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Cerebrovascular events remain a serious complication in patients undergoing transcatheter aortic valve implantation with an incidence of 2–3% at 30 days. While expanding TAVI to younger low-risk patients, prevention of periprocedural strokes becomes even more important. Different cerebral embolic protection devices have been tested but a clear clinical benefit has not been demonstrated in randomized trials. Due to the multifactorial aetiology with different predisposing factors, stroke prevention should include procedural and periprocedural strategies. This article aims to summarize different approaches and discuss open questions.

BackgroundPatients with chronic hemodialysis due to end-stage renal disease (ESRD) or severely impaired kidney function (CKD) constitute a relevant share of patients undergoing trans-catheter aortic valve implantation (TAVI). However, data on specific challenges and outcomes remain limited.AimWe aimed to characterize this patient population, evaluate clinical results and assess the significance of calcification patterns.MethodsThis retrospective single-center analysis evaluated 2,712 TAVI procedures (2012–2019) according to baseline renal function: GFR < 30 ml/min/1.73m2 (CKD; n = 210), chronic hemodialysis (ESRD; n = 119) and control (CTRL; n = 2383). Valvular and vascular calcification patterns were assessed from contrast-enhanced multi-detector computed tomography. Outcomes were evaluated in accordance with the VARC-2 definitions.ResultsOperative risk was higher in ESRD and CKD vs. CTRL (STS-score 8.4% and 7.6% vs. 3.9%, p < 0.001) and patients with ESRD had more severe vascular calcifications (49.1% vs. 33.9% and 29.0%, p < 0.01). Immediate procedural results were similar but non-procedure-related major/life-threatening bleeding was higher in ESRD and CKD (5.0% and 5.3% vs. 1.6%, p < 0.01). 3-year survival was impaired in patients with ESRD and CKD (33.3% and 35.3% vs. 65.4%, p < 0.001). Multivariable analysis identified ESRD (HR 1.60), CKD (HR 1.79) and vascular calcifications (HR 1.29) as predictors for 3-year and vascular calcifications (HR 1.51) for 30-day mortality.ConclusionPatients with ESRD and CKD constitute a vulnerable patient group with extensive vascular calcifications. Immediate procedural results were largely unaffected by renal impairment, yielding TAVI a particularly valuable treatment option in these high-risk operative patients. Mid-term survival was determined by underlying renal disease, cardiovascular comorbidities, and vascular calcifications as a novel risk marker.

Aims The aim of this study was to assess the prognostic value of the H2FPEF score in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) and preserved left ventricular ejection fraction (EF). Methods and results In this multicentre study, a total of 832 patients from two German high‐volume centres, who received TAVI for severe AS and preserved EF (≥50%), were identified for calculation of the H2FPEF score. Patients were dichotomized according to low (0–5 points; n = 570) and high (6–9 points; n = 262) H2FPEF scores. Kaplan–Meier and Cox regression analyses were applied to assess the prognostic impact of the H2FPEF score. We observed a decrease in stroke volume index (−2.04 mL/m2/point) and mean transvalvular gradients (−1.14 mmHg/point) with increasing H2FPEF score translating into a higher prevalence of paradoxical low‐flow, low‐gradient AS among patients with high H2FPEF score. One year after TAVI, the rates of all‐cause (low vs. high H2FPEF score: 8.0% vs. 19.4%, P < 0.0001) and cardiovascular (CV) mortality (1.9% vs. 9.0%, P < 0.0001) as well as the rate of CV mortality or rehospitalization for congestive heart failure (6.4% vs. 23.2%, P < 0.0001) were higher in patients with high H2FPEF score compared with those with low H2FPEF score. After multivariable analysis, a high H2FPEF score remained independently predictive of all‐cause mortality [hazard ratio 1.59 (1.28–2.35), P = 0.018] and CV mortality or rehospitalization for congestive heart failure [hazard ratio 2.92 (1.65–5.15), P < 0.001]. Among the H2FPEF score variables, atrial fibrillation, pulmonary hypertension, and elevated left ventricular filling pressure were the strongest outcome predictors. Conclusions The H2FPEF score serves as an independent predictor of adverse CV and heart failure outcome among TAVI patients with preserved EF. A high H2FPEF score is associated with the presence of paradoxical low‐flow, low‐gradient AS, the HFpEF in patients with AS. By identifying patients in advanced stages of HFpEF, the H2FPEF score might be useful as a risk prediction tool in patients with preserved EF scheduled for TAVI.

We investigated the effect of systemic infection or lead endocarditis on the complexity and the success of laser lead extraction (LLE) procedures. Medical records of all patients undergoing LLE between January 2012 and March 2017 were screened with regard to information on systemic infection or lead endocarditis. We treated 184 patients using high-frequency 80 Hz laser sheaths in patients with lead implant duration of ≥ 12 months. Indications for lead extraction were systemic infection and lead endocarditis in 52 cases (28.3%), local infection in 74 cases (40.2%), lead dysfunction in 37 cases (20.1%) and other indications in 21 cases (11.4%). 386 leads were scheduled for LLE: 235 (60.9%) pacing, 105 (27.2%) ICD and 46 (11.9%) CS leads. The mean time from initial lead implantation (systemic infection 96.8 ± 74.7 months vs. 102.1 ± 82.6 non-infected: months; p  = 0.4155) and ratio of ICD leads (26.8 vs. 27.4%; p  = 0.3411) did not differ significantly between the two groups. Complete procedural success was significantly higher in the systemic infection group (100 vs. 94.7%; p  = 0.0077). The mean laser treatment (60.2 ± 48.7 vs. 72.4 ± 61.5 s; p  = 0.2038) was numerically lower in the infection group, while fluoroscopy time (9.3 ± 7.6 vs. 12.8 ± 10.3 min; p  = 0.0275) was significantly lower in this group. Minor and major complications were low in both groups and did not reveal any statistically significant difference (infected group: one minor complication; pocket hematoma, non-infected: three major complications; emergent sternotomy due to pericardial tamponade). No extraction related mortality was observed. The presence of systemic infection or lead endocarditis in LLE procedures allows for higher complete procedural success. When compared with LLE of non-infected leads, the infected leads require less laser and fluoroscopy times. Due to the scarcity of minor and major complications in general, no statistical significance was found in that regard.

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871–base pair designer eukaryotic chromosome, synlll, which is based on the 316,617–base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.

BackgroundA small aortic annulus is associated with increased risk of prosthesis–patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI). Whether specific transcatheter heart valve (THV) designs yield superior hemodynamic performance in these small anatomies remains unclear.MethodsData from 8411 consecutive patients treated with TAVI from May 2012 to April 2019 at four German centers were retrospectively evaluated. A small aortic annulus was defined as multidetector computed tomography-derived annulus area < 400 mm2. TAVI was performed with a balloon-expanding intra-annular (Sapien-3, n = 288), self-expanding intra-annular (Portico, n = 110), self-expanding supra-annular (Evolut, n = 179 and Acurate-Neo, n = 428) and mechanically expanding infra-annular (Lotus, n = 64) THV according to local practice. PPM was defined as indexed effective orifice area ≤ 0.85cm2/m2.ResultsA small annulus was found in 1069 (12.7%) patients. PPM was detected in 38.3% overall with a higher prevalence after implantation of a balloon-expanding intra-annular or mechanically expanding infra-annular THV compared to self-expanding intra- and supra-annular THV. Multivariable analysis linked self-expanding THV (Evolut: Odds ratio [OR] 0.341, Acurate-Neo: OR 0.436, Portico: OR 0.291), postdilatation (OR 0.648) and age (OR 0.968) to lower rates of PPM, while aortic valve calcification was associated with an increased risk (OR 1.001). Paravalvular regurgitation > mild was more frequent after TAVI with self-expanding THV (p = 0.04).ConclusionIn this large contemporary multicenter patient population, a substantial number of patients with a small aortic anatomy were left with PPM after TAVI. Self-expanding supra- and intra-annular THV demonstrated superior hemodynamics in these patients at risk, however at the cost of higher rates of residual paravalvular regurgitation.Graphic abstract

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.

Background Previous reports suggest septal hypertrophy with an interventricular septum depth (IVSD) ≥ 14 mm may adversely affect outcomes after transcatheter aortic valve implantation (TAVI) due to suboptimal valve placement, valve migration, or residual increased LVOT pressure gradients. Aims This analysis investigates the impact of interventricular septal hypertrophy on acute outcomes after TAVI. Methods Between 2009 and 2021, 1033 consecutive patients (55.8% male, 80.5 ± 6.7 years, EuroSCORE II 6.3 ± 6.5%) with documented IVSD underwent TAVI at our center and were included for analysis. Baseline, periprocedural, and 30-day outcome parameters of patients with normal IVSD (< 14 mm; group 1) and increased IVSD (≥ 14 mm; group 2) were compared. Data were retrospectively analyzed according to updated Valve Academic Research Consortium-3 (VARC-3) definitions. Comparison of outcome parameters was adjusted for baseline differences between groups using logistic and linear regression analyses. Results Of 1033 patients, 585 and 448 patients were allocated to groups 1 and 2, respectively. There was no significant difference between groups regarding transfemoral access rate (82.6% ( n  = 478) vs. 86.0% ( n  = 381), p  = 0.157). Postprocedural mean transvalvular pressure gradient was significantly increased in group 2 (group 1, 7.8 ± 4.1 mmHg, vs. group 2, 8.9 ± 4.9 mmHg, p  = 0.046). Despite this finding, there was no significant difference between groups regarding the rates of VARC-3 adjudicated composite endpoint device success (90.0% ( n  = 522) vs. 87.6% ( n  = 388), p  = 0.538) or technical success (92.6% ( n  = 542) vs. 92.6% ( n  = 415), p  = 0.639). Moreover, the groups showed no significant differences regarding the rates of paravalvular leakage ≥ moderate (3.1% ( n  = 14) vs. 2.6% ( n  = 9), p  = 0.993), postprocedural permanent pacemaker implantation (13.4% ( n  = 77) vs. 13.8% ( n  = 61), p  = 0.778), or 30-day mortality (5.1% ( n  = 30) vs. 4.5% ( n  = 20), p  = 0.758). Conclusion Although transvalvular mean pressure gradients were significantly higher in patients with increased IVSD after TAVI, acute outcomes were comparable between groups suggesting no early impact of adverse hemodynamics due to elevated IVSD. However, how these differences in hemodynamic findings may affect mid- and long-term outcomes, especially in terms of valve durability, needs to be evaluated in further investigations. Graphical Abstract

BackgroundHeyde syndrome (HS) is known as the association of severe aortic stenosis (AS) and recurrent gastrointestinal bleeding (GIB) from angiodysplasia. Data on the prevalence of HS and results after TAVI remain scarce.Methods2548 consecutive patients who underwent TAVI for the treatment of AS from 2008 to 2017 were evaluated for a history of GIB and the presence of HS. The diagnosis of HS was defined as a clinical triad of severe AS, a history of recurrent GIB, and an endoscopic diagnosis of angiodysplasia. These patients (Heyde) were followed to investigate clinical outcomes, bleeding complications and the recurrence of GIB and were compared to patients with GIB unrelated to HS (Non-Heyde).ResultsA history of GIB prior to TAVI was detected in 190 patients (7.5%). Among them, 47 patients were diagnosed with HS (1.8%). Heyde patients required blood transfusions more frequently compared to Non-Heyde patients during index hospitalization (50.0% vs. 31.9%, p = 0.03). Recurrent GIB was detected in 39.8% of Heyde compared to 21.2% of Non-Heyde patients one year after TAVI (p = 0.03). In patients diagnosed with HS and recurrent GIB after TAVI, the rate of residual ≥ mild paravalvular leakage (PVL) was higher compared to those without recurrent bleeding (73.3% vs. 38.1%, p = 0.05).ConclusionA relevant number of patients undergoing TAVI were diagnosed with HS. Recurrent GIB was detected in a significant number of Heyde patients during follow-up. A possible association with residual PVL requires further investigation to improve treatment options and outcomes in patients with HS.Graphic abstract

Compared to high gradient aortic stenosis (AS), patients with low-flow, low-gradient AS have higher mortality after transcatheter aortic valve replacement (TAVR), but distinct outcome predictors in this patient subset are yet to be determined. The present study investigated the prognostic impact of aortic valve calcification (AVC) in patients with low-flow, low-gradient AS undergoing TAVR. This retrospective single-center analysis includes all patients undergoing TAVR for severe low-flow, low-gradient AS (n = 526), ie, low EF low gradient AS (LEF-LG AS; n = 290) and paradoxical low-flow, low-gradient AS (PLF-LG AS; n = 236), in whom AVC was quantified from contrast-enhanced multislice computed tomography images. AVCdensity was defined as calcium volume per annulus area. Patients were trichotomized according to sex-specific AVCdensity tertiles in both subgroups. All-cause mortality was assessed by Kaplan-Meier analyses and independent outcome predictors were determined by multivariable analyses. In both subgroups, patients with high AVCdensity had higher mean transvalvular gradients at baseline and higher rates of PVL after TAVR. High AVCdensity was associated with lowest 1- and 3-year mortality after TAVR in the LEF-LG AS but not in the PLF-LG AS group. According to multivariable analysis AVCdensity was independently associated with better survival in LEF-LG AS patients (HR 0.73 [0.60-0.88], P = .0011), but not in those with PLF-LG AS (HR 0.91 [0.73-1.14], P = .42). Quantification of AVC may not only be of diagnostic but also of prognostic value, as it facilitates the selection of LEF-LG AS patients with higher probability of beneficial outcome after TAVR. [Display omitted]