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Aortic valve replacement improves and prolongs lives of patients with aortic valve disease, but requires significant healthcare resources, which are mainly determined by the length of associated hospital stays. Therefore, this study aims to identify risk factors for extended length of stay after surgical aortic valve replacement. Between 2018 and 2023, 458 consecutive patients underwent isolated surgical aortic valve replacement at our center and were included in our analysis. To identify independent predictors for hospital and intensive care unit stay, multivariable linear regression analysis using backward elimination process was performed. Upon multivariable linear regression, endocarditis [regression coefficient (β) 2.98; 95% confidence interval (CI) 1.51, 4.45; p<0.001)] and prior aortic valve surgery (β 1.72; 95% CI 0.18, 3.26; p=0.029) were associated with prolonged hospital stay. Prior aortic valve surgery was associated with prolonged intensive care unit stay (β 0.99; 95% CI 0.39, 1.59; p=0.001) as well as chronic obstructive pulmonary disease (β 1.61; 95% CI 0.66, 2.55; p=0.001), smaller prosthetic valve sizes (β -0.18; 95% CI -0.30, -0.06; p=0.003), preoperative atrial fibrillation (β 1.06; 95% CI 0.32, 1.79; p=0.005), and reduced left ventricular ejection fraction (β -0.03; 95% CI -0.05, -0.01; p=0.006). Pending further validation, structured programs aiming to accelerate intensive care unit and hospital discharge after surgical aortic valve replacement should focus on patients with prior cardiac surgery, atrial fibrillation, and chronic obstructive pulmonary disease. Surgeons should aim to implant large-diameter valves. Furthermore, the identified predictors should be used to discuss surgical versus transcatheter procedures in the interdisciplinary heart team., Competing Interests: CONFLICT OF INTEREST: AS received lecture fees/travel support from Abbott, Boston Scientific, and Edwards Lifesciences. AS is a proctor for Abbott. FUNDING: Till Demal was funded by the Clinician Scientist Programme of the German Center for Cardiovascular Research (Grant number DZHK; FKZ 81X3710109)., (Thieme. All rights reserved.)

Prosthesis-patient mismatch (PPM) is a common phenomenon after transcatheter aortic valve implantation (TAVI), especially in patients with small aortic annuli. Whether factors during implantation, such as the implantation depth, have an impact on the occurrence of PPM is currently unclear. The objectives of our study were to (1) investigate the influence of procedure planning- and implantation-related factors on the occurrence of PPM and (2) evaluate the impact of PPM on long-term mortality after TAVI. Data from 315 patients with small aortic annuli, defined as multidetector computed tomography-derived annulus area <400 mm 2 , treated with transfemoral TAVI between 2014 and 2021 were retrospectively analyzed. TAVI was performed with ballon-expandable valves (BEVs) in 113 and self-expanding valves (SEVs) in 202 cases. PPM was defined according to Valve Academic Research Consortium 3 and follow-up was obtained within 5 years after TAVI. Overall, PPM occurred in 121 patients (38.4%) and was significantly more frequent in patients treated with BEVs (54.9%) than with SEVs (29.2%, p <0.001). Evaluation of planning- and implantation-related factors found that deeper implantation of BEVs significantly increased the risk of PPM (p = 0.014), whereas no association was observed in SEVs. The overall mortality rates at 3 and 5 years were 25.5% and 43.1%, respectively, without significant differences between patients with and without PPM. In conclusion, PPM occurred frequently, especially after BEV implantation. In these patients, implantation depth was identified as a predictor of PPM, whereas no association was found for SEV implantation. In addition, there was no difference in longer-term mortality between patients with and without PPM., Competing Interests: Declaration of competing interest Dr. Voigtlaender-Buschmann reports a relation with German Center for Cardiovascular Research that includes funding grants. Dr. Schofer reports a relation with Edwards Lifesciences and St Jude Medical that includes travel reimbursement; and Boston Scientific that includes: speaking and lecture fees and travel reimbursement. Dr. Conradi reports a relation with Abbott, Medtronic, and JenaValve that includes board membership; Edwards Lifesciences, Boston Scientific, VenusMedtech, MicroPort, PiCardia, MicroInterventions, Neovasc, and Smartcanula Sarl that includes consulting or advisory. Dr. Seiffert reports a relation with JenaValve and Boston Scientific that includes: consulting or advisory; Edwards Lifesciences, JenaValve Technology Inc., Boston Scientific, and Biotronik that includes travel reimbursement; and Medtronic that includes speaking and lecture fees. The remaining authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2024. The Author(s).)

(1) Background: Transfemoral transcatheter aortic valve implantation (TAVI) has become the standard treatment for most patients with severe symptomatic aortic stenosis. Intravascular lithotripsy may facilitate transfemoral TAVI (IVL-TAVI) even in patients with severely calcified iliofemoral disease. We assessed technical aspects and clinical outcomes of this novel approach compared to alternative transaxillary access (TAX-TAVI). (2) Methods: IVL-TAVI was performed for severe iliofemoral calcifications precluding standard transfemoral access in 30 patients from 2019 to 2022 at a single academic heart center. IVL was performed as part of the TAVI procedure in all cases. Results were compared to a control group of 44 TAX-TAVI procedures performed for the same indication from 2016 to 2021. The safety outcome was a composite of all-cause death, stroke, access-related bleeding ≥ type 2 within 24 h and major vascular access site complications at 30 days. The efficacy outcome was defined as a technical success according to VARC-3. (3) Results: Median age was 78.2 [74.3, 82.6] years, 45.9% were female and mean STS-PROM was 3.6% [2.3, 6.0]. Iliofemoral calcifications were more severe in the IVL-TAVI vs. TAX-TAVI groups (lesion length: 63.0 mm [48.6, 80.3] vs. 48.5 mm [33.1, 68.8]; p = 0.043, severe calcification at target lesion: 90.0% vs. 68.2%; p = 0.047, and median arc calcification 360.0° [297.5, 360.0] vs. 360.0° [180.0, 360.0]; p = 0.033). Technical success was achieved in 93.3% vs. 81.8% ( p = 0.187) in IVL- and TAX-TAVI and the safety outcome occurred in 10.0% vs. 31.8% in IVL- and TAX-TAVI ( p = 0.047), respectively. (4) Conclusions: IVL-assisted transfemoral TAVI was feasible and safe with favorable outcomes compared to TAX-TAVI. IVL may further expand the number of patients eligible for transfemoral TAVI and may help overcome limitations of an alternative access.

Objectives: Transcatheter aortic valve implantation (TAVI) using balloon-expandable (BE) transcatheter heart valves (THV) in aortic annuli above 29 mm includes particular procedural steps, mainly involving overfilling of the deployment balloon. Data on overfilling strategies in clinical daily practice is scarce. We herein aimed for a retrospective description of utilized overfilling strategies in those patients., Methods: Between January 2016 and December 2022, 45 patients (100% male, 76.9 ± 6.1 years) received TAVI in aortic annuli above 29 mm using a BE THV. Overfilling volumina of the deployment balloon were left to operators' discretion. Clinical and multislice computed tomography data were retrospectively collected. Clinical endpoints were adjudicated in accordance with the updated standardized VARC-3 definitions., Results: Profound overfilling (+4/5 mL) was used in patients with a mild calcium burden (˂750 mm³) even in aortic annuli of 29.0-30.0 mm. Nominal/slight overfilling (+1 mL) was used in aortic annuli up to 32.5 mm but an intermediate to severe calcific burden (>750-3200 mm³). Accordingly, a low calcification group (˂750 mm³, n = 17) compared to a significant calcification group (≥750 mm³, n = 28), presented with higher overfilling volumina (2.1 ± 1.4 vs. 0.8 ± 1.0; p ˂ 0.001), although aortic annulus diameter was not different (29.8 ± 0.8 vs. 29.9 ± 0.9 mm; p = 0.7). All-cause 30-day mortality was 0%. Device success was 97.8%. Transvalvular mean pressure gradient at discharge was 9.5 ± 3.6 mmHg. No case of PVL >mild was documented., Conclusion: Extent of overfilling of the deployment balloon largely depends on calcification burden in addition to aortic annulus diameter with significant and profound overfilling particularly in patients with a calcification burden of the aortic valve complex ˂750 mm³., (© 2023 Wiley Periodicals LLC.)

Background: Valve-in-valve (ViV) transfemoral transcatheter aortic valve implantation (TAVI) for failing aortic surgical bioprostheses or transcatheter heart valves (THV) has demonstrated a reasonable clinical and hemodynamic efficacy. Traditionally, self-expanding (SE) supra-annular THV are considered to result in superior hemodynamics compared with balloon-expandable intra-annular THV after ViV. However, so far no data are found on latest-generation intra-annular SE THV for aortic ViV procedures which might be superior with regard to coronary access or subsequent valve reintervention., Aim: We herein aim to evaluate a latest-generation SE intra-annular THV for aortic ViV procedures., Materials and Methods: Between May 2022 and November 2022, five consecutive patients (4/5 female with mean age of 76.2 years and mean Society of Thoracic Surgeons predicted risk of mortality score of 2.9%) received ViV TAVI using the Navitor system (Abbott, Chicago, IL, USA) for treatment of failing surgical bioprostheses or THV. Data were retrospectively analyzed according to updated Valve Academic Research Consortium 3 (VARC-3) definitions., Results: At 30 days, absence of mortality and VARC-3 adjudicated clinical endpoints were documented. Echocardiography at 30 days revealed complete absence of paravalvular leakage and single-digit mean transvalvular gradients (mean of 6.0 mmHg) in all patients., Conclusion: The investigated intra-annular SE THV results in excellent 30-day outcomes for aortic ViV procedures for failing surgical bioprostheses or THV. Despite the intra-annular design, hemodynamic results were excellent, even in small bioprostheses. Ease of use of this valve platform is reflected by only two cycles of resheathing in five ViV procedures with hemodynamic stability during all steps of valve deployment., Competing Interests: AS received speaker honoraria from Abbott. LC is an advisory board member for Abbott, Medtronic, JenaValve, and MicroPort and has received honoraria from Edwards Lifesciences, Boston Scientific, Neovasc, Highlife, PiCardia, and MicroInterventions. MS received speaker honoraria from Abbott Vascular, Abiomed, Amgen, AstraZeneca, Boston Scientific, BMS/Pfizer, Daiichi Sankyo, Edwards Lifesciences, Inari, Medtronic, Philips, Shockwave Medical, and Siemens. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Schaefer, Demal, Bhadra, Grundmann, Voigtläender, Waldschmidt, Schirmer, Pecha, Schneeberger, Schofer, Sörensen, Blankenberg, Reichenspurner, Seiffert and Conradi.)

Background: Reducing rates of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is important for achieving the best procedural outcomes. The cusp overlap technique (COT) implements procedural steps including an overlap angulation of the right and left coronary cusp to mitigate this complication., Aims: We investigated the incidence of PPI and complication rates following the COT compared to the standard three-cusp implantation technique (3CT) in an all-comers cohort., Methods: A total of 2,209 patients underwent TAVI with the self-expanding Evolut platform from January 2016 to April 2022 at five sites. Baseline, procedural and in-hospital outcome characteristics were compared for both techniques before and after one-to-one propensity score matching., Results: A total of 1,151 patients were implanted using the 3CT and 1,058 using the COT. At discharge, the rates of PPI (17.0 vs 12.3%; p=0.002) and moderate/severe paravalvular regurgitation (4.6% vs 2.4%; p=0.006) were significantly reduced with the COT compared with 3CT within the unmatched cohort. Overall procedural success and complication rates were similar; major bleeding was less common in the COT group (7.0% vs 4.6%; p=0.020). These results remained consistent after propensity score matching. In multivariable logistic regression analysis, right bundle branch block (odds ratio [OR] 7.19, 95% confidence interval [CI]: 5.18-10.0; p<0.001) and diabetes mellitus (OR 1.38, 95% CI: 1.05-1.80; p=0.021) emerged as predictors of PPI, whereas the COT (OR 0.63, 95% CI: 0.49-0.82; p<0.001) was protective., Conclusions: The introduction of the COT was associated with a significant and relevant reduction of PPI and paravalvular regurgitation rates without an increase in complication rates.

Background: Ejection time (ET), acceleration time (AT) and time between left ventricular and aortic systolic pressure peaks (T-LVAo) might be of diagnostic and prognostic use in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI)., Aim: We aimed to assess the diagnostic value and prognostic impact of invasively measured ET, AT, and T-LVAo in patients undergoing TAVI., Methods: A total of 1274 patients received invasive measurement of ET, AT and T-LVAo prior to TAVI. Anatomic AS severity was assessed by CT-derived aortic valve calcification density (AVC d ). Impact on all-cause mortality was retrospectively analyzed., Results: In multivariable linear regression, T-LVAo showed the strongest correlation with AVC d . No prognostic impact of T-LVAo was found according to uni- and multivariable analyses. In contrast, using an individual C-statistic derived cutoff (C D ), patients with ET or AT ≥ C D showed lower mortality rates compared to patients with ET or AT < C D (1-year mortality: ET ≥ vs. < C D : 15.01vs. 33.1%, AT ≥ vs < C D 16.3 vs. 26.5%, p < 0.001). Moreover, multivariable analysis identified ET ≥ C D (HR 0.61 [95% CI 0.43-0.87; p < 0.007]) to be associated with beneficial outcome after TAVI, independent from clinical risk factors and echocardiography-derived parameters., Conclusion: Among the studied hemodynamic parameters T-LVAo provides the highest diagnostic value, whereas ET is an outcome predictor beyond clinical risk factors and echocardiographic parameters in AS patients following TAVI. These parameters could be of considerable use in diagnostic evaluation and risk assessment of patients scheduled for TAVI. T-LVAo (yellow): defined as time between left ventricular and aortic systolic pressure peaks. ET (green): Ejection Time defined as time from the start to flow end. AT (orange): Acceleration time defined as time from the start to the peak flow. AOP: aortic pressure, AVC: aortic valve calcification, CI: confidence interval, HGAS: high-gradient aortic stenosis, LGAS: low-gradient aortic stenosis, LVP: left ventricular pressure, SD: standard deviation., (© 2023. The Author(s).)

Background: Beneficial results of transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) in patients at all risk strata have led to substantial changes in guideline recommendations for valvular heart disease., Aim: To examine influence of these guideline changes on a real-world TAVI cohort, we evaluated how risk profiles and outcomes of TAVI patients developed in our single-center patient cohort over a period of 12 years., Methods: Baseline, procedural and 30-day outcome parameters of TAVI patients were retrospectively compared between three time periods (period 1: 2008-2012, period 2: 2013-2017, period 3: 2018-2020)., Results: Between 03/2008 and 12/2020, a total of 3678 patients underwent TAVI at our center. The median age was 81.1 years (25th, 75th percentile: 76.7, 84.9) with no significant change over time. The EuroSCORE II showed a continuous and significant decline from 5.3% (3.3, 8.6) in period 1 to 2.8% (1.7, 5.0) in period 3 (p < 0.001). Furthermore, rates of permanent pacemaker implantation, acute kidney injury, and paravalvular leakage ≥ moderate continuously declined over time. Accordingly, the 30-day mortality fell from 9.3% in period 1 to 4.3% in period 3 (p < 0.001)., Conclusion: Despite substantial guideline alterations, median patient age remained largely unchanged in our TAVI cohort over the past 12 years. Therefore, increased age still appears to be the main reason to choose TAVI over SAVR. However, risk profiles declined substantially. Significant improvements in early outcomes suggest favorable influence of less invasive access routes, improved device platforms and growing user experience., (© 2023. The Author(s).)

Mutualistic interactions are by definition beneficial for each contributing partner. However, it is insufficiently understood how mutualistic interactions influence partners throughout their lives. Here, we used animal species-explicit, microhabitat-structured integral projection models to quantify the effect of seed dispersal by 20 animal species on the full life cycle of the tree Frangula alnus in Białowieża Forest, Eastern Poland. Our analysis showed that animal seed dispersal increased population growth by 2.5%. The effectiveness of animals as seed dispersers was strongly related to the interaction frequency but not the quality of seed dispersal. Consequently, the projected population decline due to simulated species extinction was driven by the loss of common rather than rare mutualist species. Our results support the notion that frequently interacting mutualists contribute most to the persistence of the populations of their partners, underscoring the role of common species for ecosystem functioning and nature conservation., (© 2023. The Author(s).)

Background: Patients 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., Aim: We aimed to characterize this patient population, evaluate clinical results and assess the significance of calcification patterns., Methods: This retrospective single-center analysis evaluated 2,712 TAVI procedures (2012-2019) according to baseline renal function: GFR < 30 ml/min/1.73m 2 (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., Results: Operative 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., Conclusion: Patients 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., (© 2021. The Author(s).)

Background: Transcatheter mitral valve implantation (TMVI) represents a novel treatment alternative for patients with severe mitral regurgitation (MR) considered ineligible for standard therapies. Data on the management of patients after TMVI screening are scarce., Aims: We aimed to investigate outcomes of patients with severe MR undergoing TMVI evaluation treated with either TMVI, bailout-transcatheter edge-to-edge repair (bailout-TEER) or medical therapy (MT)., Methods: Between May 2016 and February 2021, 121 patients with MR considered ineligible for standard therapy were screened for TMVI. Outcomes were assessed for the subgroups of patients treated with TMVI, bailout-TEER and MT. The primary composite endpoint was all-cause death or heart failure hospitalisation after one year., Results: The subgroups of TMVI (N=38), bailout-TEER (N=28) and MT (N=44) differed significantly with regard to MR aetiology (secondary MR: TMVI 68.4%, bailout-TEER 39.3%, MT 38.6%, p=0.014) and left ventricular ejection fraction (TMVI 37.0% [31.4-51.2], bailout-TEER 48.0% [35.3-58.3], MT 54.5% [40.8-60.0], p<0.001). At discharge and after one year, MR was reduced to ≤mild residual MR in all patients undergoing TMVI, while ≥moderate residual MR was present in 25.9% and 20.0% of patients, respectively, after bailout-TEER, and in 100.0% of patients on MT at one year. The primary endpoint occurred in 72.2% of patients remaining on MT, in 51.6% of patients undergoing TMVI and in 40.2% of those receiving bailout-TEER., Conclusions: In MR patients considered ineligible for standard therapy, TMVI provided acceptable clinical outcomes and MR elimination in the majority of patients. In screen-failed patients, bailout-TEER represented a reasonable alternative while MT was associated with poor outcomes.

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., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the adverse impact of elevated postprocedural mitral valve pressure gradient (MPG) on outcome in a real-world population of patients with severe mitral regurgitation (MR) who underwent transcatheter mitral valve edge-to-edge repair (TEER)., Background: TEER has become a routine treatment alternative for patients with severe MR at high surgical risk. The consequences of elevated MPG after TEER have been subject to controversial debates., Methods: All consecutive patients undergoing TEER for either severe degenerative MR (DMR) or functional MR (FMR) at a high-volume center between September 2008 and January 2020 were prospectively included and followed periodically. Postprocedural MPG by discharge transthoracic echocardiography was considered elevated at ≥5 mm Hg. The primary combined endpoint was death or heart failure rehospitalization after 5 years., Results: A total of 713 patients undergoing TEER (DMR, n = 265; FMR, n = 445) were included. Elevated postprocedural MPG was present in 37.0% of those with DMR (n = 98) and 22.0% of those with FMR (n = 98). In contrast to patients with FMR, 6-minute walk distance did not improve in patients with DMR with elevated MPG. Kaplan-Meier analyses did not demonstrate significant differences for the primary endpoint in patients with DMR (low vs elevated MPG, 67.3% vs 74.4%; P = 0.06) and those with FMR (78.6% vs 74.8%; P = 0.54). After adjustment, elevated MPG was an independent predictor of the primary endpoint in patients with DMR (HR: 1.59; 95% CI: 1.03-2.45; P = 0.034) but not in those with FMR (HR: 0.87; 95% CI: 0.63-1.22; P = 0.43)., Conclusions: Elevated postprocedural MPG is an independent predictor of adverse clinical and functional outcomes in patients with DMR but not in those with FMR., Competing Interests: Funding Support and Author Disclosures Dr Ludwig has received travel expenses from Edwards Lifesciences. Dr Schofer has received nonfinancial support from Abbott and Edwards Lifesciences. Dr Blankenberg has received grants and personal fees from Abbott. Dr Conradi has received personal fees from Edwards Lifesciences; and is a proctor and consultant for Abbott. Dr Lubos has received speaker honoraria, travel expenses, and research grants from Abbott. Dr Kalbacher has received speaker honoraria from Abbott; and has received travel expenses and proctor fees from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite continuous improvements in transcatheter aortic valve implantation (TAVI), periprocedural strokes remain a devastating complication. Randomized controlled trials failed to demonstrate a reduction in clinically apparent strokes or mortality after TAVI due to cerebral embolic protection (CEP). To identify potential targets of CEP strategies during TAVI, we evaluated affected brain regions, and temporal patterns of stroke onset in a routine clinical sample., Methods and Results: A total of 3,164 consecutive patients treated with TAVI from 2008 to 2019 at a single center were screened for cerebrovascular events. Affected cerebral regions were determined according to clinical symptoms and brain imaging. Rates of disabling stroke and non-disabling stroke at 30 days were 2.2% and 1.4%, respectively. The frequency of all strokes decreased from 5.0% to 3.0% over time (P = .012). Patients with impaired left-ventricular function (OR 2.19), increased CHA2DS2-VASc (OR 1.39) and moderate/severe spontaneous echo contrast (OR 3.60) had a higher stroke risk. Acute symptom onset occurred during TAVI (19.4%), within 24 hours (40.3%) or later (25.0%); 98.3% of strokes were of ischemic origin. In intraprocedural strokes, 53.2% of lesions were found in locations considered protected by current CEP devices, and 37.5% of patients with intraprocedural strokes were exclusively affected in these areas. Baseline or procedural parameters were not associated with embolic distribution patterns., Conclusions: Most strokes occurred early after TAVI - but not necessarily during the procedure - and affected multiple brain regions only partially protected by current CEP devices. Efficient prevention of cerebrovascular events may require strategies beyond the TAVI procedure to minimize stroke risk and additional randomized controlled trials will be required to clarify the role of CEP in efficient stroke prevention during TAVI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Left ventricular outflow tract (LVOT) calcification is known to be associated with adverse outcomes after transcatheter aortic valve implantation (TAVI) in patients receiving first-generation transcatheter heart valves (THV)., Aims: The aim of the present study was to assess the prevalence of LVOT calcification as well as its impact on outcomes in a contemporary TAVI patient cohort., Methods: This retrospective single-centre analysis includes 1,207 patients who underwent transfemoral TAVI between 2012 and 2018 and in whom adequate contrast-enhanced multislice computed tomgraphy (MSCT) imaging for quantification of LVOT calcification was available., Results: Significant LVOT calcification, defined as >10 mm 3 , was present in 37.4% (n=451) of the patient cohort. After applying propensity score matching there was no difference between patients without (w/o; n=358) and with (w; n=358) significant LVOT calcification with respect to baseline clinical characteristics. At 30 days, the composite of all-cause mortality and non-disabling/disabling stroke occurred more often in patients w LVOT calcification compared to those w/o (4.6 vs 10.1%, p=0.008). Moreover, the composite VARC-3 endpoint of device success at 30 days was in favour of patients w/o LVOT calcification (82.2% vs 73.4%, p=0.007). According to Kaplan-Meier analysis, all-cause mortality one year after TAVI was higher in patients w vs w/o LVOT calcification (12.9 vs 21.4 %, p=0.004)., Conclusions: In patients undergoing TAVI, the presence of significant LVOT calcification is common and associated with worse short-term clinical and functional outcomes as well as higher one-year mortality rates compared to patients w/o LVOT calcification.

Background: Heyde 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., Methods: 2548 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)., Results: A 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)., Conclusion: A 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., (© 2021. The Author(s).)

Objectives: This study aimed to assess the clinical outcome of the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary obstruction (BASILICA) technique in a single-center patient cohort considered at high or prohibitive risk of transcatheter aortic valve implantation (TAVI)-induced coronary obstruction., Methods: Between October 2019 and January 2021, a total of 15 consecutive patients (age 81.0 [78.1, 84.4] years; 53.3% female; EuroSCORE II 10.6 [6.3, 14.8] %) underwent BASILICA procedure prior to TAVI at our institution. Indications for TAVI were degeneration of stented (n = 12, 80.0%) or stentless (n = 1, 6.7%) bioprosthetic aortic valves, or calcific stenosis of native aortic valves (n = 2, 13.3%), respectively. Individual risk of TAVI-induced coronary obstruction was assessed by pre-procedural computed tomography analysis. Procedural and 30-day outcomes were documented in accordance with Valve Academic Research Consortium (VARC)-2 criteria., Results: BASILICA was attempted for single left coronary cusp in 12 patients (80.0%), for single right coronary cusp in 2 patients (13.3%), and for both cusps in 1 patient (6.7%), respectively. The procedure was feasible in 13 patients (86.7%) resulting in effective prevention of coronary obstruction, whilst TAVI was performed without prior successful bioprosthetic leaflet laceration in two patients (13.3%). In one of these patients (6.7%), additional chimney stenting immediately after TAVI was performed. No all-cause deaths or strokes were documented after 30 days., Conclusion: The BASILICA technique appears to be a feasible, safe and effective concept to avoid iatrogenic coronary artery obstruction during TAVI in both native and bioprosthetic valves of patients at high or prohibitive risk. ClinicalTrials.gov Identifier: NCT04227002 (Hamburg AoRtic Valve cOhoRt)., (© 2021. The Author(s).)

Objectives: Due to high rates of transcatheter mitral valve replacement (TMVR) screening failure, a substantial proportion of patients with severe mitral regurgitation (MR) remains on optimal medical treatment (OMT) only. Data on outcomes of these patients ineligible for mitral interventions are scarce. This study aimed to assess characteristics and outcomes of severe MR patients treated medically following TMVR screening failure., Methods: From 2016-2020, a total of 111 patients with severe MR underwent screening for TMVR. Screening failure occurred in 66 cases. Among these, 30 patients were treated with OMT only. Characteristics of these patients were analyzed, Kaplan-Meier estimates calculated, and univariate regression analysis performed. Median follow-up time was 2.26 years (95% confidence interval, 1.24-3.25)., Results: Anatomical reasons for screening failure in the study cohort (n = 30) were left ventricular (LV) restraints, risk of LV outflow tract obstruction, mitral annulus calcification, and sizing issues. Median ejection fraction was 56.0% (interquartile range, 38.8%-60.0%). Concomitant tricuspid regurgitation and severe pulmonary hypertension were present in 36.7% and 46.2%, respectively. Intercommissural diameters ranged from 22.5-52.0 mm. Mortality was 23.6% after 6 months and 35.7% after 1 year. Factors associated with mortality were female sex, MR severity, ischemic MR, high N-terminal pro-brain natriuretic peptide levels, and small annulus diameters., Conclusions: Despite growing experience with TMVR, the subset of MR patients anatomically eligible for TMVR is small and many patients are treated medically. Mortality in these patients remains high, underlining an unmet need for adequate therapeutic alternatives. TMVR devices adapting to broader annular size ranges with smaller ventricular profiles might fill this gap.

Aims: The aim of this study was to assess the prognostic value of the H 2 FPEF 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 H 2 FPEF score. Patients were dichotomized according to low (0-5 points; n = 570) and high (6-9 points; n = 262) H 2 FPEF scores. Kaplan-Meier and Cox regression analyses were applied to assess the prognostic impact of the H 2 FPEF score. We observed a decrease in stroke volume index (-2.04 mL/m 2 /point) and mean transvalvular gradients (-1.14 mmHg/point) with increasing H 2 FPEF score translating into a higher prevalence of paradoxical low-flow, low-gradient AS among patients with high H 2 FPEF score. One year after TAVI, the rates of all-cause (low vs. high H 2 FPEF 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 H 2 FPEF score compared with those with low H 2 FPEF score. After multivariable analysis, a high H 2 FPEF 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 H 2 FPEF score variables, atrial fibrillation, pulmonary hypertension, and elevated left ventricular filling pressure were the strongest outcome predictors., Conclusions: The H 2 FPEF score serves as an independent predictor of adverse CV and heart failure outcome among TAVI patients with preserved EF. A high H 2 FPEF 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 H 2 FPEF score might be useful as a risk prediction tool in patients with preserved EF scheduled for TAVI., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The relevance of spontaneous echo contrast (SEC) and left atrial appendage thrombus (LAAT) in patients undergoing transcatheter aortic valve implantation (TAVI) remains unclear. In this study, we aimed to assess the prevalence of SEC and LAAT and evaluate the impact on periprocedural outcome after TAVI., Methods and Results: A total of 2,549 consecutive patients underwent TAVI between 2008 and 2017. After exclusion of cases with insufficient imaging, concomitant procedures or severe intraprocedural complications, 1,558 cases were analysed. Three groups were defined according to (pre)thrombotic formations - moderate or severe SEC (n=89), LAAT (n=53), and reference (n=1,416). The primary outcome was disabling ischaemic stroke within 24 hours. The prevalence was 4.4% for LAAT and 5.4% for moderate/severe SEC. The primary outcome occurred more frequently in patients with moderate/severe SEC (6.8%) compared to the reference (2.1%) and LAAT (1.9%) groups (p=0.020). SEC was identified as an independent risk factor for the primary outcome (OR 3.54 [95% CI: 1.30-9.61], p=0.013). LAAT was associated with an impaired unadjusted one-year survival (43.4%) compared to the SEC (27.3%) and reference groups (18.7%, p<0.001)., Conclusions: SEC and LAAT were detected in a relevant number of patients undergoing TAVI. SEC may represent an important risk factor for intraprocedural stroke; increased mortality was observed in patients with LAAT.

Background: 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., Methods: 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. AVC density was defined as calcium volume per annulus area. Patients were trichotomized according to sex-specific AVC density tertiles in both subgroups. All-cause mortality was assessed by Kaplan-Meier analyses and independent outcome predictors were determined by multivariable analyses., Results: In both subgroups, patients with high AVC density had higher mean transvalvular gradients at baseline and higher rates of PVL after TAVR. High AVC density 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 AVC density 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)., Conclusions: 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating., Competing Interests: The authors have declared that no competing interests exist.