Extracellular Vesicles to Predict Outcomes After Transcatheter Aortic Valve Implantation - a Prospective, Multicenter Cohort Study.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at intermediate and high surgical risk. Circulating extracellular vesicles (EVs) are nanoparticles involved in cardiovascular diseases. We aimed to (i) determine the effect of TAVI on plasma concentrations of five EV subtypes and (ii) evaluate the predictive value of EVs for post-TAVI outcomes. METHODS: Blood samples were collected 1 day before TAVI and at hospital discharge. Concentrations of EVs were evaluated using flow cytometry. RESULTS: Concentration of leukocytes EVs decreased after TAVI, compared to the measurement before (p = 0.008). Among 123 patients discharged from the hospital, 19.5% experienced MACCE during the median of 10.3 months. Increased pre-TAVI concentration of phosphatidylserine-exposing EVs was an independent predictor of MACCE in multivariable analysis (OR 5.313, 95% CI 1.164-24.258, p = 0.031). CONCLUSIONS: Patients with increased pre-TAVI concentration of procoagulant, PS-exposing EVs have over fivefold higher odds of adverse outcomes.

Long-term mortality after transcatheter aortic valve implantation for aortic stenosis in immunosuppression-treated patients: a propensity-matched multicentre retrospective registry-based analysis.

Introduction: Data regarding patients with a previous medical record of immunosuppression treatment who have undergone transcatheter aortic valve implantation (TAVI) are limited and extremely inconclusive. Available studies are mostly short term observations; thus there is a lack of evidence on efficacy and safety of TAVI in this specific group of patients. Aim: To compare the in-hospital and long-term outcomes between patients with or without a medical history of immunosuppressive treatment undergoing TAVI for aortic valve stenosis (AS). Material and methods: We conducted a retrospective registry-based analysis including patients undergoing TAVI for AS at 5 centres between January 2009 and August 2017. The primary endpoint was long-term all-cause mortality. Secondary endpoints comprised major vascular complications, life-threatening or disabling bleeding, stroke and new pacemaker implantation. Results: Of 1451 consecutive patients who underwent TAVI, two propensity-matched groups including 25 patients with a history of immunosuppression and 75 patients without it were analysed. No differences between groups in all-cause mortality were found in a median follow-up time of 2.7 years following TAVI (p = 0.465; HR = 0.73; 95% CI: 0.30-1.77). The rate of major vascular complications (4.0% vs. 5.3%) was similar in the two groups (p = 1.000). There were no statistically significant differences in the composite endpoint combining life-threatening or disabling bleeding, major vascular complications, stroke and new pacemaker implantation (40.0% vs. 20.0%, p = 0.218). Conclusions: Patients who had undergone TAVI for AS had similar long-term mortality regardless of whether they had a previous medical record of immunosuppression. Procedural complication rates were comparable between the groups.

Impact of previous coronary artery revascularization on outcomes in patients undergoing transcatheter aortic valve implantation.

Introduction: Coexistence of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) raises questions regarding the safety and efficacy of TAVI in this subset of patients. Aim: To evaluate the impact of previous coronary revascularization in terms of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on clinical outcomes after TAVI. Material and methods: A total of 507 consecutive patients who underwent TAVI were divided into: non-revascularization (NR), post-PCI and post-CABG groups. The endpoints were established according to VARC-2 definitions. Results: Patients with previous coronary revascularization (36.7% of the population) were younger, more often male and their EuroSCORE II risk evaluation was significantly higher (NR 7.9% vs. post-PCI 8.0% vs. post-CABG 20.5%, p < 0.0001). Patients after PCI or CABG prior to TAVI had similar 30-day all-cause mortality rates as those without coronary revascularization at baseline (NR vs. post-PCI vs. post-CABG: 8.1% vs. 5.5% vs. 6.8%, respectively; p = 0.6). There were no differences in 12-month all-cause mortality rates between groups (NR vs. post-PCI vs. post-CABG: 15.3% vs. 14.2% vs. 16.9%, respectively; log-rank p = 0.67). In the Cox proportional-hazards regression model, acute kidney injury stage 2-3 (HR = 3.7, 95% CI: 2.14-6.33; p < 0.001) and post-TAVI stroke (HR = 3.5, 95% CI: 1.57-7.8; p = 0.002) were independently correlated with 1-year mortality. Conclusions: TAVI seems to be a safe and effective procedure for the treatment of severe AS in patients with previous coronary revascularization.

Valve-in-valve transcatheter transfemoral mitral valve implantation (ViV-TMVI): Characteristics and early results from nationwide registry.

BACKGROUND: Valve-in-valve transcatheter transfemoral mitral valve implantation (ViV-TMVI) is an emerging treatment alternative to reoperation in high surgical risk patients with a failed mitral bioprostheses. AIM: To describe characteristics and evaluate 30-day outcomes of ViV-TMVI in the Polish population. METHODS: Nationwide registry was initiated to collect data of all patients with failed mitral bioprosthesis undergoing ViV-TMVI in Poland. This study presents 30-days clinical and echocardiographic follow-up. RESULTS: Overall, 27 ViV-TMVI were performed in 8 centers until May 2022 (85% since 2020). Mean (standard deviation [SD]) age was 73 (11.6) years with the median (interquartile range [IQR]) STS score of 5.3% (4.3%-14.3%). Mean (SD) time between surgical implantation and ViV-TMVI was 8.2 (3.2) years. Failed Hancock II (29%) and Perimount Magna (22%) were most frequently treated. Mechanisms of failure were equally often pure mitral regurgitation or stenosis (both 37%) with mixed etiology in 26%. Balloon-expandable Sapien 3/Ultra were used in all but 1 patient. Technical success was 96.3% (1 patient required additional prosthesis). Mean (SD) transvalvular mitral gradient reached 6.7 (2.2) mm Hg and mitral valve area was 1.8 (0.4) cm². None of the patients had moderate or severe mitral regurgitation with only 14.8% graded as mild. In 92.6% device success (2 patients had mean gradient ≥10 mm Hg) and in 85.6% procedural success was present. There were no deaths, cerebrovascular events or need for mitral valve surgery during 30-day follow-up. CONCLUSIONS: In short-term observation ViV-TMVI is safe and effective alternative for patients with failed mitral bioprosthesis at high surgical risk of re-operation. Longer observations on larger sample are warranted.

Nationwide experience with transcarotid transcatheter aortic valve implantation: Insights from the POL-CAROTID registry.

BACKGROUND: The carotid artery is an alternative access route for transcatheter aortic valve implantation (TAVI), especially useful in patients unsuitable for traditional access routes including transfemoral (TF), subclavian, transapical, and aortic. AIMS: To investigate the feasibility and safety of transcarotid (TC) access for TAVI in comparison to the TF approach in a multicenter setting. METHODS: A total of 41 patients, treated between December 2014 and December 2018, were retrospectively reported to the Polish Registry of Common Carotid Artery Access for TAVI (POL-CAROTID). The median follow-up time was 619 (365-944) days, and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. Clinical outcomes were compared with 41 propensity-matched TF-TAVI patients. RESULTS: The mean (standard deviation [SD]) patients' age was 78.0 (7.2) years, and 29 patients (70.7%) were men. Prohibitive iliofemoral anatomy and/or obesity (46.3%) and/or the presence of a stent graft in the abdominal aorta (31.7%) were the most common indications for TC-TAVI. Device success for TC-TAVI was comparable with the matched TF-TAVI group (90.2% vs. 95.3%, respectively, P = 0.396), and no periprocedural mortality was observed. Moreover, early safety was similar between the two groups (92.7% vs. 95.3%, respectively, log-rank P = 0.658) with only 1 case of non-disabling stroke during the first month after TC-TAVI. Consequently, no cerebrovascular events were observed in the mid-term, and the clinical efficacy of TC-TAVI corresponded well with TF-TAVI (90.2% vs. 92.7%, respectively, log-rank P = 0.716). A total of 4 (9.8%) deaths were noted in the TC-TAVI cohort in comparison to 3 (7.3%) in the TF-TAVI group. CONCLUSIONS: The results of the study indicated that the first cohort of Polish patients with implantations of second-generation transcarotid transcatheter heart valves had a similar prognosis to TF-TAVI with regard to safety and feasibility. TC access may be considered an optimal alternative for patients in whom the TF approach is precluded.

Machine learning for prediction of all-cause mortality after transcatheter aortic valve implantation.

AIMS: Prediction of adverse events in mid-term follow-up after transcatheter aortic valve implantation (TAVI) is challenging. We sought to develop and validate a machine learning model for prediction of 1-year all-cause mortality in patients who underwent TAVI and were discharged following the index procedure. METHODS AND RESULTS: The model was developed on data of patients who underwent TAVI at a high-volume centre between January 2013 and March 2019. Machine learning by extreme gradient boosting was trained and tested with repeated 10-fold hold-out testing using 34 pre- and 25 peri-procedural clinical variables. External validation was performed on unseen data from two other independent high-volume TAVI centres. Six hundred four patients (43% men, 81 ± 5 years old, EuroSCORE II 4.8 [3.0-6.3]%) in the derivation and 823 patients (46% men, 82 ± 5 years old, EuroSCORE II 4.7 [2.9-6.0]%) in the validation cohort underwent TAVI and were discharged home following the index procedure. Over the 12 months of follow-up, 68 (11%) and 95 (12%) subjects died in the derivation and validation cohorts, respectively. In external validation, the machine learning model had an area under the receiver-operator curve of 0.82 (0.78-0.87) for prediction of 1-year all-cause mortality following hospital discharge after TAVI, which was superior to pre- and peri-procedural clinical variables including age 0.52 (0.46-0.59) and the EuroSCORE II 0.57 (0.51-0.64), P < 0.001 for a difference. CONCLUSION: Machine learning based on readily available clinical data allows accurate prediction of 1-year all-cause mortality following a successful TAVI.

Expression of miR-223 to predict outcomes after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at increased surgical risk. Up to 29% of patients annually experience major adverse cardiac and cerebrovascular events (MACCE) after TAVI. MicroRNAs (miRNA) are currently widely investigated as novel cardiovascular biomarkers. The aim of this study was to determine the influence of TAVI on the expressions of selected miRNAs associated with platelet function (miR-125a-5p, miR-125b and miR-223), and evaluate the predictive value of these miRNAs for MACCE in 65 patients undergoing TAVI. METHODS: Venous blood samples for miRNA expression analysis were collected 1 day before TAVI and at hospital discharge. The expression of miR-223, miR-125a-5p, miR-125b was evaluated in platelet-depleted plasma. RESULTS: The expression of miR-223 and miR-125b increased after TAVI, compared to the measurement before (p = 0.020, p = 0.003, respectively). Among 63 patients discharged from the hospital, 18 patients experienced MACCE (29%) during the median 15 months of observation. Baseline low miR-223 expression was a predictor of MACCE in univariate Cox regression analysis (hazard ratio [HR]: 2.71, 95% confidence interval [CI]: 1.04-7.01; p = 0.041). After inclusion of covariates, age, gender (male), New York Heart Association class and diabetes into the multivariate Cox regression model, miR-223 did not reach statistical significance (HR: 2.56, 95% CI: 0.79-8.33; p = 0.118). CONCLUSIONS: To conclude, miR-223 might improve risk stratification after TAVI. Further studies are required to confirm the clinical applicability of this promising biomarker.

Long-Term Mortality After TAVI for Bicuspid vs. Tricuspid Aortic Stenosis: A Propensity-Matched Multicentre Cohort Study.

Objectives: Patients with bicuspid aortic valve (BAV) stenosis were excluded from the pivotal trials of transcatheter aortic valve implantation (TAVI). We compared the in-hospital and long-term outcomes between patients undergoing TAVI for bicuspid and tricuspid aortic valve (TAV) stenosis. Methods: We performed a retrospective registry-based analysis on patients who underwent TAVI for BAV and TAV at five different centers between January 2009 and August 2017. The primary outcome was long-term all-cause mortality. Secondary outcomes were in-hospital mortality, procedural complications, and valve performance. Results: Of 1,451 consecutive patients who underwent TAVI, two propensity-matched cohorts consisting of 130 patients with BAV and 390 patients with TAV were analyzed. All-cause mortality was comparable in both groups up to 10 years following TAVI (HR 1.09, 95% CI: 0.77-1.51). Device success and in-hospital mortality were comparable between the groups (96 vs. 95%, p = 0.554 and 2.3 vs. 2.1%, p = 0.863, respectively). Incidence of procedural complications was similar in both groups, with a trend toward a higher rate of stroke in patients with BAV (5 vs. 2%, p = 0.078). Incidence of moderate or severe paravalvular leak (PVL) at discharge was comparable in both groups (2 vs. 2%, p = 0.846). Among patients with BAV, all-cause mortality was similar in self-expanding and balloon-expandable prostheses (HR 1.02, 95% CI: 0.52-1.99) and lower in new-generation devices compared to old-generation valves (HR 0.27, 95% CI 0.12-0.62). Conclusion: Patients who had undergone TAVI for BAV had comparable mortality to patients with TAV up to 10 years after the procedure. The device success, in-hospital mortality, procedural complications, and PVL rate were comparable between the groups. The high rate of neurological complications (5%) in patients with BAV warrants further investigation.

Transcatheter aortic valve­in­valve implantation for failed surgical bioprostheses: results from the Polish Transcatheter Aortic Valve-in-Valve Implantation (ViV­TAVI) Registry

INTRODUCTION: Transcatheter aortic valve­in ­valve implantation (ViV­TAVI) has emerged as an alternative to redo surgery in patients with failed surgical aortic bioprosthesis. OBJECTIVES: We evaluated the safety and efficacy of ViV­TAVI in Polish patients after surgical aortic valve replacement. PATIENTS AND METHODS: This was a nationwide multicenter registry of ViV­TAVI procedures. Data were collected using an online form, and the clinical follow ­up lasted 1 year. RESULTS: From 2008 to 2020, 130 ViV­TAVI procedures were performed (1.9% of all transcatheter aortic valve implantation [TAVI] cases). A considerable increase in ViV­TAVI procedures since 2018 has been observed (n = 59, 45% of ViV­TAVI cases). Hancock II, Freestyle, and homograft were the most frequently treated bioprostheses. The self ­expanding supra ­annular Corevalve / Evolut valve was used in 76% of cases. In 21% of cases, the mean postprocedural pressure gradient (PG) exceeded 20 mm Hg. All­cause mortal­ity at 1 year was 10.8%. Aortic valve stenosis was associated with a higher mean PG than aortic valve regurgitation or mixed disease (P = 0.004). Supra ­annular transcatheter aortic valves were associated with lower mean PGs than intra ­annular valves (P = 0.004). Second ­generation devices were associated with shorter procedure time (120 min vs 135 min, P = 0.04), less frequent need for additional TAVI (2% vs 10%, P = 0.04), and lower 1­year cardiovascular mortality (95% vs 82.8%, P = 0.03) than first­generation valves. CONCLUSIONS: Transcatheter treatment of failed bioprostheses is increasingly common, with the best hemodynamic effect shown for supra ­annular valves. The introduction of second­generation valves has improved procedural and clinical outcomes.

Ten-year experience with transcatheter aortic valve implantation in bicuspid aortic valve: lessons learned and future perspectives.

Bicuspid aortic valve (BAV) stenosis has traditionally been perceived as a contraindication to transcatheter aortic valve implantation (TAVI) due to its specific anatomical characteristics including extensive calcifications, high leaflet coaptation and frequently encountered aortic root dilation, which may result in worse procedural outcomes and higher risk of complications. Hence, BAV patients were not included in previous clinical trials. In the recent years, improved pre-procedural imaging and technological advances have gradually enabled expansion of TAVI to patients with complex anatomy, including those with BAV. Moreover, indications for TAVI are expanding to a younger group of patients with fewer comorbidities, and BAV is more prevalent in this population. Contemporary multicenter registry-based studies indicate that patients undergoing TAVI for BAV have similar outcomes as those with tricuspid aortic valve stenosis. In this article, we provide a thorough overview of the available clinical data regarding the outcomes of TAVI in BAV, from the perspective of an experienced TAVI center with over 150 TAVIs in this group of patients, performed in our institution since the year 2009. We present anatomical and clinical classifications of BAV, differences in outcomes in patients with bicuspid and tricuspid valves, as well as important topics regarding choice of an adequate valve and valve size.

Protamine sulfate during transcatheter aortic valve implantation (PS TAVI) - a single-center, single-blind, randomized placebo-controlled trial.

BACKGROUND: Bleeding complications after transcatheter aortic valve implantation (TAVI) negatively affect the post-procedural prognosis. Routine use of protamine sulfate (PS) to reverse unfractionated heparin after TAVI was never assessed in a randomized controlled trial. AIMS: The aim of this study was to assess the impact of PS on bleeding complications after TAVI. METHODS: Between December 2016 and July 2020 311 patients qualified to TAVI in one academic center were screened. Patients that met the inclusion criteria were randomized to either PS or normal saline administration at the moment of optimal valve deployment. Baseline, procedural, and follow-up data for up to 30 days were collected and analyzed. The primary endpoint (PE) was a composite of life-threatening and major bleeding according to Valve Academic Research Consortium within 48 hours after the procedure. RESULTS: Overall, 100 patients (48 males, median age 82 years) met the inclusion criteria and were included in the study. Forty-seven subjects (47%) were randomized to PS. The primary endpoint occurred in 29% of the study population. Despite numerically lower rates of PE in patients randomized to PS, a statistical significance was not reached (21% in the PS group and 36% in the placebo group; odds ratio [OR], 0.48; 95% confidence intervals [CI] 0.2-1.2; P = 0.11). There were no significant differences in secondary endpoints. CONCLUSIONS: Routine protamine sulfate administration did not significantly decrease the rate of major and life-threatening bleeding complications after TAVI. Larger studies are required to assess the impact of routine PS use.

Temporal trends of transcatheter aortic valve implantation in a high-volume academic center over 10 years.

BACKGROUND: Indications for transcatheter aortic valve implantation (TAVI) have gradually expanded since its introduction. AIMS: The aim was to analyze temporal trends in TAVI characteristics based on the experience of a high-volume academic center over the period of 10 years. METHODS: Five hundred and six consecutive (n = 506) patients with 1-year follow-up were divided into early (G1, years 2010-2013, n = 130), intermediate (G2, 2014-2016, n = 164) and recent (G3, 2017-2019, n = 212) experience groups. RESULTS: Patient's age remained constant over time (mean [SD]; G1 = 79.1 [7.1] years vs G2 = 79.1 [7.1] years vs G3 = 79.7 [6.6] years, P = 0.73) but surgical risk in G3 was lower (log Euroscore, median [IQR]: G1 = 14.0 [8.4-20.2] vs G2 = 12.0 [7.0-22.2] vs G3 = 5.1 [3.5-8.5]; P <0.001). Major/life-threatening bleeding (G1 = 26.9% vs G2 = 12.8% vs G3 = 9.4%; P <0.001), major vascular complications (G1 = 15.4% vs G2 = 8.5% vs G3 = 5.7%; P = 0.02) and moderate/severe paravalvular leak (G1 = 16.2% vs G2 = 11% vs G3 = 7.5%; P = 0.046) were decreasing with time. There was a significant drop in all-cause 1-year mortality in G3 (G1 = 20% vs G2 = 17.7% vs G3 = 9.1%; log rank = 0.01). CONCLUSIONS: The age of TAVI recipients remained unchanged over the last decade. Decreasing surgical risk coupled with improvements in procedural technique and care resulted in fewer periprocedural complications and better 1-year survival.