Cardiovascular Events In Children Research Articles

Prediction of adverse cardiovascular events in children using artificial intelligence-based electrocardiogram

BackgroundConvolutional neural networks (CNNs) have emerged as a novel method for evaluating heart failure (HF) in adult electrocardiograms (ECGs). However, such CNNs are not applicable to pediatric HF, where abnormal anatomy of congenital heart defects plays an important role. ECG-based CNNs reflecting neurohormonal activation (NHA) may be a useful marker of pediatric HF. This study aimed to develop and validate an ECG-derived marker of pediatric HF that reflects the risk of future cardiovascular events. MethodsBased on 21,378 ECGs from 8324 children, a CNN was trained using B-type natriuretic peptide (BNP) and the occurrence of major adverse cardiovascular events (MACEs). The output of the model, or the electrical heart failure indicator (EHFI), was compared with the BNP regarding its ability to predict MACEs in 813 ECGs from 295 children. ResultsEHFI achieved a better area under the curve than BNP in predicting MACEs within 180 days (0.826 versus 0.691, p = 0.03). On Cox univariable analyses, both EHFI and BNP were significantly associated with MACE (log10 EHFI: hazard ratio [HR] = 16.5, p < 0.005 and log10 BNP: HR = 4.4, p < 0.005). The time-dependent average precisions of EHFI in predicting MACEs were 32.4%–67.9% and 1.6–7.5-fold higher than those of BNP in the early period. Additionally, the MACE rate increased monotonically with EHFI, whereas the rate peaked at approximately 100 pg/mL of BNP and decreased in the higher range. ConclusionsECG-derived CNN is a novel marker of HF with different prognostic potential from BNP. CNN-based ECG analysis may provide a new guide for assessing pediatric HF.

Cardiovascular events in children with brain injury: A systematic review

BackgroundBrain injury is a leading cause of morbidity and mortality in the pediatric population. Neurogenic stunned cardiomyopathy is a complication associated with several neurological conditions that can lead to worse outcomes. It presents as alterations in blood pressure, cardiac rhythm disturbances and the increase in cardiac injury biomarkers. This systematic review aims to assess the hemodynamic consequences of brain injury in the pediatric population to identify better management strategies and improve outcomes. MethodsAn electronic literature search was performed in Pubmed, Scopus and WebOfScience, up until October 3rd, 2022. The selected articles underwent quality assessment using the National Heart, Lung and Blood Institute tools for cohort and case-control studies. ResultsThis systematic review includes thirteen articles on the effects of brain injury in arterial pressure, rhythm disturbances and biomarkers of myocardial injury. These studies showed the following key results: both hypotension and hypertension are associated with worse outcomes; brain injury could be related to longer QTc intervals; neurogenic stunned cardiomyopathy was a common found after brain injury. ConclusionThis is the first systematic review to report cardiovascular abnormalities arising from brain injury in children. An early arterial pressure, electrocardiographic and echocardiographic evaluation, as well as the measure of serum biomarkers for myocardial injury, can be critical in identifying poor prognostic factors. Further research is required to understand the implications of our findings in clinical practice.

Updates in the management of pediatric dyslipidemia.

Pediatric dyslipidemias increase the risk of atherosclerosis and clinical cardiovascular disease and are the leading cause of morbidity and mortality. Lifestyle modifications and pharmacotherapies have measurably improved abnormal lipids and reduced cardiovascular events. The review will focus on current standards of care and investigative medications with the potential to improve cardiovascular health in children and adults. Lifestyle interventions and statins remain cornerstones in the treatment of pediatric hyperlipidemias. Bile acid sequestrants and ezetimibe continue to be used in the pediatric population as well. In recent years, successful clinical trials have approved use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in children with familial hypercholesterolemia. Use of angiopoietin-like protein 3 (ANGPTL3) inhibitors is also promising as it causes marked improvement in low-density lipoprotein cholesterol with safe side effect profiles. Additional medications undergoing pediatric clinical trials include inclisiran, bempedoic acid, and lomitapide. Recent advances in pharmacotherapy, especially for treatment of familial hypercholesterolemia, greatly impact treatment of dyslipidemias in children. Despite the overall progress in the development of these medications, therapies targeted towards treating hypertriglyceridemia have lagged behind. Continuing research for the treatment of pediatric dyslipidemias remains an important endeavor to reduce the risk of atherosclerosis and future cardiovascular events in children.

Obesity Affects Maternal and Neonatal HDL Metabolism and Function.

Pregravid obesity is one of the major risk factors for pregnancy complications such as gestational diabetes mellitus (GDM) and an increased risk of cardiovascular events in children of affected mothers. However, the biological mechanisms that underpin these adverse outcomes are not well understood. High-density lipoproteins (HDLs) are antiatherogenic by promoting the efflux of cholesterol from macrophages and by suppression of inflammation. Functional impairment of HDLs in obese and GDM-complicated pregnancies may have long-term effects on maternal and offspring health. In the present study, we assessed metrics of HDL function in sera of pregnant women with overweight/obesity of the DALI lifestyle trial (prepregnancy BMI ≥ 29 kg/m2) and women with normal weight (prepregnancy BMI < 25 kg/m2), as well as HDL functionalities in cord blood at delivery. We observed that pregravid obesity was associated with impaired serum antioxidative capacity and lecithin−cholesterol acyltransferase activity in both mothers and offspring, whereas maternal HDL cholesterol efflux capacity was increased. Interestingly, functionalities of maternal and fetal HDL correlated robustly. GDM did not significantly further alter the parameters of HDL function and metabolism in women with obesity, so obesity itself appears to have a major impact on HDL functionality in mothers and their offspring.

Assessment of aortic elasticity parameters in obese and overweight children.

Aortic elasticity is a predictor and recognized factor for future cardiovascular events in children. The aim of the study was to evaluate the aortic stiffness in obese and overweight children compared to healthy ones. The study evaluated 98 sex matched children aged 4 to 16 years that were equally distributed in asymptomatic obese or overweight and healthy children groups. All the participants were free of any heart diseases. Arterial stiffness indices were determined using two-dimensional echocardiography. The mean ages in the obese and healthy children were 10.40±2.50 years and 10.06±1.53 years, respectively. Aortic strain was significantly higher in obese children (20.70±5.04%), compared to healthy (7.06±3.77%) and overweight children (18.59±8.08%, p < 0.001). Aortic distensibility (AD) was significantly higher in obese children (0.010±0.005 cm < sup > 2 < /sup > dyn-1x10-6), compared to healthy (0.0036±0.004 cm < sup > 2 < /sup > dyn-1x10 < sup > -6 < /sup > ) and overweight children (0.009±0.005 cm < sup > 2 < /sup > dyn-1x10 < sup > -6 < /sup > , p < 0.001). Aortic strain beta (ASβ) index, was significantly higher in healthy children (9.26±6.17). Pressure-strain elastic modulus (PSEM) was significantly higher in healthy children (7.52±4.76 kPa). Systolic blood pressure increased with body mass index (BMI) significantly (p < 0.001) but diastolic blood pressure did not change (p=0.143). BMI had significant effect on arterial stiffness (AS) (β=0.732, p < 0.001), AD (β=0.636, p < 0.001), ASβ index (β=-0.573, p < 0.001) and PSEM (β=-0.578, p < 0.001). Age had significant effect on systolic diameter of the aorta (β=0.340, p < 0.001) and diastolic diameter of the aorta (β=0.407, p < 0.001). We concluded that aortic strain and aortic distensibility increased in obese children when aortic strain beta index and PSEM decreased. This result suggests that, as atrial stiffness is a predictor for future heart diseases, dietary treatment for children with overweight or obese status is important.

Incidence of cardiovascular disease and mortality in childhood solid organ transplant recipients: a population-based study.

With improved survival among children after transplantation, our understanding of the risk for developing other comorbidities is improving, yet little is known about the long-term risk of cardiovascular events and mortality after solid organ transplantation. In a cohort study using health administrative data, we compared cardiovascular events in children (n = 615) with liver, lung, kidney, small bowel, or multi-organ transplant at the Hospital for Sick Children, Toronto, Canada, with asthmatic children (n = 481,697) between 1996 and 2014. Outcomes included non-fatal cardiovascular events, cardiovascular death, all-cause mortality, and a composite of non-fatal and fatal cardiovascular events. Time-stratified Cox proportional hazards models were used. Among 615 children, 317 (52%) were recipients of kidneys, 253 (41%) of livers, and the remaining 45 (7%) had lung, small bowel, or multi-organ transplants. Median follow-up was 12.1 [7.2, 16.7] years. Non-fatal incident cardiovascular events were 34 times higher among solid organ transplant recipients than non-transplanted children (incidence rate ratio (IRR) 34.4, 95% CI: 25.5, 46.4). Among transplant recipients, the cumulative incidence of non-fatal and fatal cardiovascular events was 2.3% and 13.0%, 5 and 15years after transplantation, respectively. Increased rate of cardiovascular events in children after transplantation highlights the need for surveillance during transition into adulthood and beyond. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prognostic factors in hypertrophic cardiomyopathy in children: An MRI based study

BackgroundClinical and prognostic role of cardiac magnetic resonance (CMR) in adult population with hypertrophic cardiomyopathy (HCM) have been largely assessed.We sought to investigate the role of CMR for predicting cardiovascular events in children with HCM. MethodsCMR was performed in 116 patients with HCM (37 sarcomeric mutations, 31 other mutations, mean age 10.4 ± 4.3 yrs). CMR protocol included cine imaging for evaluation of morphology and function and late gadolinium enhancement (LGE). Hard cardiac events (sustained VT, resuscitated cardiac arrest, sudden cardiac death, end-stage heart failure, heart transplant and appropriate ICD intervention) were recorded through a median follow-up of 4 (1–7) years. ResultsDuring follow-up 21 heart cardiac events occurred. At maximal-rank statistic the optimal cut-point for LGE extent for predicting events was ≥2%. Syncope, non-sustained ventricular tachycardia (NSVT) and LGE extent ≥2% were independent predictors of events. At Harrel's C statistic combination of LGE extent ≥2% and syncope was the strongest model for predicting events. HR of patients with LGE extent ≥2% and no history of syncope was 3.6 (1.1–12.2) that increased to 37.6 (5.4–161) in those with LGE extent ≥2% and syncope. The median time dependent AUC of LGE extent (0.88, 95% CI 0.86–0.89) was significantly higher than that of syncope (0.63, 95% CI 0.61–0.66, p < 0.0001) and NSVT (0.52, 95% CI 0.50–0.53, p < 0.0001). ConclusionsIn children with HCM, LGE and syncope were independent predictors of hard cardiac events at follow-up.

Predicting Major Adverse Cardiovascular Events in Children With Age-Adjusted NT-proBNP

BackgroundN-terminal pro–B-type natriuretic peptide (NT-proBNP) is frequently used as a valuable prognostic biomarker in cardiac diseases. In children, however, it has not been established because of its strong age dependency. To overcome this obstacle, we recently introduced the zlog value of N-terminal pro–B-type natriuretic peptide (zlog-proBNP) as an age-adjusted reference. ObjectivesThis study evaluates the prognostic power of zlog-proBNP for the occurrence of major adverse cardiovascular events (MACE) throughout childhood in patients with congenital heart diseases (CHD). MethodsA total of 910 children with CHD (median age 5 months; range 0.0-18.0 years) were included. MACE was defined as death, resuscitation, mechanical circulatory support, or hospitalization caused by cardiac decompensation. Because the physiological NT-proBNP concentration decreases significantly during childhood, zlog values were applied for an age-independent evaluation. ResultsMACE occurred in 138 children during a median follow-up of 6 months (range 1 day to 7.6 years). High zlog-proBNP values (>+3.0) were most strongly associated with adverse events (n = 93; adjusted HR: 21.1; 95% CI: 2.9-154.2; P < 0.001). Among all evaluated indicators, zlog-proBNP was the best predictor for MACE (adjusted HR: 1.52; 95% CI: 1.31-1.76; P < 0.001) along with age and predictively superior to absolute NT-proBNP values. A cutoff value of +1.96 (age-independent upper limit of the physiological NT-proBNP concentration) achieved a negative predictive value of >96%. ConclusionsZlog-proBNP overcomes the strong age dependency of NT-proBNP and is a powerful prognostic marker for age-independent exclusion and prediction of MACE in children with CHD. We therefore expect zlog-proBNP to play a pivotal role in the future management of children with heart diseases.

Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.

The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics. We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6-30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004-2012), Korea (2010-2016), Hong Kong (2001-2014) and the UK (1997-2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1-30 days, 30-90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia). We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20-1.38). The pooled IRR was 0.98 (0.90-1.06) for 1-30 days and 0.88 (0.76-1.02) for 31-90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74-4.64) for 1-30 days, 1.35 (0.74-2.47) for 31-90 days and 1.29 (0.98-1.70) for 90 + days. Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.

Ambulatory Blood Pressure Phenotypes in Children and Adolescents

Ambulatory Blood Pressure Phenotypes in Children and Adolescents

Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder.

BackgroundPsychostimulants and atomoxetine have been shown to increase blood pressure, heart rate, and QT interval in children and adolescents; however, based on current literature, it is unclear if these “attention-deficit/hyperactivity disorder (ADHD) medications” are also associated with serious cardiovascular (SCV) events. We addressed this question in commonly exposed groups of children and adolescents with either ADHD or autism spectrum disorder (ASD).MethodsUsing commercial (years 2000–2016) and Medicaid (years 2012–2016) administrative claims data from the United States (US), we conducted two case–control studies, nested within respective cohorts of ADHD and ASD children aged 3–18 years. We defined cases by a composite outcome of stroke, myocardial infarction, or serious cardiac arrhythmia. For each case, we matched ten controls on age, sex, and insurance type. We conducted conditional logistic regression models to test associations between SCV outcomes and a primary exposure definition of current ADHD medication use. Additionally, we controlled for resource use, cardiovascular and psychiatric comorbidities, and use of medications in a variety of sensitivity analyses.ResultsWe identified 2,240,774 children for the ADHD cohort and 326,221 children for the ASD cohort. For ADHD, 33.9% of cases (63 of 186) versus 32.2% of controls (598 of 1860) were exposed, which yielded an odds ratio (OR) and 95% confidence interval (CI) of 1.08 (0.78–1.49). For ASD, 12.5% of cases (6 of 48) versus 22.1% of controls (106 of 480) were exposed [OR 0.49 (0.20–1.20)]. Covariate-adjusted results and results for individual outcomes and other exposure definitions were consistent with no increased risk of SCV events.ConclusionUsing large US claims data, we found no evidence of increased SCV risk in children and adolescents with ADHD or ASD exposed to ADHD medications.Electronic supplementary materialThe online version of this article (10.1007/s40263-019-00686-4) contains supplementary material, which is available to authorized users.

Incidence of cardiovascular events and risk markers in a prospective study of children diagnosed with Marfan syndrome

Little is known about the incidence of cardiovascular events (CVEs) and their associated risk markers in children with Marfan syndrome (MFS). To assess the incidence of CVEs and determine risk markers in a cohort diagnosed with Marfan syndrome during childhood and followed for several years. From a French multicentre nationwide database, 462 patients with MFS diagnosed during childhood were included prospectively. Patients' files were screened for a period of 20 years (1993-2013). CVEs (e.g. death, aortic dissection, cardiac valve or aortic root surgery) were assessed during the prospective follow-up. Median (interquartile range) age at the end of follow-up was 17.2 (11.1-21.3) years. CVEs were reported for 35 participants (7.6%; 95% confidence interval [CI] 5.3-10.4%). First CVEs were prophylactic aortic root surgery (n=29), aortic dissection (n=4; two aged <18 years) and death (n=2). Kaplan-Meier cumulative incidence of CVEs was 5.3% (95% CI 3.3-8.7%) during childhood (aged≤18 years) and 19.4% (95% CI 13.3-27.9%) at 25years of age. The cumulative rate of CVEs was higher in case of Valsalva sinus Z-score increase of≥0.1 per year (P=0.0003), maximal Valsalva sinus diameter growth speed ≥5mm per year (P=0.03), aortic regurgitation≥2 (P=0.0005) and maximal Valsalva sinus Z-score≥3 before 16 years of age (P<0.0001). In a multivariable Cox proportional analysis, the Valsalva sinus Z-score remained significantly related to outcome. Considering aortic root evolution, aortic regurgitation, age at diagnosis and beta-blocker therapy were related to Valsalva sinus Z-score evolution during follow-up. CVEs in children with MFS are mainly related to prophylactic aortic root surgery. Aortic dissections are rarely observed in children. The Valsalva sinus Z-score is a strong indicator of subsequent CVEs in children with MFS. Attention to follow-up and beta-blocker observance may be warranted in high-risk children.

Stimulants and Pediatric Cardiovascular Risk.

Concerns about serious cardiovascular (CV) events among stimulant-treated youth have led to clinical and policy debates. Accordingly, several population-based empirical studies have assessed the risk of CV events in children and adolescents treated with stimulants. The main objective of this review was to summarize findings and to evaluate the strengths and weaknesses of these population-based studies. In addition, we discuss the CV monitoring and policy implications for a clinically focused audience. A computerized literature search of Medline and PsycINFO was conducted for the calendar years 1990-2015 to identify population-based studies assessing stimulant treatment-emergent CV events in youth. Additional reports, peer-reviewed or gray literature, for example, government reports, were also included. Nine population-based studies (one case-control and eight retrospective cohort designs) were included in this review. The case-control study compared sudden unexplained death cases to age-matched controls (motor vehicle passenger deaths) with respect to prior stimulant use and found a significant association (odds ratio = 7.4 [95% CI: 1.4-74.9]). By contrast, most retrospective cohort studies assessed the risk of serious CV events (i.e., sudden death, myocardial infarction, and stroke) and did not find an association with current stimulant exposure. The absolute rate for these serious events was low, but other data support risk. For example, cardiac-related emergency department visits showed a 20% increased risk for current stimulant users compared with nonusers in one study, and another study showed a 64% and 90% increased risk for concurrent use of stimulants with antidepressants and antipsychotics, respectively. Similarly, in another study, compared with nonusers, stimulant users had twofold greater odds of CV-related inpatient or outpatient services. In the face of mixed results from population-based safety studies, this review supports the inclusion of baseline and ongoing monitoring of cardiac status to assure a favorable benefit risk profile for stimulant users, particularly in concomitant regimens with antipsychotics and antidepressants.

0365 : Risk markers of cardiac events in patients with Marfan syndrome diagnosed during childhood

Risk markers of cardio-vascular events in children with Marfan syndrome remain little known. We assessed the prognostic value of aortic root z-score in patients with Marfan syndrome diagnosed during childhood. From the French multicenter database, 457 patients with Marfan syndrome, diagnosed before 18 y.o., were prospectively included in this cohort study. Echocardiographic measurements of aortic root diameters were performed at each visit. We calculated the Z-score of aortic root measurements using the Bichat formula. Mean z-score was defined as the mean of the z-score (MeanZS15) calculated for each measurement before the age of 16. Median age at end of FU was 15.9years (interquartile 10.9-20.3). FU was complete for 69.5% of patients. Median FU was 4.6years. A cardiovascular event occurred in 17 patients (3.7%, prophylactic aortic surgery n=14, aortic dissection n=1 and deaths n=2). Survival free of cardiac events was 85.1% in patients with a meanZS15 of the Valsalva diameter <3 and 56.4% in patients with a meanZS15 of the Valsalva diameter ε3 (p<0.0001 by log-rank test). In univariate analysis, Valsalva meanZS15 ε3, age at inclusion in the database, a lower heart rate and an increased arm/height ratio were associated with an increasing risk of cardiac events (p<0.0001, p=0.04, p=0.01 and p=0.04 respectively). After multivariate adjustment using a cox proportional hazards model, only Valsalva meanZS15 ≥3 and lack of FBN1 or TGBB mutation identified were associated with an increasing risk of cardiac events, p<0.0001 and p=0.04 respectively). Valsalva meanZS15 may help to identify high-risk children.

0537: Risk markers of cardiac events in patients with Marfan syndrome diagnosed during childhood

Risk markers of cardio-vascular events in children with Marfan syndrome remain little known. Aortic root z-score measurements have been recently updated. We assessed the prognostic value of aortic root z-score in patients with Marfan syndrome diagnosed during childhood. From the French multicenter database, 457 patients with Marfan syndrome, diagnosed before 18 y.o., without a history of cardiac event were prospectively included in this cohort study. Echocardiographic measurements of aortic root diameters were performed at each visit. We calculated the Zscore of aortic root measurements using the Bichat formula for each visit. Mean z-score was defined as the mean of the z-score (MeanZS15) calculated for each measurement before the age of 16. Median age at end of FU was 15.9 years (interquartile 10.9-20.3). FU was complete for 69.5% of patients. Median FU was 4.6 years. A cardiovascular event occurred in 17 patients (3.7%, prophylactic aortic surgery n=14, aortic dissection n=1 and deaths n=2). Survival free of cardiac events was 85.1% in patients with a meanZS15 of the Valsalva diameter <3 and 56.4% in patients with a meanZS15 of the Valsalva diameter ≥3 (p<0.0001 by log-rank test).In univariate analysis, Valsalva meanZS15 ≥3, age at inclusion in the database, a lower heart rate and an increased arm/height ratio were associated with an increasing risk of cardiac events (p<0.0001, p=0.04, p=0.01 and p=0.04 respectively). After multivariate adjustment using a cox proportional hazards model, only Valsalva meanZS15 ≥3 and lack of FBN1 or TGBB mutation identified were associated with an increasing risk of cardiac events (p<0.0001 and p=0.04 respectively). Valsalva meanZS15 may help to predict whose children with a Marfan syndrome will have a cardio-vascular event. Therefore a particular attention to beta-blockade treatment observance and a regular follow-up may be suggested in high-risk children. Abstract 0537 - Figure: k.m. survival estimate free from cardiac events

PO-0023 Warfarin And Aspirin Combination Therapy For Giant Coronary Arterial Aneurysm In Kawasaki Disease

<h3>Introduction</h3> This study sought to assess whether warfarin and aspirin combination therapy can prevent cardiovascular events in children with giant coronary artery aneurysm (CAA) caused by Kawasaki disease. <h3>Method</h3> Children with giant CAA secondary to Kawasaki disease in our hospital were included. They were randomly divided into warfarin group (warfarin + aspirin) and control group (aspirin only). The dose of warfarin was adjusted by INR (1.5–2.0). Follow-up time included 2nd week, 1st month, 3rd month, 6th month and every 6 months afterward. Clinical data and complications were recorded. <h3>Result</h3> Sixty-five children were included with age of 3 months to 13 years. CAA most commonly occurs in right coronary artery, then left anterior descending, and main trunk. Left circumflex artery is rarely affected. CAA in 17 cases (53.1%) retracted in warfarin group, 5(41.7%)in controls. During follow-up, 2 children (6.3%) presented with intracoronary thromboses in warfarin group, 3 (25%) in controls. One case in warfarin group suffered myocardial infarction, 3 (25%) in control. Two children in control group died, while none in warfarin group. Coronary artery stenosis occurred in 2 children (16.7%) in controls, while one in warfarin group. Bleeding event occurred in 9 children including 1 with subarachnoid haemorrhage in warfarin group while only in 3 in the controls. <h3>Conclusion</h3> Warfarin therapy could decrease the risk of thrombosis, myocardial infarction and mortality. Minor bleeding event is common and need to be monitored.

Risk markers of cardiac events in patients with Marfan syndrome diagnosed during childhood

Risk markers of cardiovascular events in children with Marfan syndrome remain little known. We assessed the prognostic value of aortic root Z-score in patients with Marfan syndrome diagnosed during childhood. From the French multicenter database, 457 patients with Marfan syndrome, diagnosed before 18 y.o., were prospectively included in this cohort study. Echocardiographic measurements of aortic root diameters were performed at each visit. We calculated the Z-score of aortic root measurements using the Bichat formula. Mean Z-score was defined as the mean of the Z-score (mean ZS15) calculated for each measurement before the age of 16. Median age at end of FU was 15.9 years (interquartile 10.9–20.3). FU was complete for 69.5% of patients. Median FU was 4.6 years. A cardiovascular event occurred in 17 patients (3.7%, prophylactic aortic surgery n = 14, aortic dissection n = 1 and deaths n = 2). Survival free of cardiac events was 85.1% in patients with a mean ZS15 of the Valsalva diameter < 3 and 56.4% in patients with a mean ZS15 of the Valsalva diameter ≥ 3 ( P < 0.0001 by log-rank test) ( Fig. 1 ). In univariate analysis, Valsalva mean ZS15 ≥ 3, age at inclusion in the database, a lower heart rate and an increased arm/height ratio were associated with an increasing risk of cardiac events ( P < 0.0001, P = 0.04, P = 0.01 and P = 0.04 respectively). After multivariate adjustment using a cox proportional hazards model, only Valsalva mean ZS15 ≥ 3 and lack of FBN1 or TGBB mutation identified were associated with an increasing risk of cardiac events, P < 0.0001 and P = 0.04 respectively) ( Fig. 1 ). Valsalva mean ZS15 may help to identify high-risk children.

Cardiovascular Safety of Stimulants in Children: Findings from Recent Population-Based Cohort Studies

The past decade has seen a heated debate over the cardiac safety of central nervous system stimulants in the treatment of ADHD. This review discusses five controlled population-based studies that investigated this risk in children in the United States. All studies utilized administrative claims data of private or public insurance to compare risk of stimulant use to non-use. Two studies with smaller sample size lacked the ability to investigate serious events but report a slightly increased risk of emergency department visits attributed to cardiac symptoms such as tachycardia or palpitation. Three studies that enrolled more than one million patients found no association between stimulants and composite endpoints of sudden cardiac death, myocardial infarction, stroke and ventricular arrhythmia. The studies concur that background rates of serious cardiovascular events in children are extremely small. No study exceeded an average follow-up of two years, prohibiting inferences about long-term effects of stimulants.

ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults

ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults

ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults

ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults