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Objectives: Patients with a bicuspid aortic valve (BAV) have an increased risk for developing thoracic aortic aneurysm, which is characterized by the destruction of the elastic media of the aortic wall. Several important enzymes have been characterized to play key roles in extracellular matrix homeostasis, namely matrix metalloproteinases (MMPs). In this study, we investigated MMP-2 levels and their epigenetic regulation via the miR-29 family., Methods: Aortic tissue samples from 58 patients were collected during cardiac surgery, of which 30 presented with a BAV and 28 with a tricuspid aortic valve. Polymerase chain reaction, western blot analysis and immunohistochemistry were performed to analyse MMP-2. In addition, enzyme-linked immunosorbent assay measurements were carried out to investigate both MMP-2 and tissue inhibitor of metalloproteinase-2 levels. To examine the epigenetic regulation of aortic extracellular matrix homeostasis, we furthermore studied the expression levels of miR-29 via qRT-PCR., Results: Patients with a BAV were significantly younger at the time of surgery, presented significantly less frequently with arterial hypertension and displayed more often with an additional valvular disease. On a molecular level, we found that MMP-2 is increased on gene and protein level in BAV patients. Tissue inhibitor of metalloproteinase-2 levels do not differ between the groups. Interestingly, we also found that only miR-29A is significantly downregulated in BAVs., Conclusions: Our findings highlight the importance of MMP-2 in the context of extracellular matrix destruction in BAV patients. We present new evidence that miR-29A is a crucial epigenetic regulator of these pathomechanistic processes and might hold promise for future translational research., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Cardioplegic solutions induce cardiac arrest and protect cardiac tissue from ischaemia-reperfusion injury. However, the effects on the brain, which is vulnerable to cardiopulmonary bypass (CPB) surgery and ischaemia-reperfusion injury, mostly remain unknown. We investigated if cardioplegic solutions differ in their effects in altered oxygen conditions and in their ability to induce cerebral inflammation., Methods: Thirty pigs were subjected to a midline sternotomy and CPB at 34°C with 90 min cardiac arrest followed by 120 min reperfusion. Following randomization on a 1:1:1 basis, they received either a single shot of histidine-tryptophan-α-ketoglutarate (HTK)-Bretschneider solution (n = 10), histidine-tryptophan-α-ketoglutarate-N (HTK-N; n = 10) or HTK plus 1.2 mg/l cyclosporine A (HTK/CsA; n = 10). Brain regions of interest (frontal cortex, cerebellum, brain stem, diencephalon, colliculus superior) were analysed by real time quantitative reverse transcriptase polymerase chain reaction for hypoxia-inducible factor-1α (HIF-1α), tumour necrosis factor-α, interleukin (IL)-10, IL-1β and IL-1β receptor as well as by immunohistochemical analysis for HIF-1α. Blood gas and electrolyte analyses were performed., Results: Comparisons between baseline and reperfusion period levels revealed that HTK-N cardioplegia induced a smaller reduction of the haemoglobin content and blood calcium concentrations (hbbaseline: 5.97 ± 0.63 mmol/l; hbreperfusion: 6.16 ± 0.66 mmol/l; P = 0.428; Cabaseline2+: 1.36 ± 0.05 mmol/l; Careperfusion2+: 1.28 ± 0.05 mmol/l; P < 0.001) compared to HTK (hbbaseline: 5.93 ± 0.45 mmol/l; hbreperfusion: 4.72 ± 0.79 mmol/l; P = 0.001; Cabaseline2+: 1.34 ± 0.07 mmol/l; Careperfusion2+: 1.24 ± 0.06 mmol/l; P = 0.004) and HTK/CsA cardioplegia (hbbaseline: 5.88 ± 0.44 mmol/l; hbreperfusion: 5.14 ± 0.87 mmol/l; P = 0.040; Cabaseline2+: 1.38 ± 0.04 mmol/l; Careperfusion2+: 1.20 ± 0.14 mmol/l; P = 0.001). Brain region-specific regulation of the HIF-1α expression, no general HIF-1α activation and a lower tumour necrosis factor-α expression (pto HTK = 0.050, pto HTK/CsA = 0.013) were documented for HTK-N cardioplegia., Conclusions: HTK-N (Custodiol-N) induced fewer cerebral effects and less inflammation during CPB surgery than HTK and HTK/CsA cardioplegia. These data suggest that HTK-N exerts brain protective effects during and after CPB surgery., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Valve-in-valve implantation is an alternative to reoperation for patients with degenerated bioprostheses. This case report presents a 75-year-old woman presenting with worsening dyspnoea according New York Heart Association (NYHA) Class III after she had received a Sorin Perceval® S sutureless valve due to severe aortic valve stenosis 5 years ago. Echocardiography revealed a degenerated Perceval valve with severe valvular aortic regurgitation and stenosis. After exclusion of acute infective endocarditis, an Edwards SAPIEN 3 was implanted leading to an immediate haemodynamic improvement. A cerebral protection device caught a big embolized piece of material in the left carotid artery filter. The case demonstrates that not only suture-based stented and stentless bioprostheses can be treated by a valve-in-valve strategy, but it is also feasible to treat a failed sutureless Sorin Perceval using a balloon-expandable SAPIEN 3., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The complexity of the mitral valve (MV) anatomy and function is not yet fully understood. Assessing the dynamic movement and interaction of MV components to define MV physiology during the complete cardiac cycle remains a challenge. We herein describe a novel semi-automated 4D MV model., Methods: The model applies quantitative analysis of the MV over a complete cardiac cycle based on real-time 3D transoesophageal echocardiography (RT3DE) data. RT3DE data of MVs were acquired for 18 patients. The MV annulus and leaflets were semi-automatically reconstructed. Dimensions of the mitral annulus (anteroposterior and anterolateral-posteromedial diameter, annular circumference, annular area) and leaflets (MV orifice area, intercommissural distance) were acquired. Variability and reproducibility (intraclass correlation coefficient, ICC) for interobserver and intraobserver comparison were quantified at 4 time points during the cardiac cycle (mid-systole, end-systole, mid-diastole and end-diastole)., Results: Mitral annular dimensions provided highly reliable and reproducible measurements throughout the cardiac cycle for interobserver (variability range, 0.5-1.5%; ICC range, 0.895-0.987) and intraobserver (variability range, 0.5-1.6%; ICC range, 0.827-0.980) comparison, respectively. MV leaflet parameters showed a high reliability in the diastolic phase (variability range, 0.6-9.1%; ICC range, 0.750-0.986), whereas MV leaflet dimensions showed a high variability and lower correlation in the systolic phase (variability range, 0.6-22.4%; ICC range, 0.446-0.915) compared with the diastolic phase., Conclusions: This 4D model provides detailed morphological reconstruction as well as sophisticated quantification of the complex MV structure and dynamics throughout the cardiac cycle with a precision not yet described., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)