Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Platelet glycoprotein IIb/IIIa inhibitor tirofiban in clopidogrel-naïve patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The safety of administration of tirofiban, a platelet glycoprotein IIb/IIIa inhibitor, followed by a clopidogrel loading dose in clopidogrel-naïve patients undergoing ad-hoc percutaneous coronary intervention (PCI) is not yet clear. METHODS: In a retrospective observational cohort analysis, clopidogrel-naïve patients undergoing ad-hoc PCI who received a high-dose bolus of tirofiban (25 µg/kg) followed by a 600-mg clopidogrel loading dose (group 1) were compared with patients undergoing elective PCI who were pretreated with clopidogrel (group 2), between September 2014 and October 2021. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction, stroke, target-lesion revascularisation and bleeding at 30 days. Secondary outcomes were MACE at 7 days and individual components of the primary outcome at 7 and 30 days. RESULTS: A total of 1404 patients were included: 432 (31%) in group 1 and 972 (69%) in group 2. Median age was 69 years, and 28% were female. At 7­day follow-up, MACE occurred in 1.4% in group 1 versus 3.0% in group 2 (p = 0.08). 30-day MACE were observed in 1.9% in group 1 and 4.2% in group 2 (p = 0.03). Secondary outcomes were comparable between the groups. Cox regression analysis, corrected for baseline differences, revealed no significant difference in the primary outcome (hazard ratio: 1.8; 95% confidence interval: 0.8-3.9). CONCLUSION: Ad-hoc PCI in clopidogrel-naïve patients who were treated with high-dose bolus of tirofiban followed by a clopidogrel loading dose immediately after the procedure appeared to be safe.

Long-term outcome after deferred revascularization due to negative fractional flow reserve in intermediate coronary lesions.

OBJECTIVES: The aim was to assess long-term outcome after deferring intervention of coronary lesions with a fractional flow reserve (FFR) value of >0.80 in a real-world patient population and then to identify factors associated with deferred target lesion failure (DTLF). BACKGROUND: Deferring coronary interventions of intermediate lesions based on FFR measurement is safe, irrespective of the extent of coronary artery disease. However, FFR values near the cut-off of >0.80 may have less favorable outcome. METHODS: A retrospective analysis was performed in patients with deferred coronary intervention based on FFR value >0.80. The primary endpoint was DTLF, a composite of acute coronary syndrome (ACS) and any coronary revascularization, related to the initially deferred stenosis. RESULTS: A total of 600 patients, mean age of 66 ± 10 years, and 751 coronary lesions with negative FFR values (mean 0.88 ± 0.04) were included. The mean follow-up was 27 ± 15 months. DTLF occurred in 44 patients (7.3%), revascularization in 42 (7%), and ACS without revascularization in 2 patients (0.3%). Patients with DTLF more often had diabetes mellitus, previous coronary artery bypass grafting, multivessel disease (MVD), and lower FFR at inclusion. Multivariable regression analysis showed that lower deferred FFR values [FFR 0.81-0.85: hazard ratio (HR) 2.79 (95% CI [confidence interval]; 1.46-5.32), p .002], MVD [HR 1.98 (95% CI; 1.05-3.75), p .036], distal lesions [HR 2.43 (95% CI; 1.29-4.57), p .006], and lesions located in a saphenous vein graft (SVG) [HR 6.35 (95% CI; 1.81-22.28), p .004] were independent predictors for DTLF. CONCLUSIONS: The long-term rate of DTLF of initially deferred coronary lesions was 7.3%. Independent predictors for DTLF are lower deferred FFR value, the presence of MVD, distal lesions, and lesions in SVG.

Urgent transcatheter aortic valve implantation in an all-comer population: a single-centre experience.

BACKGROUND: When compared with older reports of untreated symptomatic aortic valve stenosis (AoS), urgent transcatheter aortic valve implantation (u-TAVI) seems to improve mortality rates. We performed a single centre, retrospective cohort analysis to characterize our u-TAVI population and to identify potential predictors of worse outcomes. METHODS: We performed a retrospective analysis of 631 consecutive TAVI patients between 2013 and 2018. Of these patients, 53 were categorized as u-TAVI. Data was collected from the local electronic database. RESULTS: Urgent patients had more often a severely decreased left ventricular ejection fraction (LVEF < 30%) and increased creatinine levels (115.5 [88-147] vs 94.5 [78-116] mmol/l; p = 0.001). Urgent patients were hospitalised for 18 [10-28] days before and discharged 6 [4-9] days after the implantation. The incidence of peri-procedural complications and apical implantations was comparable among the study groups. Urgent patients had higher in-hospital (11.3% vs 3.1%; p = 0.011) and 1-year mortality rates (28.2% vs 8.5%, p < 0.001). An increased risk of one-year mortality was associated with urgency (HR 3.5; p < 0.001), apical access (HR 1.9; p = 0.016) and cerebrovascular complications (HR 4.3; p = 0.002). Within the urgent group, the length of pre-hospital admission was the only significant predictor of 1-year mortality (HR 1.037/day; p = 0.003). CONCLUSIONS: Compared to elective procedures, u-TAVI led to increased mortality and comparable complication rates. This detrimental effect is most likely related to the length of pre-procedural hospitalisation of urgent patients.

Incidence and predictors of permanent pacemaker implantation after surgical aortic v alve replacement: Data of the Netherlands Heart Registration (NHR).

OBJECTIVE: Permanent pacemaker implantation (PPI) after surgical aortic valve replacement (SAVR) remains a frequent complication. Predictors, however, have been mainly investigated in single-center studies. Therefore, nationwide data were used to identify patients-and procedural risk factors for postoperative PPI. MATERIALS AND METHODS: Data were retrospectively collected from the Netherlands Heart Registration (NHR). Patients enrolled in the NHR undergoing isolated SAVR from 2013 to 2019 were analyzed. Primary endpoint was in-hospital PPI during hospitalization after SAVR. RESULTS: From the NHR database, 5600 patients with symptomatic aortic valve stenosis were included in the study. Crude incidence of post-SAVR PPI was 4.0%. Backward regression analysis identified previous cardiac surgery (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.18-2.76), extra-corporeal circulation time (OR: 1.01; 95% CI: 1.00-1.01), vasopressor use (OR: 2.66; 95% CI: 1.79-3.96) and in-hospital cardiac conduction abnormalities (OR: 4.48; 95% CI: 3.36-5.98) as potential predictors for PPI. Across the time, PPI after SAVR significantly increased (OR: 1.11; 95% CI: 1.03-1.21). CONCLUSIONS: From this nationwide analysis, PPI after SAVR remains a low but increasingly frequent complication. Several predictive factors for postoperative PPI after SAVR have been identified and might be useful for patient informed consent about potential adverse event rate.

Effective Distance between Aortic Valve and Conduction System Is an Independent Predictor of Persistent Left Bundle Branch Block during Transcatheter Aortic Valve Implantation.

Background and objectives: Persistent left bundle branch block (P-LBBB) has been associated with poor clinical outcomes of transcatheter aortic valve implantation (TAVI) procedures. We hypothesized that the distance from the aortic valve to the proximal conduction system, expressed as the effective distance between the aortic valve and conduction system (EDACS), can predict the occurrence of P-LBBB in patients undergoing a TAVI procedure. Materials and methods: In a retrospective study, data from 269 patients were analyzed. EDACS was determined using two longitudinal CT sections. Results: Sixty-four of the patients developed P-LBBB. EDACS ranged between -3 and +18 mm. EDACS was significantly smaller in P-LBBB than in non-P-LBBB patients (4.6 (2.2-7.1) vs. 8.0 (5.8-10.2) mm, median values (interquartile range); p < 0.05). Receiver operating characteristic analysis showed an area under the curve of 0.78 for predicting P-LBBB based on EDACS. In patients with EDACS of ≤3 mm and >10 mm, the chance of developing P-LBBB was ≥50% and <10%, respectively. Conclusions: A small EDACS increases the risk for the development of P-LBBB during TAVI by a factor of >25. As EDACS can be measured pre-procedurally, it may be a valuable additional factor to weigh the risks of transcatheter and surgical aortic valve replacement.

Occurrence and Persistency of Conduction Disturbances during Transcatheter Aortic Valve Implantation.

Background and Objectives: Conduction disturbances such as left bundle branch block (LBBB) and complete atrio-ventricular block (cAVB) are relatively frequent complications following trans-catheter aortic valve implantation (TAVI). We investigated the dynamics of these conduction blocks to further understand luxating factors and predictors for their persistency. Materials and Methods: We prospectively included 157 consecutive patients who underwent a TAVI procedure. Electrocardiograms (ECGs) were obtained at specific time points during the TAVI procedure and at follow-up until at least six months post-procedure. Results: Of the 106 patients with a narrow QRS complex (nQRS) before TAVI, ~70% developed LBBB; 28 (26.4%) being classified as super-transient (ST-LBBB), 20 (18.9%) as transient (T-LBBB) and 24 (22.6%) as persistent (P-LBBB). Risk of LBBB was higher for self-expandable (SE) than for balloon-expandable (BE) prostheses and increased with larger implant depth. During the TAVI procedure conduction disturbances showed a dynamic behavior, as illustrated by alternating kinds of blocks in 18 cases. Most LBBBs developed during balloon aortic valvuloplasty (BAV) and at positioning and deployment of the TAVI prosthesis. The incidence of LBBB was not significantly different between patients who did and did not undergo BAV prior to TAVI implantation (65.3% and 74.2%, respectively (p = 0.494)). Progression to cAVB was most frequent for patients with preexisting conduction abnormalities (5/34) patients) and in patients showing ST-LBBB (6/28). Conclusions: During the TAVI procedure, conduction disturbances showed a dynamic behavior with alternating types of block in 18 cases. After a dynamic period of often alternating types of block, most BBBs are reversible while one third persist. Patients with ST-LBBB are most prone to progressing into cAVB. The observation that the incidence of developing LBBB after TAVI is similar with and without BAV suggests that a subgroup of patients has a substrate to develop LBBB regardless of the procedure.

Clinical assessment of aortic valve stenosis: Comparison between 4D flow MRI and transthoracic echocardiography.

BACKGROUND: The prevalence of valvular aortic stenosis (AS) increases as the population ages. Echocardiographic measurements of peak jet velocity (Vpeak ), mean pressure gradient (Pmean ), and aortic valve area (AVA) determine AS severity and play a pivotal role in the stratification towards valvular replacement. A multimodality imaging approach might be needed in cases of uncertainty about the actual severity of the stenosis. PURPOSE: To compare four-dimensional phase-contrast magnetic resonance (4D PC-MR), two-dimensional (2D) PC-MR, and transthoracic echocardiography (TTE) for quantification of AS. STUDY TYPE: Prospective. POPULATION: Twenty patients with various degrees of AS (69.3 ± 5.0 years). FIELD STRENGTH/SEQUENCES: 4D PC-MR and 2D PC-MR at 3T. ASSESSMENT: We compared Vpeak , Pmean , and AVA between TTE, 4D PC-MR, and 2D PC-MR. Flow eccentricity was quantified by means of normalized flow displacement, and its influence on the accuracy of TTE measurements was investigated. STATISTICAL TESTS: Pearson's correlation, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. RESULTS: 4D PC-MR measured higher Vpeak (r = 0.95, mean difference + 16.4 ± 10.7%, P <0.001), and Pmean (r = 0.92, mean difference + 14.9 ± 16.0%, P = 0.013), but a less critical AVA (r = 0.80, mean difference + 19.9 ± 20.6%, P = 0.002) than TTE. In contrast, unidirectional 2D PC-MR substantially underestimated AS severity when compared with TTE. Differences in Vpeak between 4D PC-MR and TTE showed to be strongly correlated with the eccentricity of the flow jet (r = 0.89, P <0.001). Use of 4D PC-MR improved the concordance between Vpeak and AVA (from 0.68 to 0.87), and between PGmean and AVA (from 0.68 to 0.86). DATA CONCLUSION: 4D PC-MR improves the concordance between the different AS parameters and could serve as an additional imaging technique next to TTE. Future studies should address the potential value of 4D PC-MR in patients with discordant echocardiographic parameters. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:472-480.

Protracted aortic valve closure during peripheral veno-arterial extracorporeal life support: is intra-aortic balloon pump an effective solution?

BACKGROUND: Left ventricular (LV) afterload increase with protracted aortic valve (AV) closure may represent a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). The aim of the present study was to assess the effects of an intra-aortic balloon pump (IABP) to overcome such a hemodynamic shortcoming in patients submitted to peripheral V-A ECMO. METHODS: Among 184 adult patients who were treated with peripheral V-A ECMO support at Medical University Center Maastricht Hospital between 2007 and 2018, patients submitted to IABP implant for protracted AV closure after V-A ECMO implant were retrospectively identified. All clinical and hemodynamic data, including echocardiographic monitoring, were collected and analyzed. RESULTS: During the study period, 10 subjects (mean age 60 years old, 80% males) underwent IABP implant after peripheral V-A ECMO positioning due to the diagnosis of protracted AV closure and inefficient LV unloading as assessed by echocardiography and an absence of pulsation in the arterial pressure wave. Recovery of blood pressure pulsatility and enhanced LV unloading were observed in 8 patients after IABP placement, with no significant differences in the main hemodynamic parameters, inotropic therapy or in the ECMO flow (p=0.48). The weaning rate in this patient subgroup (mean ECMO duration 8 days), however, was only 10%, with another patient finally transplanted, leading to a 20% survival-to-hospital discharge. CONCLUSION: IABP placement was an effective solution in order to reverse the protracted AV closure and impaired LV unloading observed during peripheral V-A ECMO support. However, the impact on the weaning rate and survival needs further investigations.

Reservations about the Selvester QRS score in left bundle branch block - Experience in patients with transcatheter aortic valve implantation.

BACKGROUND: The Selvester QRS score (S-score) estimates myocardial scar using electrocardiographic criteria. We evaluated the S-score for left bundle branch block (LBBB). MATERIAL AND METHODS: Studied were 36 patients who developed persistent LBBB upon transcatheter aortic valve implantation (TAVI, TAVI-LBBB group) and 36 matched patients with persistent narrow QRS (TAVI-nQRS group). Electrocardiograms were recorded before and briefly after TAVI and during ~6months follow-up. S-score was calculated using criteria for hypertrophic (in absence of LBBB) or LBBB hearts. RESULTS: In TAVI-LBBB patients correlation between S-scores pre-TAVI and post-TAVI was absent (R2=0.023). High S-scores post-TAVI occurred in patients with low pre-TAVI scores. Pre-post TAVI scores correlated weakly in TAVI-nQRS (R2=0.182), indicating a possible influence of ventricular unloading by TAVI. In both groups S-scores at post-TAVI and follow-up compared reasonably (R2=0.389 and R2=0.386), indicating reproducibility in more stable conditions. CONCLUSION: This study indicates that the use of the LBBB S-score criteria overestimates scar size and that caution is recommended in the use of the score in patients with LBBB.

Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and impair survival. Current guidelines recommend the temporary addition of clopidogrel in the initial period after TAVI to prevent thromboembolic events. However, explorative studies suggest that this is associated with a higher rate of major bleeding without a decrease in thromboembolic complications. METHODS: The POPular TAVI trial is a prospective randomized, controlled, open-label multicenter clinical trial to test the hypothesis that monotherapy with aspirin or oral anticoagulation (OAC) after TAVI is safer than the addition of clopidogrel for 3 months, without compromising clinical benefit. This trial encompasses 2 cohorts: cohort A, patients are randomized 1:1 to aspirin vs aspirin + clopidogrel, and cohort B, patients on OAC therapy are randomized 1:1 to OAC vs OAC + clopidogrel. Primary outcome is freedom from non-procedure-related bleeding at 1 year. Secondary net-clinical benefit outcome is freedom from the composite of cardiovascular death, non-procedural-related bleeding, myocardial infarction, or stroke at 1 year. The primary outcome is analyzed for superiority, whereas the secondary outcome is analyzed for noninferiority. Recruitment began in February 2014, and the trial will continue until a total of 1,000 patients (684 expected in cohort A and 316 in cohort B) are included and followed up for 1 year. SUMMARY: The POPular TAVI trial (NCT02247128) is the first large randomized controlled trial to test if monotherapy with aspirin or OAC vs additional clopidogrel after TAVI reduces bleeding with a favorable net-clinical benefit.

Gradual increase in thrombogenicity of juvenile platelets formed upon offset of prasugrel medication.

In patients with acute coronary syndrome, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor like prasugrel is prescribed for one year. Here, we investigated how the hemostatic function of platelets recovers after discontinuation of prasugrel treatment. Therefore, 16 patients who suffered from ST-elevation myocardial infarction were investigated. Patients were treated with aspirin (100 mg/day, long-term) and stopped taking prasugrel (10 mg/day) after one year. Blood was collected at the last day of prasugrel intake and at 1, 2, 5, 12 and 30 days later. Platelet function in response to ADP was normalized between five and 30 days after treatment cessation and in vitro addition of the reversible P2Y12 receptor antagonist ticagrelor fully suppressed the regained activation response. Discontinuation of prasugrel resulted in the formation of an emerging subpopulation of ADP-responsive platelets, exhibiting high expression of active integrin αIIbß3. Two different mRNA probes, thiazole orange and the novel 5'Cy5-oligo-dT probe revealed that this subpopulation consisted of juvenile platelets, which progressively contributed to platelet aggregation and thrombus formation under flow. During offset, juvenile platelets were overall more reactive than older platelets. Interestingly, the responsiveness of both juvenile and older platelets increased in time, pointing towards a residual inhibitory effect of prasugrel on the megakaryocyte level. In conclusion, the gradual increase in thrombogenicity after cessation of prasugrel treatment is due to the increased activity of juvenile platelets.

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non-ST-elevation myocardial infarction patients: design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial.

BACKGROUND: Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA. STUDY DESIGN: In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness. CONCLUSION: The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

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.

Iliofemoral Tortuosity Increases the Risk of Access-Site-Related Complications After Aortic Valve Implantation and Plug-Based Access-Site Closure.

Background: Access-site-related complications are often related to high-risk anatomy and technical pitfalls and impair the outcomes of transfemoral aortic valve implantations (TAVIs). Calcification and tortuosity are widely recognized risk factors, and their impact on procedural planning is left to the implanting experts' discretion. To facilitate decision-making, we introduced a quantitative measure for iliofemoral tortuosity and assessed its predictive value for access-site-related vascular and bleeding complications. Methods: We performed a single-centre prospective cohort study of consecutive, percutaneous transfemoral TAVI performed between April 2019 and March 2020. Medical history and all-cause mortality were extracted from the electronic patient files. Arterial anatomy and calcifications were evaluated using 3mensio Structural Heart software. The primary outcome was access-site-related vascular or bleeding complications. Results: In this elderly, intermediate-risk population, we registered the primary outcome in 43 patients (39%), and major access-site complications in 10 patients (9.2%). Complete hemostasis was achieved in 77 patients (70.6%), by the application of the MANTA plug alone. In the group with access-site-related adverse events, compared with the group without, the tortuosity index was higher median (26% interquartile range [IQR 18%-33%] vs median 19% [IQR 13%-29%], respectively; P = 0.012), as was maximal angulation median (50° [IQR 40°-59°] vs median 43° [IQR 36°-51°], respectively; P = 0.026) were higher. Both variables had a significant effect on our primary outcome, with odds ratios (OR) of 3.1 (tortuosity, P = 0.005) and 2.6 (angulation, P = 0.020). The degree of angulation was a predictor of major complications too (odds ratio 7 [1.4-34.8]; P = 0.017). Conclusions: Steeper angles and greater arterial elongation increase the risk of vascular and bleeding complications after femoral TAVI with the utilization of a plug-based closure device.

Introduction: Les complications liées au site d'accès qui sont souvent associées à une anatomie qui expose à des risques élevés et aux pièges techniques nuisent aux résultats cliniques des implantations valvulaires aortiques par cathéter (TAVI) par voie fémorale. Il est largement reconnu que la calcification et la tortuosité sont des facteurs de risque. Par conséquent, leurs conséquences sur la planification interventionnelle sont laissées à la discrétion des experts en implantation. Pour faciliter la prise de décision, nous avons mis en place une mesure quantitative de tortuosités iliofémorales et évalué sa valeur prédictive sur la survenue de complications vasculaires et hémorragiques liées au site d'accès. Méthodes: Nous avons réalisé une étude de cohorte prospective unicentrique de TAVI percutanées par voie fémorale consécutives effectuées entre avril 2019 et mars 2020. Nous avons extrait les antécédents médicaux et la mortalité toutes causes confondues des dossiers médicaux électroniques. Nous avons évalué l'anatomie artérielle et les calcifications à l'aide du logiciel 3mensio Structural Heart. Le critère de jugement principal était les complications vasculaires ou hémorragiques liées au site d'accès. Résultats: Dans cette population âgée exposée à un risque intermédiaire, nous avons enregistré le critère de jugement principal de 43 patients (39 %), et les principales complications du site d'accès de 10 patients (9,2 %). Soixante-dix-sept patients (70,6 %) ont obtenu l'hémostase complète par la seule application du bouchon MANTA. L'indice de tortuosité était plus élevé dans le groupe qui avait subi des événements défavorables liés au site d'accès que dans le groupe qui n'avait pas subi d'événements défavorables (26 % [18 %-33 %] vs 19 % [13 %-29 %], respectivement; P = 0,012). Il en était de même pour l'angulation maximale (50° [40°-59°] vs 43° [36°-51°], respectivement; P = 0,026) qui était plus grande. Les deux variables ont eu des effets significatifs sur le critère de jugement principal, soit des rapports de cotes (RC) de 3,1 (tortuosité, P = 0,005) et de 2,6 (angulation, P = 0,020). Le degré d'angulation était aussi un prédicteur de complications majeures (rapport de cotes 7 [1,4-34,8]; P = 0,017). Conclusions: Des angles plus prononcés et une plus grande élongation des artères augmentent le risque de complications vasculaires et hémorragiques après la TAVI par voie fémorale lors de l'utilisation d'un dispositif de fermeture à bouchon.

Evolving concepts in the management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation.

Thromboembolic and bleeding complications negatively impact recovery and survival after transcatheter aortic valve implantation (TAVI). Particularly, there is a considerable risk of ischaemic stroke and vascular access related bleeding, as well as spontaneous gastro-intestinal bleeding. Therefore, benefit and harm of antithrombotic therapy should be carefully balanced. This review summarizes current evidence on peri- and post-procedural antithrombotic treatment. Indeed, in recent years, the management of antithrombotic therapy after TAVI has evolved from intensive, expert opinion-based strategies, towards a deescalated, evidence-based approach. Besides per procedural administration of unfractionated heparin, this encompasses single antiplatelet therapy in patients without a concomitant indication for oral anticoagulation (OAC); and OAC monotherapy in patients with such indication, mainly being atrial fibrillation. Combination therapy should generally be avoided to reduce bleeding risk, except after recent coronary stenting where a period of dual antiplatelet therapy (aspirin plus P2Y12-inhibitor) or P2Y12-inhibitor plus OAC (in patients with an independent indication for OAC) is recommended to prevent stent thrombosis. This new paradigm in which reduced antithrombotic intensity leads to improved patient safety, without a loss of efficacy, may be particularly suitable for elderly and fragile patients. Whether this holds in upcoming populations of younger and lower-risk patients and in specific populations as patients with subclinical valve thrombosis, is yet to be proven. Finally, whether less intensive or alternative approaches should be also applied for the periprocedural management of the antithrombotic therapy, has to be determined by ongoing and future studies.

Incidence and Predictors of Permanent Pacemaker Implantation after Transcatheter Aortic Valve Procedures: Data of The Netherlands Heart Registration (NHR).

Atrioventricular conduction disturbance leading to permanent pacemaker (PM) implantation is a frequent and relevant complication after transcatheter aortic valve implantation (TAVI). We aimed to evaluate the rate of post-TAVI permanent PM implantation over time and to identify the predictive factors for post-TAVI PM. The data were retrospectively collected by the Netherlands Heart Registration (NHR). In total, 7489 isolated TAVI patients between 2013 and 2019 were included in the final analysis. The primary endpoint was a permanent PM implantation within 30 days following TAVI. The incidence of the primary endpoint was 12%. Post-TAVI PM showed a stable rate over time. Using multivariable logistic regression analysis, age (OR 1.01, 95% CI 1.00-1.02), weight (OR 1.00, 95% CI 1.00-1.01), creatinine serum level (OR 1.15, 95% CI 1.01-1.31), transfemoral TAVI approach (OR 1.34, 95% CI 1.11-1.61), and TAVI post-dilatation (OR 1.58, 95% CI 1.33-1.89) were shown to be independent predictors of PM. Male sex (OR 0.80, 95% CI 0.68-0.93) and previous aortic valve surgery (OR 0.42, 95% CI 0.26-0.69) had a protective effect on post-TAVI PM. From a large national TAVI registry, some clinical and procedural factors have been identified as promoting or preventing post-TAVI PM. Further efforts are required to identify high-risk patients for post-TAVI PM and to reduce the incidence of this important issue.

One-year pacing dependency after pacemaker implantation in patients undergoing transcatheter aortic valve implantation: Systematic review and meta-analysis.

Objectives: Atrioventricular conductions disturbances, requiring permanent pacemaker implantation (PPI), represent a potential complication after transcatheter aortic valve implantation (TAVI), However, little is known about the pacemaker dependency after PPI in this patient setting. This systematic review analyses the incidence of PPI, the short-term (1-year) pacing dependency, and predictors for such a state after TAVI. Methods: We performed a systematic search in PUBMED, EMBASE, and MEDLINE to identify potentially relevant literature investigating PPI requirement and dependency after TAVI. Study data, patients, and procedural characteristics were extracted. Odds ratio (OR) with 95% confidence intervals were extracted. Results: Data from 23 studies were obtained that included 18,610 patients. The crude incidence of PPI after TAVI was 17% (range, 8.8%-32%). PPI occurred at a median time of 3.2 days (range, 0-30 days). Pacing dependency at 1-year was 47.5% (range, 7%-89%). Self-expandable prosthesis (pooled OR was 2.14 [1.15-3.96]) and baseline right bundle branch block (pooled OR was 2.01 [1.06-3.83]) showed 2-fold greater risk to maintain PPI dependency at 1 year after TAVI. Conclusions: Although PPI represents a rather frequent event after TAVI, conduction disorders have a temporary nature in almost 50% of the cases with recovery and stabilization after discharge. Preoperative conduction abnormality and type of TAVI are associated with higher PPI dependency at short term.