Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification.

BAV patients constitute an importantly heterogeneous population in terms of risk and features of aortic disease. The most common condition is an ectasia of the mid-ascending tract, with unaffected or mildly involved root. If further confirmed, this could suggest that surgical approach may spare the root in most BAV patients. Mid-ascending dilatation is proportional to stenosis severity, suggesting a post-stenotic causative mechanism. Root dilatation is rarer, mostly observed in younger men, and unrelated to the presence and severity of stenosis. The two different aortic dilatation phenotypes (mid-ascending and root) may be subtended by different pathogeneses.

Smooth muscle cell apoptosis with bicuspid aortic valve stenosis occurred before overt aortic dilation, mainly at the convexity, where wall stress is expectedly higher. In this setting, a matrix-dependent proapoptotic signaling was evidenced by increased Bcl-2-modifying factor-Bcl-2 binding. Stress-dependent bicuspid aortic valve matrix changes may trigger early apoptosis by inducing cytoskeletal rearrangement.

In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.

TEVAR is feasible and reveals promising early results in selected patients with type A aortic dissection who are poor candidates for surgical repair. The current iteration of stent-graft technology, however, needs to be adapted to features specific to the ascending aorta.

Vascular injury aimed at stenosis removal induces local reactions often leading to restenosis. The aim of this study was a concerted transcriptomic-proteomics analysis of molecular variations in a model of rat carotid arteriotomy, to dissect the molecular pathways triggered by vascular surgical injury and to identify new potential anti-restenosis targets. RNA and proteins extracted from inbred Wistar Kyoro (WKY) rat carotids harvested 4 hrs, 48 hrs and 7 days after arteriotomy were analysed by Affymetrix rat microarrays and by bidi-mensional electrophoresis followed by liquid chromatography and tandem mass spectrometry, using as reference the RNA and the proteins extracted from uninjured rat carotids. Results were classified according to their biological function, and the most significant Kyoro Encyclopedia of Genes and Genomes (KEGG) pathways were identified. A total of 1163 mRNAs were differentially regulated in arteriotomy-injured carotids 4 hrs, 48 hrs and 7 days after injury (P < 0.0001, fold-change ≥2), while 48 spots exhibited significant changes after carotid arteriotomy (P < 0.05, fold-change ≥2). Among them, 16 spots were successfully identified and resulted to correspond to a set of 19 proteins. mRNAs were mainly involved in signal transduction, oxidative stress/inflammation and remodelling, including many new potential targets for limitation of surgically induced (re)stenosis (e.g. Arginase I, Kruppel like factors). Proteome analysis confirmed and extended the microrarray data, revealing time-dependent post-translational modifications of Hsp27, haptoglobin and contrapsin-like protease inhibitor 6, and the differential expression of proteins mainly involved in contractility. Transcriptomic and proteomic methods revealed functional categories with different preferences, related to the experimental sensitivity and to mechanisms of regulation. The comparative analysis revealed correlation between transcriptional and translational expression for 47% of identified proteins. Exceptions from this correlation confirm the complementarities of these approaches.

Key PointsQuestionIs transcatheter aortic valve implantation (TAVI) noninferior to surgical aortic valve replacement (surgery) in patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk?FindingsIn this randomized clinical trial that included 913 patients at moderately increased operative risk due to age or comorbidity, all-cause mortality at 1 year was 4.6% with TAVI vs 6.6% with surgery, a difference that met the prespecified noninferiority margin of 5%.MeaningAmong patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, treatment with TAVI was noninferior to surgery with respect to all-cause mortality at 1 year.

Aims Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real‐world data have not yet been reported. This study aimed to assess procedural and 30‐day outcomes of TMVI in a real‐world patient cohort. Method and results All consecutive patients undergoing implantation of a transapically delivered self‐expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high‐risk patients included (43% female, mean age 75 ± 7 years, mean STS‐PROM 7.2 ± 5.3%), 25% was treated for an off‐label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30‐day all‐cause mortality was 12%. At early clinical follow‐up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off‐label indication (74% vs. 81% for off‐ vs. on‐label, p = 0.41). Conclusion In a real‐world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement.