Percutaneous pulmonary valve implantation (PPVI) in non-obstructive right ventricular outflow tract: limitations and mid-term outcomes.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) has been established as a safe and effective alternative to surgery treating patients with a failing pulmonary valve conduit. Nevertheless, the majority of patients in need of a valve have a native, non-obstructive right ventricular outflow tract (RVOT). The current approved stent-valves have a balloon-expandable design. Pre-stenting of the RVOT to create a landing zone and also protect the valve stability is usually mandatory; large, non-obstructive RVOTs need pre-stenting to reduce the RVOT-diameter for a balloon-expandable valve implantation. METHODS: A retrospective study design was used to analyze the medium-term outcome after PPVI in a series of 26 patients with native or reconstructed RVOT. RESULTS: PPVI was successfully performed in all, but 1 (96%). Within the follow-up of a minimum of 2 years, the percutaneous implanted valves remained competent; a significant pressure gradient was not detected. Furthermore, no PPVI-related complications such as endocarditis, migration or stent fractures were observed. The electrocardiogram at rest, in particular the QRS duration remained unchanged immediate post-PPVI as well as at medium-term follow-up of 24 months. However, ventricular arrhythmias were documented in 3 patients (11.5%); all patients were successfully treated with antiarrhythmic drugs, utilizing metoprolol. A trial of an invasive catheter based RVOT-ablation in one remained unsuccessful; pre-stented RVOT did not allow a successful intervention. CONCLUSIONS: Medium-term follow-up showed excellent results of the mechanical valve function. PPVI utilizing balloon-expandable stent-valves in a native RVOT remains an off-label use. Despite our encouraging results, advanced manipulations of the patched or native RVOT might be associated with significant ventricular arrhythmias. There is a need for less invasive RVOT reduction devices.

Reduced Biventricular Volumes and Myocardial Dysfunction Long-term After Pediatric Heart Transplantation Assessed by CMR.

BACKGROUND: Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function. METHODS: Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y). RESULTS: LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (ß = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance. CONCLUSIONS: Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

Percutaneous closure of perimembranous ventricular septal defects utilizing almost ideal Amplatzer Duct Occluder II: Why limitation in sizes?

AIM: The purpose of this study is to describe the special aspects of perimembranous ventricular septal defects (pmVSD) closure by utilizing Amplatzer Duct Occluder II (ADO II) devices with a rational request for bigger ADO-II sizes, based on our experience in transcatheter device closure of pmVSD. METHODS AND RESULTS: At our institution, placement of an ADO II device was used in 15 patients with pmVSD; the patients' age ranged between 6 months and 20 years. The indications for closure were CHF (n = 4), hemodynamically significant shunt (n = 7), tricuspid regurgitation (n = 3), and high risk for infective endocarditis (n = 2), respectively. The location of the VSD was infracristal in 13 patients, supracristal in 1, and a postsurgical Gerbode VSD in another one. Implantation of the device was successfully performed without embolization, any evidence of an AV block, or other conductance abnormalities during implantation and follow-up in the mean of 2.5 years (range 2 months-6.5 years). CONCLUSIONS: Transcatheter closure of a pmVSD with ADO II is feasible in all pediatric and young adult age groups, by considering the device diameter limitations. The off-label use of ADO II implantation seems to be safe for VSDs closure up to 6 mm of size and feasible for various locations including unusual morphology such as postsurgical Gerbode defect.

Fulminant cytomegalovirus myocarditis in an infant with concomitant large atrial and ventricular septal defects: medical intervention strategy for functional cardiac regeneration.

A cytomegalovirus-associated heart failure in a young infant with atrial and ventricular septal defects is reported in this case report. The patient recovered by an anti-congestive and anti-viral therapy with an extra percutaneous transcatheter treatment strategy. In the context of bi-ventricular predominant right heart failure associated with supra-systemic pulmonary hypertension, the already closed arterial duct was re-opened and stented to unload the right ventricle and thereby augment the systemic blood flow. Either the left-to-right shunting atrial septal defect or bi-directional shunting ventricular septal defect was involved in the disease process and was not able to avoid global heart failure. After clinical improvement, the stented duct was shunted left-to-right and was occluded with an ADO-II-AS. During the same procedure the atrial septal defect was closed with an Amplatzer-ASD occluder, while the peri-membranous ventricular septal defect was closed with an ADO-II occluder 2 months later.

Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: palliative treatment with a rapamycin analog.

Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and malignant HCM. In the boy, progressive HCM was diagnosed during the first week of life and a diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in PTPN11. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated enhanced Akt/mTOR pathway activity. Because of the patient's critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9,600 to <1,000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could principally be feasible for infantile NSML. The preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling.

Balloon angioplasty of the bilateral renal arteries by Takayasu arteritis with a paclitaxel-eluting balloon.

We report about a 12-year-old girl who presented with a blood pressure difference between the extremities with the suspicion of an aortic coarctation. After imaging and laboratory tests, the diagnosis of Takayasu arteritis was made. Owing to persistent arterial hypertension despite medical treatment, we initiated a treatment with a balloon angioplasty of the renal arteries with an eluting balloon.

EBV load in whole blood correlates with LMP2 gene expression after pediatric heart transplantation or allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Epstein-Barr virus (EBV) is associated with posttransplant lymphoproliferative disease (PTLD), and EBV load measurement is an important tool to monitor transplant patients. Although EBV DNA quantification has high sensitivity to identify patients at risk for PTLD, it lacks specificity. We examined whether EBV gene expression in peripheral B cells can increase specificity or correlates with EBV load. METHODS: Altogether, 220 blood samples were collected from pediatric patients after heart transplantation (HTx, n=57), renal transplantation (n=1), or hematopoietic stem cell transplantation (n=21). In each blood sample, EBV load was quantified in whole blood, plasma, and B cells using qPCR. Additionally EBV gene expression (EBNA2, LMP1, LMP2, and BZLF1) in B cells was analyzed using relative quantitative RT-qPCR. RESULTS: Positive expression of at least one gene was detected in 112 (51%) of 220 samples. Patients with PTLD or chronic high viral loads after solid organ transplantation exhibited no homogeneous EBV gene expression pattern. Expression of LMP2, LMP1, or EBNA2 was only observed when EBV load exceeded 1000 copies/mL. A high correlation between the level of LMP2 expression and EBV load in B cells or whole blood was observed (ρ=0.72 or ρ=0.6, HTx population). CONCLUSION: The analysis of EBV gene expression in peripheral B cells does not provide additional information about patients' risk of developing PTLD. As EBV load in whole blood correlates well with LMP2 gene expression in EBV-infected B cells, EBV DNA quantification in whole blood alone seems to be a sufficient tool to monitor these patients.

Renal function in children with heart transplantation after switching to CNI-free immunosuppression with everolimus.

Renal impairment because of CNI contributes to long-term morbidity. Therefore, CNI avoiding or sparing treatment strategies are important. In this article, we describe the results of a CNI-free treatment protocol with regard to recovery of renal function. Twenty-eight patients with heart transplantation were switched from CNI regimen to everolimus and mycophenolate, when cGFR was <75 mL/min/1.73 m(2). In all patients, CNI was stopped, when everolimus trough levels of 5-8 ng/L were achieved. Serum creatinine and cGFR were determined before and after 6 and 12 months. Median serum creatinine decreased from 1.2 mg/dL (range 0.7-3.7) before everolimus to 1.0 (range 0.6-1.8) and 1.0 (range 0.5-1.9) mg/dL after 6 and 12 months. Median cGFR was 47.81 (range 18.3-72.6) mL/min/1.73 m(2) before everolimus and 63.1 (range 37.8-108.7) mL/min/1.73 m(2) at six months and 64.8 (range 37.7-106.6) mL/min/1.73 m(2) after 12 months. All changes from baseline to six and 12 months were statistically significant (p < 0.05). Adverse events were infections (n = 3) and rejections (n = 3). Therapy was discontinued in four patients. Conversion to CNI-free immunosuppression resulted in significant improvements of renal function within six months of CNI withdrawal. Side effects are common. However, more studies are required to demonstrate the effectiveness in children.