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Background: The Single Ventricle Reconstruction (SVR) trial compared survival after Norwood procedure with either modified Blalock Taussig shunt (MBTS) or right ventricle pulmonary artery shunt (RVPAS)., Methods: Data from all 549 participants in the SVR trial were used to develop the MBTS TFSA algorithms, which predict the transplantation-free survival advantage (TFSA) after MBTS vs RVPAS at 1 and 6 years after Norwood procedure. Linear regression analysis of the MBTS TFSA values was performed to identify factors related to more optimal outcomes with MBTS at each timepoint. The impact of discordant management (ie, predicted shunt type did not equal the one actually received) on outcomes and the extent of inconsistencies between predictions were evaluated., Results: The MBTS TFSA algorithm favored MBTS over RVPAS for only 6.2% of participants at 1 year and for 27.0% at 6 years. In terms of both 1- and 6-year outcomes, MBTS was favored with younger age at Norwood procedure and pre-Norwood intubation, while RVPAS was favored with younger gestational age and metrics indicating larger right ventricle size in the parasternal echocardiographic views. Other predictors were timepoint-specific. MBTS TFSA based allocation could have led to an absolute risk reduction in heart transplantation and mortality of 8.0% at 1 year and 16.8% at 6 years, mostly by preventing discordant MBTS management. Notably, separate predictions from the 1-year and 6-year algorithms produced discordant predictions for 136 participants (24.8%)., Conclusions: The incorporation of data-derived patient-specific factors for selection of shunt type for the Norwood procedure may produce more optimal transplantation free survival. These precision medicine algorithms require prospective validation., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal semi-dominant lipid metabolism disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. The objective of this study was to investigate sex-differences in the treatment and outcomes of patients with HoFH., Methods: We examined clinical characteristics, lipid-lowering therapy (LLT), and cardiovascular events using descriptive statistics of patients in the Canadian HoFH registry. Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U test and Fisher's Exact test, respectively., Results: This study included 48 patients (27 (56%) female). The median age at diagnosis in females was 14.0 (interquartile range (IQR) 9.0-30.0) and in males was 8.0 (IQR 2.0-23.0) (p = 0.07). Baseline clinical characteristics were comparable between both sexes. The median baseline LDL-C was 12.7 mmol/L (10.0-18.3) in females and 15.3 (10.5-20.0) in males (p = 0.51). Follow up LDL-C levels were 7.6 mmol/L (IQR 4.8-11.0) in females and 6.3 (IQR 4.6-7.5) in males (p = 0.1). Most patients were taking 3 or more LLTs, with comparable proportions in both sexes (p = 0.26). Apheresis was similar in both sexes, 14 (51.8%) vs. 10 (47.6%) (p = 0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p = 0.2)., Conclusion: Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pulmonary artery banding (PAB) in isolation or combined with a congenital cardiac surgical procedure is common and has important mortality. We aimed to determine patient characteristics, clinical outcomes, variation in clinical outcomes by diagnoses, and center variation in PAB use., Methods: Using The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD), this study evaluated outcomes of patients undergoing PAB across diagnoses, participating centers, and additional procedures. Patients were identified by procedure and diagnosis codes from 2016 to 2019. We separated patients into groups of main and bilateral PAB and described their outcomes, focusing on patients with main PAB., Results: This study identified 3367 PAB procedures from 2016 to 2019 (3% of all STS CHSD cardiovascular cases during this period): 2677 main PAB, 690 bilateral PAB. Operative mortality was 8% after main PAB and 26% after bilateral PAB. There was significant variation in use of main PAB by center, with 115 centers performing at least 1 main PAB procedure (range, 1-134; Q1-Q3, 8-33). For patients with main PAB, there were substantial differences in mortality, depending on timing of main PAB relative to other procedures. The highest operative mortality (25%; P < .0001) was in patients who underwent main PAB after another separate procedure during their admission, with extracorporeal membrane oxygenation being the most frequent preceding procedure., Conclusions: PAB is a frequently used congenital cardiac procedure with high mortality and variation in use across centers. Outcomes vary widely by banding type and patient diagnosis. Main PAB after cardiac surgical procedures, especially extracorporeal membrane oxygenation, is associated with very high operative mortality., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection., Methods: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure)., Results: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities., Conclusions: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 shares clinical similarities to Kawasaki disease (KD). We sought to determine whether cardiac biomarker levels differentiate MIS-C from KD and their association with cardiac involvement., Methods: Subjects included 38 MIS-C patients with confirmed prior COVID-19 and 32 prepandemic and 38 contemporaneous KD patients with no evidence of COVID-19. Patient, clinical, echocardiographic, electrocardiographic, and laboratory data timed within 72 hours of cardiac biomarker assessment were abstracted. Groups were compared, and regression analyses were used to determine associations between biomarker levels, diagnosis and cardiac involvement, adjusting for clinical factors., Results: MIS-C patients had fewer KD clinical features, with more frequent shock, intensive care unit admission, inotrope requirement, and ventricular dysfunction, with no difference regarding coronary artery involvement. Multivariable regression analysis showed that both higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (TnI) were associated with MIS-C vs KD, after adjusting for significant covariates. Receiver operating characteristic curves for diagnosis showed that any detectable TnI greater than 10 ng/L was predictive of MIS-C vs KD with 91% sensitivity and 76% specificity. NT-proBNP > 2000 ng/L predicted MIS-C vs KD with 82% sensitivity and 82% specificity. Higher TnI but not NT-proBNP was associated with lower LV ejection fraction. Neither biomarker was associated with coronary artery involvement., Conclusions: Positive TnI and higher NT-proBNP may differentiate MIS-C from KD, which may become more relevant as evidence of prior COVID-19 becomes more challenging to determine. Cardiac biomarkers may have limited associations with cardiac involvement in this setting., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein-as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens-are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Multisystem inflammatory syndrome in children (MIS-C) is a new illness that evolved during the COVID-19 pandemic with initial reports of severe disease including use of extracorporeal membrane oxygenation and death. Institutions rapidly assembled task forces to develop treatment algorithms. At the national/international levels, collaboratives and associations assembled consensus writing groups to draft guidelines. These guidelines and algorithms were initially on the basis of expert opinion and small case series. Some groups used the Delphi approach, and the resultant guidelines often mimicked those for other conditions that resembled MIS-C, like Kawasaki disease (KD). For instance, intravenous immunoglobulin (IVIG), a known effective treatment for KD, was recommended for MIS-C. Early in the pandemic many favoured IVIG over steroids as first-line therapy. As evidence evolved so did some guidelines, which now endorse the dual use of IVIG with steroids as first-line therapy. In contrast, withholding immunotherapy became an option for some MIS-C patients with mild symptoms. Herein, we review guidelines and discuss the evidence informing early recommendations, how this has evolved, the role and limitations of expert opinion and observational data, and the importance of leveraging existing research infrastructures, such as the intensive care unit collaborative (Overcoming COVID-19 surveillance registry), and the International Kawasaki Disease Registry. Finally, we discuss strategies to rapidly develop, deploy, and adapt clinical trials evaluating the treatment of such rare conditions in children, which might include alternatives to conventional clinical trial design. The emergence of MIS-C during the COVID-19 pandemic has highlighted unmet needs regarding research of a new condition., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: Clustering of cardiometabolic risk factors (CMRFs) indicates cardiometabolic risk (CMR), a key driver of cardiovascular disease. Early detection and treatment of CMR are important to decrease this risk. To facilitate the identification of individuals at risk, CMRFs are commonly combined into a CMR Score. This scoping review aims to identify CMRFs and methods used to calculate adolescent CMR Scores., Data Synthesis: Systematic searches were executed in Child Development and Adolescent Studies, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, EBSCO CINAHL, Scopus Elsevier, Cochrane CENTRAL, and Nursing and Allied Health. No limits were placed on publication date or geographic location. Studies were included if participants were 10-19 years and the study reported CMRFs in a composite score. Key extracted information included participant characteristics, CMRFs comprising the scores, and methods of score calculation. CMRFs were categorized and data were reported as frequencies. This study identified 170 studies representing 189 CMR Scores. The most common CMRF categories were related to lipids, blood pressure, and adiposity. The most frequent CMRFs were triglyceride z-score, systolic blood pressure z-score, and inverse high-density lipoproteins z-score. Scores were mostly calculated by summing CMRF z-scores without weighting., Conclusions: The range of CMRFs and Scores identified in adolescent CMR literature limits their use and interpretation. Published CMR Scores commonly contain two main limitations: (a) use of an internal cohort as the z-score reference population, and (b) Scores relying on adiposity measures. We highlight the need for a standard set of CMRFs and a consensus for a CMR Score for adolescents., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the author(s)., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Patients with a Fontan circulation for single-ventricle physiology are at increased risk of developing thromboembolic events. Thromboembolic events can lead to failure of the Fontan circulation, chronic sequelae in case of stroke, and early mortality. Controversies exist regarding the substrates, risk factors, and optimal detection methods for thromboembolic events. Despite the major clinical implications, there is currently no consensus regarding the optimal antithrombotic therapy to prevent or treat thromboembolic events after the Fontan procedure. In this review we aimed to untangle the available literature regarding antithrombotic prophylaxis and treatment for pediatric and adult Fontan patients. A decision-tree algorithm for thromboprophylaxis in Fontan patients is proposed. Additionally, the current state of knowledge is reviewed with respect to the epidemiology, pathophysiology, and detection of thromboembolic events in Fontan patients, and important evidence gaps are highlighted., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients receiving a right ventricle to pulmonary artery conduit (PC) in infancy will require successive procedures or replacements, each with variable longevity. We sought to identify factors associated with time-related risk of a subsequent surgical replacement (PC3) or transcatheter pulmonary valve insertion (TPVI) after a second surgically placed PC (PC2)., Methods: From 2002 to 2016, 630 patients from 29 Congenital Heart Surgeons' Society member institutions survived to discharge after initial valved PC insertion (PC1) at age ≤ 2 years. Of those, 355 underwent surgical replacement (PC2) of that initial conduit. Competing risk methodology and multiphase parametric hazard analyses were used to identify factors associated with time-related risk of PC3 or TPVI., Results: Of 355 PC2 patients (median follow-up, 5.3 years), 65 underwent PC3 and 41 TPVI. Factors at PC2 associated with increased time-related risk of PC3 were smaller PC2 Z score (hazard ratio [HR] 1.6, P < .001), concomitant aortic valve intervention (HR 7.6, P = .009), aortic allograft (HR 2.2, P = .008), younger age (HR 1.4, P < .001), and larger Z score of PC1 (HR 1.2, P = .04). Factors at PC2 associated with increased time-related risk of TPVI were aortic allograft (HR: 3.3, P = .006), porcine unstented conduit (HR 4.7, P < .001), and older age (HR 2.3, P = .01)., Conclusions: Aortic allograft as PC2 was associated with increased time-related risk of both PC3 and TPVI. Surgeons may reduce risk of these subsequent procedures by not selecting an aortic homograft at PC2, and by oversizing the conduit when anatomically feasible., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The emergence of increasing reports worldwide of a severe inflammatory process and shock in pediatric patients resembling Kawasaki disease (KD)-and, more specifically, Kawasaki disease shock syndrome (KDSS)-prompted us to explore KDSS in a preamble of a systematic comparison between the 2 conditions., Methods: We completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls., Results: A total of 10 case-control series were included in the meta-analysis. Patients with KDSS were older (38.4 ± 30.6 vs 21.9 ± 19.5 months; P < 0.001) compared with standard KD with equal sex distribution and completeness of clinical diagnostic criteria. KDSS present higher C-reactive protein (59.4 ± 29.2 mg/dL vs 20.8 ± 14.8 mg/dL; P < 0.001), lower albumin (2.7 ± 0.5 g/dL vs 3.3 ± 0.5 g/dL; P < 0.01), and lower platelets (255 ± 149 109/L vs 394 ± 132 109/L; P < 0.001) but only borderline higher white blood cells (P = 0.06). Differences in alanine transaminase, aspartate aminotransferase, and erythrocyte sedimentation rate were nonsignificant. The odds of intravenous immunoglobulin resistance (44.4% vs 9.6%; (P < 0.001) and the hospital length of stay (10.9 ± 5.8 vs 5.0 ± 3.0 days; P < 0.001) were higher in KDSS, as were the odds of coronary-artery abnormalities (33.9% vs 8.6%; P < 0.001)., Conclusions: This first meta-analysis on KDSS vs KD represents a basis for future works on KDSS and opens the opportunity for future multicentre studies in the search of causal relationships between presenting elements and the eventual complications of KDSS. The similarities between SARS-CoV-2 multisystem inflammatory syndrome in children and KDSS open new horizons to the understanding of the etiology and pathophysiology related to KDSS., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Pediatric cardiology has evolved over time with reductions in childhood mortality due to congenital heart disease. Surgical innovation drove early changes in care. Increasingly, the need for more robust evidence provided by randomised controlled trials (RCTs) has been recognised. Although the number of RCTs has increased, there remains a relative paucity of truly impactful trials in the field. However, those trials that have changed practice have demonstrated the potential and importance of this work. Examples include the PRIMACORP trial, which established the safety and efficacy of milrinone after cardiac surgery, and the Single Ventricle Reconstruction trial, which was the first multicentre pediatric cardiac surgical RCT. The successful conduct and important findings emanating from these trials serve as beacons as clinicians strive to improve the evidence base in this field. The establishment of national and international networks such as the Pediatric Heart Network and the Canadian Pediatric Cardiology Research Network provide a strong foundation for future collaborative work. Despite this progress, there remain important challenges to designing and executing RCTs in pediatric cardiology. These include issues of greater disease and patient heterogeneity and increased costs. The use of innovative study designs and analytic methods and the establishment of core outcome measures have the potential to overcome some of the issues related to the smaller patient numbers compared with adult disciplines. As pediatric cardiologists look to the future, it is imperative that we work together to derive the maximum benefit from the considerable efforts directed toward conducting impactful clinical trials in pediatric cardiology., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Kawasaki disease (KD) may lead to coronary artery aneurysms (CAA) with potential for thrombosis. We aimed to determine the bleeding risk during thromboprophylaxis regimens with dual and triple therapy., Methods: KD patients with medium to large CAAs receiving combination thromboprophylaxis therapy (dual or triple therapy with acetylsalicylic acid (ASA), clopidogrel, low molecular weight heparin (LMWH) or warfarin) were reviewed (1979-2017). Treatment periods <30 days were excluded. Bleeding events were classified using the Bleeding Academic Research Consortium (BARC) Score. The incidence of bleeding events per patient year of exposure was determined for each regimen., Results: n = 98 of 3022 KD (23 females:75 males) were included. Median age at diagnosis was 2.6 years (IQR: 0.6-6.2), median maximum CAA z-score was 18.0 (range: 5-65.5, IQR: 10.8-28.0, m = 6) and median follow-up duration was 6.5 years (IQR: 2.5-20.2). The incidence of type ≥2 bleeds per patient-year for each regimen was 0 (ASA + clopidogrel+LMWH), 0.03 (ASA + clopidogrel), 0.06 (ASA + warfarin), 0.06 (ASA + clopidogrel+warfarin), and 0.1 (ASA + LMWH) in ascending order. 31 bleeding events requiring medical attention (type ≥2) occurred in 30 patients (median age 7.8 years). Of the 17 type ≥2 bleeds on warfarin with an International Normalised Ratio (INR) available, 13 occurred with an INR >3. For patients receiving triple therapy (dual antiplatelet with anticoagulant), there were 57 bleeding events over 20 treatment periods., Conclusions: The overall bleeding risk was low in KD patients receiving combination thromboprophylaxis, and not significantly different across all regimens. Type ≥2 bleeding events that occurred on warfarin were most frequently associated with high INR values., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the effectiveness of anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for thromboprophylaxis in large CAAs., Methods: Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up., Results: From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range [IQR] 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval [CI] 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25)., Conclusions: LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis in its earliest stages is associated with the same traditional cardiovascular disease (CVD) risk factors as are associated with manifest CVD events in adulthood. Clustering of risk factors is associated with exponential increases in atherosclerotic burden from a young age. Some medical conditions and risk behaviours occurring in children can either increase the likelihood of higher levels of risk factors (such as chronic kidney disease) or the presence of risk factor clustering (such as obesity and cardiometabolic syndrome) or are associated with acquired coronary artery pathology (such as Kawasaki disease). This creates a milieu for-or increases the impact of-accelerated atherosclerosis that, in turn, increases the likelihood of premature CVD. This review highlights the importance of considering the total risk factor and risk-condition profile of pediatric patients. An algorithm is provided for stratifying patients into high-, moderate-, and at-risk categories, and practical examples are provided as to how the evaluation and management of 1 risk factor or risk condition might need to be intensified in the context of additional risk factors or risk conditions. For example, for treatment of an adolescent with familial hypercholesterolemia, the target low-density lipoprotein cholesterol level might be lowered by the concomitant presence of low high-density lipoprotein cholesterol or elevated lipoprotein(a) levels. As awareness of cardiovascular risk and atherosclerosis in pediatric patients increases, new at-risk conditions that warrant consideration are emerging. The identification and management of high-risk individuals is an important part of the overall practice of pediatric preventive cardiology., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The pediatric lipid screening and treatment practices, attitudes, and perceived barriers of Canadian pediatricians are not known. We sought to evaluate this in a survey of pediatricians through the Canadian Pediatric Surveillance Program (CPSP) in March 2019. The survey included an assessment of lipid screening of 9- to 11-year-old youth and a hypothetical case of persistent severe dyslipidemia to ascertain management practices. There were 759 respondents (28% response rate, 759 of 2742), of whom 236 provided outpatient primary care to 9- to 11-year-old youth as part of their routine clinical practice. Among primary care-providing pediatricians, universal lipid screening of healthy 9- to 11-year-old youth most or all of the time was reported by 3% (8 of 230). Reported screening practices most or all of the time were more common for youth with risk factors such as overweight and obesity (54%, 127 of 235) and a family history of premature cardiovascular disease (39%, 85 of 217). Most respondents would refer a child with severe persistent dyslipidemia to dieticians (69%, 152 of 220) and a lipid specialist (64%, 144 of 220) most or all of the time, whereas 7% (16 of 220) would start statin therapy themselves. A lack of Canadian pediatric lipid guidelines was reported as a major barrier for 49% (114 of 233) and minor barrier for 40% (93 of 213). The rate of routine lipid screening of healthy 9- to 11-year-old youth among Canadian primary care-providing pediatricians is low and at odds with current US guidelines. This discrepancy may be due at least in part to a lack of Canadian guidelines on pediatric dyslipidemia, the development of which may address certain perceived barriers and influence future attitudes., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Up to 25% of children with congenital heart disease are obese, which may have negative physiologic consequences for patients with repaired tetralogy of Fallot (rTOF)., Methods: Patients with rTOF who underwent cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise testing from 2007 to 2018 were reviewed. Complex rTOF patients were excluded. Obese patients (body mass index [BMI] ≥ 95th percentile) were compared with normal-weight patients (BMI < 85th percentile). CMR data were indexed to actual body surface area (aBSA), height, and BSA assuming ideal body weight (iBSA)., Results: We compared 32 obese patients matched with 64 normal-weight patients. Obese vs normal-weight patients had significantly lower right (RV; median 45% [interquartile range 42%-48%] vs 52% [47%-55%]; P < 0.0001) and left (LV; 52% [47%-56%] vs 56% [54%-60%]; P < 0.0001) ventricular ejection fractions (EFs). There were no statistically significant differences regarding aBSA-indexed volumes of the RV or LV at either end-diastole (EDV) or end-systole (ESV). However, when indexed to either height or iBSA, obese patients had significantly greater RVEDV and LVEDV, greater LV mass, and higher RV and LV stroke volumes. Obese patients had lower peak oxygen consumption and oxygen consumption at anaerobic threshold. These results did not change after adjusting for degree of pulmonary regurgitation., Conclusions: Obesity is associated with increased biventricular size, decreased biventricular EFs, and impaired exercise performance after rTOF. These data suggest a potential role for cardiac rehabilitation for weight management and to optimize fitness., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Together with heart-healthy lifestyle habits, statins serve as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease in adults. Several conditions, most notably familial hypercholesterolemia (FH), cause early dyslipidemia and vascular disease, contributing to the development and progression of atherosclerosis from childhood and increased cardiovascular risk. In recent decades, studies increasingly have evaluated the safety and efficacy of statins in such high-risk youth. The strongest evidence for pediatric statin use is for the heterozygous FH population, whereby statin use has been shown to lower low-density lipoprotein cholesterol effectively, slow the progression of atherosclerosis and vascular dysfunction, and significantly reduce cardiovascular risk in early adulthood. Numerous meta-analyses and Cochrane reviews have demonstrated that attributed adverse effects, including liver toxicity, myositis, and rhabdomyolysis, occur no more frequently in youth receiving statins than placebos, with no impact on growth or development. However, further studies evaluating the long-term safety of pediatric statin use are required. In the current review, we summarize the pediatric experience of statin use to date, focusing on its utility for FH, Kawasaki disease, post-heart transplantation, and other at-risk populations. Current guidelines and indications for use are summarized, and the short- and medium-term safety experience is reviewed. Finally, a clinical approach to the indications, initiation, and monitoring of statins in youth is provided., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Doppler ultrasound measurements of the peak systolic velocity of the middle cerebral artery can be used to noninvasively diagnose fetal anemia but are less precise following fetal blood transfusion and in late gestation. We have previously demonstrated the feasibility of estimating fetal hematocrit in vitro using magnetic resonance imaging relaxation times. Here we report the use of magnetic resonance imaging as a noninvasive tool to accurately detect fetal anemia in vivo., Objectives: This study has 2 objectives: (1) to determine the feasibility and accuracy of magnetic resonance imaging in estimating hematocrit in anemic fetuses and (2) to compare magnetic resonance imaging and middle cerebral artery Doppler in detecting moderate to severe fetal anemia., Study Design: Fetuses undergoing fetal blood sampling or transfusion underwent magnetic resonance imaging examinations prior to and following their procedures at 1.5 Tesla (Siemens Avanto). A modified Look-Locker inversion pulse sequence and T 2 preparation sequence were applied for T 1 and T 2 mapping of the intrahepatic umbilical vein. Estimated fetal hematocrit was calculated using a combination of T 1 and T 2 values and compared with conventional hematocrit obtained from fetal blood samples and middle cerebral artery Doppler measurements., Results: Twenty-three fetuses were assessed during 33 magnetic resonance imaging scans. The mean absolute difference between the laboratory and magnetic resonance imaging-estimated hematocrit was 0.06 ± 0.05 with a correlation of 0.77 (P < .001) determined by a multilevel, mixed-effects model adjusting for the repeated measurements from the same participants, multiple gestation pregnancies, and the scan type (ie, before or after transfusion scan). Bland-Altman analysis revealed a systematic bias of -0.03 between the magnetic resonance imaging and fetal blood sampling measurements. Magnetic resonance imaging and middle cerebral artery Doppler had similar sensitivities of approximately 90% to detect moderate to severe anemia. However, magnetic resonance imaging had a higher specificity (93% [13/14], 95% confidence interval, 66-100%) than Doppler (71% [10/14], 95% confidence interval, 42-92%)., Conclusion: Moderate to severe fetal anemia can be detected noninvasively by magnetic resonance imaging with high sensitivity and specificity. Our results suggest an adjunct role for magnetic resonance imaging in fetuses with suspected anemia, particularly following previous transfusion and in late gestation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Improved survival for patients with dextro-transposition of the great arteries (d-TGA) has led to an increased focus on functional health status (FHS). We assessed late survival and patient-perceived FHS for repaired TGA patients., Methods: From 1985-1990, 830 neonates admitted to 24 Congenital Heart Surgeons' Society (CHSS) institutions with d-TGA underwent repair, including 516 arterial switch, 110 Mustard, 175 Senning, and 29 Rastelli operations. Median follow-up was 24.0 years (range, 0-32.7 years). We performed multiphase parametric hazard analysis for death after repair. Patients completed Pediatric Quality of Life Inventory (PedsQL) Core Scales and Cardiac Module Adult Forms. Patient and operative factors and CHSS General Questionnaire responses were analyzed for association with FHS using multiple linear regression., Results: Survival at 30 years after repair was arterial switch, 80% ± 2%; Mustard, 81% ± 5%; Senning, 70% ± 4%; and Rastelli, 86% ± 8%. The arterial switch had the lowest hazard for late death. TGA patients reported FHS similar to a healthy population in all domains except physical health (lower scores). Symptoms, including chest pain and fainting, and having a pacemaker were associated with lower, and being employed with higher, self-reported physical health. Arterial switch patients reported higher FHS than the atrial switch patients in all domains., Conclusions: Arterial switch patients have a lower risk of premature death and better FHS than those with an atrial switch. Increased surveillance in atrial switch patients is warranted because of their increased risk of late death. Presence of symptoms, pacemaker, and lack of employment are associated with reduced FHS., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Body mass index measures excess weight for size, and does not differentiate between fat mass (FM) and fat-free mass (FFM). Bioelectrical impedance analysis (BIA) is most commonly used to assess FM and FFM as it is simple and inexpensive. Variables from BIA measurements are used in predictive equations to estimate FM and FFM. To date, these equations have not been validated for use in adolescents with severe obesity., Objectives: In a cohort of adolescents with severe obesity (SO), a BMI ≥ 120% of the 95th percentile, this study aimed to 1) derive a BIA predictive equation data from air displacement plethysmography (ADP) measurements; 2) reassess the equation in a second validation cohort; and 3) compare the accuracy of existing body composition equations., Methods: Adolescents with SO were assessed using ADP and BIA. FM values derived from ADP measurements from the first cohort (n = 27) were used to develop a BIA predictive equation (i.e., Hamilton). A second cohort (n = 65) was used to cross-validate the new and 9 existing BIA predictive equations., Results: Ninety-two adolescents (15.8 ± 1.9 y; BMI: 46.1 ± 9.9 kg/m2) participated. Compared with measured FFM using ADP: 1) the Lazzer, Hamilton, Gray, and Kyle equations were without significant bias; 2) the Hamilton and Gray equations had the smallest absolute and relative differences; 3) the Kyle and Gray equations showed the strongest correlation; 4) the Hamilton equation most accurately predicted FFM within ± 5% of measured FFM; and 5) 8 out of 9 equations had similar root mean squared prediction error values (6.03-6.64 kg)., Conclusion: The Hamilton BIA equation developed in this study best predicted body composition values for groups of adolescents with severe obesity in a validation cohort., (Copyright © American Society for Nutrition 2019.)

Background: Thrombosis is a major adverse outcome associated with coronary artery aneurysms (CAAs) resulting from Kawasaki disease (KD). Clinical guidelines recommend initiation of anticoagulation therapy with maximum CAA diameter (D max ) ≥8 mm or Z-score ≥ 10. Here, we investigate the role of aneurysm hemodynamics as a superior method for thrombotic risk stratification in KD patients., Methods and Results: We retrospectively studied ten KD patients with CAAs, including five patients who developed thrombosis. We constructed patient-specific anatomic models from cardiac magnetic resonance images and performed computational hemodynamic simulations using SimVascular. Our simulations incorporated pulsatile flow, deformable arterial walls and boundary conditions automatically tuned to match patient-specific arterial pressure and cardiac output. From simulation results, we derived local hemodynamic variables including time-averaged wall shear stress (TAWSS), low wall shear stress exposure, and oscillatory shear index (OSI). Local TAWSS was significantly lower in CAAs that developed thrombosis (1.2 ± 0.94 vs. 7.28 ± 9.77 dynes/cm 2 , p = 0.006) and the fraction of CAA surface area exposed to low wall shear stress was larger (0.69 ± 0.17 vs. 0.25 ± 0.26%, p = 0.005). Similarly, longer residence times were obtained in branches where thrombosis was confirmed (9.07 ± 6.26 vs. 2.05 ± 2.91 cycles, p = 0.004). No significant differences were found for OSI or anatomical measurements such us D max and Z-score. Assessment of thrombotic risk according to hemodynamic variables had higher sensitivity and specificity compared to standard clinical metrics (D max , Z-score)., Conclusions: Hemodynamic variables can be obtained non-invasively via simulation and may provide improved thrombotic risk stratification compared to current diameter-based metrics, facilitating long-term clinical management of KD patients with persistent CAAs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease. It affects 1 in 250 individuals worldwide, and of the approximately 145,000 Canadians estimated to have FH, most are undiagnosed. Herein, we provide an update of the 2014 Canadian Cardiovascular Society position statement on FH addressing the need for case identification, prompt recognition, and treatment with statins and ezetimibe, and cascade family screening. We provide a new Canadian definition for FH and tools for clinicians to make a diagnosis. The risk of atherosclerotic cardiovascular disease in patients with "definite" FH is 10- to 20-fold that of a normolipidemic individual and initiating treatment in youth or young adulthood can normalize life expectancy. Target levels for low-density lipoprotein cholesterol are proposed and are aligned with the Canadian Cardiovascular Society guidelines on dyslipidemia. Recommendation for the use of inhibitors of proprotein convertase kexin/subtilisin type 9 are made in patients who cannot achieve therapeutic low-density lipoprotein cholesterol targets on maximally tolerated statins and ezetimibe. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology in the preparation of the present document, which offers guidance for practical evaluation and management of patients with FH. This position statement also aims to raise awareness of FH nationally, and to mobilize patient support, promote knowledge translation, and availability of treatment and health care resources for this under-recognized, but important medical condition., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease. Definitions for FH rely on complex algorithms that are on the basis of levels of total or LDL-C, clinical features, family history, and DNA analysis that are often difficult to obtain. We propose a novel simplified definition for FH. Definite FH includes: (1) elevated LDL-C (≥ 8.50 mmol/L); or (2) LDL-C ≥ 5.0 mmol/L (for age 40 years or older; ≥ 4.0 mmol/L if age younger than 18 years; and ≥ 4.5 mmol/L if age is between 18 and 39 years) when associated with at least 1 of: (1) tendon xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the proband or first-degree relative. Probable FH is defined as subjects with an elevated LDL-C (≥ 5.0 mmol/L) and the presence of premature atherosclerotic cardiovascular disease in the patient or a first-degree relative or an elevated LDL-C in a first-degree relative. LDL-C cut points were determined from a large database comprising > 3.3 million subjects. To compare the proposed definition with currently used algorithms (ie, the Simon Broome Register and Dutch Lipid Clinic Network), we performed concordance analyses in 5987 individuals from Canada. The new FH definition showed very good agreement compared with the Simon Broome Register and Dutch Lipid Clinic Network criteria (κ = 0.969 and 0.966, respectively). In conclusion, the proposed FH definition has diagnostic performance comparable to existing criteria, but adapted to the Canadian population, and will facilitate the diagnosis of FH patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We have previously documented an increase in the incidence of Kawasaki disease (KD) in Ontario followed by a stabilization from 1995 to 2006. We sought to validate the estimation of incidence of KD using administrative data and to describe the epidemiology of KD across Canada from 2004 to 2014., Methods: We queried the Canadian Hospital Discharge Database for hospital admissions associated with a discharge diagnosis of KD. The data set was manually curated and estimates of incidence were compared with those obtained from the retrospective triennial surveillances of KD performed in 2007 and 2010., Results: The average number of cases per year identified through administrative data was 245 ± 45 vs 229 ± 33 from retrospective surveillance. This overestimation, representing 7 ± 6%, is similar to the historical percentage of patients originally diagnosed with KD in whom the diagnosis is subsequently excluded. The annual incidence of KD in Canada was 19.6, 6.4, and 1.3 cases per 100,000 children younger than 5 years, 5-9 years, and 10-14 years old, respectively, with important regional and seasonal differences. The incidence remained stable over the study period in the youngest age group but increased in both older age categories. Coronary artery aneurysms affected 3.5% of all patients, and 0.8% experienced associated major cardiac complications., Conclusions: Reliance on administrative data to determine incidence of KD is feasible and accurate with manual curation of the data. The incidence of KD in Canada seems to have plateaued for younger children. Differences in annual incidence observed between provinces remain to be explained, and might reflect genetic or environmental differences., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Severe obesity in children and adolescents is now a serious global health concern. Accurate measurements of resting energy expenditure (REE) is a key foundation for successful obesity treatment. Clinical dietitians rely heavily on measured or calculated REE to tailor dietary interventions. Indirect calorimetry (IC) is the gold standard for measuring REE. However, predictive resting energy expenditure (PREE) equations are commonly used when IC is unavailable due to cost or practicality. PREE equations differ based on variables such as age, gender, weight, and height and selecting the most accurate PREE for an individual is crucial to avoid over or underestimation of energy requirements. Published studies investigating the accuracy of PREE equations in obese children and adolescents have reported inconsistent findings, which likely result from heterogeneity in the patient populations studied. Accordingly, this study aimed to (a) assess the accuracy of the published PREE equations in a group of severely obese (SO) adolescents using IC measurement, and (b) determine if there is a BMI threshold at which the PREE equations become less accurate., Methods: SO adolescents were studied using IC. REE was calculated using nine commonly used PREE equations. Generalized linear regression equations were used to compare absolute and relative differences between calculated and measured REE (MREE) for each PREE equation. Accuracy was calculated as the percentage of subjects with PREE values within 10 percent of MREE., Results: 226 SO adolescents (mean ± SD age: 15.9 ± 1.9 years; weight: 126.9 ± 24.5 kg; BMI: 44.9 ± 8.1 kg/m 2 ) participated. Mean MREE was 2163 ± 443 kcal/d. PREE calculated by the Mifflin equation was the only equation without a statistically significant bias compared to MREE (mean bias of -23 ± 307 kcal/d; p = 0.26). Mifflin was also the most accurate with 61% of individuals within ±10% of MREE. PREE equations accuracy was not associated with degree of BMI elevation (31-69 kg/m 2 )., Conclusions: In adolescents with severe obesity, the Mifflin equation best predicts REE. This should be the equation applied when using PREE to optimize nutritional care in this population., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: While the risk is reduced, patients may develop coronary artery (CA) aneurysms after Kawasaki disease (KD) despite receiving intravenous immunoglobulin (IVIG) within 10days of symptom onset. Risk factors for CA aneurysms may differ compared to those patients with delayed or no treatment., Methods: Patients diagnosed with KD between 1990 and 2013 were included. Patients with maximum coronary artery z-scores>5 were classified as having CA aneurysms. Separate multivariable regression models were used to determine factors associated with CA aneurysms for those with versus without prompt treatment., Results: Of 1358 patients included, 83% (n=1126) were treated with IVIG within 10days and 5% (n=53) developed CA aneurysms. Patients who had delayed (>10days) or no IVIG treatment were at increased odds of developing CA aneurysms (OR: 3.1,95% CI: 1.9-5.1, p<0.001). For patients with prompt treatment with IVIG, factors associated with increased odds of CA aneurysms were: longer duration of fever prior to treatment (OR: 1.2/day, p=0.04), age<1year (OR: 3.9, p=0.001), higher pre-IVIG white blood cell count (OR: 1.05/×10 9 /L, p=0.007), lower hemoglobin (OR: 1.4/g/L, p=0.004) and non-response to initial IVIG treatment (OR: 2.5, p<0.001). For patients with delayed or no treatment, factors associated with increased odds of CA aneurysms were: males (OR: 5.4, p=0.009), age<1year (OR: 29.9, p<0.001), and higher platelet count (OR: 1.4/100×10 12 /L, p=0.001). Delayed treatment with IVIG did not reduce the risk of CA aneurysms (OR: 1.9, p=0.28), and total duration of fever was not associated with CA aneurysms for this group (OR: 1.04/day, p=0.16)., Conclusions: Factors associated with the development of CA aneurysms are generally similar for those treated promptly versus those with delayed or no treatment. For those with delayed diagnosis, treatment with IVIG does not appear to be effective to prevent CA aneurysms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: It is unknown whether continuous cardiac resynchronization therapy (CRT) can lead to sustained improvement in hemodynamics after surgery for congenital heart disease (CHD)., Objective: We investigated whether CRT improves cardiac index (CI) and blood pressure in infants after biventricular repair of CHD., Methods: We randomized infants younger than 4 months after biventricular CHD surgery to standard care or standard care plus CRT for 48 hours or until extubation if sooner. Change in the primary outcome of CI and blood pressure over time was compared between groups. For subgroup analysis, QRS duration was considered prolonged if greater than the 98th percentile., Results: Forty-two patients were randomized: 21 controls and 21 patients receiving CRT (median weight 4 kg). There were no identified adverse events from pacing. The change in CI over time was not different between patients receiving CRT and controls, but trended toward improvement in patients with wide QRS who received CRT (n = 9) vs controls with wide QRS (n = 8) (+1.65 (0.86) L/(min·m 2 ); P = .06). Controls with wide QRS experienced the smallest increase in CI (0.33 L/(min·m 2 )). Blood pressure was significantly higher in infants with wide QRS who received CRT than in controls (+7.14 (3.08) mm Hg; P = .02). Serum lactate level, catecholamine use, ventilation time, and length of intensive care unit stay were similar between the 2 groups., Conclusion: CRT improved blood pressure and a trend toward higher CI in infants after repair of biventricular CHD with prolonged QRS duration. These findings warrant further study of CRT to improve postoperative recovery in infants with electrical dyssynchrony., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In the registry of the International Society for Heart and Lung Transplantation (ISHLT), cerebrovascular accidents are the fifth most common cause for mortality after pediatric heart transplantation (PHTx), but details are lacking in the literature. The purpose of this analysis of the ISHLT registry was to determine the prevalence, risk factors and outcomes of stroke after PHTx., Methods: Data from the ISHLT registry (1998 to 2010) were used to identify all patients whose primary transplantation was performed at <18 years of age. Of the 10,441 transplants reviewed, 9,837 primary transplants and 604 retransplants were analyzed., Results: Three hundred thirty-three (3%) patients had a stroke after PHTx; 54% were male, median age at PHTx was 6 years (0 to 17 years), and 44% had a diagnosis of congenital heart disease (CHD). Freedom from stroke was 99% at 1 month, 97% at 5 years, 95% at 10 years and 91% at 20 years post-PHTx. After a stroke, survival at 1 month, 1 year and 5 years was 83%, 69% and 55%, respectively. Multivariable independent risk factors for stroke included a primary diagnosis of congenital heart disease [hazard ratio (HR) 1.4 (1.1 to 1.7), p = 0.01], previous stroke [HR 4.5 (3.2 to 6.2), p < 0.001], history of aborted sudden death [HR 1.5 (1.1 to 2), p = 0.01], ventricular assist device [HR 1.5 (1.1 to 2.2), p = 0.03] or extracorporeal membrane oxygenation [HR 1.7 (1.2 to 2.2), p = 0.01], post-operative dialysis [HR 3.3 (2.3 to 4.7), p < 0.001], infection requiring antibiotics before discharge [HR 1.9 (1.4 to 2.5), p < 0.001], pacemaker implantation [HR 1.6 (1 to 2.5), p = 0.04] or drug-treated hypertension [HR 1.4 (1.1 to 1.8), p = 0.003] during follow-up., Conclusions: Stroke after pediatric heart transplantation is associated with increased mortality. Congenital heart disease and mechanical support both portend greater risk, in addition to markers of increased pre- and post-transplant medical acuity., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Guidelines recommend initiating statins early to reduce low-density lipoprotein cholesterol (LDL-C). Studies have evaluated rosuvastatin in children aged ≥10 years, but its efficacy and safety in younger children is unknown., Methods: Children with HeFH and fasting LDL-C >4.92 mmol/L (190 mg/dL) or >4.10 mmol/L (>158 mg/dL) with other cardiovascular risk factors received rosuvastatin 5 mg daily. Based on LDL-C targets (<2.85 mmol/L [<110 mg/dL]), rosuvastatin could be uptitrated to 10 mg (aged 6-9 years) or 20 mg (aged 10-17 years). Treatment lasted 2 years. Changes in lipid values, growth, sexual maturation, and adverse events (AEs) were assessed., Results: The intention-to-treat analysis included 197 patients. At 24 months, LDL-C was reduced by 43, 45, and 35% vs baseline in patients aged 6-9, 10-13, and 14-17 years, respectively (P < .001 for all groups). Most AEs were mild. Intermittent myalgia was reported in 11 (6%) patients and did not lead to discontinuation of rosuvastatin treatment. Serious AEs were reported by 9 (5%) patients, all considered unrelated to treatment by the investigators. No clinically important changes in hepatic biochemistry were reported. Rosuvastatin treatment did not appear to adversely affect height, weight, or sexual maturation., Conclusions: In HeFH patients aged 6-17 years, rosuvastatin 5-20 mg over 2 years significantly reduced LDL-C compared with baseline. Treatment was well tolerated, with no adverse effects on growth or sexual maturation., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Childhood and adolescent overweight and obesity is an important and increasingly prevalent public health problem in Canada and worldwide. High adiposity in youth is indicated in clinical practice by plotting body mass index on appropriate percentile charts normed for age and sex, although waist measures might be a further tool. High adiposity can lead to adiposopathy in youth, with associated increases in inflammation and oxidative stress, changes in adipokines, and endocrinopathy. This is manifest as cardiometabolic risk factors in similar patterns to those in noted in obese adults. Obesity and cardiometabolic risk factors have been shown to be associated with vascular changes indicative of early atherosclerosis, and ventricular hypertrophy, dilation, and dysfunction. These cardiovascular consequences are evident in youth, but childhood obesity is also predictive of similar consequences in adulthood. Childhood obesity and risk factors have been shown to track into adulthood and worsen in most individuals. The result is an exponential acceleration of atherosclerosis, which can be predicted to translate into an epidemic of premature cardiovascular disease and events. A change in paradigm is needed toward preventing and curing atherosclerosis and not just preventing cardiovascular disease. This would necessarily create an imperative for preventing and treating childhood obesity. Urgent attention, policy, and action are needed to avoid the enormous future social and health care costs associated with the cardiovascular consequences of obesity in youth., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Regarding long-term cardiovascular health, obesity may have greater implications for children with congenital heart disease (CHD). We sought to determine trends in anthropometry over time and its association with exercise capacity., Methods: Medical records of pediatric patients with CHD were randomly sampled. Serial measurements of weight and height were abstracted, body mass index (BMI) was calculated, and measurements were converted to percentiles and z scores. Analyses of trends were performed using regression models adjusted for repeated measures., Results: Median follow-up after diagnosis for 725 patients was 7.1 years (interquartile range, 1.9-12.8 years). The median initial weight z score was -1.1 (fifth/95th percentile, -3.6/+1.1) and increased over time (+0.103 [0.007] standard deviations [SD]/y; P < 0.001). BMI and height z scores could only be calculated for patients > 2 years old; at that age, the median BMI z score was -0.2 (fifth/95th percentile, -2.6/+1.9) and increased over time (+0.042 [0.007] SD/y; P < 0.001), whereas the median height z score was -0.3 (fifth/95th percentile, -2.7/+1.4) with no change over time (-0.007 [0.006] SD/y; P = 0.18). Using standard BMI percentile cut points to define overweight and obesity, 28% of patients had at least 1 BMI measurement indicating overweight and 17% indicating obesity. Available exercise test results (n = 153) showed that overweight/obese patients had lower percent predicted maximum oxygen consumption (-16 [2]%; P < 0.001), higher peak systolic blood pressure (+11 [4] mm Hg; P = 0.002), and higher systolic blood pressure response (+7 [3] mm Hg; P = 0.01) than normal weight patients., Conclusions: In conclusion, children with repaired CHD have an important risk of overweight/obesity over time that may increase their cardiovascular risk and impair their exercise capacity., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Data on myocardial response to exercise after pediatric heart transplant (HTx) are limited. In this study we used semi-supine bicycle ergometry (SSCE) stress echocardiography to evaluate left ventricular (LV) systolic and diastolic reserve in pediatric HTx recipients., Methods: Forty-three HTx patients and 23 controls underwent stepwise SSCE stress echocardiography. Color tissue Doppler imaging (TDI) peak systolic (s') and early diastolic (e') velocities in the LV lateral wall and basal septum, and LV peak global longitudinal and circumferential strain were measured at rest and during different stages of exercise. LV myocardial acceleration during isovolumic contraction (IVA) was measured at incremental heart rates (HRs) to determine the force-frequency relationship (FFR)., Results: At rest, compared with controls, HTx patients showed lower TDI velocities in the basal septum (s': 4.7 ± 1.1 vs 5.8 ± 0.8 cm/s, p = 0.002; e': 8.5 ± 2.1 vs 11.3 ± 1.7 cm/s, p < 0.001), whereas in the LV lateral wall only e' was lower (11.2 ± 2.6 vs 13.8 ± 2.3 cm/s, p < 0.001). LV IVA was not different between the groups (p = 0.10). LV peak global longitudinal strain was lower in HTx patients (18 ± 1.9% vs 20 ± 2.2%, p = 0.001), but peak circumferential strain was not different (p = 0.50). At peak, HR was lower in the HTx group (141 ± 12 vs 165 ± 15, p < 0.001), and all systolic and diastolic parameters, except circumferential strain, were lower in HTx recipients. When assessing the increase in TDI and strain values in relation to HR, the slopes were not significantly different between patients and controls., Conclusions: Despite resting differences in myocardial functional parameters, pediatric HTx recipients have preserved LV diastolic and systolic myocardial reserve in response to exercise., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)