An intramural course in an anomalous aortic origin of a coronary artery (AAOCA) is a high-risk feature for sudden cardiac death (SCD). One of the proposed mechanisms for this association involves a “flap valve” effect in the intramural segment. The (patho-)histological characteristics of this segment may contribute to risk stratification, however, current data are scarce. The aim of this study was to identify the histological features of the intramural segment and their potential relevance to vascular wall properties and the aortic valve commissure, thereby providing insights into possible functional implications of AAOCA. This prospective multicenter study included consecutive pediatric and adult AAOCA patients who underwent surgical unroofing between 2021 and 2024. The excised arterial vascular wall tissue (i.e. the intramural segment), was immunohistochemically examined for vascular wall components. Two independent observers reviewed the data, correlating findings with preoperative CTA to assess spatial relationships with surrounding aortic and AAOCA tissues. Results were also compared with a post-mortem AAOCA specimen and control tissues. Fifteen patients (mean age 42.9 ± 14.0 years, age range 11–66 years, 60

Unguarded tricuspid orifice is a rare anomaly of the tricuspid valve characterized by complete absence of tricuspid valve tissue and chordae on a proportion of the annulus. Management strategies vary widely. We report a case of successful repair of an unguarded tricuspid orifice with a simplified technique. A 35-year-old male presented with severe tricuspid regurgitation and right ventricular volume overload. Intraoperative inspection of the valve revealed an unguarded tricuspid orifice. For repair, sliding plasty of the anterior and posterior leaflets was performed, followed by ring annuloplasty and commissuroplasty. Postoperative, echocardiogram showed minimal residual tricuspid regurgitation and significantly improved right ventricular dimensions. This case highlights the possibility of successful repair of an unguarded tricuspid orifice. If feasible, repair can be a good choice.

Children and adolescents with congenital aortic stenosis often need multiple reoperations due to early intervention and somatic growth. When valve replacement is considered, selecting an optimally sized prosthesis is essential. The Konno aortoventriculoplasty enables annular enlargement to accommodate larger valves. Patients with unicuspid or bicuspid valves are increasingly recognized as having intrinsic and extrinsic risk factors for aortopathy, sometimes progressing to aneurysmal degeneration requiring concomitant root replacement. We describe a surgical approach combining the Konno procedure with a Bentall operation for selected patients.

Pediatric patients undergoing cardiac surgery are at risk of developing postoperative acute kidney injury (AKI). We hypothesized that a reduction in intraoperative renal (SrO2) or cerebral (ScO2) tissue oxygen saturation is associated with postoperative AKI. We conducted a prospective observational study including fifty pediatric patients with non-cyanotic heart disease undergoing elective surgical repair with cardiopulmonary bypass. Intraoperative SrO2 and ScO2 were monitored using near-infrared spectroscopy (O3® Regional Oximetry). Relative decreases of 10

Heart transplantation is considered as the ultimate treatment for patients with advanced heart failure (HF). Chronic HF is associated with hepatic congestion and reduced cardiac output, which can lead to progressive liver disease. This issue is particularly relevant in patients with congenital heart disease, especially those with a single functional ventricle managed through Fontan-type surgery. The presence of advanced liver disease may contraindicate isolated heart transplantation and thus require consideration of combined heart-liver transplantation (CHLT). However, consensus criteria for CHLT have not yet been established. To illustrate the clinical and scientific discussions on this topic, we present the clinical course of two patients with a Fontan circulation who were evaluated for CHLT and discuss decision-making factors based on a review of current literature. We conclude that establishing a CHLT program represents a promising therapeutic pathway for patients in the Netherlands with advanced HF and concomitant liver disease. Both isolated heart transplantation and CHLT are viable treatment approaches for carefully selected patients with HF and liver disease. However, early identification of potential candidates and timely referral for a comprehensive evaluation are essential for the effective management of this high-risk patient group.

Background:The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era. Objectives:The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events. Methods:A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined. Results:At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2). Conclusions:TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.

The purpose of this study is to evaluate the diagnostic and therapeutic yield of a specialized clinic for children with suspicion of a hereditary thoracic aortic disease (HTAD), including Marfan Syndrome (MFS), and to investigate the diagnostic value of presenting symptoms and findings during evaluation. This retrospective observational study included all patients younger than 18 years old at initial referral between 1998 and 2018. Clinical data, medical treatment, surgical interventions, and clinical events during surveillance were collected until December 2023. A case-control comparison between patients with and without an eventual diagnosis of HTAD was performed using logistic regression analysis to investigate the diagnostic value of collected variables. A total of 355 children were referred and evaluated at the clinic, resulting in 89 new diagnoses, with a diagnostic yield of 21% HTAD, including 59 cases of MFS. Younger age at referral, ectopia lentis, aortic dilatation, and facial features were among the strongest predictors of MFS and other HTAD, while pectus excavatum and arm span-height ratio had no predictive value at childhood age. Of patients with MFS, 65% received antihypertensive medication, and 8% of patients with HTAD underwent prophylactic aortic surgery, in some cases even during childhood. Conclusion: Evaluation of children for HTAD in our specialized Marfan clinic resulted in a high diagnostic yield and subsequent therapeutic implications. Indeed, early recognition of symptoms and signs and referral to such a specialized clinic may lead to early diagnosis, surveillance, and timely treatment, thereby possibly limiting acute aortic events and even mortality.

OBJECTIVES: Anomalous aortic origin of a coronary artery (AAOCA) is a group of rare congenital heart defects with various clinical presentations. The lifetime-risk of an individual living with AAOCA is unknown, and data from multicentre registries are urgently needed to adapt current recommendations and guide optimal patient management. The European AAOCA Registry (EURO-AAOCA) aims to assess differences with regard to AAOCA management between centres. METHODS: EURO-AAOCA is a prospective, multicentre registry including 13 European centres. Herein, we evaluated differences in clinical presentations and management, treatment decisions and surgical outcomes across centres from January 2019 to June 2023. RESULTS: A total of 262 AAOCA patients were included, with a median age of 33 years (12-53) with a bimodal distribution. One hundred thirty-nine (53.1%) were symptomatic, whereas chest pain (n = 74, 53.2%) was the most common complaint, followed by syncope (n = 21, 15.1%). Seven (5%) patients presented with a myocardial infarction, 2 (1.4%) with aborted sudden cardiac death. Right-AAOCA was most frequent (150, 57.5%), followed by left-AAOCA in 51 (19.5%), and circumflex AAOCA in 20 (7.7%). There were significant differences regarding diagnostics between age groups and across centres. Seventy-four (28.2%) patients underwent surgery with no operative deaths; minor postoperative complications occurred in 10 (3.8%) cases. CONCLUSIONS: Currently, no uniform agreement exists among European centres with regard to diagnostic protocols and clinical management for AAOCA variants. Although surgery is a safe procedure in AAOCA, future longitudinal outcome data will hopefully shed light on how to best decide towards optimal selection of patients undergoing revascularization versus conservative treatment.

Objective: Compared with fresh frozen plasma (FFP), Omniplasma has been attributed to an increased coagulation potential and an increased fibrinolytic potential. This study aimed to compare Omniplasma and FFP used for cardiopulmonary bypass (CPB) priming regarding the incidence of postoperative thrombotic or hemorrhagic complications and outcomes in pediatric patients undergoing cardiac surgery. Design: A retrospective observational cohort study Setting: This single -center study was performed at the University Medical Center Groningen. Participant: All pediatric patients up to 10 kg undergoing cardiac surgery with CPB. Interventions: Procedures in which FFP was used for CPB priming were compared with those in which Omniplasma was used. Measurements and Main Results: The primary outcome parameter was a composite endpoint consisting of the following: (1) pediatric intensive care unit (PICU) mortality, (2) thromboembolic complications, and (3) hemorrhagic complications during PICU stay. The authors included 143 procedures in the analyses, 90 (63%) in the FFP group and 53 (37%) in the Omniplasma group. The occurrence of the combined primary endpoint (FFP 20% v Omniplasma 11%, p = 0 . 18) and its components did not differ between the used CPB priming agent). Omniplasma for CPB priming was associated with decreased unfractionated heparin administration per kg bodyweight (585 IU v 510 IU, p = 0 . 03), higher preoperative and postoperative activated clotting times (ACT) discrepancy (90% v 94%, p = 0 . 03), a lower postoperative ACT value (125 v 118 seconds, p = 0 . 01), and less red blood cell transfusion per kilogram bodyweight (78 v 55 mL, p = 0 . 02). However, none of the variables differed statistically significantly in the multivariate logistic regression analyses. Conclusions: The authors did not find an association between the plasma used for CPB priming and thromboembolic and hemorrhagic complications and death in neonates and infants undergoing cardiac surgery. Omniplasma seems to be safe to use in this population.

Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM-VSMC network.

Journal Article Congenital heart disease plus infective endocarditis: complexity squared, but what is the outcome? Get access Floris J Heinen, Floris J Heinen Department of Cardiology, Haga Hospital, the Hague, Netherlands https://orcid.org/0000-0003-3000-0151 Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilco Tanis, Wilco Tanis Department of Cardiology, Haga Hospital, the Hague, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Ryan E Accord, Ryan E Accord Center for Congenital Heart Diseases, Department of Cardiothoracic Surgery, University Medical Center Groningen, Groningen, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Joost P van Melle Joost P van Melle Center for Congenital Heart Diseases, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands Corresponding author. Center for Congenital Heart Diseases, Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands. Tel: +31-50-3612355; e-mail: j.p.van.melle@umcg.nl (J. van Melle). https://orcid.org/0000-0002-4282-4628 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Journal of Cardio-Thoracic Surgery, Volume 63, Issue 5, May 2023, ezad185, https://doi.org/10.1093/ejcts/ezad185 Published: 11 May 2023 Article history Received: 25 April 2023 Published: 11 May 2023 Corrected and typeset: 31 May 2023

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5–5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of <55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue–cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell–matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.

OBJECTIVES:The most recent valve-sparing root replacement technique combines the advantages of the reimplantation (David) and remodelling (Yacoub) techniques. The aortic root is reconstructed according to the remodelling technique, the aortic valve is repaired according to the principle of effective height, and an external ring provides annular support. The purpose of this study was to evaluate operative and mid-term outcomes using this technique in patients with Marfan syndrome. METHODS:Adult patients with Marfan syndrome who had an indication for aortic root surgery according to European Society of Cardiology guidelines and were operated on using this new root replacement technique were retrospectively evaluated. Follow-up was obtained from standard outpatient visits and included echocardiography. RESULTS:The study group comprised 22 patients (mean age 36 years, 68% males). Mean follow-up was 7.5 years. There were no mortalities. Two patients required aortic valve replacement because of aortic regurgitation. In both patients, the aortic root was severely dilated (≥65 mm) preoperatively, with grade III aortic valve regurgitation and aortic valve cusps that were very fragile. Aortic regurgitation was grade ≤I on follow-up in 18 of the remaining 20 patients. CONCLUSIONS:Valve-sparing root replacement using remodelling combined with aortic-ring annuloplasty is safe in patients with Marfan syndrome. The mid-term outcome is promising in patients undergoing elective valve-sparing root replacement at recommended root diameters. However, in patients with extremely dilated aortic roots and already severe aortic regurgitation, the technique should be used cautiously as aortic cusps are fragile and might not be suitable for durable repair. CLINICAL REGISTRATION NUMBER:UMCG Research registry #11208.

Background Neonates with critical congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at risk of brain injury that may result in adverse neurodevelopment. To date, no therapy is available to improve long-term neurodevelopmental outcomes of CCHD neonates. Allopurinol, a xanthine oxidase inhibitor, prevents the formation of reactive oxygen and nitrogen species, thereby limiting cell damage during reperfusion and reoxygenation to the brain and heart. Animal and neonatal studies suggest that allopurinol reduces hypoxic-ischemic brain injury and is cardioprotective and safe. This trial aims to test the hypothesis that allopurinol administration in CCHD neonates will result in a 20% reduction in moderate to severe ischemic and hemorrhagic brain injury. Methods This is a phase III, randomized, quadruple-blinded, placebo-controlled, multicenter trial. Neonates with a prenatal or postnatal CCHD diagnosis requiring cardiac surgery with CPB in the first 4 weeks after birth are eligible to participate. Allopurinol or mannitol-placebo will be administered intravenously in 2 doses early postnatally in neonates diagnosed antenatally and 3 doses perioperatively of 20 mg/kg each in all neonates. The primary outcome is a composite endpoint of moderate/severe ischemic or hemorrhagic brain injury on early postoperative MRI, being too unstable for postoperative MRI, or mortality within 1 month following CPB. A total of 236 patients ( n = 188 with prenatal diagnosis) is required to demonstrate a reduction of the primary outcome incidence by 20% in the prenatal group and by 9% in the postnatal group (power 80%; overall type 1 error controlled at 5%, two-sided), including 1 interim analysis at n = 118 ( n = 94 with prenatal diagnosis) with the option to stop early for efficacy. Secondary outcomes include preoperative and postoperative brain injury severity, white matter injury volume (MRI), and cardiac function (echocardiography); postnatal and postoperative seizure activity (aEEG) and regional cerebral oxygen saturation (NIRS); neurodevelopment at 3 months (general movements); motor, cognitive, and language development and quality of life at 24 months; and safety and cost-effectiveness of allopurinol. Discussion This trial will investigate whether allopurinol administered directly after birth and around cardiac surgery reduces moderate/severe ischemic and hemorrhagic brain injury and improves cardiac function and neurodevelopmental outcome in CCHD neonates. Trial registration EudraCT 2017-004596-31. Registered on November 14, 2017. ClinicalTrials.gov NCT04217421. Registered on January 3, 2020

Objective: During ligation of the ductus arteriosus, cerebrovascular autoregulation (CAR) may deteriorate. It is unknown whether different surgical approaches affect changes in CAR differently. The objective of this study was to compare the potential change in CAR in preterm infants during and after ligation comparing two surgical approaches: sternotomy and posterolateral thoracotomy. Design: This was an observational cohort pilot study. Setting: Level III NICU. Patients: Preterm infants (GA < 32 weeks) requiring ductal ligation were eligible for inclusion. Interventions: Halfway the study period, our standard surgical approach changed from a posterolateral thoracotomy to sternotomy. We analyzed dynamic CAR, using an index of autoregulation (COx) correlating cerebral tissue oxygen saturation and invasive arterial blood pressure measurements, before, during, and after ligation, in relation to the two approaches. Measurements and Main Results: Of nine infants, four were approached by thoracotomy and five by sternotomy. Median GA was 26 (range: 24.9-27.9) weeks, median birth weight (BW) was 800 (640-960) grams, and median post-natal age (PNA) was 18 (15-30) days, without differences between groups. COx worsened significantly more during and after thoracotomy from baseline (Δρ from baseline: during surgery: Δ + 0.32, at 4 h: Δ + 0.36, at 8 h: Δ + 0.32, at 12 h: Δ + 0.31) as compared with sternotomy patients (Δρ from baseline: during surgery: Δ + 0.20, at 4 h: Δ + 0.05, at 8 h: Δ + 0.15, at 12 h: Δ + 0.11) (F = 6.50; p = 0.038). Conclusions: In preterm infants, CAR reduced significantly during and up to 12 h after ductal ligation in all infants, but more evident during and after posterolateral thoracotomy as compared with sternotomy. These results need to be confirmed in a larger population.

Background. The aim of this study was to evaluate early and mid-term outcomes (mortality and prosthetic valve reintervention) after mitral valve replacement with 15- to 17-mm mechanical prostheses. Methods. A multicenter, retrospective cohort study was performed among patients who underwent mitral valve replacement with a 15- to 17-mm mechanical prosthesis at 6 congenital cardiac centers: 5 in The Netherlands and 1 in the United States. Baseline, operative, and follow-up data were evaluated. Results. Mitral valve replacement was performed in 61 infants (15 mm, n = 17 [28%]; 16 mm, n = 18 [29%]; 17 mm, n = 26 [43%]), of whom 27 (47%) were admitted to the intensive care unit before surgery and 22 (39%) required ventilator support. Median age at surgery was 5.9 months (interquartile range [IQR] 3.2-17.4), and median weight was 5.7 kg (IQR, 4.5-8.8). There were 13 in-hospital deaths (21%) and 8 late deaths (17%, among 48 hospital survivors). Major adverse events occurred in 34 (56%). Median follow-up was 4.0 years (IQR, 0.4-12.5) First prosthetic valve replacement (n = 27 [44%]) occurred at a median of 3.7 years (IQR, 1.9-6.8). Prosthetic valve endocarditis was not reported, and there was no mortality related to prosthesis replacement. Other reinterventions included permanent pacemaker implantation (n = 9 [15%]), subaortic stenosis resection (n = 4 [7%]), aortic valve repair (n = 3 [5%], and aortic valve replacement (n = 6 [10%]). Conclusions. Mitral valve replacement with 15- to 17-mm mechanical prostheses is an important alternative to save critically ill neonates and infants in whom the mitral valve cannot be repaired. Prosthesis replacement for outgrowth can be carried out with low risk. (C) 2020 by The Society of Thoracic Surgeons. Published by Elsevier Inc.

Background. The aim of this study was to evaluate early and long-term outcomes (mortality and prosthetic valve replacement) after mitral valve replacement with the 15-mm St Jude Medical prosthesis (St Jude Medical, St Paul, MN). Methods. A multicenter, retrospective cohort study was performed among patients who underwent mitral valve replacement with a 15-mm St Jude Medical Masters prosthesis at 4 congenital cardiac centers in The Netherlands. Operative results were evaluated and echocardiographic data studied at 0.5, 1, 2, 3, 5, and 10 years after surgery. Results. Surgery was performed in 17 infants. Ten patients (59%) were treated in the intensive care unit before surgery; 8 (47%) were on ventilator support. Median age at surgery was 3.2 months (interquartile range [IQR], 1.2-5.6), and median weight was 5.2 kg (IQR 3.9-5.7). There was 1 early cardiac death and 1 late noncardiac death. Median follow-up time was 9.6 years (IQR, 2.4-13.2), including 8 patients with a follow-up more than 10 years. The first prosthetic valve explantation (n = 11) occurred at a median of 2.9 years (IQR, 2.0-5.4). Other reinterventions were permanent pacemaker implantation (n = 3), subaortic stenosis resection (n = 2), and paravalvular leak repair (n = 1). Prosthetic valve gradients increased from a mean of 5.0 mm Hg (at discharge) to a mean of 14.3 mm Hg (at 5-year follow-up). Conclusions. Mitral valve replacement with the 15-mm prosthesis can safely be performed in infants and even in neonates. Median freedom from prosthesis replacement for outgrowth is 3.5 years. Thromboembolic complications were rare. (C) 2020 by The Society of Thoracic Surgeons

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant in GDF2 (c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for the GDF2 variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant in GDF2 with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis.