Stenting of native right ventricular outflow tract obstructions in symptomatic infants: histological work-up of explanted specimen.

BACKGROUND: Stenting of stenotic right ventricular outflow tract is a palliative measure for severely impaired small babies with Tetralogy of Fallot or similar pathologies. Little is known about the histopathological fate of the stents in the right ventricular outflow tract. METHODS: Eight samples of surgically removed right ventricular outflow tract stents were histologically analysed according to a predefined protocol. RESULTS: The most frequent diagnosis was Tetralogy of Fallot in four patients, pulmonary atresia with ventricular septal defect in two patients, double outlet right ventricle with pulmonary obstruction in one patient, and muscular obstruction of the right ventricular outflow tract in one patient with a syndromic disease with hypertrophic cardiomyopathy. Stents mean implantation duration was 444 days ranging from 105 to 1117 days (median 305.5 days). Histology revealed a variable degree of pseudointima formation consisting of fibromuscular cells surrounded by extracellular matrix. Four of the specimen contained adjacent myocardial tissue fragments, which showed regressive changes. Neither myocardium nor pseudointima tissue or tissue parts locally related to stent struts were infiltrated by inflammatory cells. CONCLUSIONS: Histological analysis after explantation of early-in-life implanted right ventricular outflow tract stents revealed predominantly pronounced neo-intimal proliferation with a visible endothelial layer, no signs of inflammation, and no prolapse of muscular tissue through the stent struts. Thus, implantation of stents in early life seems to interfere little with the hosts' immune system and might help to open up the right ventricular outflow tract by mechanical forces and regressive changes in adjacent muscular tissue.

Leitlinie Myokarditis der Deutschen Gesellschaft für Pädiatrische Kardiologie.

This consensus statement presents updated recommendations on diagnosis and treatment of myocarditis in childhood.

Recovery of Biventricular Function After Catheter Intervention or Surgery for Neonatal Coarctation of the Aorta.

Background: Critical coarctation of the aorta (CoA) is a life-threatening condition in newborns that is associated with biventricular dysfunction. Objectives: The purpose of this study was to examine clinical outcome and echocardiographic changes in isthmus diameter and biventricular function in newborns with critical CoA treated with balloon dilation/stent placement or surgery. Methods: This is a retrospective single-center cohort study of 26 consecutive neonates with isolated critical CoA, who underwent transcatheter intervention (balloon angioplasty/stent; n = 10) or surgical CoA-repair (n = 16) (2012-2021). Isthmus dimensions and biventricular function at baseline and at hospital discharge were examined by echocardiography, including strain analysis of systolic and diastolic function using 2-dimensional speckle tracking. Results: Cardiogenic shock at hospital admission was more frequent in the interventional vs the surgical cohort (50% vs 25% of neonates). Echocardiographic isthmus diameter increased with therapy by 0.9 ± 0.1 mm and 1.0 ± 0.1 mm, respectively. Severe systolic left ventricular (LV) dysfunction was more common in interventional patients pre-therapy (LV ejection fraction <50% in 90% vs 38% of surgical patients), resulting in strongly reduced longitudinal strain (LV: -12.3% vs -16.3%; right ventricle:-13.8% vs -16.1% in the interventional and surgical patients, respectively). Prior to hospital discharge, all 26 patients had full recovery of biventricular systolic function, including normalization of longitudinal, radial, and circumferential LV strain and longitudinal right ventricular free wall strain. Improvement of LV diastolic function by strain analysis was evident in both cohorts pre-hospital discharge. Conclusions: Initial treatment of isolated CoA by percutaneous transcatheter intervention or surgical repair results in recovery of biventricular systolic function, making transcatheter treatment particularly suitable as rescue therapy for neonates with critical CoA.

Long-term outcome of primary percutaneous stent angioplasty for pediatric posttransplantation portal vein stenosis.

This study aims to evaluate the long-term efficacy and reintervention rate after primary percutaneous portal vein stent angioplasty for portal vein stenosis (PVS) in pediatric liver transplantation (LT) recipients. From 2004 to 2020, a total of 470 pediatric LTs were performed in our center. All cases were screened for interventional PVS treatment and analyzed retrospectively. We identified 44 patients with 46 percutaneous angioplasties for posttransplantation PVS. The median interval from LT to percutaneous catheter intervention was 5 months (16 days-104 months) with a median follow-up (f/u) period after catheter intervention of 5.7 years (2-156 months). In 40 patients, an endovascular stent was placed as primary (n = 38) or secondary (n = 2) intervention. The median age at stent placement was 23 (6-179) months with a median weight of 10 kg (6-46 kg). Technical success and relief of PVS were achieved in all patients irrespective of age or weight. Adverse events occurred peri-interventionally in two patients and were resolved with standard care. All primary portal vein (PV) stents remained patent until the end of f/u. Reinterventions have been successfully performed in 10 patients for suspected or proven restenosis, resulting in a primary patency rate of 75% and an assisted patency rate of 25%. The median time to reintervention was 6.2 years (range 1-10 years). The need for reintervention was independent of age or weight at both transplantation and initial angioplasty as well as of additional risk factors due to portal hypertension. Percutaneous transhepatic PV stent angioplasty in children is safe and effective in all age groups, with excellent long-term patency. Primary stent angioplasty should be considered as first-line treatment for PVS after pediatric LT.

Interventional Bronchus Occlusion Using Amplatzer Devices - A Promising Treatment Option for Children with Persistent Air Leak.

BACKGROUND: Persistent air leak (PAL) is a severe complication of secondary spontaneous pneumothorax (SSP). Surgical interventions are usually successful when medical treatment fails, but can be associated with significant complications and loss of potentially recoverable lung parenchyma. METHODS: Retrospective analysis of efficacy and safety of interventional bronchus occlusions (IBO) using Amplatzer devices (ADs) in children with PAL secondary to SSP. RESULTS: Six patients (four males, 4-15 years of age) underwent IBO using ADs as treatment for PAL. Necrotizing pneumonia (NP) was the most common cause (n=4) of PAL. Three patients were previously healthy and three suffered from chronic lung disease. All patients required at least two chest tubes prior to the intervention for a duration of 15-43 days and all required oxygen or higher level of ventilatory support. In three cases, previous surgical interventions had been performed without success. All children improved after endobronchial intervention and we observed no associated complications. All chest tubes were removed within 5-25 days post IBO. In patients with PAL related to NP (n=4), occluders were removed bronchoscopically without re-occurrence of pneumothorax after a mean of 70 days (IQR: 46.5-94). CONCLUSION: IBO using ADs is a safe and valuable treatment option in children with PAL independent of disease severity and underlying cause. A major advantage of this procedure is its less invasiveness compared to surgery and the parenchyma- preserving approach.

Circulating Interleukin-7 in Human Pulmonary Arterial Hypertension.

Objectives: Interleukin-7 (IL-7) secures B cell maturation, regulatory T and natural killer (NK) cell survival, and homeostasis, all of which are important for beneficial immunomodulation in pulmonary arterial hypertension (PAH). However, the role and potential impact of IL-7, VEGF-C and the vascular injury markers ICAM-1, and VCAM-1 on the pathobiology and severity of PAH is unknown. Methods: EDTA blood was collected during cardiac catheterization from the superior vena cava (SVC), pulmonary artery (PA), and ascending aorta (AAO) in children with pulmonary hypertension (PH) [n = 10; 9.1 (3.9-18.5) years] and non-PH controls [n = 10; 10.5 (2.0-17.3) years]. Compartment-specific plasma concentrations of IL-7, VEGF-C, aldosterone, ICAM-1, and VCAM-1 were determined using Meso Scale Discovery's multi array technology and the LIAISON Aldosterone Assay. Results: Children with PH had approximately 50% lower IL-7 (p < 0.01) and 59% lower VEGF-C plasma levels (p < 0.001) in the SVC, PA, and AAO versus non-PH controls. IL-7 and VEGF-C concentrations negatively correlated with the pulmonary vascular resistance (PVR)/systemic vascular resistance (SVR) ratio (rho = -0.51 and r = -0.62, respectively). Central-venous IL-7 strongly positively correlated with VEGF-C (r = 0.81). Most patients had a step down in ICAM-1 and VCAM-1 plasma concentrations across the pulmonary circulation and both ICAM-1 and VCAM-1 transpulmonary gradients negatively correlated with invasive hemodynamics. Conclusion: This manuscript is the first report on decreased circulating IL-7 and VEGF-C plasma concentrations in human PAH and their inverse correlations with invasive surrogates of PAH severity. Additional and larger studies are needed to explore the role of the immune-modulatory IL-7 and VEGF-C in pediatric and adult PAH.

Valve-sparing aortic root replacement in adult patients with congenital heart disease.

OBJECTIVES: Aortic root dilatation is frequently observed in patients with congenital heart defects (CHD), but has received little attention in terms of developing a best practice approach for treatment. In this study, we analysed our experience with aortic valve-sparing root replacement in patients following previous operations to repair CHD. METHODS: In this study, we included 7 patients with a history of previous surgery for CHD who underwent aortic valve-sparing operations. The underlying initial defects were tetralogy of Fallot (n = 3), transposition of great arteries (n = 2), coarctation of the aorta (n = 1), and pulmonary atresia with ventricle septum defect (n = 1). The patients' age ranged from 20 to 40 years (mean age 31 ± 6 years). RESULTS: David reimplantation was performed in 6 patients and a Yacoub remodelling procedure was performed in 1 patient. Four patients underwent simultaneous pulmonary valve replacement. The mean interval between the corrective procedure for CHD and the aortic valve-sparing surgery was 26 ± 3 years. There was no operative or late mortality. The patient with transposition of great arteries following an arterial switch operation was re-operated 25 months after the valve-sparing procedure due to severe aortic regurgitation. In all other patients, the aortic valve regurgitation was mild or negligible at the latest follow-up (mean 8.7 years, range 2.1-15.1 years). CONCLUSIONS: Valve-sparing aortic root replacement resulted in good aortic valve function during the first decade of observation in 6 of 7 patients. This approach can offer a viable alternative to root replacement with mechanical or biological prostheses in selected patients following CHD repair.

Trans-right ventricle and transpulmonary metabolite gradients in human pulmonary arterial hypertension.

OBJECTIVE: While metabolic dysfunction occurs in several pulmonary arterial hypertension (PAH) animal models, its role in the human hypertensive right ventricle (RV) and lung is not well characterised. We investigated whether circulating metabolite concentrations differ across the hypertensive RV and/or the pulmonary circulation, and correlate with invasive haemodynamic/echocardiographic variables in patients with PAH. METHODS: Prospective EDTA blood collection during cardiac catheterisation from the superior vena cava (SVC), pulmonary artery (PA) and ascending aorta (AAO) in children with PAH (no shunt) and non-PAH controls (Con), followed by unbiased screens of 427 metabolites and 836 lipid species and fatty acids (FAs) in blood plasma (Metabolon and Lipidyzer platforms). Metabolite concentrations were correlated with echocardiographic and invasive haemodynamic variables. RESULTS: Metabolomics/lipidomics analysis of differential concentrations (false discovery rate<0.15) revealed several metabolite gradients in the trans-RV (PA vs SVC) setting. Notably, dicarboxylic acids (eg, octadecanedioate: fold change (FC)_Control=0.77, FC_PAH=1.09, p value=0.044) and acylcarnitines (eg, stearoylcarnitine: FC_Control=0.74, FC_PAH=1.21, p value=0.058). Differentially regulated metabolites were also found in the transpulmonary (AAO vs PA) setting and between-group comparisons, that is, in the SVC (PAH-SVC vs Con-SVC), PA and AAO. Importantly, the differential PAH-metabolite concentrations correlated with numerous outcome-relevant variables (e.g., tricuspid annular plane systolic excursion, pulmonary vascular resistance). CONCLUSIONS: In PAH, trans-RV and transpulmonary metabolite gradients exist and correlate with haemodynamic determinants of clinical outcome. The most pronounced differential trans-RV gradients are known to be involved in lipid metabolism/lipotoxicity, that is, accumulation of long chain FAs. The identified accumulation of dicarboxylic acids and acylcarnitines likely indicates impaired ß-oxidation in the hypertensive RV and represents emerging biomarkers and therapeutic targets in PAH.

Trans-Right-Ventricle and Transpulmonary MicroRNA Gradients in Human Pulmonary Arterial Hypertension.

OBJECTIVES: We investigated whether concentrations of circulating microRNAs differ across the hypertensive right ventricle and pulmonary circulation, and correlate with hemodynamic/echocardiographic variables in patients with pulmonary arterial hypertension versus nonpulmonary arterial hypertension controls. DESIGN: Prospective blood collection during cardiac catheterization from the superior vena cava, pulmonary artery, and ascending aorta in 12 children with pulmonary arterial hypertension and nine matched nonpulmonary arterial hypertension controls, followed by an unbiased quantitative polymerase chain reaction array screen for 754 microRNAs in plasma. SETTING: Children's hospital at a medical school. PATIENTS: Twelve pulmonary arterial hypertension patients included as follows: idiopathic pulmonary arterial hypertension (5), pulmonary arterial hypertension (2), pulmonary arterial hypertension-repaired congenital heart disease (4), portopulmonary pulmonary hypertension (1). Nine nonpulmonary arterial hypertension controls included as follows: mild/moderate left ventricular outflow tract obstruction (7), mediastinal teratoma (1), portal vein stenosis (1). INTERVENTIONS: Standard pulmonary arterial hypertension treatment. MEASUREMENTS AND MAIN RESULTS: Analysis of differential concentrations (false discovery rate < 0.05) revealed two trans-right-ventricle microRNA gradients (pulmonary artery vs superior vena cava): miR-193a-5p (step-up in pulmonary arterial hypertension and step-down in control) and miR-423-5p (step-down in pulmonary arterial hypertension and step-up in control) and two transpulmonary microRNA gradients (ascending aorta vs pulmonary artery): miR-26b-5p (step-down only in control) and miR-331-3p (step-up only in pulmonary arterial hypertension). Between-group comparison revealed miR-29a-3p, miR-26a-5p, miR-590-5p, and miR-200c-3p as upregulated in pulmonary arterial hypertension-superior vena cava and miR-99a-5p as downregulated in pulmonary arterial hypertension-pulmonary artery. The differential microRNA-concentrations correlated with prognostic hemodynamic variables (pulmonary vascular resistance, tricuspid annular plane systolic excursion, etc.). CONCLUSIONS: We identified for the first time in human disease (pulmonary arterial hypertension) trans-right-ventricle and transpulmonary microRNA gradients in blood plasma. Several of these microRNAs regulate transcripts that drive cardiac remodeling and pulmonary arterial hypertension and are now emerging as epigenetic pulmonary arterial hypertension biomarkers and targets for therapy.

A word of caution: diabolic behaviour of AndraStents®: inflation of supporting balloon leads to "diabolo"-misconfiguration of the stent.

AIMS: Transcatheter implantation of pulmonary balloon-expandable stent-valves requires pre-stenting of the right ventricular outflow tract with large calibre stents. To increase awareness of the associated risks of this part of transcatheter pulmonary valve replacement therapy, we report potential fatal complications during the implantation of AndraStents® in the right ventricular outflow tract in six cases from five different European institutions and their management. METHOD AND RESULT: We present a retrospective case series analysis looking at the time period from 2013 to 2018. Of 127 AndraStents® implanted in the right ventricular outflow tract, in six patients, age from 13 to 71 years, a misconfiguration of the AndraStent® occurred forming a "diabolo"-configuration. During inflation of the balloon, the stent showed extreme "dog-boning", an expansion of the stent at both ends with the middle part remaining unexpanded. This led to rupture of the balloon and loss of manoeuvrability in four patients. Out of the total six cases, in four patients the stent was eventually expanded with high-pressure balloons, and in one case the stent was surgically retrieved. In one patient, in whom a percutaneous retrieval of the embolised stent was attempted, a fatal bleeding occurred. CONCLUSIONS: Pre-stenting of the right ventricular outflow tract by AndraStents® can lead to misconfiguration of the stent with potentially fatal complications. Rescue strategies of misconfigured stents include stent inflation and placement with high pressure non-compliant balloons or surgical backup. Interventional retrieval measures of AndraStents® cannot be advised.

Double semilunar valve replacement in complex congenital heart disease using decellularized homografts.

OBJECTIVES: Patients with complex congenital heart disease often require multiple reoperations, resulting in increased rates of operative morbidity and mortality. Decellularized heart valves (DHVs) have led to reduced reoperation rates compared with current other valve substitutes when used for pulmonary valve replacement and have also shown very auspicious early results in aortic valve replacement. The aim of the work was to analyse the outcome of a single-stage decellularized valve implantation in the aortic and pulmonary position. METHODS: A prospective follow-up of all patients who received a single-stage double semilunar valve replacement using DHV at our institution. RESULTS: Since 2011, 5 patients underwent combined semilunar valve replacement with DHV at our institution: two following a Ross procedure (31-year-old man and 38-year-old woman) and 3 after repair of the truncus arteriosus communis (2-year-old boy and 11-year-old and 16-year-old girls). All patients had undergone previous surgery. The Ross patients had preceding valve procedures, and the patients with truncus arteriosus communis had undergone 1 repair and subsequent operative procedures. Despite challenging operations (median bypass time 346 min, range 275-477 min; median cross-clamp time 229 min, range 140-307 min), there was no perioperative mortality or reoperations. Four of the patients were extubated within 24 h, and the other patient was extubated on postoperative day 2. During follow-up, a good semilunar valve and biventricular heart function was present in all 5 patients, and the New York Heart Association functional class was I for all the patients at the time of their latest follow-up (median 31 months, range 8-82 months). The mean echocardiographic gradient of decellularized aortic homografts was 5.4 ± 3.2 mmHg and 11.6 ± 4.2 mmHg for the decellularized pulmonary homografts. Valvular regurgitation was 0 or 0-I for all DHVs. CONCLUSIONS: A single-stage double semilunar valve replacement with DHV has shown promising early results in these 5 very complex cases, providing an additional surgical option after multiple preceding valve procedures in young patients.

Feasibility, safety and diagnostic impact of endomyocardial biopsies for the diagnosis of myocardial disease in children and adolescents.

AIMS: Endomyocardial biopsies (EMBs) are performed infrequently in children owing to significant past complication rates and controversial discussions about the therapeutic value of results. The objective of this study was to investigate the safety and feasibility of EMBs for suspected myocardial disease in relation to their clinical value. METHODS AND RESULTS: We performed a retrospective multicentre review of the Working Group for Interventional Cardiology of the German Society for Paediatric Cardiology. During three consecutive years, 206 EMBs (84 female/mean age 8.95±6.62 years) were performed and analysed at 15 heart centres. In the majority of cases, biopsies were taken from the right ventricle (RV/89.8%; p<0.001). The overall complication rate was 9.7%, whereas major complications occurred in only 0.97% of cases. Risk factors associated with a higher complication rate were biopsy during the first year of life (20.5%) and from the left ventricle (31.1%) (p<0.05). There was no procedure-related mortality. Treatment was changed in 18.0% of cases based on biopsy results. CONCLUSIONS: Today, endomyocardial biopsies in older children with suspected myocardial disease can be performed safely with a low risk of major complications and mortality, whereas the risk of complications if the biopsy is carried out in the first year of life or taken from the left ventricle remains high.

First-in-child use of the oral soluble guanylate cyclase stimulator riociguat in pulmonary arterial hypertension.

Riociguat has been approved for use in adults with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. No clinical data on its therapeutic use in children with PAH are currently available. We report the case of a now four-year-old boy who initially presented at the age of 10 months with suprasystemic pulmonary hypertension (PH) and right ventricular (RV) failure, vomiting, peripheral cyanosis, and failure to thrive. Cardiac catheterization revealed severe PAH. At radiologic suspicion of interstitial lung disease, repeated CT scan and an open lung biopsy were performed but could not clarify the entity of PAH. Given the demonstrated vasoreactivity, the boy was started on the calcium channel blocker amlodipine, in combination with the endothelin-1 receptor antagonist bosentan. Two years later, based on persistently systemic PAH with lost vasoreactivity, PAH therapy was changed to bosentan and phosphodiesterase-5 inhibitor sildenafil. No significant improvement on the aforementioned therapy was seen, so that the patient was referred to our institution. Invasive hemodynamic evaluation showed suprasystemic PAH and marked acute vasoreactivity (PAP 127/103/83 mmHg, PVRi 23.48 WU·m2 and PVR/SVR ratio 1.59 at baseline vs. PVRi 5.89 WU·m2 and PVR/SVR ratio 0.93 under O2/NO). Subsequently, we switched the patient from sildenafil to riociguat. After six months on bosentan/riociguat, the patient showed a marked decrease in PVR/SVR and transpulmonary pressure gradients, in RV hypertrophy, PA acceleration time, and left ventricular-eccentricity index. Clinically, the patient improved in pediatric functional class from 2/3 to 1. In conclusion, off-label use of oral riociguat may be considered in selected children with severe PAH.

First-in-child use of the oral selective prostacyclin IP receptor agonist selexipag in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. Selexipag is a selective prostacyclin receptor agonist with vasodilatory, anti-proliferative, anti-inflammatory, and pro-angiogenic properties. However, no clinical data on its therapeutic use in children with PAH are currently available. Here, we report the case of a 12-year-old girl who presented in World Health Organization (WHO) functional class III and right ventricular (RV) failure with recurrent syncope, dizziness, and progressive fatigue for two years. Cardiac catheterization revealed severe precapillary PAH: mean right atrial pressure (RAP) = 10-13 mmHg, right ventricular end-diastolic pressure (RVEDP) = 13 mmHg, left ventricular end-diastolic pressure (LVEDP) = 7 mmHg, mean pulmonary arterial pressure (PAP) = 81 mmHg, and mean aorta ascendens pressure = 89 mmHg. The pulmonary vascular resistance index (PVRi) was 25.2 WU × m2. An oral combination therapy was started with a phosphodiesterase type 5 inhibitor (sildenafil 3 × 20 mg) and an endothelin-1 receptor antagonist (bosentan 2 × 62.5 mg). No significant clinical/hemodynamic improvement was seen after nine months of dual therapy, so that the patient was transferred to our institution. We agreed upon the off-label add-on use of oral selexipag. Within ten days, we up-titrated selexipag to a final (max. adult) dose of 1600 mcg twice daily. After six months, the patient had: (1) decrease in PVR index, pulmonary artery acceleration time, RAP, RVEDP, right atrial/RV size; (2) re-gain of vasoreactivity; and (3) improvement of cardiac index, 6-minute walking distance, functional class, body weight, and CAMPHOR score. Our encouraging results suggest the consideration of off-label use of oral selexipag in children with severe PAH, preferably in a protocol-driven prospective study.

Interventional VSD-Closure with the Nit-Occlud® Lê VSD-Coil in 110 Patients: Early and Midterm Results of the EUREVECO-Registry.

In August 2010, the Nit-Occlud® Lê (EUREVECO) became available for transcatheter coil occlusion of ventricular septal defects (VSDs). Retrospective European Registry for VSD Closure using the Nit-Occlud® Lê-VSD-Coil; analysis of the feasibility, results, safety and follow-up of VSD-closure over a 3-year period in 18 European centers. In 102 of 111 patients (female 66), successful VSD closure was performed (mean age 8.2 years, mean weight 28.82 kg), 81 perimembranous VSDs (48 with aneurysm), 30 muscular VSDs, mean procedure time was 121.1 min, and mean fluoroscopy time was 26.3 min. Short- and midterm term follow-up was possible in 100/102 patients, there was 1 embolization and 1 explantation after 24 months. Immediate complete closure occurred in 49 of 101 patients (48.5%), trivial residual shunt was present in 51 (50.0%), closure rate was 95% after 6 months and 97% after 1 year. Out of the 102 patients, there were 2 severe complications (1.8%) (1 severe hemolysis, 1 embolization) and 8 moderate/transient (=7.2%) including 1 transient AV block. During a mean follow-up period of 31.3 months (range 24-48) and a total follow-up time of 224.75 patient years, no further problems occurred. VSD closure with the Nit-Occlud® Lê VSD coil is feasible and safe with a minimal risk of severe side effects. The long-term effects and safety require further clinical follow-up studies.

Feasibility and Accuracy of Cardiac Right-to-Left-Shunt Detection in Children by New Transpulmonary Ultrasound Dilution Method.

Transpulmonary ultrasound dilution (TPUD) method, a novel indicator dilution (ID) technique for cardiac output measurement, detects and quantifies shunts, both in children and adults. However, its accuracy and reproducibility in cardiac right-to-left-shunt (RLS) detection have not been investigated. In a prospective observational study, we assessed the validity of TPUD algorithm for RLS detection in children with congenital heart disease (CHD) and proven RLS in comparison with controls without shunts between February 2010 and October 2011. As TPUD algorithm was unknown, we tested ID curve morphology, appearance time (AT) and central blood volume index (CBVI) as diagnostic criteria. TPUD identified RLS correctly in all 16 RLS subjects [median age (range): 18 months (1 month-15 years 6 months)] and excluded RLS in all 26 controls [74 months (8 months to 17 years 4 months)]. AT was significantly shorter in RLS (P < 0.05). Applying only AT (93.8 % sensitivity, 92.3 % specificity), RLS can be detected by shortening of ≥1.69 s of normally expected AT. RLS ID curves were subdivided into four morphological categories: (I) hump-on-upslope (n = 5); (II) double-hump (n = 3); (III) pseudonormal (n = 3); (IV) abnormal width (n = 5). No correlation was found between specific type of CHD and RLS categories. CBVI measurements were significantly smaller in RLS categories I-III than in controls (P < 0.05). TPUD appears to be a valid method for cardiac RLS detection. Shortened AT and low CBVI are reliable parameters for RLS identification. RLS categories have specific implications for cardiac output, blood volume and RLS fraction measurements. TPUD is valuable to monitor shunt direction and magnitude to optimise haemodynamic and respiratory therapy.

NT-proBNP Indicates Left Ventricular Impairment and Adverse Clinical Outcome in Patients With Tetralogy of Fallot and Pulmonary Regurgitation.

BACKGROUND: The goal of this study was to interrelate N-terminal B-type natriuretic peptide (NT-proBNP) levels and cardiac magnetic resonance imaging-derived ventricular function, mass, and volumes in adults with pulmonary regurgitation after Fallot repair and to evaluate the prognostic relevance of these parameters regarding adverse clinical outcome. METHODS: Eighty-one patients (aged 26.3 ± 7.4 years; male sex, 45.7%; New York Heart Association class I, 72.8%; pulmonary valve velocity, < 3 m/s) were included. At baseline cardiac magnetic resonance imaging and NT-proBNP measurements were performed. RESULTS: During a mean observation time of 6.9 ± 2.6 years, 13 patients (16.1%) had sustained supraventricular arrhythmias or heart failure (2.4 per 100 patient-years). Multivariate Cox analysis identified NT-proBNP, left ventricular (LV) end-systolic volume index and LV ejection fraction, right ventricular (RV) end-diastolic volume index, and tricuspid regurgitation as independent predictors of adverse events. NT-proBNP correlated with LV but not with RV parameters. In receiver operating characteristic curve analysis using significant variables of the multivariate analysis, NT-proBNP was superior to all other parameters to detect patients at risk (area under the curve [AUC], 0.873; 95% confidence interval, 0.772-0.974). LV end-systolic volume index (AUC, 0.734), RV end-diastolic volume index (AUC, 0.645) und tricuspid regurgitation (AUC, 0.747) showed lower diagnostic accuracy. CONCLUSIONS: Even in mildly symptomatic patients with pulmonary regurgitation after Fallot repair NT-proBNP is a strong predictor of adverse outcome. It is rather associated with LV but not with RV impairment. In severe pulmonary regurgitation an increase in the level of NT-proBNP and LV impairment seem to provide additional useful information for the timing of pulmonary valve replacement.

Decellularized aortic homografts for aortic valve and aorta ascendens replacement.

OBJECTIVES: The choice of valve prosthesis for aortic valve replacement (AVR) in young patients is challenging. Decellularized pulmonary homografts (DPHs) have shown excellent results in pulmonary position. Here, we report our early clinical results using decellularized aortic valve homografts (DAHs) for AVR in children and mainly young adults. METHODS: This prospective observational study included all 69 patients (44 males) operated from February 2008 to September 2015, with a mean age of 19.7 ± 14.6 years (range 0.2-65.3 years). In 18 patients, a long DAH was used for simultaneous replacement of a dilated ascending aorta as an extended aortic root replacement (EARR). Four patients received simultaneous pulmonary valve replacement with DPH. RESULTS: Thirty-nine patients (57%) had a total of 62 previous operations. The mean aortic cross-clamp time in isolated cases was 129 ± 41 min. There was 1 conduit-unrelated death. The mean DAH diameter was 22.4 ± 3.7 mm (range, 10-29 mm), the average peak gradient was 14 ± 15 mmHg and the mean aortic regurgitation grade (0.5 = trace, 1 = mild) was 0.6 ± 0.5. The mean effective orifice area (EOA) of 25 mm diameter DAH was 3.07 ± 0.7 cm(2). DAH annulus z-values were 1.1 ± 1.1 at implantation and 0.7 ± 1.3 at the last follow-up. The last mean left ventricle ejection fraction and left ventricle end diastolic volume index was 63 ± 7% and 78 ± 16 ml/m(2) body surface area, respectively. To date, no dilatation has been observed at any level of the graft during follow-up; however, the observational time is short (140.4 years in total, mean 2.0 ± 1.8 years, maximum 7.6 years). One small DAH (10 mm at implantation) had to be explanted due to subvalvular stenosis and developing regurgitation after 4.5 years and was replaced with a 17 mm DAH without complication. No calcification of the explanted graft was noticed intraoperatively and after histological analysis, which revealed extensive recellularization without inflammation. CONCLUSIONS: DAHs withstand systemic circulation, provide outstanding EOA and appear as an alternative to conventional grafts for AVR in young patients. EARR using DAH is a further option in aortic valve disease associated with aorta ascendens dilatation as it avoids the use of any prosthetic material.