G protein-coupled receptor kinase 5 (GRK5) is a regulator of cardiac performance and a potential therapeutic target in heart failure in the adult. Additionally, we have previously classified GRK5 as a determinant of left-right asymmetry and proper heart development using zebrafish. We thus aimed to identify GRK5 variants of functional significance by analysing 187 individuals with laterality defects (heterotaxy) that were associated with a congenital heart defect (CHD). Using Sanger sequencing we identified two moderately frequent variants in GRK5 with minor allele frequencies <10%, and seven very rare polymorphisms with minor allele frequencies <1%, two of which are novel variants. Given their evolutionarily conserved position in zebrafish, in-depth functional characterisation of four variants (p.Q41L, p.G298S, p.R304C and p.T425M) was performed. We tested the effects of these variants on normal subcellular localisation and the ability to desensitise receptor signalling as well as their ability to correct the left-right asymmetry defect upon Grk5l knockdown in zebrafish. While p.Q41L, p.R304C and p.T425M responded normally in the first two aspects, neither p.Q41L nor p.R304C were capable of rescuing the lateralisation phenotype. The fourth variant, p.G298S was identified as a complete loss-of-function variant in all assays and provides insight into the functions of GRK5.

Congenital critical aortic valve stenosis (CAVS) is a life-threatening disease requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS and (2) describe the techniques for improved feasibility of intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs were performed in 7 patients, and 3 BAVs were performed in 2 patients. The peak trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions. In the first BAV, Δp decreased from 73.7 ± 34.5 mmHg to 39.8 ± 11.9 mmHg (p = 0.003), and the LVSF improved from 22.3 ± 13.5% to 31.6 ± 10.2% (p = 0.001). In the second BAV, Δp decreased from 73.2 ± 33.3 mmHg to 35.0 ± 20.2 mmHg (p < 0.001), and the LVSF increased from 26.7 ± 9.6% to 33.3 ± 7.4% (p = 0.004). Cardiac surgery during the neonatal period was avoided for all children. The median time to valve surgery was 5.75 years. Few complications occurred, namely mild-to-moderate aortic regurgitation, one remediable air embolism, and one intimal injury to the ascending aorta. We conclude that BAV is a successful emergency treatment for CAVS, resulting in left ventricular relief, clinical stabilization, and a time gain until cardiac surgery.

Background: Intima proliferation and in-stent restenosis is a challenging situation in interventional treatment of small vessel obstruction. Al/Al₂O₃ nanowires have been shown to accelerate vascular endothelial cell proliferation and migration in vitro, while suppressing vascular smooth muscle cell growth. Moreover, surface modification of Al/Al₂O₃ nanowires with poly[bis(2,2,2-trifluoromethoxy)phosphazene (PTFEP) coating enables further advantages such as reduced platelet adhesion. Therefore, the study's goal was to compare the biocompatibility of novel Al/Al₂O₃ + PTFEP coated nanowire bare-metal stents to uncoated control stents in vivo using optical coherence tomography (OCT), quantitative angiography and histomorphometric assessment. Methods: 15 Al/Al₂O₃ + PTFEP coated and 19 control stents were implanted in the cervical arteries of 9 Aachen minipigs. After 90 days, in-stent stenosis, thrombogenicity, and inflammatory response were assessed. Scanning electron microscopy was used to analyse the stent surface. Results: OCT analysis revealed that neointimal proliferation in Al/Al₂O₃ + PTFEP coated stents was significantly reduced compared to control stents. The neointimal area was 1.16 ± 0.77 mm² in Al/Al₂O₃ + PTFEP coated stents vs. 1.98 ± 1.04 mm² in control stents (p = 0.004), and the neointimal thickness was 0.28 ± 0.20 vs. 0.47 ± 0.10 (p = 0.003). Quantitative angiography showed a tendency to less neointimal growth in coated stents. Histomorphometry showed no significant difference between the two groups and revealed an apparent inflammatory reaction surrounding the stent struts. Conclusions: At long-term follow-up, Al/Al₂O₃ + PTFEP coated stents placed in peripheral arteries demonstrated good tolerance with no treatment-associated vascular obstruction and reduced in-stent restenosis in OCT. These preliminary in vivo findings indicate that Al/Al₂O₃ + PTFEP coated nanowire stents may have translational potential to be used for the prevention of in-stent restenosis.

Background: Systemic-to-pulmonary collaterals (SPCs) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. The treatment of SPC is controversial. The aim of our study was (1) to retrospectively analyse patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHMs) and (2) to describe the interventional technique. Methods: In this single-centre retrospective observational cohort study, we analysed clinical and imaging data of all patients who underwent transcatheter embolization of SPCs using CHMs from January 2016 to December 2023. Results: In 38 consecutive patients (65.8% male, median age 41 months, range 2–490), a total number of 141 CHMs had been implanted into 64 SPCs in 49 procedures. The majority were arterial SPCs (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPCs. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil/SPC ratio was 2.6 (range 1.3–5.3). CHM implantation was performed via four French sheaths. Both detachment and stable positioning were simple and safe. Neither non-target embolization nor coil migration occurred. One complication was a vascular injury with resulting extravasation of contrast medium. In 18/49 procedures (36.7%), coils other than CHMs or vascular plugs were additionally inserted into separate SPCs. Conclusions: CHMs are appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for the closure of collaterals with a small diameter or tortuous course. They can be used in combination with other embolization devices to achieve comprehensive collateral closure.

Background: Systemic-to pulmonary collaterals (SPC) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. Treatment of SPC is controversial. The aim of our study was (1) to analyze retrospectively patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHM) and (2) to describe the interventional technique. Methods: In this a single-center retrospective observational cohort study, we analyzed clinical and imaging data of all patients who underwent transcatheter embolization of SPC using CHM from January 2016 to December 2023. Results: In 38 consecutive patients (65.8 % male, median age 41 months, range 2 – 490), a total number of 141 CHM had been implanted into 64 SPC in 49 procedures. The majority were arterial SPC (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPC. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil / SPC ratio was 2.6 (range 1.3 – 5.3). CHM implantation was performed via 4 French sheaths. Both detachment and stable positioning was simple and safe. Neither non-target embolization nor coil migration occurred. One complication occurred with a minor vascular injury without clinical relevance. Conclusion: CHM are easy to use and appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for closure of collaterals with small diameter or tortuous course.