Univentricular Congenital Heart Disease Research Articles

Heart Transplantation Following Fontan Failure: Long-Term Survival Analysis.

Objectives: Fontan circulation presents significant challenges for patients with congenital heart disease, often necessitating heart transplantation (HTX) due to deteriorating functionality across multiple organ systems. However, the impact of prior Fontan palliation on HTX outcomes remains poorly understood, with early mortality rates suggesting a heightened risk. The aim of our study is to evaluate the long-term results after heart transplantation in patients with univentricular congenital heart disease previously palliated with Fontan circulation. Methods: A retrospective analysis was conducted on patients who underwent HTX for congenital heart disease. Patients were categorized into two groups based on the pre-HTX circulation pathway: the Failing Fontan Group (FFG) and the Biventricular Congenital Group (BCG). Data were collected from patients between 1987 and 2018. Early and late outcomes, including survival rates, were assessed and critically analyzed. Results: Of the 66 patients, 29 (43%) had a failing Fontan palliation (FFG), and 37 had biventricular congenital diseases (BCG) before heart transplantation. Early mortality (30-day) was not statistically different between the two group. The overall survival rate was 82.6 ± 13.9% at 1 year, 79.0 ± 14.9% at 5 years, 67.2 ± 17.6% at 10 years and 63.2 ± 18.2 ± at 15 years for the FFG, and 86.1 ±11.4% at 1 year, 79.5 ± 13.7% at 5 years, 75.7 ± 14.9% at 10 years, 75.7 ± 14.9% at 15 years for the BCG, with no statistically significant difference (Mantel Cox p value: 0.69, 0.89, 0.52 and 0.39, respectively). Regarding Cox-regression analysis, the long-term survival rate was not affected either by previous Fontan surgery or by the era of heart transplantation (before vs. after the year 2000). Conclusions: Although heart transplantation after Fontan palliation showed a higher risk in the early post-operative period, the medium- and long-term survival rates are comparable with biventricular circulation patients. Despite the failing Fontan patients being a challenging set of candidates for transplantation, it is a reasonable option in their treatment.

Long-term outcomes after heart transplantation in adult patients with univentricular versus biventricular congenital heart disease.

Heart transplantation (HT) is the only life-extending therapy in adults with congenital heart disease (CHD) and end-stage heart failure. HT is considered at high risk in complex CHD given the anatomical complexity and past medical history. Little is known about long-term outcomes after HT in these patients. We aimed to evaluate early and long-term outcomes after HT in adult patients with univentricular versus biventricular CHD. This multicentre retrospective cohort study included all adult CHD patients who underwent HT between 1988 and 2021 in 3 tertiary centres. Factors associated with early (<30 days) and conditional long-term survival were assessed in the entire cohort. Over a mean follow-up of 10.1 ± 7.8 years, 149 patients were included, of whom 55 (36.9%) had univentricular CHD. Sixty-four patients died during follow-up including 47 deaths before discharge from hospital. In multivariable analysis, univentricular physiology and female recipient gender were independently associated with a higher risk of early mortality (odds ratio 2.99; 95% confidence interval [1.33-6.74] and odds ratio 2.76; 95% confidence interval [1.23-6.20], respectively). For patients who survived the early period, conditional long-term survival was excellent for both groups and was not different between 2 groups (P = 0.764). Adult CHD patients have a high incidence of overall mortality due to a high rate of early mortality. Univentricular physiology was associated with a significant increased risk of early death compared to biventricular physiology. However, late mortality was excellent and no longer different between the 2 physiologies.

Review of pediatric combined heart-liver transplantation: A roadmap to success.

Combined heart-liver transplantation (CHLT) is a promising technique to address end stage organ failure in patients with concomitant heart failure and chronic liver disease. While most experience with CHLT has involved adult patients, the expanding population of children born with univentricular congenital heart disease who underwent the Fontan procedure and develop Fontan-associated liver disease (FALD) has emerged as a growing indication for pediatric CHLT. Currently, CHLT is performed at a select subset of experienced transplant centers, especially in the pediatric population. While technically demanding, CHLT may offer survival benefit when compared to heart transplant alone with decreased rejection of both synchronous allografts and equivalent outcomes with respect to waitlist time and post-operative complications. Limitations in the technique can be attributed to need for an appropriate multidisciplinary care center, challenges with donor organ availability and allocation, and the complexity associated with patient selection and peri-operative management. In this review, we summarize the history of CHLT, discuss patient selection, and highlight key facets of peri-operative care in the pediatric population.

Long-term neurodevelopmental outcome and serial cerebral magnetic resonance imaging assessment in Fontan patients at school age.

Children with univentricular congenital heart disease undergoing staged surgical palliation are at risk for impaired neurodevelopmental (ND) outcome. Little is known about the long-term effects on brain growth until school age. In a prospective two-centre study, consecutive patients undergoing stage I (Hybrid or Norwood) to stage III (Fontan procedure) were evaluated by 2 serial cerebral magnetic resonance imaging examinations, somatic growth and ND testing before Fontan procedure at 2 years of age (Bayley-III) and after Fontan at 6-8 years of age (Wechsler Intelligence Scale for Children-third edition). Magnetic resonance imaging findings were compared with 8 healthy controls. Medical and sociodemographic characteristics were documented and related to cerebral and ND findings. We examined 33 children (16 female) at a mean age of 2.3 (0.35) and 6.8 (± 0.7) years. The mean Bayley-III cognitive scales were 99.1 (9.9), language scales 98.4 (11.9) and motor scales 98.5 (13.8) at the first examination. Follow-up at school age showed a mean total IQ of 86.7 (13.6). The rate of structural brain lesions increased from 39% at 2 years to 58% at school age. Bayley-III language scale (P = 0.021) and mean Wechsler Intelligence Scale for Children-third edition (P = 0.019) were lower in children with pathological MR findings. Total brain volume (P < 0.001), total grey matter volume (P = 0.002), deep grey matter volume (P = 0.001) and white matter volume (P < 0.001) were smaller in patients compared to age- and gender-matched healthy controls. Smaller brain volumes and structural brain lesions in complex congenital heart defect patients at school age are associated with impaired ND outcome. For the evaluation of predictive surgical or clinical factors, larger multicentre studies are needed.

Mental health-related quality of life in mothers of children with surgically repaired congenital heart disease: a 13-year longitudinal study

AimsHaving a child with congenital heart disease (CHD) can affect parental health-related quality of life (HR-QoL). We investigated the long-term trajectories of mental HRQoL (m-HRQoL) in mothers of children with CHD and examined risk factors for persistent low m-HRQoL.MethodsOne hundred twenty-five mothers of children with CHD completed a standardized questionnaire on m-HRQoL (mental subscale SF-12) after the children’s first open-heart surgery and subsequently when the children were 1, 4, 6, 10, and 13 years old. A z-score for m-HRQoL was calculated with national norms. Latent class growth analysis (LCGA) was used to identify subgroups of mothers with regards to their m-HRQoL trajectories over time. Regression analysis investigated predictors for chronically low m-HRQoL.ResultsCompared to norms, mothers of children with CHD had significantly lower m-HRQoL immediately after open-heart surgery (β = −0.30 (CI-95: −0.44, −0.15)). Subsequently, m-HRQoL increased to a normal level (m-HRQoL compared to the norm from 1 to 13 years: β ranges between 0.05 and 0.27). LCGA revealed two distinct groups of m-HRQoL trajectories: A group with normal m-HRQoL (75% of mothers, means z-scores range between − 0.76 and 0.62) and a group with chronically low m-HRQoL (25% of mothers, mean z-scores range between −1.32 and −0.10). Chronically, low m-HRQoL was associated with poorer social support (OR = 3.39 (CI-95: 1.40, 8.49), p = 0.008) but not with parental education, migration background, number of open-heart surgeries, diagnosis of a univentricular CHD, or low IQ.ConclusionA quarter of mothers of children with CHD have chronically low m-HRQoL throughout their child’s development, especially those mothers with poor social support. Further studies of family-oriented approaches are needed to identify and support these mothers and reinforce parental well-being.

The Efficacy of Sildenafil in Children with Uni-Ventricle Congenital Heart Disease Post Bidirectional Cavopulmonary Shunt: An Evidence-Based Case Report

BACKGROUND: Univentricular congenital heart disease (CHD) is an anatomical heart defect where one of the ventricles does not develop. Management of univentricular defects is performed gradually; bidirectional cavopulmonary shunt (BCPS) is one of the surgical approaches conducted before the definite treatment in the Fontan procedure. Therefore, the average rate of pulmonary artery pressure and vasculature resistance is critical factors in determining good post-surgical outcomes. However, studies exploring the evidence that sildenafil administration can reduce pulmonary pressure in patients with univentricular defects are currently limited. AIM: This evidence-based case report aims to investigate whether sildenafil administration toward post-BCPS patients reduces mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) before undergoing the Fontan procedure. METHODS: Available evidence was screened through four databases in PubMed, Cochrane, Embase, and ProQuest on October 9, 2022. The keywords used were (((((single Ventricle) OR univentricular heart) AND BCPS) OR Glenn) AND sildenafil) AND hemodynamic. A result of three cohorts and one clinical trial was identified and critically appraised. RESULTS: Analytical testing of the two studies by Park I and Jeremiasen et al. shows that sildenafil significantly reduces mPAP from 19.5 ± 5.5 mmHg to 14.3 ± 3.0 mmHg (p = 0.023) and from 19 mmHg (SD = 3) to 14 mmHg (SD = 2) (p &lt; 0.01). The studies from Hill KD and Mori et al. illustrate that sildenafil significantly reduces the PVR index by as much as 24% (p &lt; 0.01) and from 3.2 ± 0.5 wood unit to 1.6 ± 0.6 wood unit (p &lt; 0.0001). CONCLUSION: The administration of sildenafil decreases pulmonary artery pressure and vasculature resistance in post-BCPS pediatric patients, allowing patients to undergo the Fontan procedure.

Enteral access and reflux management in neonates with severe univentricular congenital heart disease: literature review and proposed algorithm.

Neonates with severe congenital heart disease undergoing surgical repair may face various complications, including failure to thrive. Feeding tube placement and fundoplication are often performed to combat poor growth in neonates. With the variety of feeding tubes available and controversy surrounding when fundoplication is appropriate, there is no current protocol to determine which intervention is necessary for this patient population. We aim to provide an evidence-based feeding algorithm for this patient population. Initial searches for relevant publications yielded 696 publications; after review of these studies and inclusion of additional studies through external searches, a total of 38 studies were included for qualitative synthesis. Many of the studies utilized did not directly compare the different feeding modalities. Of the 38 studies included, five studies were randomized control trials, three studies were literature reviews, one study was an online survey, and the remaining twenty-nine studies were observational. There is no current evidence to suggest that this specific patient population should be treated differently regarding enteral feeding. We propose an algorithm to assist optimal feeding for neonates with congenital heart disease. Conclusion: Nutrition remains a vital component of the care of neonates with congenital heart disease; determining the optimal feeding strategy for these patients can be approached like other neonates.

Hepatic factor may not originate from hepatocytes.

Pulmonary arteriovenous malformations (PAVMs) develop universally in patients with univentricular congenital heart disease. They are believed to form due to lack of an unidentified factor from hepatocytes that perfuses the lungs to maintain vascular homeostasis and prevent PAVM formation. This unidentified factor is termed hepatic factor; however, the identity, mechanism, and origin of hepatic factor are unknown. Several hepatic factor candidates have been previously proposed, but few data are available to support previous hypotheses. Recent data showed that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is enriched in hepatic vein blood and may be a potential hepatic factor candidate. We used imaging and molecular approaches with wild-type mice to determine whether sVEGFR1 originates from hepatocytes in the liver. To our surprise, we identified that sVEGFR1 is negligibly expressed by hepatocytes but is robustly expressed by the non-parenchymal cell population of the liver. This suggests that hepatic factor may not originate from hepatocytes and alternative hypotheses should be considered. We believe it is necessary to consider hepatic factor candidates more broadly to finally identify hepatic factor and develop targeted therapies for CHD-associated PAVMs.

Anesthetic Management in Parturients With Fontan Physiology

Anesthetic Management in Parturients With Fontan Physiology

Evaluation of Fontan-associated Liver Disease and Ethnic Disparities in Long-term Survivors of the Fontan Procedure: A Population-based Study.

Fontan-associated liver disease (FALD) has emerged as a nearly universal chronic comorbidity in patients with univentricular congenital heart disease who undergo the Fontan procedure. There is a paucity of data reporting long-term outcomes and the impact of FALD in this population. Patients who underwent the Fontan procedure between 1992 and 2018 were identified using California registry data. Presumed FALD was assessed by a composite of liver disease codes. Primary outcomes were mortality and transplant. Multivariable regression and survival analyses were performed. Among 1436 patients post-Fontan, 75.9% studied were adults, with a median follow-up of 12.6 (8.4, 17.3) years. The population was 46.3% Hispanic. Overall survival at 20 years was >80%, but Hispanic patients had higher mortality risk compared with White patients [hazard ratio: 1.49 (1.09-2.03), P =0.012]. Only 225 patients (15.7%) had presumed FALD, although >54% of patients had liver disease by age 25. FALD was associated with later deaths [median: 9.6 (6.4-13.2) years post-Fontan] compared with patients who died without liver disease [4.1 (1.4-10.4) years, P =0.02]. Patients with FALD who underwent combined heart liver transplant had 100% survival at 5 years, compared with only 70.7% of patients who underwent heart transplant alone. In this population-based analysis of long-term outcomes post-Fontan, Hispanic ethnicity was associated with increased all-cause mortality. Further, the prevalence of FALD is underrecognized, but our data confirms that its incidence increases with age. FALD is associated with late mortality but excellent posttransplant survival. This emphasizes the need for FALD-specific liver surveillance strategies in patients post-Fontan.

Congenital Heart Disease: Growth Evaluation and Sport Activity in a Paediatric Population.

(1) Objective: To evaluate: (i) the associations of age and disease severity with anthropometric indices and weight status, (ii) the difference in the frequency of sports activity among different levels of disease severity in paediatric patients with congenital heart disease (CHD). (2) Methods: Clinical data of Caucasian children (aged 2–18 years) diagnosed with CHD (2005–2018) were retrospectively collected from the electronic register of outpatient visits. Of the 475 children with CHD, 368 children and their 1690 complete anthropometric measurements were eligible for inclusion in our analysis. (3) Results: Significant increase with age was observed for weight z-score [beta (95%CI): 0.03 (0.02, 0.05) for one-unit of age] and BMI z-score [0.06 (0.03, 0.08)] but not for height z-score. The probability of being underweight and overweight/obese increased and decreased with disease severity, respectively. The obesity probability of patients with mild CHD (0.06 [95%CI: 0.03, 0.08]) was not statistically distinguishable from that of patients with moderate CHD (0.03 [95%CI: 0.02, 0.05]), whereas it was lower in patients with severe CHD (0.004 [95%CI: 0.0, 0.009]). No obese patients with a univentricular heart defect were observed. Days spent in sport activities were equal to 1.9 [95%CI: 1.6, 2.2] days/week, 1.9 [1.5, 2.2], 1.4 [1.1, 1.7] and 0.7 [0.1, 1.3] in patients with mild, moderate, severe and univentricular CHD, respectively. (4) Conclusions: The risk of being overweight and obese should not be underestimated in paediatric patients diagnosed with CHD, especially in children with mild or moderate heart defects. It could be prevented or reduced by promoting a healthy lifestyle.

Ventricular assist device for Fontan: who, when and why?

Since the advent of the Fontan palliation, survival of patients with univentricular congenital heart disease has increased significantly. These patients will, however, ultimately develop heart failure requiring advanced therapies such as heart transplantation. As wait times are long, mechanical circulatory support (MCS) is an attractive therapy, both for bridge to transplantation and destination therapy in patients not suitable for transplantation. This review aims to summarize current thinking about how to determine which patients would benefit from a ventricular assist device (VAD), the optimal time for implantation and which device should be considered. VAD implantation in end-stage Fontan is still in its infancy; however, case reports and research interest have increased extensively in the past few years. Mortality is significantly higher than in noncongenital heart disease patients. Implantation in patients with primarily systolic dysfunction is indicated, whereas patients with increased transpulmonary gradient may not benefit from a single-VAD solution. When possible, implantation should occur prior to clinical decompensation with evidence of end-organ damage, as outcomes at this point are worse. Fontan patients demonstrating signs of heart failure should be evaluated early and often for feasibility and optimal timing of VAD implantation. The frequency of this procedure will likely increase significantly in the future.

Cognitive and Executive Function in Congenital Heart Disease: A Meta-analysis.

Cognitive function and executive function (EF) impairments contribute to the long-term burden of congenital heart disease (CHD). However, the degree and profile of impairments are insufficiently described. To systematically review and meta-analyze the evidence on cognitive function and EF outcomes in school-aged children operated for CHD and identify the risk factors for an unfavorable outcome. Cochrane, Embase, Medline, and PsycINFO. Original peer-reviewed studies reporting cognitive or EF outcome in 5- to 17-year old children with CHD after cardiopulmonary bypass surgery. Results of IQ and EF assessments were extracted, and estimates were transformed to means and SE. Standardized mean differences were calculated for comparison with healthy controls. Among 74 studies (3645 children with CHD) reporting total IQ, the summary estimate was 96.03 (95% confidence interval: 94.91 to 97.14). Hypoplastic left heart syndrome and univentricular CHD cohorts performed significantly worse than atrial and ventricular septum defect cohorts (P = .0003; P = .027). An older age at assessment was associated with lower IQ scores in cohorts with transposition of the great arteries (P = .014). Among 13 studies (774 children with CHD) reporting EF compared with controls, the standardized mean difference was -0.56 (95% confidence interval: -0.65 to -0.46) with no predilection for a specific EF domain or age effect. Heterogeneity between studies was large. Intellectual impairments in CHD are frequent, with severity and trajectory depending on the CHD subtype. EF performance is poorer in children with CHD without a specific EF profile. The heterogeneity in studied populations and applied assessments is large. A uniform testing guideline is urgently needed.

Growth and Nutritional Intake of Infants with Univentricular Circulation

To evaluate the nutritional status and early nutritional intake of infants with univentricular congenital heart disease. The included infants underwent a Norwood procedure or hybrid intervention (stage 1) within the first 6weeks of life, between January 2014 and January 2019, at Children's Health Ireland at Crumlin. Demographic, anthropometric, nutritional intake, and morbidity data were collected. Data were collected on 90 infants and 1886 neonatal admission days. There was a significant drop in mean weight-for-age z-score (WAZ) between measurements at birth, -0.01 and on discharge post stage 1 surgery -1.45 (P<.01). On hospital discharge (median hospital stay, 25days) 32% of infants had a WAZ<-2 and 11% had a WAZ<-3. Pre-stage 1, 26% received trophic feeds and 39% received parenteral nutrition. Basal metabolic requirements and target caloric intake (120kcal/kg) were met on 56% and 13% of admission days, respectively. Infants referred to a dietitian had a shorter time to any form of nutrition support, enteral feeds, and target caloric intake (P<.001, P=.016, and P=.048, respectively). At stage 3 (Fontan) surgery, 15% of infants were classified as stunted (length-for-age z-score [LAZ] <-2). The greatest decline in nutritional status occurs in the neonatal period, followed by significant growth stunting by the time of the Fontan procedure. Early involvement of dietitians is critical in the care of this nutritionally fragile group. With the currently low rate of preoperative nutritional support, there may be opportunities to improve intake at this critical stage.

SVEGFR1 Is Enriched in Hepatic Vein Blood-Evidence for a Provisional Hepatic Factor Candidate?

Background: Pulmonary arteriovenous malformations (PAVMs) are common sequelae of palliated univentricular congenital heart disease, yet their pathogenesis remain poorly defined. In this preliminary study, we used paired patient blood samples to identify potential hepatic factor candidates enriched in hepatic vein blood.Methods: Paired venous blood samples were collected from the hepatic vein (HV) and superior vena cava (SVC) from children 0 to 10 years with univentricular and biventricular congenital heart disease (n = 40). We used three independent protein analyses to identify proteomic differences between HV and SVC blood. Subsequently, we investigated the relevance of our quantified protein differences with human lung microvascular endothelial assays.Results: Two independent protein arrays (semi-quantitative immunoblot and quantitative array) identified that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is significantly elevated in HV serum compared to SVC serum. Using ELISA, we confirmed the previous findings that sVEGFR1 is enriched in HV serum (n = 24, p < 0.0001). Finally, we studied the quantified HV and SVC serum levels of sVEGFR1 in vitro. HV levels of sVEGFR1 decreased tip cell selection (p = 0.0482) and tube formation (fewer tubes [p = 0.0246], shorter tube length [p = 0.0300]) in vitro compared to SVC levels of sVEGFR1.Conclusions: Based on a small heterogenous cohort, sVEGFR1 is elevated in HV serum compared to paired SVC samples, and the mean sVEGFR1 concentrations in these two systemic veins cause pulmonary endothelial phenotypic differences in vitro. Further research is needed to determine whether sVEGFR1 has a direct role in pulmonary microvascular remodeling and PAVMs in patients with palliated univentricular congenital heart disease.

Postprandial variability of novel heart failure biomarkers in Fontan patients compared to healthy volunteers

BackgroundBlood-based biomarkers reflecting different components of cardiovascular pathophysiology are now used increasingly in patients with Fontan circulation due to univentricular congenital heart disease. Feeding alters haemodynamics significantly and, thus, may affect biomarker levels. As the haemodynamic responses to a meal differ between Fontan patients and normal subjects, we hypothesised that biomarker kinetics may also vary between these populations. MethodsIn 15 patients with Fontan physiology, and 15 matched healthy volunteers, 4 heart failure biomarkers were measured under fasting conditions, and 3 after additional timepoints over 2 h following ingestion of a standardised liquid meal. Changes in biomarker levels over time and the effect of Fontan physiology, sex and age were tested using repeated-measures mixed models. ResultsUnder fasting conditions, high-sensitivity C-reactive protein (hsCRP), mid-regional pro-adrenomedullin (MR-proADM) and C-terminal pro-endothelin-1 (CT-proET-1) were raised significantly in Fontan patients compared to controls. Postprandially, mid-regional pro-atrial natriuretic peptide (MR-proANP) decreased significantly in patients (max. mean decrease ∼7% after 120 min). Conversely, it increased in normal subjects (max. mean increase ∼8% after 60 min). The remaining biomarkers did not change significantly. ConclusionsThe ingestion of food triggers contrary deflections of MR-proANP levels in patients with Fontan circulation compared to normal subjects. Therefore, this parameter should be assessed under fasting conditions in order to correct for postprandial variability.

Glenn surgery: a safe procedure in the path of univentricular correction.

This study describes 35 years of experience in a tertiary care level hospital that treats cardiac patients with univentricular heart physiology who underwent Glenn surgery. The study consisted of a retrospective analysis of patients who underwent Glenn surgery, including variables related to pre-operative, intra-operative, and post-operative morbidity and mortality. From 1980 to 2015, 204 Glenn surgeries were performed. The most common heart disease was tricuspid atresia IB (19.2%). In 48.1% of the cases, the procedure was performed with antegrade flow. A bilateral Glenn procedure was performed in 12.5% of the cases and 10.3% were carried out without using a cardiopulmonary bypass pump. Reported complications included infections, bleeding, arrhythmias, chylothorax, neurological alterations, and pleural effusion. The mortality rate was 2.9%. Glenn surgery is a palliative surgery with good results. It significantly improves patient quality of life over a long period until a total cavopulmonary shunt is performed. The complications observed are few, and the mortality rate is low. Therefore, it is a safe surgery that should be used for univentricular congenital heart disease.

Research priorities in Fontan-associated liver disease.

Fontan-associated liver disease (FALD) is an emerging condition in patients who have undergone surgical correction of univentricular congenital heart disease. There is little known about the epidemiology of FALD, including risk factors for end-organ failure or hepatocellular carcinoma nor a consensus on surveillance guidelines. Furthermore, there is a need to understand the role of heart versus combined heart-liver transplantation in this population. Research is limited by systemic barriers hindering the ability to track longitudinal FALD outcomes. Nearly all patients post-Fontan develop histological features of FALD as a function of time post-Fontan, regardless of Fontan hemodynamics. In cases of end-organ disease, single-center studies have shown promising outcomes of combined heart-liver transplant in this population, with decreased rates of acute rejection. However, despite the burden of disease, it is not currently possible to identify the population of patients with FALD using existing clinical databases and registries due to a lack of diagnostic codes. Strategies proposed to address barriers to understanding FALD include developing appropriate diagnostic and transplant-related codes for existing registries. Efforts should also be targeted at initiating prospective studies to understand recognized comorbidities related to Fontan physiology, guided by a team of multidisciplinary subspecialists.

Adverse Events Following Cardiac Catheterization among Infants, Children, and Young Adults on Ventricular Assist Device Support

Children on ventricular assist device (VAD) support often present unique challenges, such as small size, univentricular or biventricular congenital heart disease (1V- or 2V-CHD), and need for biventricular (BiVAD) support. While cardiac catheterization (cath) can provide valuable information in the management of pediatric patients on VAD support, it is an invasive procedure with inherent risks. We sought to evaluate the safety of cath in this population. We performed a retrospective review of patients on VAD support who underwent cath at a single pediatric VAD center between 2014 and 2019. Using definitions based on Pedimacs, adverse events (AEs) following cath were identified, including respiratory failure (persistent need for intubation ≥ 48 hours post-cath), acute kidney injury (AKI), or arrhythmia within 24 hours, and stroke, pericardial effusion, device malfunction, infection, and death within 7 days. AEs were reviewed by two cardiologists, blinded to each other's assessments, and categorized as directly related or unrelated to cath. Strokes were unrelated to cath if there was documentation of baseline neurologic status after cath but prior to stroke. Descriptive statistics were employed. There were 60 caths on 39 patients. Median age was 11 years (range 2 months - 22 years) and median weight was 36 kg (3.8 - 99.2). Underlying diagnoses included dilated cardiomyopathy (DCM) (54%), 1V-CHD (31%), 2V-CHD (10%), hypertrophic cardiomyopathy (2.5%) and re-transplant (2.5%); 10% were on BiVAD support. Devices were paracorporeal pulsatile (20%), durable continuous flow (72%), and temporary continuous flow (8%). Caths were performed at a median 50 days (6 - 311) from VAD implant; 60% (36/60) were performed on patients in the intensive care unit. Of the 60 caths, there were 7 AEs following cath believed to be directly or possibly related to cath (12%, 7/60), occurring in 6 patients (2 DCM, 3 1V-CHD, 1 other): 1 major bleeding event, 1 AKI, 2 moderate pericardial effusions, and 3 episodes of respiratory failure. There were no strokes, arrhythmia, infections, or mortality attributable to cath. Despite medical complexity such as small size, complex CHD and intensive care needs, cardiac catheterization can be performed with an acceptable adverse event profile in infants, children and young adults on VAD support.

Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV-INHIBITION study design.

AimsIn univentricular hearts, selective lung vasodilators such as phosphodiesterase type 5 (PDE5) inhibitors would decrease pulmonary resistance and improve exercise tolerance. However, the level of evidence for the use of PDE5 inhibitors in patients with a single ventricle (SV) remains limited. We present the SV‐INHIBITION study rationale, design, and methods.Methods and resultsThe SV‐INHIBITION trial is a nationwide multicentre, randomized, double blind, placebo‐controlled, Phase III study, aiming to evaluate the efficacy of sildenafil on the ventilatory efficiency during exercise, in teenagers and adult patients (>15 years old) with an SV. Patients with a mean pulmonary arterial pressure >15 mmHg and a trans‐pulmonary gradient >5 mmHg, measured by cardiac catheterization, will be eligible. The primary outcome is the variation of the VE/VCO2 slope, measured by a cardiopulmonary exercise test, between baseline and 6 months of treatment. A total of 50 patients are required to observe a decrease of 5 ± 5 points in the VE/VCO2 slope, with a power of 90% and an alpha risk of 5%. The secondary outcomes are clinical outcomes, oxygen saturation, 6 min walk test, SV function, NT‐proBNP, peak VO2, stroke volume, mean pulmonary arterial pressure, trans‐pulmonary gradient, SF36 quality of life score, safety, and acceptability.ConclusionsThe SV‐INHIBITION study aims to answer the question whether PDE5 inhibitors should be prescribed in patients with an SV. This trial has been built focusing on the three levels of research defined by the World Health Organization: disability (exercise tolerance), deficit (SV function), and handicap (quality of life).