepted after repair and has been shown to have beneficial effects on the described adverse RV remodeling process by reducing PR and RV enlargement without compromising RV function. Furthermore, mild residual RV outflow tract (RVOT) gradients may also postpone the need for pulmonary valve replacement (PVR). In contrast, recent data from several studies demonstrated elevated RV pressure as an independent predictor for adverse outcome after TOF repair.   Study Population: Patients with repaired TOF were enrolled in a prospective nationwide study by the German Competence Network for Congenital Heart Defects between 2003 and 2009. For the current study, patients with cardiopulmonary exercise testing data (peak oxygen uptake and percentage predicted and peak heart rate), echocardiographic assessment of the peak systolic RVOT gradient, and a comprehensive initial CMR examination (including biventricular volumetry and quantification of pulmonary regurgitation fraction using phase-contrast flow measurements) were considered for further analysis. These examinations were performed within a close time interval at study entrance, and the patients were then prospectively followed up until July 2018. To further assess the prognostic impact of residual RV pressure load, the study population was divided into 2 groups according to a cutoff RVOT gradient of <25 and ≥25 mm Hg.   Results From the total population of 407 patients with repaired TOF enrolled in the multicenter study, 337 had a suitable data set for the intended analysis that included echocardiographic peak RVOT gradient, a comprehensive CMR analysis, and a completed cardiopulmonary exercise testing examination. The mean peak echocardiographic RVOT gradient was 20.7±14.9 mm Hg (median, 16mmHg; range, 2–83mmHg).     Figure 1: Graph displaying the study flow with the total number of 407 patients after repair of tetralogy of Fallot (TOF) who were originally included in the national TOF multicenter cardiovascular magnetic resonance (CMR) study. Note that 5 patients were excluded in the outcome analysis as these patients exhibited adverse events before the CMR study. CPET indicates cardiopulmonary exercise testing; echo, echocardiographic; EP, electrophysiologic study; ICD, implantable cardioverter-defibrillator; N, number of patients; RVOT, right ventricular outflow tract; TOF/PA, pulmonary atresia with ventricular septal defect (Fallot type); and VT, ventricular tachycardia.   Correlations Peak RVOT gradient was significantly associated with smaller RV volumes (r=−0.16; P=0.004) and less PR (r=−0.12; P=0.026), but lower RV (r=−0.23; P=0.0004) and left ventricular (LV) longitudinal systolic strain (r=−0.15; P=0.016), and lower early diastolic strain rate (r=−0.17 [P=0.01] and r=−0.22 [P=0.0006]. No significant relationships were found between RVOT gradient and RV ejection fraction (RVEF), RV mass, and RV mass/volume ratio. LV dimensions and LV ejection fraction were not related to the RVOT gradient. Although not of statistical significance, a trend toward reduced exercise capacity (both peak oxygen uptake and oxygen uptake at ventilator anaerobic threshold) was observed with increasing RVOT gradients.   Prognostic Relevance of RVOT Gradient A higher RVOT gradient was significantly associated with the combined outcome (HR, 1.03; 95% CI, 1.01–1.06; P=0.006). Other significant predictors were New York Heart Association functional class >1, peak oxygen uptake, PVR during follow-up, right ventricular end-systolic volume (RVESVi), left ventricular end- diastolic volume (LVEDVi), left ventricular end-systolic volume (LVESVi), RV longitudinal strain, RV circumferential strain, LV circumferential strain, and LV radial strain. A peak RVOT gradient of ≥ 25mmHg was associated with a >3-fold increase in adverse cardiovascular events. Patients with moderate PR and a peak RVOT gradient ≥25 mm Hg demonstrated significantly more adverse events than patients with moderate PR and a peak RVOT gradient <25 mm Hg (P<0.001). In patients with severe PR ≥25%, RVOT gradients >25 or <25 mm Hg led to no significant difference (P=0.38).   Role of Peak RVOT Gradient in the Need for PVR Data on PVR procedures during follow- up were available in 292 of the 296 patients. Using univariable Cox-regression analysis, a higher RVOT gradient was significantly associated with the need for PVR (HR, 1.02; 95% CI, 1.01–1.03; P=0.002). Other significant factors predictive for PVR were initial palliation, poorer New York Heart Association functional class, increased RV volumes and RV mass, PR severity, as well as lower RVEF and LV ejection fraction.   Discussion Our study demonstrated that a higher peak RVOT gradient was associated with less PR and smaller RV volumes in patients with repaired TOF, but also negatively affected biventricular systolic and diastolic longitudinal strain at study entry, even in a relatively young study population, and emerged as a univariate predictor for adverse cardiovascular events. More importantly, peak RVOT pressure gradients of >25mmHg were associated with a >3-fold higher risk for death and ventricular tachyarrhythmia, even in this young cohort.     Table 3. Cox Proportional Hazard Analysis Using a Bivariable Model of the Parameters That Reached a Significant Level on Univariable Testing to Identify Their Prognostic Relevance in Conjunction With the Peak RVOT Gradient   Conclusions Although higher peak RVOT gradients were associated with less PR and smaller RV dimensions, an inverse relationship with reduced systolic and diastolic biventricular longitudinal strain was present. Increased RVOT gradients also emerged as univariate predictors of adverse cardiovascular events in the long-term course. Mildly increased pressure gradients had no protective effect on later PVR procedures. These results may have implications for the indication and timing of RVOT reintervention in patients with repaired TOF. An optimal degree of pressure load, which ensures a protective effect on RV remodeling without compromising ventricular function and outcome, still needs to be determined.  

The Long-term Cardiac and Noncardiac Prognosis of Kawasaki Disease: A Systematic Review. Lee JJY, Lin E, Widdifield J, Mahood Q, McCrindle BW, Yeung RSM, Feldman BM. Pediatrics. 2022 Mar 1;149(3):e2021052567. doi: 10.1542/peds.2021-052567. PMID: 35118494   Take Home Message A systematic review of all studies reporting on long term outcome of Kawasaki disease (KD) was performed. Overall long term is favorable, with over 90% survival 30 years after KD Patients with KD and coronary involvement are at increased risk for Major Adverse Cardiovascular Events (MACE) over a follow up of 30 years. It is still unclear if children with KD without coronary involvement are at increased risk for development of MACE with up to 30 years of follow up Patients with KD may be at higher risk than the general population for atherosclerosis, and allergic diseases. Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch Introduction: KD is the leading cause of childhood acquired heart disease in developed countries. The objective of this systematic review of the literature was to determine the long-term prognosis of individuals with KD. Specifically, if previous KD exposure resulted in an increased risk in the following outcomes: all-cause mortality; major adverse cardiac events (MACE), including MI, cerebrovascular disease, heart failure, and cardiac interventions (catheterizations, coronary artery bypass graft [CABG] surgeries); chronic cardiac conditions or related comorbidities (hypertension, dyslipidemia, early atherosclerosis); and noncardiac diseases. Methods A search of databases that included Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials from inception to June 2020 was performed. A total of 77 studies were included in the review process. All studies were observational and were published between 1982 to 2020. The studies included a total of 72 487 patients from 13 countries. Fifty-five (74%) studies originated from East Asian countries.    Results: 10 studies reported on mortality outcomes in all patients with KD, with or without coronary involvement during the acute phase and found all cause mortality of 0-6% at 4-24 years of follow up. After the acute phase, patients with KD without aneurysms did not appear to be at increased risk for all-cause mortality compared with the general population 19 studies evaluated mortality in patients with coronary artery aneurysms. None of these studies had non KD comparators. The findings are shown in figure 2 below:     MACE were evaluate in 14 studies of KD patients regardless of the presence of aneurysms aneurysms and MI prevalence ranged from 0-7%. Among the 24 studies that evaluated MACE in patients with coronary artery aneurysms, MACE-free survival estimates ranged from 72% to 100% at 5 years, 66% to 91% at 10 years, 57% to 84% at 15 years, 29% to 74% at 20 years, 25% to 68.5% at 25 years, and 36% to 96% at 30 years as seen in figure 3     The development of chronic cardiovascular conditions was reported in several studies as shown in figure 4 .   Of 10 studies that evaluated the long term development of hypertension (HTN), 1 found increased risk of HTN, while 8 studies did not. Studies on hyperlipidemia showed mixed results. Two studies concluded an increased risk compared with healthy comparators, 5 reported no difference, and 4 were inconclusive. Atherosclerosis was evaluated via markers of endothelial dysfunction and arterial wall thickness or stiffness such as flow- mediated dilatation, pulse wave velocity and intima-media thickness (thickness of the carotid artery).  Of 10 studies, 7 studies concluded an increased risk, 2 reported no difference, and 1 was inconclusive. Twelve studies evaluated non cardiovascular outcomes; 6 focused on allergic diseases (asthma, atopic dermatitis, allergic rhinitis, urticaria, allergic conjunctivitis), 2 on cognition and behavior, 1 on malignancy, 1 on health-related quality of life, 1 on exercise performance, 1 on obstetrical outcomes, and 1 on respiratory infections (figure 4). The one study that evaluated the incidence of cancer, found a standardized incidence rate of 2.9 (95% CI, 1.6–5.2) with onset at least 6 years post KD.     Discussion As treatment has resulted in a significant decrease in the development of coronary artery aneurysms in the KD population, further studies are needed to evaluate the long term outcome of those without coronary artery involvement in the acute phase. Risk factors for MACE such as treatment resistance, time from onset of symptoms to treatment and age will need to be evaluated. This review did not include studies evaluating outcomes of KD like illness during the COVID 19 pandemic.   

Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot. O'Byrne ML, Glatz AC, Huang YV, Kelleman MS, Petit CJ, Qureshi AM, Shahanavaz S, Nicholson GT, Batlivala S, Meadows JJ, Zampi JD, Law MA, Romano JC, Mascio CE, Chai PJ, Maskatia S, Asztalos IB, Beshish A, Pettus J, Pajk AL, Healan SJ, Eilers LF, Merritt T, McCracken CE, Goldstein BH. J Am Coll Cardiol. 2022 Mar 29;79(12):1170-1180. doi: 10.1016/j.jacc.2021.12.036. PMID: 35331412   Take-Home Points: In children with symptomatic tetralogy of Fallot needing neonatal intervention, a total 18-month cost comparison made between those managed with staged repair (SR) vs. primary repair (PR) showed that primary repair was associated with lower costs Cost per day alive ( to account for confounding by early mortality) and department-level costs were also lower for primary repair Centers managing neonates with symptomatic tetralogy of Fallot repair should assess the feasibility and consider doing primary repair given its superior value and lower cost with similar mortality risk compared to the staged repair Commentary from Dr. Venu Amula (Salt Lake City, UT, USA), section editor of Pediatric & Fetal Cardiology Journal Watch Tetralogy of Fallot (TOF) is 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–surgical and transcatheter procedures to provide additional pulmonary blood flow, or some may consider primary repair of the intracardiac defect. In a recent study, Goldstein et al. compared the two treatment strategies of staged repair (SP) ( initial palliation [IP] followed by complete repair [CP]) and Primary repair (PR) for symptomatic neonates with TOF. 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.     The authors now merge the clinical data from that multicenter retrospective cohort study of neonates with symptomatic TOF with administrative data to compare total and departmental costs over the first 18 months in a propensity score-adjusted analysis. The individual patient-level costs were obtained from the Pediatric Health Information Systems. The primary exposure was the treatment strategy ( PR vs. SR). The primary outcome studied was the total hospital cost over the first 18 months of life. The cost per day alive was chosen as a complementary outcome to mitigate confounding due to early mortality. Secondary outcomes included all department–level costs such as clinical, imaging, supply, laboratory, pharmacy, and others. 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 original study cohort from the previous study comprised 572 patients, 230 treated with primary repair and 345 with initial palliation. To create a more contemporaneous cohort, only data from six of the nine hospitals that contributed data to the CCRC TOF study were included. The current study comprised 324 individuals. The characteristics of the PR and SR subjects were similar except for the proportion of patients receiving preprocedural ventilation (higher among the SR group) and those with prematurity (SR 25% vs. PR 17%). Clinical outcomes of mortality, 18-month risk of procedural complications, and reintervention were not significantly different between the two groups.     Total 18-month median costs for PR were significantly lower than for SR and the median cost per day alive for PR was also lower than SR. After propensity score adjustment, PR was associated with lower total 18-month costs ( cost ratio:0.73;95% CI 0.63-0.85; P<0.001). All departmental costs also favored PR.     The authors tried to address the value comparison of staged repair vs. primary repair in the setting of symptomatic neonates with tetralogy of Fallot. The large sample size from a research collaborative gave the authors a unique opportunity to merge with the administrative dataset and apply statistical methodology to adjust patient differences and provide a meaningful comparison of costs. However, not all costs are captured in PHIS, which is inpatient based. Outpatient costs and hidden costs related to loss of work, family disruption, etc., are not captured. Unmeasured confounders may also be present. Nevertheless, the association of PR with superior value and the lower cost makes it an appealing strategy to centers with the feasibility and technical expertise to do so. Given the few centers represented in the study, broad generalization is not possible. An individualized approach taken by heart center teams will benefit some symptomatic neonates with TOF and their families.    

Effects of universal critical CHD screening of neonates at a mid-sized California congenital cardiac surgery centre. Miller R, Martens T, Jodhka U, Tran J, Lion R, Bock MJ.Cardiol Young. 2022 Feb;32(2):236-243. doi: 10.1017/S1047951121001797. Epub 2021 May 24.PMID: 34024296   Take Home Points: Universal neonatal cardiac oximetry screening has 38% sensitivity in diagnosing critical CHD Neonatal cardiac oximetry screening is most useful in diagnosing TAPVR Neonatal cardiac oximetry screening does not impact length of hospital stay, mortality or survival after surgery for CHD. Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch   Introduction: Universal neonatal cardiac screening with pulse oximetry was implemented in California in July 2013. This study seeks to evaluate the outcomes of newborns with CHD diagnosed prior to or at neonatal cardiac screen compared to those diagnosed after the screen at Loma Linda University Children’s Hospital between July 1st, 2013 and December 31st, 2018. Included in the study were patients with CHD divided in two categories: the primary category was those with HLHS, PA-intact IVS, ToF, D- transposition, TAPVR, tricuspid atresia, and truncus arteriosus. Secondary lesions included all other single ventricles, coarctation of the aorta/ arch hypoplasia, Ebstein’s anomaly and DORV. The primary endpoints were postoperative length of stay, operative mortality, absolute mortality and actuarial survival.   Results: 274 patients who underwent cardiac surgery before 1 year of age were included in the study. Of those, 46% were diagnosed prenatally, and another 33% were diagnosed clinically postnatally before screening was performed. 8% of patients were diagnosed by screening and 13% tested negative on screening and were diagnosed later. The sensitivity of cardiac screening to detect CHD among those undiagnosed till then was 38%. Of those diagnosed by screening, 91% had one of the primary lesions. Of the undiagnosed primary lesions, 53% were diagnosed by screening, while only 10% of the undiagnosed secondary lesions were diagnosed by screening. There was no difference in operative or absolute mortality or postoperative length of stay based on the timing of diagnosis. The condition most commonly diagnosed was screening was TAPVR (73 %). A sub-analysis was performed comparing the outcomes of patients with TAPVR diagnosed after and before the implementation of screening, did not reveal differences in length of stay. There was no mortality in either era.   Discussion: This is a very interesting retrospective review of the efficacy of the implementation of neonatal cardiac screening. It reveals that screening has only 38% sensitivity in diagnosis, and even in those who are diagnosed by screening, there was no impact on mortality/ survival or length of stay. The study is limited in that it only evaluated patients who had surgery. It is possible that some infants may have died or suffered severe morbidity prior to surgery, and that mortality is not captured in this study. In addition, in this study only 46% of patients were diagnosed prenatally. It is likely that the improving incidence of prenatal diagnosis of CHD limits the benefit of cardiac oximetry screening. Based on this study, prenatal testing and clinical examination remain vital in diagnosing serious CHD.   

Comparison of Patent Ductus Arteriosus Stent and Blalock-Taussig Shunt as Palliation for Neonates with Sole Source Ductal-Dependent Pulmonary Blood Flow: Results from the Congenital Catheterization Research Collaborative. Bauser-Heaton H, Qureshi AM, Goldstein BH, Glatz AC, Ligon RA, Gartenberg A, Aggarwal V, Shashidharan S, McCracken CE, Kelleman MS, Petit CJ. Pediatr Cardiol. 2022 Jan;43(1):121-131. doi: 10.1007/s00246-021-02699-7. PMID: 34524483   Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch.   Take Home Points: Patent ductus arteriosus (PDA) stenting is an accepted method for securing pulmonary blood flow in cyanotic neonates. In neonates with pulmonary atresia and single source ductal-dependent pulmonary blood flow (SSPBF), PDA stenting remains controversial. Thirty-five patients with PDA stents and 156 patients with BTS were included. Interstage reintervention rates were higher in the PDA stent cohort (48.6% vs. 15.4%, p<0.001) This study supports the use of PDA stenting as a form of palliation in neonates with SSPBF (single source ductal-dependent pulmonary blood flow).   Introduction: In the most recent American Heart Association Scientific Statement, PDA stenting in the setting of SSPBF received a Class IIb recommendation of “might be reasonable. The authors hypothesized that, SSPBF as a barrier to PDA stenting may be overcome as centers and operators gain experience with the technical approach to stenting and supporting labile neonates with a single, prostaglandin-sensitive source of pulmonary blood flow. Children’s Hospital of Atlanta, Cincinnati Children’s Hospital Medical Center, Texas Children’s Hospital, and Children’s Hospital of Philadelphia cohorts were analyzed during this study from Jan 2008 to December 2015.   Methods Patients included in the cohort had a congenital cardiac diagnosis consistent with ductal dependent SSPBF and underwent BTS or PDA stent palliation in the neonatal period (≤30 days of age). Procedural outcomes, including complications, length of stay (LOS), need for post-procedural inotropic support, mechanical ventilation, and diuretic use post-palliation, were collected. Branch pulmonary artery diameter (measured at the hilum) was reviewed at the time of initial palliation as well as immediately prior to definitive surgical repair or next palliative stage (e.g., bidirectional Glenn anastomosis) using available imaging. “Reintervention” was defined as those exclusively on the PDA stent or the BTS if the reintervention occurred prior to surgical repair or planned palliation and was focused solely on the shunt or stent itself and did not involve the branch pulmonary arteries or other areas.   Results During the study period, 191 neonates with SSPBF underwent either PDA stent (n=35) or BTS (n=156). The baseline characteristics of the two cohorts were equivalent with a few notable exceptions. The PDA stent cohort was composed of more neonates with pulmonary atresia and intact ventricular septum (PA-IVS) compared with the BTS cohort (49% vs 28%, p=0.022). Single ventricle heart disease, presence of genetic syndrome, and pre-intervention clinical status were similar between the cohorts. Following initial palliation, ICU LOS was not different between the two cohorts (median ICU LOS 10 days for PDA and 7 days for BTS, p = 0.341). Hospital LOS was also similar between groups (p=0.178). The PDA stent cohort was less likely to receive inotropic support (p<0.01) or to be discharged on diuretics (OR 0.45, 95% CI [0.21–0.97], p = 0.042).     Complications and Reinterventions Procedural complications occurred in both groups at similar rates. However, major procedural complications occurred in 9 infants undergoing BTS and in no patients undergoing PDA stenting (p= 0.146). Adjusted analysis indicated no difference in overall rates of complications between PDA stent and BTS cohorts. Reintervention was more common in the PDA stent cohort when comparing any reintervention or reintervention on the shunt or stent itself Reintervention on the PDA stent itself was more common than on the BTS (adjusted p < 0.001). Similarly, rate of any reintervention following initial palliation was higher in the PDA stent cohort (adjusted p < 0.001). When considering timing of reintervention, it appears that the greatest period of risk for reintervention was >1 month from initial palliation.   Pulmonary Artery Growth & Interventions The pulmonary arteries were somewhat smaller pre-intervention in the PDA stent cohort (unadjusted median Nakata index 109 mm2 /m2 , 25th–75th 70–149) compared with the BTS cohort (unadjusted Nakata index 128 mm2 /m2 , 25th–75th 96–157, adjusted p=0.071). The increase in Nakata index from palliation to definitive repair or bidirectional Glenn was not statistically significant between cohorts. Interestingly, the branch pulmonary arteries were more asymmetric at the time of initial palliation in the PDA stent cohort (PA symmetry index 0.81, 25th–75th 0.72–0.92) compared with the BTS cohort (PA symmetry index 0.87, 25th–75th 0.79–0.95, adjusted p=0.016). At time of surgical repair or palliation, pulmonary artery symmetry was similar, with a symmetry index of 0.88 (25th–75th 0.77–0.97) in the PDA stent cohort compared with 0.82 (25th–75th 0.71–0.92), p= 0.857). At time of definitive surgical repair or staged surgical palliation, surgical pulmonary artery plasty was common in both cohorts, with 60.0% of the PDA stent cohort and 42.5% of the BTS cohort undergoing pulmonary artery plasty.     Discussion Although overall complication rates were equivalent, complications were more severe in the BTS group. The group palliated with PDA stenting underwent a higher rate of reinterventions compared with the surgical BTS group. Importantly, the two palliative cohorts had similar measures of PA growth, symmetry, and size at time of definitive repair/palliation, suggesting that candidacy for surgical repair or single ventricle palliation was preserved regardless of palliative modality. The current study does not include an equal balance of BTS and PDA stent patients and does not include data on any unsuccessful PDA stent “attempts.” The late reinterventions noted in the PDA stent cohort likely relate to the known issues of neointimal proliferation which commonly occurs in infants following PDA stenting and appears to be more common in infants with highly tortuous Type III PDAs.   Conclusion While PDA anatomy and the SSPBF physiology pose challenges, PDA stenting appears to offer equivalent clinical outcomes and durability as an initial palliative strategy compared with surgical BTS.