Cerebrovascular Autoregulation in Preterm Infants During and After Surgical Ligation of the Ductus Arteriosus, a Comparison Between Two Surgical Approaches

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

Multicentre experience with valve-sparing aortic root replacement by means of combined remodelling and external aortic ring annuloplasty in patients with Marfan syndrome

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.</p

Multicentre experience with valve-sparing aortic root replacement by means of combined remodelling and external aortic ring annuloplasty in patients with Marfan syndrome

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.</p

Multicentre experience with valve-sparing aortic root replacement by means of combined remodelling and external aortic ring annuloplasty in patients with Marfan syndrome

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.</p

Multicentre experience with valve-sparing aortic root replacement by means of combined remodelling and external aortic ring annuloplasty in patients with Marfan syndrome

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.</p

A homozygous variant in growth and differentiation factor 2(GDF2)may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis

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 inGDF2(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 theGDF2variant. 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 inGDF2with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis

The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX):An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease

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 &gt;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 &lt;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.</p

CeRebrUm and CardIac Protection with ALlopurinol in Neonates with Critical Congenital Heart Disease Requiring Cardiac Surgery with Cardiopulmonary Bypass (CRUCIAL):study protocol of a phase III, randomized, quadruple-blinded, placebo-controlled, Dutch multicenter trial

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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06098-y