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As valve-in-valve (ViV) transcatheter aortic valve implantation is still an evolving method, we evaluated the development of early and midterm outcomes after ViV and conventional redo-surgical aortic valve replacement (SAVR) over the past 2 decades. In-hospital databases were retrospectively screened for patients ≥60 years treated for failing bioprosthetic aortic valves at our center. Clinical and follow-up characteristics were compared between patients who underwent ViV or redo-SAVR according to valve academic research consortium-2 (VARC-2) definitions. The comparison of outcome parameters was adjusted for baseline differences between groups. Between June 2002 and April 2020, 209 patients with ViV and 65 redo-SAVR patients met inclusion criteria. No significant differences were found in 30 days (ViV 3.8%, SAVR 3.1%, p = 0.778) or 6-month mortality (ViV 14.0%, SAVR 7.5%, p = 0.283). As patients with ViV less frequently experienced acute kidney injury (stage II or III) and life-threatening bleeding, they more frequently reached the 30-day VARC-2 combined safety end point (79.2% vs 61.5%, odds ratio [OR] 2.540, p = 0.023). Patients with ViV less frequently reached clinical efficacy (68.3% vs 84.6%, OR 0.408, p = 0.041) and device success (79.9% vs 92.3%, OR 0.311, p = 0.040) end points, because of higher frequency of postprocedural transvalvular gradients >20 mm Hg. However, over the past decade, VARC-2 clinical efficacy and device success rates continuously increased in ViV cases. In conclusion, ViV and SAVR were associated with similar acute mortality and different beneficial and adverse outcome profiles in this single-center cohort. Results after ViV procedures have continuously improved over the past years.

Genetic factors are fundamental in the etiology of thoracic aortic aneurysm and dissection (TAAD), but the genetic cause is detected in only about 30% of cases. To define unreported TAAD-associated sequence variants, exome and gene panel sequencing was performed in 323 patients. We identified heterozygous CDKL1 variants [c.427T>C p.(Cys143Arg), c.617C>T p.(Ser206Leu), and c.404C>T p.(Thr135Met)] in 6 patients from 3 families with TAAD spectrum disorders. CDKL1 encodes a protein kinase involved in ciliary biology. Amino acid substitutions were predicted to affect CDKL1 catalytic activity or protein binding properties. CDKL1 was expressed in vascular smooth muscle cells in normal and diseased human aortic wall tissue. Cdkl1 knockdown and transient knockout in zebrafish resulted in intersomitic vessel (ISV) malformations and aortic dilation. Coinjection of human CDKL1wild-type RNA, but not CDKL1Cys143Arg and CDKL1Ser206Leu RNA, rescued ISV malformations. All variants affected CDKL1 kinase function and profiling data, and altered protein-protein binding properties, particularly with ciliary transport molecules. Expression of CDKL1 variants in heterologous cells interfered with cilia formation and length, CDKL1 localization, and p38 MAPK and Vegf signaling. Our data suggest a role of CDKL1 variants in the pathogenesis of TAAD spectrum disorders. The association between primary cilia dysregulation and TAAD expands our knowledge of the underlying molecular pathophysiology.

Objectives: Several conditions associated with type A aortic dissection may require preoperative invasive mechanical ventilation (IMV). The current literature lacks data on this subset of patients’ prevalence and postoperative outcomes. This study aims to investigate this unexplored issue in a multicenter European registry. Methods: Data from 3735 patients included in the European Registry of Type A Aortic Dissection (ERTAAD) were the subject of this analysis. Bootstrapped Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression was performed for variable selection to identify key predictors of hospital death. In the second step, a multilevel multivariable logistic regression (MMLR) was carried out, given the clustered structure of the data. Results: A total of 346 (9.3%) out of 3735 patients required preoperative IMV. Compared to the non-IMV patients, patients requiring IMV had a significantly higher rate of organ malperfusion (52% vs. 35%, p < 0.001) and a higher proportion of tears in the aortic root (p = 0.048). The in-hospital mortality rate among IMV patients was 38% vs. 15% in non-IMV patients (p < 0.001), without a difference in post-discharge survival (p = 0.84). At the MMLR, patients who required IMV had 135% higher odds of in-hospital death compared to the remaining patients. IMV yielded the second highest odds in the prediction model for in-hospital mortality (OR 2.13, CI 1.60 to 2.85, p < 0.001). Among IMV patients, the extension of surgery to the aortic arch was significantly associated with increased in-hospital mortality (p < 0.001, OR 2.98). In multivariable analysis, preoperative IMV was independently associated with increased odds of in-hospital mortality. Conclusions: The need for invasive mechanical ventilation before surgical repair for type A aortic dissection is not infrequent. In this subpopulation, the in-hospital mortality rate was twofold compared to patients who did not require IMV. The awareness of the preoperative risk profile and outcomes of this subset of patients should urge surgeons to tailor the surgical strategy more appropriately to improve the immediate postoperative results.

The perioperative bleeding risk in patients receiving fondaparinux versus low-molecular weight heparin before coronary artery bypass grafting has not been reported. We evaluated perioperative coronary artery bypass grafting-related bleeding in patients with acute coronary syndrome preoperatively treated with fondaparinux or low-molecular weight heparin. All patients with acute coronary syndrome from the prospective, European multicenter registry on coronary artery bypass grafting preoperatively treated with fondaparinux or low-molecular weight heparin undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included 3 additional definitions of major bleeding used in cardiac surgery trials. Propensity score matching was performed to adjust for differences in pre- and perioperative covariates. 1,525 patients were included, of whom 276 (18.1%) received fondaparinux and 1,249 (81.9%) low-molecular weight heparin preoperatively. In the propensity score-matched cohort (245 pairs), the risk of major bleeding according to the universal definition of perioperative bleeding severe or massive bleeding (11.8 vs 9.0%, p = 0.285) and the 3 other major bleeding definitions was similar between the fondaparinux and low-molecular weight heparin cohorts. In conclusion, preoperative treatment with fondaparinux compared with low-molecular weight heparin was associated with similar incidence of perioperative bleeding in patients with acute coronary syndrome who underwent coronary artery bypass grafting.