Leaflet Thickening and Motion After Transcatheter Aortic Valve Replacement: Design and Rationale of the Rotterdam Edoxaban Trial.

BACKGROUND: Multislice computed tomography (MSCT) may reveal hypo-attenuated leaflet thickening (HALT) and/or reduced leaflet motion (RELM) in approximately 15 % of patients after transcatheter aortic valve replacement (TAVR). These supposedly thrombogenic phenomena may be associated with neurological events and increased transprosthetic gradients. It is unclear whether oral anticoagulant therapy -specifically a factor Xa inhibitor- could affect the incidence of HALT/RELM. STUDY DESIGN: The Rotterdam EDOXaban (REDOX) trial is an investigator-initiated, single-center, prospective registry in which 100 patients with no formal indication for oral anticoagulant drugs or dual antiplatelet therapy, will receive a 3-month treatment with edoxaban, followed by a MSCT to detect HALT/RELM. The primary endpoint is the incidence of HALT at 3-months follow-up. Secondary endpoints include the incidence of RELM at 3 months; change in transprosthetic gradients at 1 year and the clinical composite endpoint of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism, valve thrombosis and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) at 1 year follow up. The study is powered to demonstrate with 90 % statistical power and a 0.025 alpha a 4 % incidence of HALT with edoxaban as compared to the expected 15 % rate with an antiplatelet regimen and will enroll 100 patients to account for loss of follow-up or CT-drop out. CONCLUSION: The REDOX trial will investigate the short-term effect of an Xa-inhibitor on the incidence of HALT after TAVR. (ClinicalTrials.gov Identifier: NCT04171726).

Left atrial appendage thrombus and cerebrovascular events post-transcatheter aortic valve implantation.

AIMS: To elucidate the frequency and clinical impact of left atrial appendage thrombus (LAAT) in patients set for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: All patients undergoing TAVI between January 2014 and June 2020 with analysable multislice computed tomography (MSCT) for LAAT were included. Baseline and procedural characteristics were collected, pre-procedural MSCT's were retrospectively analysed for LAAT presence. The primary endpoint was defined as the cumulative incidence of any cerebrovascular event (stroke or transient ischaemic attack) within the first year after TAVI. A Cox proportional hazards model was used to identify predictors.A total of 1050 cases had analysable MSCT. Median age was 80 [interquartile range (IQR) 74-84], median Society of Thoracic Surgeons' Predicted Risk Of Mortality (STS-PROM) was 3.4% (IQR 2.3-5.5). Thirty-six percent were on oral anticoagulant therapy for atrial fibrillation (AF). LAAT was present in 48 (4.6%) of cases. Patients with LAAT were at higher operative risk [STS-PROM: 4.9% (2.9-7.1) vs. 3.4% (2.3-5.5), P = 0.01], had worse systolic left ventricular function [EF 52% (35-60) vs. 55% (45-65), P = 0.01] and more permanent pacemakers at baseline (35% vs. 10%, P < 0.01). All patients with LAAT had a history of AF and patients with LAAT were more often on vitamin K antagonist-treatment than patients without LAAT [43/47 (91%) vs. 232/329 (71%), P < 0.01]. LAAT [hazard ratio (HR) 2.94 (1.39-6.22), P < 0.01] and the implantation of more than one valve [HR 4.52 (1.79-11.25), P < 0.01] were independent predictors for cerebrovascular events. CONCLUSION: Patients with MSCT-identified LAAT were at higher risk for cerebrovascular events during the first year after TAVI.

Multidimensional Prognostic Index and Outcomes in Older Patients Undergoing Transcatheter Aortic Valve Implantation: Survival of the Fittest.

Selecting patients with a high chance of endured benefit from transcatheter aortic valve implantation (TAVI) is becoming relevant with changing indications and increasing number of TAVI being performed. The aim of our study was to investigate the association of the multidimensional prognostic index (MPI) based on a comprehensive geriatric assessment (CGA) on survival. The TAVI Care & Cure program is a prospective, observational registry of patients referred for TAVI at the Erasmus MC University Medical Center. Consecutive patients who underwent a complete CGA and TAVI were included. CGA components were used to calculate the MPI score. The impact of the MPI score on survival was evaluated using Cox regression. Furthermore, 376 patients were included, 143 (38.0%) patients belonged to the MPI-1 group and 233 (61.9%) patients to the MPI-2-3 group. After 3 years, 14.9% of the patients in the MPI-1 group and 30.5% of the patients in the MPI-2-3 group died (p = 0.001). Patients in MPI-1 had increased chances of overall survival in comparison with patients in MPI group 2-3 Hazard Ratio (HR) 0.57, (95% Confidence Interval (CI) 0.33-0.98)). In this study we found that the MPI tool could be useful to assess frailty and to predict which patient will have a higher chance of enduring benefit from a TAVI procedure.

Vascular complications with a plug-based vascular closure device after transcatheter aortic valve replacement: Predictors and bail-outs.

BACKGROUND: The MANTA vascular closure device (VCD) is dedicated to large bore access closure and associated with favorable results in selected study populations. Anatomical predictors for access site complications are lacking. AIM: To evaluate MANTA in a real-world population and identify predictors for vascular complications. METHODS: All patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) between January 2016 and May 2020 with MANTA closure were included. Baseline characteristics were collected, pre-procedural computed tomography and post-deployment femoral angiograms were analyzed for anatomical differences. The primary endpoint was a composite of access site related major and minor vascular complications at 30 days follow-up according to the VARC-2 definitions. Secondary endpoints included bleeding, time to hemostasis, procedural length and incomplete arteriotomy closure or arterial occlusion by angiography. A Cox proportional hazards model was used to compare all-cause mortality for patients with and without an access site complication. RESULTS: The 512 patients underwent TAVR with MANTA access closure. Median age was 80 (IQR 75-85), 53% was male, median BMI was 26.4 kg/m2 (IQR 23.4-29.7). Access site related major- or minor vascular complication occurred in 20 (4%) and 23 (4%) of patients respectively. Median time to hemostasis was 42 s (IQR 28-98). Post deployment angiogram showed an occlusion in 24 patients (5%), incomplete closure in 60 patients (12%) or both in three patients (1%). Of these 87 patients, 36 (41%) had a vascular complication. Femoral artery diameter (OR 0.70 [0.53-0.93]), low- (OR 3.47 [1.21-10.00]) and high (OR 2.43 [1.16-5.10]) arteriotomies were independent predictors for vascular complications. CONCLUSION: In this contemporary TAVR population, access-site related complications occurred in 8% of patients and were mainly due to percutaneous closure device failure. Small artery diameter and off-target punctures were independent predictors.

Simplified Trans-Axillary Aortic Valve Replacement Under Local Anesthesia - A Single-Center Early Experience.

BACKGROUND: The axillary artery is an alternative route for patients with comorbidities and unfavorable femoral arteries who need transcatheter aortic valve replacement (TAVR). Simplified trans-axillary transcatheter aortic valve replacement (TAx-TAVR) implies a completely percutaneous approach under local anesthesia and arteriotomy closure with vascular closure techniques. Herein, we report on early experience with simplified TAx-TAVR under local anesthesia. METHODS: We enrolled all consecutive patients who underwent simplified TAx-TAVR in our center. Main study parameter was the incidence of axillary access related major vascular complications within 30 days. Secondary parameters included a composite early safety endpoint, axillary access-site related vascular/bleeding complications and short-term mortality. Post TAVR axillary stent patency was evaluated during follow-up by CT-analysis. RESULTS: Between July 2018 and April 2020, Tax-TAVR was attempted in 35 patients with a mean age of 79 years. Local anesthesia and conscious sedation were used in 91.4% (n = 32) and 8.6% (n = 3) respectively. A covered stent was needed for complete axillary hemostasis in 44.1% (n = 15). Device success was achieved in 91.2% (n = 31/34). The 30-day axillary artery major vascular and ≥major bleeding complication rates were 14% (n = 5) and 11% (n = 4). The early safety endpoint was reached in 22.9% (n = 8). Mortality rates at 30 days and six months were 2.9% and 11.6%. Computed tomography (CT) confirmed axillary stent patency during follow-up in 82% (n = 9/11). CONCLUSIONS: In patients with high/prohibitive surgical risk and unsuitable femoral access, simplified TAx-TAVR under local anesthesia offers a valuable alternative for transfemoral TAVR but requires advanced access site management techniques including covered stents. Our data suggest an unmet clinical need for dedicated TAx closure devices.

Impact of frailty on health-related quality of life 1 year after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) brings symptom relief and improvement in health-related quality of life (HRQoL) in the majority of patients treated for symptomatic, severe aortic stenosis. However, there is a substantial group of patients that do not benefit from TAVI. The aim of this study is to investigate the impact of frailty on HRQoL 1 year after TAVI. METHODS: The TAVI Care & Cure Program is an ongoing, prospective, observational study including patients referred for TAVI to our institution. A comprehensive geriatric assessment was performed to evaluate existence of frailty using the Erasmus Frailty Score (EFS). HRQoL was assessed using the EQ-5D-5 L at baseline and 1 year after TAVI. RESULTS: 239 patients underwent TAVI and completed HRQoL assessment 1 year after TAVI. Seventy (29.3%) patients were classified as frail (EFS ≥ 3). In non-frail patients, the EQ-5D-5 L index did not change (0.71(± 0.22) to 0.68(± 0.33) points, P = 0.22); in frail patients, the EQ-5D-5 L index decreased from 0.55(±0.26) to 0.44 points (±0.33) (P = 0.022). Frailty was an independent predictor of deteriorated HRQoL 1 year after TAVI (OR 2.24, 95% CI 1.07-4.70, P = 0.003). In frail patients, the absence of peripheral artery disease (OR 0.17, 95% 0.05-0.50, P = 0.001) and renal dysfunction (OR 0.13, 95% CI 0.04-0.41, P = <0.001) at baseline was associated with improved HRQoL 1 year after TAVI. CONCLUSION: Frailty is associated with deterioration of HRQoL 1 year after TAVI. Notably, HRQoL did improve in frail patients with no peripheral arterial disease or renal impairment at baseline.

Incidence, determinants and consequences of delirium in older patients after transcatheter aortic valve implantation.

BACKGROUND: delirium is an event leading to negative health outcomes and increased mortality in patients. The aim of this study is to investigate the incidence, determinants and consequences of post-operative delirium (POD) in older patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: The TAVI Care and Cure program is a prospective, observational registry in patients referred for TAVI at Erasmus University Medical Centre. The presence of delirium was evaluated by daily clinical assessment by a geriatrician pre- and up to 3 days post-TAVI. Mortality data were obtained from the Dutch Civil Registry. RESULTS: A total of 543 patients underwent TAVI between January 2014 and December 2017. Overall, the incidence of POD was 14% (75/543 patients) but declined from 18% in 2014 to 7% in 2017 (P = 0.009). Patients who developed POD were older (81.9 ± 5.8 versus 78.6 ± 8.3 years, P < 0.001), had higher prevalence of renal dysfunction and prior stroke (54% versus 40%, P = 0.02; 31% versus 18%, P = 0.01) and were more often frail (32% versus 25%, P = 0.02). From a procedural perspective, general anesthesia (odds ratios (OR), 2.31; 95% CI, 1.40-3.83; P = 0.001), non-transfemoral access (OR, 2.37; 95% CI, 1.20-4.70; P = 0.01) and longer procedural time (OR, 1.01; 95% CI, 1.01-1.02; P < 0.001) were significantly associated with POD. One-year survival rate was 68% among patients who had suffered a POD and was 85% in patients without a POD (hazard ratio's 1.8 (95% CI 1.01-3.10), P = 0.045). CONCLUSION: POD frequently occurs after TAVI and is associated with increased mortality. It might be speculated that patient selection and the minimalistic approach of TAVI may reduce the frequency of delirium.

Impact of Valvulo-Arterial Impedance on Long-Term Quality of Life and Exercise Performance After Transcatheter Aortic Valve Replacement.

BACKGROUND: In aortic stenosis, valvulo-arterial impedance (Zva) estimates the overall left ventricular afterload (valve and arterial component). We investigated the association of Zva (≥5 versus <5 mm Hg mL-1 m-2) on quality of life (QOL) and exercise performance (EP) ≥1 year after transcatheter aortic valve replacement (TAVR). METHODS: The study population consists of 250 TAVR patients in whom baseline Zva and follow-up QOL was prospectively assessed using EuroQOL-5-dimensions instruments; EP was assessed in 192 patients who survived ≥1 year after TAVR using questionnaires related to daily activities. In 124 patients, Zva at 1-year was also available and was used to study the change in Zva (baseline to 1 year) on QOL/EP. RESULTS: Elevated baseline Zva was present in 125 patients (50%). At a median of 28 (IQR, 17-40) months, patients with elevated baseline Zva were more limited in mobility (88% versus 71%; P=0.004), self-care (40% versus 25%; P=0.019), and independent daily activities (taking a shower: 53% versus 38%, P=0.030; walking 100 meter: 76% versus 54%, P=0.001; and walking stairs: 74% versus 54%, P=0.011). By multivariable analysis, elevated Zva predicted unfavorable QOL (lower EuroQOL-5-dimensions-Utility Index, odds ratio, 1.98; CI, 1.15-3.41) and unfavorable EP (any limitation in ≥3 daily activities, odds ratio, 2.55; CI, 1.41-4.62). After TAVR, the proportion of patients with elevated Zva fell from 50% to 21% and remained 21% at 1 year and was found to be associated with more limitations in mobility, self-care, and daily activities compared with patients with Zva <5 mm Hg mL-1 m-2. CONCLUSIONS: Elevated Zva was seen in half of patients and predicted unfavorable long-term QOL and EP. At 1 year after TAVR, the prevalence of elevated Zva was 21% but remained associated with poor QOL/EP.

TAVI Care and Cure, the Rotterdam multidisciplinary program for patients undergoing transcatheter aortic valve implantation: Design and rationale.

BACKGROUND: The capacity of TAVI-programs and numbers of sites performing TAVI has rapidly increased. This necessitated the initiation of the Rotterdam TAVI Care & Cure Program, aiming to improve patient-centered care during the TAVI pathway. METHODS: Consenting patients with severe aortic stenosis and an indication for TAVI will be included. The TAVI Care & Cure program will facilitate prognostic contributions to improve outcomes, patient satisfaction and quality of life in patients with valvular heart disease who are treated with a transcatheter aortic valve implantation in collaboration with the departments of cardiology, cardio-thoracic surgery, anesthesiology and geriatrics. CONCLUSION: With a single center observational registry, we aim to assess the TAVI patient clinical pathway, focusing on pre, peri and post interventional variables including functional status and HRQoL. We will evaluate the patient's complexity by applying an extended multidisciplinary approach, which includes a systematic application of geriatric assessments of frailty and cognitive function.

The Erasmus Frailty Score is associated with delirium and 1-year mortality after Transcatheter Aortic Valve Implantation in older patients. The TAVI Care & Cure program.

BACKGROUND: Frailty in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) has been associated with an increased 1-year mortality rate but the relation of frailty and short term outcomes yields conflicting results. This study investigated the association of a novel and self-developed Erasmus Frailty Score with both short and long term outcomes after TAVI. METHODS: TAVI Care & Cure is an observational ongoing study, which includes consecutive patients undergoing TAVI at the Erasmus University Medical Centre. Prior to the TAVI, frailty status was assessed. The Erasmus Frailty Score (EFS) was defined as follows: 1 point assigned if: MMSE was <27 points, MUST ≥2 points, grip strength <20 kg for females, <30 kg for males, KATZ index ≥1 limited activity, Lawton and Brody index ≥2 limited activity. The maximum score was 5. Patients were classified as frail when the score was ≥3. Presence of delirium was evaluated by daily clinical assessment by a geriatrician pre- and post-TAVI. Mortality data were obtained from the Dutch Civil Registry. The impact of frailty on short and long term outcomes was evaluated. RESULTS: 213 patients were included for analysis. Frailty was present in 28.6% (n = 61), (EFS ≥ 3). Baseline frailty was associated with patients developing a delirium [OR 3.3 (95% CI 1,55-7,10), p = 0.002] and with increased risk of 1-year mortality [HR 2.1 (95% CI 1.01-4.52), p = 0.047]. CONCLUSION: The Erasmus Frailty Score is associated with delirium and 1 year mortality in older patients after TAVI and can be used as a complement to traditional risk factors.

[10 years of transcatheter aortic valve implantation: an overview of the clinical applicability and findings]. / 10 jaar transkatheter-aortaklepvervanging: een overzicht van de klinische toepasbaarheid en bevindingen.

Aortic valve stenosis is a common heart valve disorder in adults. Its prevalence increases with age and is therefore especially seen in older patients. Thirty to forty per cent of patients with symptomatic aortic valve stenosis are not referred for surgical valve replacement because of high age, their medical history or comorbidities. In 2002, the first transcatheter aortic valve implantation (TAVI) was carried out in an inoperable patient. Since 2012, TAVI has been included in international guidelines for heart valve diseases as a treatment strategy in symptomatic patients at a high risk of complications and a life expectancy of more than one year. Decision-making about which treatment is preferable takes a multidisciplinary approach. Important complications of TAVI are bleeding, renal function disorder, stroke, conduction abnormalities, valve insufficiency and death. TAVI procedures are carried out in the Netherlands only in cardiac centres in which specific expertise is present in the areas of structural cardiovascular disease. Scientific research is important for further developments and improvements.