Pediatric heart transplantation in infants and small children under 3 years of age: Single center experience - "Early and long-term results".

OBJECTIVES: We analyzed the early and long-term survival after ABO-compatible heart transplantation in children under 3 years of age from 1991 to 2021 at our center. This retrospective and descriptive study aimed to identify serious adverse events associated with mortality after pediatric heart transplantation. PATIENTS AND METHODS: 46 patients with congenital heart failure (37%) in end-stage heart failure have undergone a pediatric heart transplantation. Primary outcome of interest was survival at follow-up time. RESULTS: Median (IQR) follow-up time (y), age (y), body-weight (kg) and BMI (kg/cm2) were 13.2 (5.7-19.5), 0.9 (0.2-2.0), 6.8 (4.3-10.0) and 14.2 (12.3-15.7). Twenty-four (52%) patients were male. 15 patients (33%) had a single ventricle physiology. At 30- days survival rate was 94 ± 4%. Survival rate at 1, 5, 10 and 15 years post HTx was 87 ± 5%, 84 ± 6%, 79 ± 6% and 63 ± 8%. One child underwent re-transplantation after 4 years, and another one after 11 years - in both cases due to graft failure. Higher early mortality in patients under 3 months of age and in patients with single ventricle physiology. Transplant free survival at 15 years was in children with cardiomyopathy better (71 ± 10%) than in those with congenital heart disease (50 ± 13%). One or more previous heart surgeries prior to HTx (n = 21) were associated to more mortality. CONCLUSION: Pediatric heart transplantation has acceptable long-term results and is still the best therapeutic option in children with end-stage cardiac failure. Underlying anomalies and single ventricle physiology, age below 3 months had a significant impact on survival.

Predicting the earliest deviation in weight gain in the course towards manifest overweight in offspring exposed to obesity in pregnancy: a longitudinal cohort study.

BACKGROUND: Obesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify "high-risk" offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system. METHODS: This study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood-Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a "higher-than-normal BMI growth pattern" preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off "at risk of overweight") at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed. RESULTS: Data of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98-26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25-3.45) and smoking (OR 1.94; 95% CI 1.27-2.95) in pregnancy were instrumental in predicting a "higher-than-normal BMI growth pattern" at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69-0.79, sensitivity 70.7-76.0%, specificity 64.7-78.1%). External validation of prediction models demonstrated adequate predictive performances. CONCLUSIONS: We devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in "high-risk" infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care.

Late-pregnancy dysglycemia in obese pregnancies after negative testing for gestational diabetes and risk of future childhood overweight: An interim analysis from a longitudinal mother-child cohort study.

BACKGROUND: Maternal pre-conception obesity is a strong risk factor for childhood overweight. However, prenatal mechanisms and their effects in susceptible gestational periods that contribute to this risk are not well understood. We aimed to assess the impact of late-pregnancy dysglycemia in obese pregnancies with negative testing for gestational diabetes mellitus (GDM) on long-term mother-child outcomes. METHODS AND FINDINGS: The prospective cohort study Programming of Enhanced Adiposity Risk in Childhood-Early Screening (PEACHES) (n = 1,671) enrolled obese and normal weight mothers from August 2010 to December 2015 with trimester-specific data on glucose metabolism including GDM status at the end of the second trimester and maternal glycated hemoglobin (HbA1c) at delivery as a marker for late-pregnancy dysglycemia (HbA1c ≥ 5.7% [39 mmol/mol]). We assessed offspring short- and long-term outcomes up to 4 years, and maternal glucose metabolism 3.5 years postpartum. Multivariable linear and log-binomial regression with effects presented as mean increments (Δ) or relative risks (RRs) with 95% confidence intervals (CIs) were used to examine the association between late-pregnancy dysglycemia and outcomes. Linear mixed-effects models were used to study the longitudinal development of offspring body mass index (BMI) z-scores. The contribution of late-pregnancy dysglycemia to the association between maternal pre-conception obesity and offspring BMI was estimated using mediation analysis. In all, 898 mother-child pairs were included in this unplanned interim analysis. Among obese mothers with negative testing for GDM (n = 448), those with late-pregnancy dysglycemia (n = 135, 30.1%) had higher proportions of excessive total gestational weight gain (GWG), excessive third-trimester GWG, and offspring with large-for-gestational-age birth weight than those without. Besides higher birth weight (Δ 192 g, 95% CI 100-284) and cord-blood C-peptide concentration (Δ 0.10 ng/ml, 95% CI 0.02-0.17), offspring of these women had greater weight gain during early childhood (Δ BMI z-score per year 0.18, 95% CI 0.06-0.30, n = 262) and higher BMI z-score at 4 years (Δ 0.58, 95% CI 0.18-0.99, n = 43) than offspring of the obese, GDM-negative mothers with normal HbA1c values at delivery. Late-pregnancy dysglycemia in GDM-negative mothers accounted for about one-quarter of the association of maternal obesity with offspring BMI at age 4 years (n = 151). In contrast, childhood BMI z-scores were not affected by a diagnosis of GDM in obese pregnancies (GDM-positive: 0.58, 95% CI 0.36-0.79, versus GDM-negative: 0.62, 95% CI 0.44-0.79). One mechanism triggering late-pregnancy dysglycemia in obese, GDM-negative mothers was related to excessive third-trimester weight gain (RR 1.72, 95% CI 1.12-2.65). Furthermore, in the maternal population, we found a 4-fold (RR 4.01, 95% CI 1.97-8.17) increased risk of future prediabetes or diabetes if obese, GDM-negative women had a high versus normal HbA1c at delivery (absolute risk: 43.2% versus 10.5%). There is a potential for misclassification bias as the predominantly used GDM test procedure changed over the enrollment period. Further studies are required to validate the findings and elucidate the possible third-trimester factors contributing to future mother-child health status. CONCLUSIONS: Findings from this interim analysis suggest that offspring of obese mothers treated because of a diagnosis of GDM appeared to have a better BMI outcome in childhood than those of obese mothers who-following negative GDM testing-remained untreated in the last trimester and developed dysglycemia. Late-pregnancy dysglycemia related to uncontrolled weight gain may contribute to the development of child overweight and maternal diabetes. Our data suggest that negative GDM testing in obese pregnancies is not an "all-clear signal" and should not lead to reduced attention and risk awareness of physicians and obese women. Effective strategies are needed to maintain third-trimester glycemic and weight gain control among otherwise healthy obese pregnant women.

Reduced arterial stiffness in very fit boys and girls.

Low cardiorespiratory fitness is associated with higher cardiovascular risk, whereas high levels of cardiorespiratory fitness protect the cardiovascular system. Carotid intima-media thickness and arterial distensibility are well-established parameters to identify subclinical cardiovascular disease. Therefore, this study investigated the influence of cardiorespiratory fitness and muscular strength on carotid intima-media thickness and arterial distensibility in 697 children and adolescents (376 girls), aged 7-17 years. Cardiorespiratory fitness and strength were measured with the test battery FITNESSGRAM; carotid intima-media thickness, arterial compliance, elastic modulus, stiffness index ß, and pulse wave velocity ß were assessed by B- and M-mode ultrasound at the common carotid artery. In bivariate correlation, cardiorespiratory fitness was significantly associated with all cardiovascular parameters and was an independent predictor in multivariate regression analysis. No significant associations were obtained for muscular strength. In a one-way variance analysis, very fit boys and girls (58 boys and 74 girls>80th percentile for cardiorespiratory fitness) had significantly decreased stiffness parameters (expressed in standard deviation scores) compared with low fit subjects (71 boys and 77 girls<20th percentile for cardiorespiratory fitness): elastic modulus -0.16±1.02 versus 0.19±1.17, p=0.009; stiffness index ß -0.15±1.08 versus 0.16±1.1, p=0.03; and pulse wave velocity ß -0.19±1.02 versus 0.19±1.14, p=0.005. Cardiorespiratory fitness was associated with healthier arteries in children and adolescents. Comparison of very fit with unfit subjects revealed better distensibility parameters in very fit boys and girls.

Beyond intima-media-thickness: Analysis of the carotid intima-media-roughness in a paediatric population.

BACKGROUND AND AIMS: Subclinical atherosclerosis assessed by sonographic intima-media-thickness measurement of the carotid artery (cIMT) is considered to be an early precursor of cardiovascular disease already in childhood. Structural analysis of the carotid intimal layer (carotid intima-media-roughness, cIMR) improves cardiovascular risk profiling for the adult patient and has been shown to be increased also in paediatric patients with elevated cardiovascular risk. To date, normal values for the paediatric age are lacking. Thus, we present normative data for a paediatric age group. METHODS: 602 healthy German school children (age 8-18 y) were studied, and cIMT and cIMR calculated; reference values were given for three age groups (group 1: 8-10.99 years; group 2: 11-13.99 years; group 3: 14-17.99 years). RESULTS: cIMT values were: 0.48 ± 0.03 mm for girls and boys in age group 1, 0.49 ± 0.03 mm for girls and boys in age group 2; and 0.45 ± 0.03 mm for girls and 0.49 ± 0.03 mm for boys in age group 3; cIMR was 0.04 ± 0.01 mm for both sexes in age group 1 and 3; while in age group 2, both sexes showed a cIMR of 0.03 ± 0.01 mm. Physical fitness was significantly negatively correlated with cIMR (r = - 0.212, p < 0.0001) and a strong predictor for cIMR increase. CONCLUSIONS: The normative data of cIMR for a paediatric age group presented here allow for the identification of patients at elevated cardiovascular risk. By including cIMR as surface analysis of the arterial wall, the individual risk stratification may be improved compared to thickness-analysis of the Intima-Media-Layer (cIMT) also at a paediatric age.

Intima-Media Thickness Does Not Differ between Two Common Carotid Artery Segments in Children.

Carotid intima-media thickness (cIMT) is a surrogate marker of early atherosclerotic changes in children. cIMT-studies are hard to compare, due to variations in ultrasound protocols, especially regarding the common carotid artery (CCA) segment measured in relation to the bulb. This study's purpose was therefore to compare two distinct CCA segments in children, to see if cIMT values differ substantially according to the site of measurement. cIMT was assessed after power calculation in 30 children (15 girls) aged 8-17, using B-Mode ultrasound (5-13 MHz) at two CCA locations. The first measurement was performed over a distance of 1 cm immediately after the bulb (A), the second 1cm proximal the bulb (B) over the same distance of 1cm length. Means of end-diastolic far wall cIMT were compared between measurement A and B. cIMT in 30 participants was 0.51±0.06 mm for measurement A and 0.51±0.05 mm for measurement B. Results did not differ significantly (p = .947) over a distance of 2 cm after the bulb. According to our results, studies measuring CCA IMT within the first 2 cm, either close to the bulb or further proximal, can be compared. This will improve interpretation of data and application of reference values.

Obese Nondiabetic Pregnancies and High Maternal Glycated Hemoglobin at Delivery as an Indicator of Offspring and Maternal Postpartum Risks: The Prospective PEACHES Mother-Child Cohort.

BACKGROUND: We investigated whether obese pregnant women negative for gestational diabetes (GDM) still experience dysglycemia, as indicated by high glycated hemoglobin (Hb A1c) at delivery, and whether this impacts offspring and long-term maternal outcomes. METHODS: Data of 462 mother-child pairs of our prospective Programming of Enhanced Adiposity Risk in Childhood - Early Screening (PEACHES) cohort study were analyzed. Of 885 obese and normal-weight pregnancies prospectively enrolled after GDM testing according to the International Association of Diabetes and Pregnancy Study Groups criteria, 462 GDM-negative mothers and their offspring were investigated. We assessed associations of maternal Hb A1c at delivery with large-for-gestational-age (LGA) birth weights, cord-blood C-peptide, and biomarkers of glucose metabolism and inflammation in obese mothers followed for 2.9 years (median) postpartum (n = 42). RESULTS: Cumulative distribution analysis in GDM-negative normal-weight women (n = 155) revealed that 12% had Hb A1c ≥5.7% at delivery (high Hb A1c). Among obese GDM-negative women (n = 307), 31.9% (95% CI, 26.7%-37.4%) equaled or exceeded this cutoff. In obese GDM-negative women with Hb A1c ≥5.7% (n = 98) vs <5.7% (n = 209) at delivery, newborns were more likely to be born LGA [adjusted odds ratio 3.56 (95% CI, 1.64-8.02)], and mean cordblood serum C-peptide was increased by 0.09 ng/mL (95% CI, 0.01-0.17 ng/mL). In the mothers at follow-up, mean postpartum Hb A1c, fasting glucose, high-sensitivity C-reactive protein, and fibrinogen concentrations were higher by 0.3% (95% CI, 0.1%-0.5%), 6.0 mg/dL (95% CI, 2.4-9.5 mg/dL), 6.8 mg/L (95% CI, 1.4-12.3 mg/L), and 74.9 mg/dL (95% CI, 13.6-136.2 mg/dL), respectively. CONCLUSIONS: Increased Hb A1c in obese GDM-negative women at delivery indicates gestational dysglycemia, potentially conferring offspring and long-term maternal health risks. These findings should raise awareness as to careful monitoring of obese pregnancies. Measurement of Hb A1c at delivery could help select women who may need closer postpartum health checks.

Increased intima-media thickness is not associated with stiffer arteries in children.

OBJECTIVE: Subclinical atherosclerosis can be assessed via sonographic measurement of intima-media thickness and carotid artery distensibility, both may already be pathologically altered in childhood. Therefore, the purpose of this study was to provide reference percentiles and investigate possible associations between alterations of intima-media thickness and distensibility. METHODS: Carotid intima-media thickness and distensibility was measured via B- and M-mode ultrasound. Distensibility was defined by arterial compliance, elastic modulus, stiffness parameter ß, and local pulse wave velocity ß. Age- and height-dependent reference values were calculated separately for boys and girls among 690 (intima-media thickness) and 870 (distensibility) non-obese children aged 7-17 years. RESULTS: Intima-media thickness and distensibility did not increase significantly with age or differ between boys and girls. Systolic blood pressure and body mass index were independent predictors of intima-media thickness, while an increased systolic blood pressure or pulse pressure was associated with stiffer arteries. Increased intima-media thickness was accompanied by higher arterial compliance and lower stiffness. CONCLUSION: Using this healthy cohort, we describe a functional and non-pathological arterial adaptation wherein an increase in intima-media thickness is not associated with stiffer arteries.

Intima-media thickness and arterial function in obese and non-obese children.

BACKGROUND: Obesity is an independent cardiovascular risk factor that contributes to the development of atherosclerosis. Subclinical forms of the disease can be assessed via sonographic measurement of carotid intima-media thickness (cIMT) and distensibility - both may already be altered in childhood. As childhood obesity increases to an alarming extent, this study compares vascular data of obese with normal weight boys and girls to investigate the influence of obesity on cIMT and distensibility of the carotid arteries. METHODS: cIMT and distensibility of 46 obese children (27 girls) aged 7-17 years were compared with measures of 46 sex- and age-matched normal weight controls. cIMT and distensibility were measured by B- and M-mode ultrasound and expressed as standard deviation scores (SDS). Arterial distensibility was defined by arterial compliance (AC), elastic modulus (Ep), stiffness index ß (ß), and local pulse wave velocity ß (PWV ß). RESULTS: Obese girls had significantly stiffer arteries compared with normal weight girls (Ep SDS 0.64 ± 1.24 vs. 0 ± 1.06, ß SDS 0.6 ± 1.17 vs. -0.01 ± 1.06 p < .01, PWV ß 0.54 ± 1.2 vs. -0.12 ± 1.05 p < .05). No significant differences were observed for boys. In multiregression analysis, BMI significantly influenced Ep, ß and PWV ß but not cIMT and AC. CONCLUSIONS: Obese girls seemed to be at higher cardiovascular risk than boys, expressed by stiffer arteries in obese girls compared with normal weight girls. Overall, BMI negatively influenced parameters of arterial stiffness (Ep, ß and PWV ß) but not compliance or cIMT.

Bacterial nanocellulose as a new patch material for closure of ventricular septal defects in a pig model.

OBJECTIVES: Current materials for closure of cardiac defects such as ventricular septal defects (VSDs) are associated with compliance mismatch and a chronic inflammatory response. Bacterial nanocellulose (BNC) is a non-degradable biomaterial with promising properties such as high mechanical strength, favourable elasticity and a negligible inflammatory reaction. The aim of this study was the evaluation of a BNC patch for VSD closure and the investigation of its in vivo biocompatibility in a chronic pig model. METHODS: Young's modulus and tensile strength of BNC patches were determined before and after blood exposure. Muscular VSDs were created and closed with a BNC patch on the beating heart in an in vivo pig model. Hearts were explanted after 7, 30 or 90 days. Macropathology, histology and immunohistochemistry were performed. RESULTS: Young's modulus and tensile strength of the BNC patch decreased after blood contact from 6.3 ± 1.9 to 3.86 ± 2.2 MPa (P < 0.01) and 0.33 ± 0.06 to 0.26 ± 0.06 MPa (P < 0.01), respectively, indicating the development of higher elasticity. Muscular VSDs were closed with a BNC patch without residual shunting. After 90 days, a mild chronic inflammatory reaction was present. Moreover, there was reduced tissue overgrowth in comparison with polyester. Proceeding cellular organization characterized by fibromuscular cells, production of extracellular matrix, neoangiogenesis and complete neoendothelialization were found. There were no signs of thrombogenicity. CONCLUSIONS: BNC patches can close VSDs with good mid-term results and its biocompatibility can be considered as satisfactory. Its elasticity increases in the presence of blood, which might be advantageous. Therefore, it has potential to be used as an alternative patch material in congenital heart disease.

Influence of pulmonary artery size on early outcome after the Fontan operation.

BACKGROUND: Small pulmonary arteries (PAs) are often considered as a contraindication for the Fontan operation (FO). The aim of this study was to evaluate if the PA size is still one of the major impact factors on the postoperative early outcome. METHODS: Data of 146 patients, with a median age of 2.0 years (range, 1.5 to 18 years) and a median weight of 12.45 kg (range, 7.7 to 64.7 kg) who underwent a modified FO in the same center between 2007 and 2012 were retrospectively analyzed with respect to the traditional McGoon ratio, Nakata index, and modified indices (measuring the narrowest diameters). RESULTS: Patients with a McGoon ratio of 1.6 or less (modified≤1.2) or a Nakata index of 150 mm2/m2 or less (modified≤100 mm2/m2) were not at a higher risk of longer mechanical ventilation (p=0.87 [0.1] and p=0.68 [0.52], respectively), longer stay (p=0.52 [0.18] and p=0.54 [0.38], respectively) in the intensive care unit, prolonged hospital stay (p=0.08 [0.26] and p=0.22 [0.29], respectively) or effusions (p=0.25 [0.37] and p=0.13 [0.06]), respectively). Younger and smaller children tended to have smaller PAs, but younger age (<24 months) and lower weight (<12 kg) were not predictive for poor early postoperative outcome. CONCLUSIONS: Small PAs do not significantly affect the early postoperative period after FO. In our opinion, there is no need to postpone the FO due to "smaller" PAs. The palliative procedures performed before FO to increase the size of the PA at the expense of volume overload of the single ventricle and the possible complications of prolonged cyanosis must be carefully weighed.

Extracorporeal life support and left ventricular unloading in a non-intubated patient as bridge to heart transplantation.

INTRODUCTION: Veno-arterial extracorporeal life support (ECLS) is a well-established bridging therapy in patients with cardiac or pulmonary failure to maintain organ function and is frequently performed in patients who are not intubated. However, severly impaired cardiac function can occur pulmonary edemy in these patients, necessitating left ventricular unloading. METHODS AND RESULTS: In this study we report a 37-year old female patient with familiar dilated cardiomyopathy suffering from acute biventricular heart failure. After implantation of a peripheral ECLS, the decreased ventricular led to refractory pulmonary edema. To unload the left ventricle, an percutaneous balloon atrioseptostomy was performed without intubating the patient. The left ventricle was vented by the venous cannula resting inside the atrioseptostomy. After twelve days on ECLS, the patient underwent orthotopic heart transplantation. The postoperative course was uneventful and the patient discharged from intensive care unit four days after surgery. CONCLUSIONS: In this report we present a patient in which the hybrid technique of ECLS with secondary left ventricular unloading was successfully used as a bridge to transplant therapy. This procedure may offer an alternative bridge-to-decision options in selected patients, including those that were not intubated or anaesthetized.

ABO-incompatible heart transplantation in early childhood: an international multicenter study of clinical experiences and limits.

BACKGROUND: Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries. METHODS: Data from six centers in Europe and North America on ABOi transplantation were collected in a standardized survey. RESULTS: Fifty-eight ABOi transplants were performed in 57 patients. Median age at transplant was 6.8 months (0.03 to 90 months); post-transplant follow-up was 37.7 months (0.46 to 117 months), accumulating 188 patient-years. Forty-seven percent of the patients received pretransplant mechanical circulatory support. Donors were either blood group A (n = 25), B (n = 18) or AB (n = 15). The median peak antibody titer to the donor BG pretransplant was 1:8 (0 to 1:64) for anti-A and 1:4 (0 to 1:32) for anti-B. Titers against the donor BG were lower post- than pretransplant in B recipients (p = 0.02), whereas third-party antibodies in BG O recipients developed normally post-transplant. Induction immunosuppression included anti-thymocyte globulin (61%), basiliximab (32%) or none (7%). All patients received calcineurin inhibitors, including 62% with mycophenolate mofetil, 10% with azathioprine, 2% with everolimus and 24% with steroids. There were 4 episodes of cellular rejection (Grade≥2R) and 7 antibody-mediated rejections. Five patients underwent antibody removal post-transplant. One patient developed severe graft vasculopathy. Freedom from death or retransplantation was 100%/96%/69% at 1/5/10 years. No graft loss was attributed to BG antibodies. CONCLUSIONS: Successful ABOi heart transplantation can be performed at an older age and with higher isohemagglutinin titers than initially assumed and using similar immunosuppressive regimens as for ABO-compatible transplants. Rejection and graft vasculopathy are rare. Persistently low titers of antibodies to the donor BG post-transplant suggest elements of tolerance and/or accommodation.

An unusual form of supracardiac total anomalous pulmonary venous return via a right-sided vertical vein in a heterotaxy syndrome case.

Heterotaxy syndromes comprise a great variety of possible cardiac defects. Anomalies of the pulmonary venous system are well recognized in heterotaxy syndromes but constitute a frequently underdiagnosed subgroup. The case report describes a girl with a rare form of supracardiac total anomalous pulmonary venous return via a right-sided vertical vein to the right innominate vein in heterotaxy syndrome with dextrocardia, unbalanced atrioventricular septal defect with severe left ventricular hypoplasia, and transposition of the great arteries with pulmonary stenosis. Careful evaluation and imaging before surgical repair is crucial for such complex cardiac anomalies.

Hypertension after heart and heart/lung transplantation in childhood--study on the evolution of short-term blood pressure regulation.

Arterial hypertension complicates the follow-up of heart- and heart/lung-transplanted children. We investigated the evolution of BRS as short-time BP regulation mechanism and BP after heart and heart/lung transplantation. Twenty patients (15 males; mean age 15.1 ± 4.3 yr) were studied twice at intervals of 2.96 ± 0.87 yr. BRS was calculated using non-invasive beat-to-beat BP measurement system. HRV was calculated (LF, sympathetic influence; HF, parasympathetic influence). BRS increased in 10 patients (3.67 ± 1.43 ms/mmHg vs. 7.59 ± 3.40 mmHg, p = 0.005) (group 1). Six of 10 patients received antihypertensive medication. BRS decreased or remained unchanged in 10 patients (8.93 ± 7.9 ms/mmHg vs. 5.32 ± 6.6 ms/mmHg, p = 0.008) (group 2) with 9/10 patients necessitating antihypertensive medication. Group 1 showed LF/HF increase (LF/HF 1.03 ± 0.9 vs. 4.36 ± 2.32, p = 0.03); group 2 showed LF/HF decrease (LF/HF 3.7 ± 2.1 vs. 1.84 ± 1.1, p = 0.023). Evolution of BRS after heart and heart/lung transplantation in childhood seems to influence the necessity of antihypertensive medication. With time, increasing short-time BP regulation involving sympathetic reinnervation may improve BP.

The effect of cardiovascular risk factors on the longitudinal evolution of the carotid intima medial thickness in children with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima media thickness (cIMT) in children and adolescents with type 1 diabetes mellitus (T1DM) using standardized methods. METHODS: We re-evaluated cIMT in 70 (38 f) of initial 150 (80 f) patients with T1DM after 4 years. At re-evaluation, mean (±SD) age was 16.45±2.59 y, mean diabetes duration was 9.2±3.24 y and patients had a mean HbA1c of 8.14±1.06%. RESULTS: Mean cIMT z-scores increased significantly during 4 years (0.58±0.75, p<0.001) as well as BMI-z-score (0.41±0.81, p<0.01), systolic blood pressure (0.77±1.15, p<0.01) and HbA1c (0.90±1.07, <0.001). In a linear regression model systolic blood pressure z-score at first measurement (0.02, CI: 0.01, 0.04) was a significant predictor for the mean effect on cIMT z-score. In a logistic regression model significant risk factors for an increase in IMT of ≥1.5 z-scores were BMI z-scores (OR: 3.02, CI:1.11, 10.14), diabetes duration (OR:1.32, CI:1.04, 1.77) and systolic blood pressure (OR: 1.14, CI: 1.04, 1.27) at first measurement each. CONCLUSIONS: Longitudinal cIMT measurements revealed progression in subclinical atherosclerosis during a four year period in diabetic children and adolescents. Systolic blood pressure and BMI were related to cIMT increment. Control of these risk factors by lifestyle and medical intervention may prevent progression of cIMT in diabetic children.