Abnormalities in pulmonary function and volumes in patients with CHD: a systematic review.

BACKGROUND: Lung function and cardiac function are naturally correlated by sharing the thoracic cage and handling the whole cardiac output sequentially. However, lung function studies are rare in patients with CHD, although results worthy of investigation could be expected. This review summarises existing studies with the lung function parameters (spirometry and body plethysmography) in CHD patients during the last decade. METHODS: A systematic review was performed in the relevant database (PubMed, Cochrane, and Scopus) in studies including paediatric and adult patients with CHD where lung parameters (spirometry, body plethysmography) were investigated from January 2010 to December 2020. Two independent reviewers evaluated the studies according to the Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute. RESULTS: Eight studies investigated patients with Fontan palliation including 704 patients (306 female). Four studies included patients after repaired tetralogy of Fallot examining 219 patients (103 female), with one study using double. Further six studies included 3208 (1324 female) children and adults with various CHDs. Overall, four studies were categorised as "good", ten as "fair", and four as "poor". While the measurements were consistently standardised, references to calculate %predicted differed substantially across all studies. All evaluated studies showed reduced forced vital capacity in the majority of CHD patients. CONCLUSIONS: Many CHD patients have a reduced forced vital capacity independent of their underlying defect. Spirometry should not only follow a standardised measure according to ATS (update 2019) but also stick to the 2012 GLI reference values.

Diabetes mellitus in pediatric solid organ recipients without and with cystic fibrosis: An analysis from the German-Austrian diabetes database (Diabetes Patienten Verlaufsdokumentation).

INTRODUCTION: Posttransplantation diabetes mellitus (PTDM) increases the risk of cardiovascular disease, graft loss, and decreased survival. Follow-up treatment after solid organ transplantation (SOT) needs to focus on, inter alia, maintaining balanced glucose metabolism. This study aimed to ascertain the prevalence of PTDM and describe patient characteristics in the large DPV (Diabetes Patienten Verlaufsdokumentation) pediatric diabetes database. METHODS: DPV data of 71 902 patients from the January 01, 1995 to January 04, 2015 period were analyzed for patients with and without cystic fibrosis (CF) after SOT (kidney, liver, heart, and lung). Multivariable analysis served to assess differences between SOT patient groups at risk for developing diabetes. RESULTS: Out of 109 SOT patients, 51 had CF; 72.5% received steroids and 62% were additionally given tacrolimus. PTDM developed in 45% of CF patients and 12% of non-CF patients. SOT patients were older at diabetes onset (mean age, 12.50 ± 3.98 years), shorter (height z-score, -1.67 ± 1.25), and lighter (weight z-score, -1.59 ± 1.57) than non-SOT diabetes patients (P < 0.01). With transplantation, glycated hemoglobin (HbA1c) was significantly lower and treatment for hypertension and dyslipidemia was increased. Among SOT patients, weight and body mass index (BMI) z-scores were significantly lower in patients with CF-related diabetes (P < 0.05). CONCLUSIONS: SOT was present in 6.6% of children with diabetes, and this might aggravate the risk of cardiovascular disease in populations with already increased rates of hypertension and dyslipidemia. Dystrophy and short stature were also present, particularly in transplant recipients with CF and diabetes. Comorbidities and long-term consequences call for multidisciplinary collaboration.

Retrieval of large Occlutech Figula Flex septal defect occluders using a commercially available bioptome: proof of concept.

OBJECTIVES: This study aimed to develop a method for retrieval of the new meshed nitinol atrial septal defect occluders - Ceraflex and Occlutech. BACKGROUND: The newly developed atrial septal defect occluders have potential benefits considering implantation, but concerns regarding their removal in case of embolisation have been raised. METHODS: Over 21 years, 1449 patients underwent interventional atrial septal defect occlusion in our institution. We reviewed the cases of embolisation of the device, developed a strategy for device removal, and tested it on the benchside and in animal tests. RESULTS: In 11 patients (0.8%), the intended atrial septal defect occlusion was complicated by an embolisation of the device. In contrast to the Amplatzer septal occluders, retrieval of Occlutech devices larger than 16 mm with snare techniques was impossible. In benchside tests, this was confirmed and a new method for removal of large meshed devices was developed. This involved the commercially available Maslanka® biopsy forceps. The feasibility of this technique in vivo was tested in a pig model. During animal tests, using the Maslanka biopsy forceps it was possible to interventionally retrieve embolised Ceraflex and Occlutech devices of different sizes - 10, 16, 30, and 40 mm - into a 12-F sheath. CONCLUSION: It was impossible to retrieve Occlutech and Ceraflex devices larger than 16 mm into a large sheath in vivo and during benchside tests. However, this was feasible on the bench and in vivo using the Maslanka biopsy forceps even with the largest available devices.

Impact of the operative technique on mid- and long-term results following paediatric heart transplantation.

AIMS: The aim of this study is to evaluate and compare the impact of the bicaval technique versus the biatrial technique (by Lower and Shumway) in paediatric heart transplant patients. Only a few studies investigate this matter regarding the long-term outcome after paediatric heart transplantation. We compared the two surgical methods regarding survival, the necessity of pacemaker implantation. METHODS AND RESULTS: All 134 patients (aged <18 years) - (group-1) biatrial (n = 84), versus (group-2) bicaval (n = 50), who underwent heart transplantation between October 1988 and December 2021, were analysed. Freedom from events were estimated using the Kaplan-Meier method. Potential differences were analysed using the log rank test and Cox proportional hazard models. Mean ± standard deviation: Bypass time (per minutes) was higher in the group 1 as compared with group 2 (P = 0.050). Survival was not significantly different (P = 0.604) in either groups. Eighteen patients required permanent pacemaker implantation in the group 1 and only one patient required it in the group 2 (P = 0.001). CONCLUSIONS: Paediatric heart transplantation using bicaval technique results similar long-term survival compared with the biatrial technique. The incidence of atrial rhythm disorders was significantly higher in the biatrial group, requiring a higher frequency of pacemaker implantation in this group. As a results, the bicaval technique has replaced the biatrial technique in our centre.

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

AIM: Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. METHODS: In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. RESULTS: In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. CONCLUSION: While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

Endosteal bone storage in young adults born small for gestational age - a study using peripheral quantitative computed tomography.

OBJECTIVE: Poor growth early in life is associated with numerous adverse conditions including decreased bone mass. The aim is to investigate bone and body composition in young adults born small for gestational age (SGA). DESIGN: Observational study. PARTICIPANTS: A total of 76 young adults born SGA (34f) at a mean age of 19·68 ± 0·5 years were enrolled. METHOD: Bone mineral density (BMD), bone geometry and body composition were analysed using peripheral quantitative computed tomography. RESULTS: Adults born SGA had significantly lower z-score for height (-0.86 ± 0·87), weight (-0·61 ± 0·78) and BMI (-0·38 ± 1·04) as well as fat cross-sectional area (CSA) (-0·62 ± 0·80) compared with a healthy reference population (P < 0·05). Z-scores for trabecular and cortical BMD were normal. After correction for reduced height, z-scores for total CSA (-0·14 ± 1·11) and muscle CSA (-0·21 ± 0·99) were normal and medullary cavity (-0·71 ± 0·80) was reduced. Those with a birthweight of ≤ 1500 g had even lower height-corrected z-scores for medullary cavity (-1·12 ± 0·69) and total bone CSA (-0·58 ± 0·93) (P < 0·05). After adjustment for sex and weight, significant partial correlations were detectable between BMI at the age of 48 months and height-corrected z-scores for medullary cavity (r = 0·33, P = 0·020) and total CSA (r = 0·29, P = 0·04). CONCLUSION: Environmental factors early in life seem to influence bone geometry in adulthood. Young adults born SGA have normal total bone CSA but smaller medullary cavity. Those with very low birthweight, however, show compromised bone size development that may alter bone stability later in life.

Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography.

BACKGROUND: Intimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. METHODS AND RESULTS: We used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). CONCLUSION: In our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

Rationale and feasibility of transcatheter pulmonary valve implantation in small conduits with the Edwards Sapien valves.

BACKGROUND: Conduit dilatation above 110% and TPVI in conduits <16 mm is not recommended. However, if we want to reach normal values for RVOT diameters and diminish reintervention rates, pushing these boundaries is essential. METHODS: Analysis of subsequent patients who underwent TPVI with Edwards Sapien valves in conduits ≤16 mm between 2010 and 2020. RESULTS: In n = 33 cases median age was 13 years (5-20 y) and median weight 47 kg (15-91 kg). Preexisting RVOT grafts were n = 28 Contegra® conduits and n = 5 homografts (12 mm n = 15; 14 mm n = 11; 16 mm n = 7). Implanted were the Sapien (n = 8), Sapien XT (n = 10) and Sapien 3 valve (n = 15) with 20 mm (n = 4), 23 mm (n = 19), 26 mm (n = 9) and 29 mm (n = 1). Mean minimal RVOT diameter after TPVI was 22,7 ± 2,3 mm (18-30 mm) which is 150% of the mean minimal RVOT diameter before TPVI (15,1 ± 4,3 mm). Covered stents were used in n = 10 cases. Contained conduit rupture occurred in n = 7 cases (21%). Residual RVOT gradients of 5,7 ± 4,9 mmHg (0-18 mmHg) showed adequate RV unloading. CONCLUSION: TPVI could be performed successfully in all patients. Dilatation above 150% and a valve/conduit diameter ratio up to 2,4 were well tolerated. There was a considerable amount of conduit rupture but all were confined without further need for intervention or surgery.

Effect and safety of treatment with ACE-inhibitor Enalapril and ß-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy - a randomized, double-blind, placebo-controlled trial.

BACKGROUND: X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the ß-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. METHODS TRIAL DESIGN: Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. INCLUSION CRITERIA: DMD boys aged 10-14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS < 28%. Secondary: changes of a) LV-FS from baseline, b) blood pressure, c), heart rate and autonomic function in ECG and Holter-ECG, e) cardiac biomarkers and neurohumeral serum parameters, f) quality of life, and g) adverse events. RESULTS: From 3/2010 to 12/2013, 38 patients from 10 sites were centrally randomized after run-in, with 21 patients continuing enalapril and metoprolol medication and 17 patients receiving placebo. Until end of study 12/2015, LV-FS < 28% was reached in 6/21 versus 7/17 patients. Cox regression adjusted for LV-FS after run-in showed a statistically non-significant benefit for medication over placebo (hazard ratio: 0.38; 95% confidence interval: 0.12 to 1.22; p = 0.10). Analysis of secondary outcome measures revealed a time-dependent deterioration of LV-FS with no statistically significant differences between the two study arms. Blood pressure, maximal heart rate and mean-NN values were significantly lower at the end of open run-in treatment compared to baseline. Outcome analysis 19 months after randomization displayed significantly lower maximum heart rate and higher noradrenalin and renin values in the intervention group. No difference between treatments was seen for quality of life. As a single, yet important adverse event, the reversible deterioration of walking abilities of one DMD patient during the run-in period was observed. CONCLUSIONS: Our analysis of enalapril and metoprolol treatment in DMD patients with preserved left ventricular function is suggestive to delay the progression of the intrinsic cardiomyopathy to left ventricular failure, but did not reach statistical significance, probably due to insufficient sample size. CLINICAL TRIAL REGISTRATION: DRKS-number 00000115, EudraCT-number 2009-009871-36.

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.

Reinnervation after heart transplantation in children: results of short-time heart rate variability testing.

AIMS: To detect impairment in short-term heart rate variability (HRV) in children after heart and heart-lung transplantation (TX) as reported in adults. To assess vagal and sympathetic influence on the donor heart rate using frequency domain analysis of HRV. METHODS AND RESULTS: Measurement of short-term HRV was performed in 17 patients (age 16.9+/-3.6, 6.1+/-3.7 yr after TX) and 12 healthy controls (age 14.8+/-3.0 yr). Testing consisted of a resting phase of 15 minutes followed by a tilt phase of 45 min. All HRV parameters were significantly impaired in transplanted patients: RR interval (RRI) 717.2+/-122.5 m/s (controls 827+/-139.7, p<0.05), standard deviation of RR interval (RRI-SD) 20.1+/-15.5 (89.9+/-38.4, p<0.001), RRI at tilt 607.9+/-79.7 (654.0+/-104.7, NS), RRI-SD at tilt 21.1+/-20.0 (60.4+/-31.4, p<0.001). Low-frequency (LF)/High-frequency (HF) ratio of HRV showed prominent sympathetic influence in TX-patients (3.38+/-5.60 vs. 1.18+/-0.86, NS) increasing during tilting (5.91+/-8.36 vs. 4.74+/-5.27, NS). In subgroup analysis, 4 yr after TX an increasing sympathetic control of heart rate was observed. CONCLUSION: Short-term HRV is severely impaired in children after TX. If changes are observed, they are time-related and show increasing sympathetic influence starting from 4 yr after TX.