A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Quality of Life Measures in Aortic Stenosis Research: A Narrative Review.

BACKGROUND: Elderly patients with aortic stenosis (AS) not only have a reduced life expectancy but also a reduced quality of life (QoL). The benefits of an AS intervention may be considered a balance between a good QoL and a reasonably extended life. However, the different questionnaires being used to determine the QoL were generally not developed for the specific situation of patients with AS and come with strengths and considerable weaknesses. The objective of this article was to provide an overview of the available QoL instruments in AS research, describe their strengths and weaknesses, and provide our assessment of the utility of the available scoring instruments for QoL measurements in AS. SUMMARY: We identified and reviewed the following instruments that are used in AS research: Short Form Health Survey (SF-36/SF-12), EuroQol-5D (EQ-5D), the Illness Intrusiveness Rating Scale (IIRS), the HeartQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHF), the MacNew Questionnaire, and the Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ). KEY MESSAGES: There is no standardized assessment of QoL in patients with AS. Many different questionnaires are being used, but they are rarely specific for AS. There is a need for AS-specific research into the QoL of patients as life prolongation may compete for an improved QoL in this elderly patient group.

Feasibility and safety of early discharge after transfemoral transcatheter aortic valve implantation - rationale and design of the FAST-TAVI registry.

BACKGROUND: There is an increasing trend towards shorter hospital stays after transcatheter aortic valve implantation (TAVI), in particular for patients undergoing the procedure via transfemoral (TF) access. Preliminary data suggest that there exists a population of patients that can be discharged safely very early after TF-TAVI. However, current evidence is limited to few retrospective studies, encompassing relatively small sample sizes. METHODS: The Feasibility And Safety of early discharge after Transfemoral TAVI (FAST-TAVI) registry is a prospective observational registry that will be conducted at 10 sites across Italy, the Netherlands and the UK. Patients will be included if they have been scheduled to undergo TF-TAVI with the balloon-expandable SAPIEN 3 transcatheter heart valve (THV; Edwards Lifesciences, Irvine, CA). The primary endpoint is a composite of all-cause mortality, vascular-access-related complications, permanent pacemaker implantation, stroke, re-hospitalisation due to cardiac reasons, kidney failure and major bleeding, occurring during the first 30 days after hospital discharge. Patients will be stratified according to whether they were high or low risk for early discharge (≤3 days) (following pre-specified criteria), and according to whether or not they were discharged early. Secondary endpoints will include time-to-event (Kaplan-Meier) analysis for the primary outcome and its individual components, analysis of the relative costs of early and late discharge, and changes in short- and long-term quality of life. Multivariate logistic regression will be used to identify factors that indicate that a patient may be suitable for early discharge. DISCUSSION: The data gathered in the FAST-TAVI registry should help to clarify the safety of early discharge after TF-TAVI and to identify patient and procedural characteristics that make early discharge from hospital a safe and cost-effective strategy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02404467 (registration first received March 23rd 2015).

Setting a benchmark for resource utilization and quality of care in patients undergoing transcatheter aortic valve implantation in Europe-Rationale and design of the international BENCHMARK registry.

BACKGROUND: The use of transcatheter aortic valve implantation (TAVI) for treating aortic stenosis (AS) has increased exponentially in recent years. Despite the availability of clinical practice guidelines for the management of valvular heart disease, disparities in quality of care (QoC) for TAVI patients remain widespread across Europe. Tailored QoC measures will help to reduce resource utilization and improve patient outcomes without compromising patient safety. Using a clear set of QoC measures, the BENCHMARK registry aims to document the progress that can be achieved if such tailored QoC measures are implemented. METHODS: The BENCHMARK registry (BENCHMARK) is a non-interventional, multicenter registry in patients with severe symptomatic AS undergoing TAVI with a 1- and 12-months follow-up. BENCHMARK will be conducted at 30 centers across Europe and will enroll a total of 2400 consecutive TAVI patients. Patients suffering from severe symptomatic AS who undergo TAVI with a balloon-expandable transcatheter aortic valve will be included. The registry will comprise four phases: (1) a retrospective baseline evaluation phase; (2) an education phase; (3) an implementation phase; and (4) a prospective effect documentation phase (prospective phase). The registry's primary objectives are to reduce the length of hospital stay and accelerate the post-procedural patient recovery pathway, but without compromising safety. The study started in April 2021 and has an estimated completion date of May 2023. DISCUSSION: BENCHMARK will establish QoC measures to reduce resource utilization, intensive care unit bed occupancy, and overall length of hospitalization with uncompromised patient safety post-TAVI (ClinicalTrials.gov Identifier: NCT04579445).

Quality of life after transcatheter or surgical aortic valve replacement using the Toronto Aortic Stenosis Quality of Life Questionnaire.

BACKGROUND: The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) is a validated instrument for assessing quality of life (QoL) in patients with severe aortic stenosis (AS). In this study, we evaluated health status outcomes, based on the TASQ, in patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). METHODS: The TASQ registry was a prospective observational registry. Patients with severe AS from nine centres in Europe and one in Canada underwent either SAVR or transfemoral TAVR. Patients completed the TASQ, Kansas City Cardiomyopathy Questionnaire and Short Form-12 V.2 prior to the intervention, predischarge, and at 30-day and 3-month follow-ups. Primary end point was the TASQ score. RESULTS: In both the TAVR (n=137) and SAVR (n=137) cohorts, significant increases were observed in all three scores. The overall TASQ score improved as did all but one of the individual domains at 3 months after the intervention (p<0.001). TASQ health expectations were the only domain which worsened (p<0.001). Across TASQ subscores, significant changes were evident from the time of discharge in the TAVR and 30-day follow-up in the SAVR cohort. In a categorical analysis of the TASQ, 39.7% of the TAVR group and 35.0% of the SAVR group had a substantially improved health status at 3 months compared with baseline. CONCLUSIONS: The TASQ captured changes in QoL among patients with severe AS who were treated with TAVR or SAVR. QoL improved substantially after either intervention, as indicated by changes in the TASQ overall score at 3 months. TRIAL REGISTRATION NUMBER: NCT03186339.

Aortic valve replacement: validation of the Toronto Aortic Stenosis Quality of Life Questionnaire.

AIMS: There is no quality of life tool specifically developed for patients with severe aortic stenosis (AS) to assess how this chronic condition and its treatment affect patients. The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) has been developed to overcome this gap. The results of the validation of the TASQ in patients undergoing treatment for severe AS are presented. METHODS AND RESULTS: Prospective study at 10 centres in Europe and Canada, which enrolled 274 patients with severe symptomatic AS undergoing surgical or transcatheter aortic valve replacement. Mean TASQ score at baseline was 71.2 points and increased to 88.9 three months after aortic valve implantation (P < 0.001). Increases were seen for the emotional impact (32.0 to 39.0; P < 0.001), physical limitations (14.8 to 22.0; P < 0.001), and physical symptoms (8.5 vs. 11.0; P < 0.001) domains. Internal consistency was good/excellent for overall TASQ score (α = 0.891) and for the physical limitation, emotional impact, and social limitation domains (α = 0.815-0.950). Test-retest reliability was excellent or strong for the overall TASQ (intraclass correlation coefficient of 0.883) and for the physical symptoms, physical limitation, emotional impact, and social limitation domains (intraclass correlation coefficient of 0.791-0.895). Responsiveness was medium overall (Cohen's d = 0.637) and medium/large for physical symptoms, emotional impact, and physical limitations (0.661-0.812). Sensitivity to change was significant for physical symptoms, physical limitations (both P < 0.001), emotional impact (P = 0.003), and social limitations (P = 0.038). CONCLUSIONS: The TASQ is a new, brief, self-administered, and clinically relevant health-specific tool to measure changes in quality of life in patients with AS undergoing an intervention.

Prespecified Risk Criteria Facilitate Adequate Discharge and Long-Term Outcomes After Transfemoral Transcatheter Aortic Valve Implantation.

Background Despite the availability of guidelines for the performance of transcatheter aortic valve implantation (TAVI), current treatment pathways vary between countries and institutions, which impact on the mean duration of postprocedure hospitalization. Methods and Results This was a prospective, multicenter registry of 502 patients to validate the appropriateness of discharge timing after transfemoral TAVI, using prespecified risk criteria from FAST-TAVI (Feasibility and Safety of Early Discharge After Transfemoral [TF] Transcatheter Aortic Valve Implantation), based on hospital events within 1-year after discharge. The end point-a composite of all-cause mortality, vascular access-related complications, permanent pacemaker implantation, stroke, cardiac rehospitalization, kidney failure, and major bleeding-was reached in 27.0% of patients (95% CI, 23.3-31.2) within 1 year after intervention; 7.5% (95% CI, 5.5-10.2) had in-hospital complications before discharge and 19.6% (95% CI, 16.3-23.4) within 1 year after discharge. Overall mortality within 1 year after discharge was 7.3% and rates of cardiac rehospitalization 13.5%, permanent pacemaker implantation 4.2%, any stroke 1.8%, vascular-access-related complications 0.7%, life-threatening bleeding 0.7%, and kidney failure 0.4%. Composite events within 1 year after discharge were observed in 18.8% and 24.3% of patients with low risk of complications/early (≤3 days) discharge and high risk and discharged late (>3 days) (concordant discharge), respectively. Event rate in patients with discordant discharge was 14.3% with low risk but discharged late and increased to 50.0% in patients with high risk but discharged in ≤3 days. Conclusions The FAST-TAVI risk assessment provides a tool for appropriate, risk-based discharge that was validated with the 1-year event rate after transfemoral TAVI. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02404467.

Trial protocol for the validation of the 'Toronto Aortic Stenosis Quality of Life (TASQ) Questionnaire' in patients undergoing surgical aortic valve replacement (SAVR) or transfemoral (TF) transcatheter aortic valve implantation (TAVI): the TASQ registry.

Background: Patients with severe aortic stenosis (AS) have a reduced life expectancy and quality of life (QoL), owing to advanced age and the presence of multiple comorbidities. Currently, there is no AS-specific QoL measurement tool, which prevents an accurate assessment of how this chronic condition and its treatment affect patients. The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) was developed in order to address this deficiency. Methods: The present trial protocol was designed to enable validation of the TASQ, which has been produced in five languages (English, French, German, Italian and Spanish) to increase usability. Patients with severe AS who are undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) will be asked to complete the TASQ and, for comparative purposes, the Kansas City Cardiomyopathy Questionnaire and the general health-related QoL Short Form-12 questionnaire. The questionnaires will be completed prior to the intervention, at discharge, as well as at 30 days and 3 months follow-up. A total of 290 patients will be recruited across one Canadian and nine European centres. Overall, the protocol validation aims to include 120 patients undergoing transfemoral TAVI (TF-TAVI), 120 undergoing SAVR and up to 50 being treated medically. The primary objective of the registry is to validate the TASQ in five different languages. The secondary objective is to assess the utility of the TASQ for assessing differences in QoL outcome between patients undergoing TF-TAVI, SAVR or medical management for their AS. Discussion: Validation and roll-out of the TASQ will enable clinicians to capture an accurate assessment of how AS and its management affects the QoL of patients and will help them to determine the most appropriate treatment strategy for individual patients. Trial registration number: NCT03186339.

Relevance of Sp Binding Site Polymorphism in WWOX for Treatment Outcome in Pancreatic Cancer.

BACKGROUND: A genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects. METHODS: This study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy. The primary outcome was the relationship between germline polymorphisms and OS. Functional assays addressed pharmacological dose-response effects in lymphoblastoid cell lines (LCLs) and pancreatic cancer cell lines (including upon RNAi), gene expression analyses, and allele-specific transcription factor binding. All statistical tests were two-sided. RESULTS: The A allele (26% in Caucasians) at SNP rs11644322 in the putative tumor suppressor gene WWOX conferred worse prognosis. Median OS was 14 months (95% confidence interval [CI] = 12 to 15 months), 13 months (95% CI = 11 to 15 months), and nine months (95% CI = 7 to 12 months) for the GG, GA, and AA genotypes, respectively (P trend < .001 for trend in univariate log-rank assuming a codominant mode of inheritance; advanced disease subgroup P trend < .001). Mean OS was 25 months (95% CI = 21 to 29 months), 19 months (95% CI = 15 to 22 months), and 13 months (95% CI = 10 to 16 months), respectively. This effect held true after adjustment for age, performance status according to Eastern Cooperative Oncology Group classification, TNM, grading, and resection status and was comparable with the strongest established prognostic factors in multivariable analysis. Consistently, reduced responsiveness to gemcitabine, but not 5-fluorouracil, along with lower WWOX expression was demonstrated in LCLs harboring the AA genotype. Likewise, RNAi-mediated WWOX knockdown in pancreatic cancer cells confirmed differential cytostatic drug sensitivity. In electrophoretic mobility shift assays, the A allele exhibited weaker binding of Sp family members Sp1/Sp3. CONCLUSIONS: WWOX rs11644322 represents a major predictive factor in gemcitabine-treated pancreatic cancer. Decreased WWOX expression may interfere with gemcitabine sensitivity, and allele-specific binding at rs11644332 might be a causative molecular mechanism behind the observed clinical associations.

Plant polyphenols and oxidative metabolites of the herbal alkenylbenzene methyleugenol suppress histone deacetylase activity in human colon carcinoma cells.

Evidence has been provided that diet and environmental factors directly influence epigenetic mechanisms associated with cancer development in humans. The inhibition of histone deacetylase (HDAC) activity and the disruption of the HDAC complex have been recognized as a potent strategy for cancer therapy and chemoprevention. In the present study, we investigated whether selected plant constituents affect HDAC activity or HDAC1 protein status in the human colon carcinoma cell line HT29. The polyphenols (-)-epigallocatechin-3-gallate (EGCG) and genistein (GEN) as well as two oxidative methyleugenol (ME) metabolites were shown to inhibit HDAC activity in intact HT29 cells. Concomitantly, a significant decrease of the HDAC1 protein level was observed after incubation with EGCG and GEN, whereas the investigated ME metabolites did not affect HDAC1 protein status. In conclusion, dietary compounds were found to possess promising HDAC-inhibitory properties, contributing to epigenetic alterations in colon tumor cells, which should be taken into account in further risk/benefit assessments of polyphenols and alkenylbenzenes.