Upper extremity versus lower extremity for secondary access during transcatheter aortic valve implantation: rationale and design of the randomised TAVI XS trial.

BACKGROUND: During transcatheter aortic valve implantation (TAVI), secondary access is required for angiographic guidance and temporary pacing. The most commonly used secondary access sites are the femoral artery (angiographic guidance) and the femoral vein (temporary pacing). An upper extremity approach using the radial artery and an upper arm vein instead of the lower extremity approach using the femoral artery and femoral vein may reduce clinically relevant secondary access site-related bleeding complications, but robust evidence is lacking. TRIAL DESIGN: The TAVI XS trial is a multicentre, randomised, open-label clinical trial with blinded evaluation of endpoints. A total of 238 patients undergoing transfemoral TAVI will be included. The primary endpoint is the incidence of clinically relevant bleeding (i.e. Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding) of the randomised secondary access site (either diagnostic or pacemaker access, or both) within 30 days after TAVI. Secondary endpoints include time to mobilisation after TAVI, duration of hospitalisation, any BARC type 2, 3 or 5 bleeding, and early safety at 30 days according to Valve Academic Research Consortium­3 criteria. CONCLUSION: The TAVI XS trial is the first randomised trial comparing an upper extremity approach to a lower extremity approach with regard to clinically relevant secondary access site-related bleeding complications. The results of this trial will provide important insights into the safety and efficacy of an upper extremity approach in patients undergoing transfemoral TAVI.

Assessment of paravalvular regurgitation after transcatheter aortic valve replacement using 2D multi-venc and 4D flow CMR.

AIMS: To compare the novel 2D multi-venc and 4D flow acquisitions with the standard 2D flow acquisition for the assessment of paravalvular regurgitation (PVR) after TAVR using cardiac magnetic resonance (CMR)-derived regurgitant fraction (RF). METHODS AND RESULTS: In this prospective study, patients underwent CMR one month after TAVR to assess PVR using 2D multi-venc and 4D flow, in addition to standard 2D flow. Scatterplots and Bland-Altman plots were used to assess correlation and visualize agreement between techniques. Reproducibility of measurements was assessed with intraclass correlation coefficients. The study included 21 patients (mean age, 80 years ± 5 [SD], 9 men). Mean RF was 11.7 ± 10.0% using standard 2D flow, 10.6 ± 7.0% using 2D multi-venc flow, and 9.6 ± 7.3% using 4D flow. There was a very strong correlation between the RFs assessed with 2D multi-venc and standard 2D flow (r = 0.88, p < 0.001), and a strong correlation between the RFs assessed with 4D flow and standard 2D flow (r = 0.74, p < 0.001). Bland-Altman plots revealed no significant bias between the RFs (2D multi-venc: 1.3%; 4D flow: 0.3%). Intra- and interobserver reproducibility for 2D multi-venc flow were 0.98 and 0.97, respectively; and 0.92 and 0.90 for 4D flow, respectively. CONCLUSION: 2D multi-venc and 4D flow produce accurate quantification of PVR after TAVR. The fast acquisition of the 2D multi-venc sequence, and the free-breathing acquisition with retrospective plane selection of the 4D flow sequence provide useful advantages in clinical practice, especially in the frail TAVR population.

Using Upper Arm Vein as Temporary Pacemaker Access Site: A Next Step in Minimizing the Invasiveness of Transcatheter Aortic Valve Replacement.

Background The femoral vein is commonly used as a pacemaker access site during transcatheter aortic valve replacement (TAVR). Using an upper arm vein as an alternative access site potentially causes fewer bleeding complications and shorter time to mobilization. We aimed to assess the safety and efficacy of an upper arm vein as a temporary pacemaker access site during TAVR. Methods We evaluated all patients undergoing TAVR in our center between January 2020 and January 2023. Upper arm, femoral, and jugular vein pacemaker access was used in 255 (45.8%), 191 (34.3%), and 111 (19.9%) patients, respectively. Clinical outcomes were analyzed according to pacemaker access in the overall population and in a propensity-matched population involving 165 upper arm and 165 femoral vein patients. Primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 pacemaker access site-related bleeding. Results In the overall population, primary endpoint was lowest for upper arm, followed by femoral and jugular vein access (2.4% vs. 5.8% vs. 10.8%, p = 0.003). Time to mobilization was significantly longer (p < 0.001) in the jugular cohort compared with the other cohorts. In the propensity-matched cohort, primary endpoint showed a trend toward lower occurrence in the upper arm compared with the femoral cohort (2.4% vs. 6.1%, p = 0.10). Time to mobilization was significantly shorter (480 vs. 1140 min, p < 0.001) in the upper arm cohort, with a comparable skin-to-skin time (83 vs. 85 min, p = 0.75). Cross-over from upper arm pacemaker access was required in 17 patients (6.3% of attempted cases via an upper arm vein). Conclusions Using an upper arm vein as a temporary pacemaker access site is safe and feasible. Its use might be associated with fewer bleeding complications and shorter time to mobilization compared with the femoral vein.

Periprocedural continuation versus interruption of oral anticoagulant drugs during transcatheter aortic valve implantation: rationale and design of the POPular PAUSE TAVI trial.

About one-third of patients undergoing transcatheter aortic valve implantation (TAVI) use oral anticoagulants (OAC), mainly due to atrial fibrillation. General guidelines advise interrupting OAC in patients with a high risk of bleeding undergoing interventions. However, preliminary observational data suggest that the continuation of OAC during TAVI is safe and may reduce the risk of periprocedural thromboembolic events. The Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI) is a multicentre, randomised clinical trial with open-label treatment and blinded endpoint assessment. Patients are randomised 1:1 to periprocedural continuation versus interruption of OAC and are stratified for vitamin K antagonist or direct oral anticoagulant use. The primary endpoint is a composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding within 30 days after TAVI, according to the Valve Academic Research Consortium-3 criteria. Secondary endpoints include separate individual and composite outcomes, quality of life and cost-effectiveness. Since continuation of OAC is associated with the ancillary benefit that it simplifies periprocedural management, the primary outcome is first analysed for non-inferiority; if non-inferiority is proven, superiority will be tested. Recruitment started in November 2020, and the trial will continue until a total of 858 patients have been included and followed for 90 days. In summary, POPular PAUSE TAVI is the first randomised clinical trial to assess the safety and efficacy of periprocedural continuation versus interruption of OAC in patients undergoing TAVI.

Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.

AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Diastolic delta best predicts paravalvular regurgitation after transcatheter aortic valve replacement as assessed by cardiac magnetic resonance: the APPOSE trial.

AIMS: Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement (TAVR) that poses an increased risk of rehospitalization for heart failure and mortality. The aim of this study was to assess the accuracy of haemodynamic indices to predict relevant PVR. METHODS AND RESULTS: In this prospective single-centre clinical trial, four haemodynamic indices of PVR measured during TAVR were assessed for their correlation with gold standard cardiac magnetic resonance (CMR)-derived regurgitant fraction (CMR-RF) at 1 month follow-up: diastolic delta (DD), heart rate-adjusted diastolic delta (HR-DD), aortic regurgitation index (ARI), and aortic regurgitation index ratio (ARI ratio). These haemodynamic indices were analysed for their ability to predict relevant PVR (defined as CMR-RF > 20%) using receiver operating characteristic (ROC) curves with corresponding area under the ROC curves (AUCs). A total of 77 patients were included and had CMR performed 41 ± 14 days after TAVR. Mean CMR-RF was 12.4 ± 9.3%. Fifteen (19.5%) patients had CMR-RF > 20%. DD had the best correlation with CMR-RF and the highest AUC to predict relevant PVR (0.82; 95% CI, 0.72-0.92), followed by HR-DD (AUC 0.78; 95% CI, 0.67-0.89), ARI (AUC 0.78; 95% CI, 0.66-0.89), and ARI ratio (AUC 0.65; 95% CI, 0.49-0.81). The optimal cut-off value for DD was 32 mmHg, with sensitivity of 69% and specificity of 77% in predicting relevant PVR. CONCLUSION: DD measured during TAVR best predicts relevant PVR. Correction for heart rate (HR-DD) or systolic blood pressure (ARI, ARI ratio) did not improve this predictive value.

Reduction of Gastrointestinal Bleeding in Patients With Heyde Syndrome Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Heyde syndrome is the co-occurrence of aortic stenosis and gastrointestinal bleeding secondary to angiodysplasias. Surgical aortic valve replacement effectively reduces bleeding, but the effects of transcatheter aortic valve implantation (TAVI) are largely unknown. This study aimed to describe the reduction of gastrointestinal bleeding in patients with Heyde syndrome after TAVI and to identify the factors associated with rebleeding. METHODS: We enrolled patients with Heyde syndrome from a prospective TAVI registry. Gastrointestinal bleeding episodes were assessed by the Bleeding Academic Research Consortium classification, and cumulative incidence functions were used to calculate cessation rates. Factors potentially associated with rebleeding were analyzed using logistic regression. Differences between Heyde and non-Heyde patients were assessed through a case-cohort study. RESULTS: Between December 2008 and June 2020, 1111 patients underwent TAVI. There were 70 patients with Heyde syndrome (6.3%). In the first year following TAVI, gastrointestinal bleeding ceased in 46 of 70 patients (62% [95% CI, 50%-74%]). Bleeding episodes decreased from 3.2 (95% CI, 2.5-4.2) to 1.6 ([95% CI, 1.2-2.2] P=0.001) and hemoglobin levels increased from 10.3 (95% CI, 10.0-10.8) to 11.3 (95% CI, 10.8-11.6) g/dL (P=0.007). Between 1 and 5 years after TAVI (35 [interquartile range, 21-51] months), 53 of 62 patients (83% [95% CI, 72%-92%]) no longer experienced gastrointestinal bleeding. Paravalvular leakage (≥mild) was associated with rebleeding risk (odds ratio, 3.65 [95% CI, 1.36-9.80]; P=0.010). Periprocedural bleeding was more common in Heyde than in control patients (adjusted odds ratio, 2.55 [95% CI, 1.37-4.73]; P=0.003). CONCLUSIONS: Patients with Heyde syndrome are at increased risk for periprocedural bleeding. Post-TAVI, gastrointestinal bleeding disappears in the majority of patients. Paravalvular leakage may curtail these clinical benefits.

Transcatheter aortic valve replacement during the COVID-19 pandemic-A Dutch single-center analysis.

BACKGROUND AND AIM OF THE STUDY: The coronavirus disease 2019 (COVID-19) pandemic has put an enormous strain on healthcare systems and intensive care unit (ICU) capacity, leading to suspension of most elective procedures, including transcatheter aortic valve replacement (TAVR). However, deferment of TAVR is associated with significant wait-time mortality in patients with severe aortic valve stenosis. Conversely, there is currently no data available regarding the safety and feasibility of a continued TAVR program during this unprecedented crisis. The aim of this study is to evaluate the safety and feasibility of patients undergoing TAVR during the COVID-19 pandemic in our center, with specific emphasis on COVID-19 related outcomes. METHODS: All patients who underwent TAVR in our center between February 27, 2020, and June 30, 2020, were evaluated. Clinical outcomes were described in terms of Valve Academic Research Consortium 2 definitions. Patient follow-up was done by chart review and telephone survey. RESULTS: A total of 71 patients have undergone TAVR during the study period. Median age was 80 years, 63% were men, and 25% were inpatients. Procedural success was 99%. After TAVR, 30% involved admission to the ICU, and 94% were ultimately discharged to the cardiac care unit on the same day. Two patients (3%) had confirmed COVID-19 a few days after TAVR, and both died of COVID-19 pneumonia within 2 weeks after hospital discharge. CONCLUSIONS: A continued TAVR program during the COVID-19 pandemic is feasible despite limited hospital resources. However, COVID-19 related mortality after TAVR is of concern.

Rationale and design of the PRAETORIAN-COVID trial: A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease.

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2-infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.