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 αIIbβ3. 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.
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.
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.
On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. ...Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.
Data regarding the impact of infra-Hisian conduction disturbances leading to permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) remain limited. The aim of ...this study was to determine the impact of right and/or left bundle branch block (RBBB/LBBB) on post-TAVI PPI. We performed a systematic literature review to identify studies reporting on RBBB and/or LBBB status and post-TAVI PPI. Study design, patient characteristics, and the presence of branch block were analyzed. Odds ratios (ORs) with 95% CI were extracted. The final analysis included 36 studies, reporting about 55,851 patients. Data on LBBB were extracted from 33 studies. Among 51,026 patients included, 5503 showed pre-implant LBBB (11.9% (10.4%–13.8%)). The influence of LBBB on post-TAVI PPI was not significant OR 1.1474 (0.9025; 1.4588), p = 0.2618. Data on RBBB were extracted from 28 studies. Among 46,663 patients included, 31,603 showed pre-implant RBBB (9.2% (7.3%–11.6%)). The influence of RBBB on post-TAVI PPI was significant OR 4.8581 (4.1571; 5.6775), p < 0.0001. From this meta-analysis, the presence of RBBB increased the risk for post-TAVI PPI, independent of age or LVEF, while this finding was not confirmed for patients experimenting with LBBB. This result emphasizes the need for pre-operative evaluation strategies in patient selection for TAVI.
Bioprosthetic aortic valve thrombosis is a rare complication after transcatheter aortic valve implantation; however, one with a high mortality. We describe the case of a patient with a completely ...thrombosed transcatheter aortic valve prosthesis 9 months after implantation and review the diagnosis and management of this complication.
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.
Aims
Therapeutic windows for residual platelet reactivity in patients with coronary artery disease on P2Y12 inhibitors were proposed in a consensus document. We aimed to explore the level of ...agreement between windows for different platelet function tests (PFTs) used to classify patients in low, optimal, and high on-treatment platelet reactivity categories, and to identify variables contributing to the level of agreement.
Methods and results
In this explorative clinical study, the VerifyNow P2Y12, Multiplate adenosine diphosphate (ADP), and light transmission aggregometry (LTA) 20 μmol/L ADP were performed simultaneously in 145 consecutive vulnerable patients. Measurements were performed within 6 months of percutaneous intervention. Patients were considered vulnerable if they had ≥2 risk factors for bleeding or ischaemic events. Window-agreement between PFT pairs was slight to moderate. Multiplate–VerifyNow agreed in 72 patients (50%), κ = 0.41; VerifyNow–LTA agreed in 76 patients (52%), κ = 0.36; and LTA–Multiplate agreed in 64 patients (44%), κ = 0.20. Several variables including the type of P2Y12 inhibitor, aspirin, haemoglobin level, platelet count, age, and previous stroke significantly influenced agreement between PFTs.
Conclusions
Our results suggest that the PFTs, with accompanying therapeutic windows, are not interchangeable when determining the response to antiplatelet therapy in vulnerable coronary artery disease patients on P2Y12 inhibitors. Hence, the type of PFT can directly affect the treatment strategy, which may be especially relevant for patients with multiple factors influencing individual PFTs and thereby test agreement.
We present the use of intraoperative open-heart coronary angiography in a patient with aortic valve endocarditis and extensive coronary calcification on coronary computed tomography angiography. ...Open-heart angiography was performed intraoperatively and revealed no significant stenoses. Aortic valve replacement without concomitant bypass surgery was performed, and the patient had an uneventful postoperative course.
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.
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.
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, I
=0%). Although the estimated posterior probability of
benefit was 94.4%, the probability of a
was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses.
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.
CRD42023407006.
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