Pediatric Cardiology

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.