Background: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. Methods: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. Results: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76–996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510–1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR ( P <0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients ( P =0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P <0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P =0.02). The rates of Mitral Valve Academic Research Consortium–defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P =0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74–12.56; P =0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88–21.53; P <0.001) were both independently associated with repeat mitral valve replacement. Conclusions: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10⁻⁰⁸) and was replicated in an independent case–control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10⁻¹⁶), GATA4 (P = 1.61 × 10⁻⁰⁹), and TEX41 (P = 7.68 × 10⁻⁰⁴). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

A novel software (“Dynamic Coronary Roadmap”) was developed, which offers a real-time, dynamic overlay of the coronary tree on fluoroscopy. Once the roadmap has been automatically generated during angiography it can be used for navigation during percutaneous coronary interventions (PCI). As a feasibility study, we aimed to investigate the feasibility of real-time dynamic coronary roadmapping and consecutive coronary overlay during elective PCI. We studied 936 overlay runs, created following the same amount of angiographies, which were generated during 36 PCIs. Feasibility of dynamic coronary roadmapping was analyzed using a dedicated software tool. Roadmap quality (correct dynamic imaging of the vessels without relevant artefacts or missing parts) was distinguished from overlay quality (congruence of dynamic coronary roadmapping and coronary anatomy). Additionally, we assessed procedural success and the occurrence of major cardiac and cerebrovascular events (MACCE). Roadmap quality was defined as “fit for use” in 99.5%. In 97.4% of runs overlay quality was deemed “fit for use”. Overall, we observed low inter and intra observer variability (ICC R = 0.84 for roadmap quality and R = 0.75 for overlay quality). Procedural success rate was 100%. MACCE occurred in two (5.6%) patients during post-interventional in-hospital stay and were not software-related. Dynamic coronary roadmapping provides in > 98% of cases sufficient roadmap quality with an anatomically correct overlay of the coronary vessels with good inter and intra observer variability. Future randomized studies are warranted to test possible advantages like procedure time reduction and less consumption of contrast medium.

Background: An increased degree of aortic angulation (AA) represents a challenging feature for bioprosthesis positioning. Whether AA has an impact on procedural outcomes of contemporary self-expanding valves remains unsettled. The aim of this study was to evaluate the impact of AA on procedural outcomes of transcatheter aortic valve replacement with contemporary self-expanding valves. Methods: The HORSE (Horizontal Aorta in Transcatheter Self-Expanding Valves) is an international, retrospective registry including 3862 consecutive patients undergoing transcatheter aortic valve replacement with either Evolut R/PRO (n=1959) or ACURATE neo (n=1903) devices. Patients undergoing Evolut R 34 mm implantation were excluded as no comparable prosthesis size for ACURATE neo is available. AA was evaluated with preprocedural computed tomography, and its impact on device success was evaluated. Results: In the overall population, AA did not have any impact upon device success, also when adjusting for in-study outcome predictors (odds ratio for 1° increment, 0.99 [95% CI, 0.98–1.01], P =0.306). However, increased AA was associated with lower device success with use of the Evolut R/PRO valves (odds ratio, 0.97 [95% CI, 0.95–0.99]; P =0.004), but not the ACURATE neo valves (odds ratio, 1.00 [95% CI, 0.98–1.03], P =0.304). The best AA cutoff value predicting device success was 49° (47% of the study cohort). Among patients with AA≥49°, Evolut R/PRO valves were associated with lower device success as compared to the ACURATE neo valve (inverse probability weighting odds ratio, 0.62 [95% CI, 0.46–0.83]; P =0.002). Conclusions: Horizontal aorta, as defined by an AA ≥49°, is a common feature among transcatheter aortic valve replacement candidates and predicts device failure of the Evolut R/PRO valves, but not of the ACURATE neo valve. AA may be an effect modifier of the association between self-expanding valve type and device success.

Objectives: This meta‐analysis sought to assess predictors of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with focus on preprocedural multi‐slice computed tomography (MSCT) derived data.Background: Transcatheter aortic valve replacement (TAVR) has expanded to a well‐established treatment for severe symptomatic aortic stenosis at high and intermediate surgical risk. PPI after TAVR remains one of the most frequent procedure‐related complications and appears to be influenced by several factors.Methods: The authors conducted a literature search in PubMed/MEDLINE and EMBASE databases to identify studies that investigated preprocedural MSCT data and the rate of PPI following TAVR with new‐generation devices.Results: Ten observational studies (n = 2707) met inclusion criteria for the final analysis. PPI was performed in 387 patients (14.3%) after TAVR. Patients requiring PPI had a larger annulus perimeter (MD: 1.66 mm; p < .001) and a shorter membranous septum length (MD: −1.1 mm; p < .05). Concerning calcification distribution, patients with requirement for new pacemaker implantation showed increased calcification of the left coronary cusp (MD: 47.6 mm³; p < .001), and the total left ventricular outflow tract (MD: 24.42 mm³; p < .01). Lower implantation depth (MD: 0.95 mm; p < .05) and oversizing (MD: 1.52%; p < .05) were procedural predictors of PPI following TAVR.Conclusions: Besides the well‐known impact of electrocardiographic and procedure‐related factors on conduction disturbances, MSCT derived distribution of the aortic valve and left ventricular outflow tract calcification, as well as membranous septum length, are associated with an increased risk of PPI following TAVR.