Non-High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events.

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. Objective: To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events. Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Exposures: Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia. Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records. Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Conclusions and Relevance: Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.

Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events.

BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. METHODS: This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. RESULTS: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.

Impact of Hematopoietic Cell Transplantation on Cardiovascular Risk Factors and Insulin Sensitivity.

The use of hematopoietic cell transplantation (HCT) for treating malignant conditions in children has increased over the past five decades, leading to a growing population of long-term survivors.This population of childhood HCT survivors faces increased risks of adverse medical effects due to cancer treatments, including adverse cardiovascular disease (CVD) risk factors such as metabolic syndrome, insulin resistance. but the impact of exposure to HCT preparative conditioning regimen has not been clearly delineated. These risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance (IR), are significant contributors to premature cardiovascular disease and represent a leading cause of non-relapse deaths in childhood cancer and HCT survivors. This study aimed to assess the early development of CVD risk factors and their relationship to insulin resistance in a large population of pediatric and young adult HCT survivors of childhood hematologic malignancies. The study compared their cardiovascular risk profiles, insulin resistance (measured by euglycemic hyperinsulinemic clamp studies), and body composition (determined by dual X-ray absorptiometry - DXA) with a cohort of sibling controls. We enrolled 151 HCT recipients (26.36 ±0.90 years at study enrollment; time since HCT of 2.6-31.5 years) and 92 sibling controls to complete at cardiovascular risk assessment including insulin sensitivity by hyperinsulinemic euglycemic clamp, anthropometry, body composition by dual X-ray absorptiometry, blood pressure, and serum biomarkers. We used linear models to test for mean differences in all continuous outcomes between survivors and siblings, accounting for intra-family correlations with generalized estimating equations. Recipients of HCT were found to have lower insulin sensitivity and more likely to have adverse CVD risk factors in comparison to their healthy siblings. Significantly higher percent fat mass and visceral adipose tissue, and significantly lower lean body mass were noted in HCT recipients than sibling controls despite having a similar body mass index between the two groups. Total body irradiation in the conditioning regimen was one of the strongest factors associated with lower insulin sensitivity, dyslipidemia and abnormal body composition leading to sarcopenic obesity. This study reveals that pediatric and young adult HCT survivors are more insulin resistant and have a higher prevalence of adverse cardiovascular risk factors compared to sibling controls. The presence of cardiovascular risk factors at a relatively young age raises concerns about an escalating trajectory of cardiovascular disease in this population. Therefore, regular monitoring of HCT survivors for cardiometabolic risk factors and early intervention will be crucial for preventing cardiovascular-related complications in the future. The findings underscore the importance of survivorship care for pediatric and young adult HCT survivors, with a focus on managing cardiovascular risk factors and promoting a healthy lifestyle to mitigate long-term adverse effects. Early identification and targeted interventions can significantly improve the long-term health outcomes of this vulnerable population, reducing the burden of cardiovascular disease and related complications.

Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the heart was exposed, are at increased risk of cardiomyopathy. Symptomatic cardiomyopathy is typically preceded by a series of gradually progressive, asymptomatic changes in structure and function of the heart that can be ameliorated with treatment, prompting specialist organisations to endorse guidelines on cardiac surveillance in at-risk survivors of cancer. In 2015, the International Late Effects of Childhood Cancer Guideline Harmonization Group compiled these guidelines into a uniform set of recommendations applicable to a broad spectrum of clinical environments with varying resource availabilities. Since then, additional studies have provided insight into dose thresholds associated with a risk of asymptomatic and symptomatic cardiomyopathy, have characterised risk over time, and have established the cost-effectiveness of different surveillance strategies. This systematic Review and guideline provides updated recommendations based on the evidence published up to September, 2020.

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. RESULTS: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. CONCLUSIONS: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

Corrigendum: Translating planetary health principles into sustainable primary care services.

[This corrects the article DOI: 10.3389/fpubh.2022.931212.].

Translating Planetary Health Principles Into Sustainable Primary Care Services.

Global anthropogenic environmental degradations such as climate change are increasingly recognized as critical public health issues, on which human beings should urgently act in order to preserve sustainable conditions of living on Earth. "Planetary Health" is a breakthrough concept and emerging research field based on the recognition of the interdependent relationships between living organisms-both human and non-human-and their ecosystems. In that regards, there have been numerous calls by healthcare professionals for a greater recognition and adoption of Planetary Health perspective. At the same time, current Western healthcare systems are facing their limits when it comes to providing affordable, equitable and sustainable healthcare services. Furthermore, while hospital-centrism remains the dominant model of Western health systems, primary care and public health continue to be largely undervalued by policy makers. While healthcare services will have to adapt to the sanitary impacts of environmental degradations, they should also ambition to accompany and accelerate the societal transformations required to re-inscribe the functioning of human societies within planetary boundaries. The entire health system requires profound transformations to achieve this, with obviously a key role for public health. But we argue that the first line of care represented by primary care might also have an important role to play, with its holistic, interdisciplinary, and longitudinal approach to patients, strongly grounded in their living environments and communities. This will require however to redefine the roles, activities and organization of primary care actors to better integrate socio-environmental determinants of health, strengthen interprofessional collaborations, including non-medical collaborations and more generally develop new, environmentally-centered models of care. Furthermore, a planetary health perspective translated in primary care will require the strengthening of synergies between institutions and actors in the field of health and sustainability.

Body-mass index trajectories from childhood to mid-adulthood and their sociodemographic predictors: Evidence from the International Childhood Cardiovascular Cohort (i3C) Consortium.

Background: Understanding lifecourse trajectories of body-mass index (BMI) is important for identifying groups at high risk of poor health and potential target points for intervention. This study aimed to describe BMI trajectories from childhood to mid-adulthood in four population-based cohorts established in the 1970s and 1980s and to identify childhood sociodemographic factors related to trajectory membership. Methods: Between Dec 17, 1970 and Dec 15, 1994, data were collected at the first visit from 9830 participants from the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes participants from Australia (1985), Finland (1980) and the USA (1970-1994). Participants had at least three measures of height and weight, including one in childhood (6-18 years) and one in adulthood (>18 years), and were aged 30-49 years at last measurement. Latent Class Growth Mixture Modelling was used to identify lifecourse BMI trajectory groups and log multinomial regression models were fit to identify their childhood sociodemographic predictors. Findings: Five consistent BMI trajectory groups were identified amongst the four cohorts: persistently low (35.9-58.6%), improving from high (0.7-4.8%), progressing to moderate (9.3-43.7%), progressing to high (1.1-6.0%), and progressing to very high (0.7-1.3%). An additional three BMI trajectory groups were identified in some, but not all, cohorts: adult onset high (three cohorts; 1.8-20.7%), progressing to moderate-high (two cohorts; 5.2-13.8%), and relapsing yo-yoers (alternating upward and downward; one cohort; 1.3%). In pooled analyses, each predictor variable in childhood, including age, gender, parental education and race, was associated with increased likelihood of belonging to the most (e.g., improving from high) and least (e.g., progressing to very high) favourable BMI trajectory groups, suggesting a U-shaped (or inverse U-shaped) pattern of association. Interpretation: Five consistent BMI trajectory groups were identified across four cohorts from Australia, Finland, and the USA, mainly across two eras of birth. While most participants remained on a persistently low trajectory (50%), many demonstrated worsening BMI trajectories (47%), with only few demonstrating improving trajectories (<5%). Age, gender, parental education, and race appear to be important predictors of BMI trajectory group membership and need consideration in preventive and management strategies. Funding: This study was supported by funding from the National Institutes of Health, National Heart, Lung and Blood Institute (grant number R01 HL121230).

Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.

Prevalence Implications of the 2017 American Academy of Pediatrics Hypertension Guideline and Associations with Adult Hypertension.

OBJECTIVE: To evaluate the impact of the 2017 American Academy of Pediatrics hypertension Clinical Practice Guideline (CPG), compared with the previous guideline ("Fourth Report"), on the frequency of hypertensive blood pressure (BP) measurements in childhood and associations with hypertension in adulthood using data from the International Childhood Cardiovascular Cohort Consortium. STUDY DESIGN: Childhood BPs were categorized in normal, prehypertensive/elevated, and hypertensive (stage 1 and 2) ranges using the Fourth Report and the CPG. Participants were contacted in adulthood to assess self-reported hypertension. The associations between childhood hypertensive range BPs and self-reported adult hypertension were evaluated. RESULTS: Data were available for 34 014 youth (10.4 ± 3.1 years, 50.6% female) with 92 751 BP assessments. Compared with the Fourth Report, the CPG increased hypertensive readings from 7.6% to 13.5% and from 1.3% to 2.5% for stage 1 and 2 hypertensive range, respectively (P < .0001). Of 12 761 adults (48.8 ± 7.9 years, 43% male), 3839 (30.1%) had self-reported hypertension. The sensitivity for predicting adult hypertension among those with hypertensive range BPs at any point in childhood, as defined by the Fourth Report and the CPG, respectively, was 13.4% and 22.4% (specificity 92.3% and 85.9%, P < .001), with no significant impact on positive and negative predictive values. Associations with self-reported adult hypertension were similar and weak (c-statistic range 0.61-0.68) for hypertensive range BPs as defined by the Fourth Report and CPG. CONCLUSIONS: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension.

The role of FSH in body composition in hematopoietic cell transplant recipients.

BACKGROUND: Childhood cancer survivors who received a hematopoietic cell transplantation (HCT) are at increased risk for follicle-stimulating hormone (FSH) abnormalities, which may have a significant negative impact on bone health and body composition. This study's purpose was to examine FSH and body composition in HCT recipients, non-HCT recipients and healthy controls. METHODS: The study included HCT recipients (n = 24), non-HCT recipients (n = 309), and a control group of healthy siblings (n = 211) all aged 9-18 years. A fasting blood sample was collected to measure FSH. All participants underwent a dual X-ray absorptiometry scan to assess total and regional percent fat, lean mass (LM), fat mass (FM), bone mineral content (BMC), bone mineral density (BMD), and visceral adipose tissue (VAT) mass. RESULTS: FSH was significantly higher in HCT recipients compared to non-HCT recipients and healthy controls. HCT recipients had significantly lower total body weight, total LM, arm and leg LM, BMC and BMD compared to non-HCT recipients and healthy controls (p < .05). Non-HCT recipients had significantly higher total, trunk, android, gynoid, arm and leg FM compared to healthy controls. Also, healthy controls had significantly lower VAT mass compared to non-HCT recipients. CONCLUSIONS: This study's results show that HCT recipients have significant reductions in BMD, worse body composition, and abnormal FSH levels compared to non-HCT recipients and healthy controls.

Outcomes from a pilot genetic counseling intervention using motivational interviewing and the extended parallel process model to increase cascade cholesterol screening.

Familial hypercholesterolemia (FH) is an inherited condition resulting in increased risk of premature cardiovascular disease. This risk can be reduced with early diagnosis and treatment, but it can be challenging to identify individuals with FH. Cascade screening, the most efficient and cost-effective identification method, requires FH patients to communicate with their at-risk family and encourage them to pursue screening. Beyond FH, patients with conditions increasing disease risk to family members report barriers to the communication process such as insufficient knowledge of the condition and discomfort informing relatives. We conducted a pilot study of a genetic counseling intervention incorporating behavior-change principles from motivational interviewing (MI) and the extended parallel process model (EPPM) to help parents of children with FH overcome these barriers and improve cascade screening rates for FH. Of the 13 participants who completed the intervention and post-intervention surveys, 6 reported contacting and/or screening additional relatives. A large effect size in increasing communication and screening was observed (η2  = 0.20), with the mean percent of at-risk relatives contacted rising from 33% to 45%, and the mean percent screened rising from 32% to 42%. On average, 2.23 new relatives were contacted and 2.46 were screened, per participant, by the end of the study. Direct content analysis revealed that despite the open-ended nature of the goal-setting process, participant goals fell into two categories including those who set goals focused on communicating with and screening family members (n = 9) and those who set goals only focused on managing FH (n = 4). Overall, the communication and screening rates reported after the intervention were higher than previous observations in adult FH populations. These results suggest this EPPM/MI genetic counseling intervention could be a useful tool for increasing communication and cascade screening for FH. With further research on goal-setting techniques, the intervention could be refined and replicated to identify more individuals affected by FH or modified for use with other actionable genetic conditions.

The Role of Follicle-stimulating Hormone in Vascular Dysfunction Observed in Hematopoietic Cell Transplant Recipients.

Childhood cancer survivors who receive a hematopoietic cell transplantation (HCT) are at increased risk for follicle-stimulating hormone (FSH) abnormalities, which may have a substantial negative impact on vascular function. The purpose of this study was to examine the association of vascular function with FSH in HCT recipients, non-HCT recipients and healthy controls. The study included childhood cancer survivors who were HCT recipients (n=24) and non-HCT recipients (n=308), and a control group of healthy siblings (n=211) all between 9 and 18 years old. Vascular measures of carotid artery structure and function (compliance and distensibility), brachial artery flow-mediated dilation and endothelial-independent dilation were measured using ultrasound imaging. A fasting blood sample was collected to measure hormone levels. FSH was significantly higher in HCT recipients compared with non-HCT recipients and healthy controls (P<0.01). Carotid compliance and distensibility were significantly lower in HCT and non-HCT recipients compared with healthy controls (P<0.05). Higher FSH was associated with decreased carotid compliance (P<0.05). This study's results suggest that higher levels of FSH in HCT recipients may result in significant reductions in vascular function compared with non-HCT recipients and healthy controls. Therefore, gonadotropin endocrine dysfunction, particularly abnormal FSH levels, may be an underlying mechanism of vascular dysfunction.

Gore Cardioform atrial septal occluder: deployment procedure and techniques for closing challenging secundum atrial septal defects.

Ostium secundum atrial septal defects are mostly closed in the cardiac catheterisation laboratories using either Amplatzer® (Abbott Laboratories, IL) atrial septal occluder, Gore® Cardioform septal occluder and more recently using the recently approved (US FDA approval June 2019) Gore® Cardioform atrial septal defect occluder (W. L. Gore & Associates, AZ). Similar to any new device in the market, there is a learning curve to the deployment of this device. We therefore aim to report the key features about this new Gore Cardioform atrial septal defect occluder device with special emphasis on technical aspects that can be employed during transcatheter closure of challenging ostium secundum atrial septal defects using this device.

Cardiovascular risk factors before and during pregnancy: Does pregnancy unmask or initiate risk?

OBJECTIVES: To understand if pregnancy unmasks previously silent cardiovascular (CV) adverse factors, or initiates lasting injury. METHODS: Pre-pregnancy and during pregnancy CV risk factors (blood pressure, fasting lipids, and glucose) from 296 women belonging to studies in the International Childhood Cardiovascular Cohort (i3C) Consortium, a group of studies assessing the relationship between child and adolescent CV risk factors and adult outcomes, were used. Correlation coefficients between the pre- and during pregnancy measures were calculated, and the mean difference between the measures was modeled with adjustment for age, body mass index, race, smoking, and study. RESULTS: Measures were strongly correlated at pre- and during-pregnancy visits (p < 0.01), with r of between 0.30 and 0.55. In most cases, the difference between pre-pregnancy and during-pregnancy did not differ significantly from 0 after adjustment for confounders. Stratification by gestational age indicated stronger correlations with measurements obtained during the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre-pregnancy and pregnancy visits. CONCLUSIONS: Pre- and during-pregnancy CV risk factors are moderately well correlated. This may indicate that susceptible women enter pregnancy with higher risk rather than pregnancy inducing new vascular or metabolic effects.

Long Term Outcomes of Tetralogy of Fallot With Absent Pulmonary Valve (from the Pediatric Cardiac Care Consortium).

Tetralogy of Fallot with absent pulmonary valve (TOF-APV) is a rare form of tetralogy with unique challenges due to the combination of pulmonary annular stenosis, severe pulmonary regurgitation, and airway compression secondary to aneurysmal dilatation of the pulmonary arteries. Data on the long-term outcomes of repaired TOF-APV are scarce. We used the Pediatric Cardiac Care Consortium (PCCC), a large US-based registry, to describe the postrepair transplant-free survival of patients with TOF-APV. We queried the PCCC for patients operated for TOF-APV between 1982 and 2003. Death or transplant events were ascertained from the PCCC and by linkage with the US National Death Index and the Organ Procurement Transplantation Network through December 2019. A total of 126 patients were identified with TOF-APV repair (primary n = 119, staged n = 7). The majority of them were repaired with a right ventricular to pulmonary artery conduit (n = 80, 64%) and 43 (34%) with transannular patch. In-hospital mortality occurred in 31 patients (25%); post discharge and over a median period of 19 years (IQR 0.37 to 23.7 years), 5 patients died and 2 underwent heart transplant, one of whom subsequently died. The 25-year transplant-free survival post discharge after TOF-APV repair was 92%, which was similar with the outcome of patients with simple TOF undergoing non-valve sparing procedures (94% log-rank test p = 0.455; aHR 1.37; 95% CI: 0.63 to 2.97, p = 0.432). In conclusion, early in-hospital mortality is high for TOF-APV; however, once repaired and survived to discharge, long term survival is similar to simple TOF with non-valve sparing procedures.

Anatomic Approach and Outcomes in Children Undergoing Percutaneous Pericardiocentesis.

Pericardiocentesis is traditionally performed using a subxiphoid approach. Hepatomegaly or loculated and noncircumferential effusions warrant nonstandard approaches to drain effusions; echocardiographic guidance has made these less traditional, non-subxiphoid approaches feasible. The study is aimed at comparing clinical outcomes of the subxiphoid and non-subxiphoid approaches to percutaneous pericardiocentesis in a pediatric population. This is a retrospective chart review of all children undergoing percutaneous pericardiocentesis from August 2008 to December 2019 at a single-center. A total of 104 patients underwent echocardiography-guided pericardiocentesis during the timeframe. Additionally, fluoroscopy was also used in 80 patients. Hematopoietic stem cell transplantation was the most common underlying diagnosis (n = 53, 50.9%). A non-subxiphoid approach was used in 58.6% (n = 61) of patients. The fifth and sixth intercostal spaces were the most commonly used (n = 17 each). The non-subxiphoid group tended to be older (95.9 vs. 21.7 months, p = 0.006) and weighed more (23.6 vs. 11.2 kgs, p = 0.013) as compared to the subxiphoid group. Non-subxiphoid approach was associated with shorter procedure times (21 vs. 37 min, p = 0.005). No major complications were seen. Five minor complications occurred and were equally distributed in the two groups. Complications were more likely in younger patients (p = 0.047). The technique and anatomic approach to pericardiocentesis, and the location or size of effusion did not influence the risk of complications. Echocardiography-guided percutaneous pericardiocentesis in children was associated with low complication rates in this single-center pediatric experience. The use of a non-traditional, non-subxiphoid approach was associated with shorter procedure times and did not significantly affect complication rates.

Pediatric Micra leadless pacemaker implantation via the internal jugular and femoral vein: a single-center, US experience.

Background: In the pediatric population, conventional transvenous and epicardial pacemaker systems carry complications such as lead distortion due to growth/activity, in addition to other lead/pocket complications. Materials & methods: A retrospective review of pediatric leadless pacing at the University of Minnesota Masonic Children's Hospital from 2018 to 2020 was performed. Rationale for pacing, demographics of patients, thresholds and longevity of devices were recorded. Results: Seven leadless pacemaker insertions and one removal were performed successfully, in patients weighing between 19 kg and 58 kg. Three patients had Micra implantation via internal jugular vein. One pericardial effusion occurred perioperatively in a 19 kg patient with baseline thrombocytopenia, sideroblastic anemia and Pearson Marrow Pancreas syndrome. Conclusion: Leadless pacemaker implantation/early retrieval is feasible in pediatric patients.