Radosław Wilimski

Incidence, Predictors and Impact of Severe Periprocedural Bleeding According to VARC-2 Criteria on 1-Year Clinical Outcomes in Patients After Transcatheter Aortic Valve Implantation

There are differences in reporting bleeding complications after transcatheter aortic valve implantation (TAVI), which is a consequence of the lack of consensus for their definition. Furthermore, the amount of data on the impact of peri-procedural bleeding on the mid-term prognosis is still limited. The aim of this study was to investigate the incidence, predictors, and impact of life-threatening and major bleedings as defined by the Valve Academic Research Consortium 2 (VARC-2) in patients after TAVI over the mid-term prognosis.Consecutive patients who underwent TAVI from March 2010 to December 2013 were included. All data were classified according to the VARC-2 criteria. We assessed the incidence and the predictors of serious bleeding events (SBE), defined as life-threatening/disabling (LT/D) or major bleeding, and analyzed their impact on 30-day and 1-year clinical outcome.A total of 129 patients were included (79.1 ± 8.3 years; mean EuroSCORE = 17.8 ± 12.7). The SBE occurred in 25 patients (19.4%), of which 9 (7.0%) had LT/D and 16 (12.4%) had major bleeding. Trans-subclavian (TS) access (OR 4.38, 95% CI 2.13-14.29, P = 0.01) and diabetes (OR 2.93, 95% CI 1.08-7.93, P = 0.03) were identified as independent predictors of SBE. Patients with SBE had higher 30-day mortality (20.0% versus 4.0% P = 0.02) and 1-year mortality (40.0% versus 11.1%, P < 0.002). SBE independently predicted 1-year, all-cause mortality (HR 5.88, 95% CI 1.7319,94, P = 0.005).SBE are frequent after TAVI and are associated with decreased short and mid-term survival. Diabetes and TS access are independent risk factors for SBE.

Outcome prediction following transcatheter aortic valve implantation: Multiple risk scores comparison.

BACKGROUND The aim of the study was to compare 7 available risk models in the prediction of 30-day mortality following transcatheter aortic valve implantation (TAVI). Heart team decision supported by different risk score calculations is advisable to estimate the individual procedural risk before TAVI. METHODS One hundred and fifty-six consecutive patients (n = 156, 48% female, mean age 80.03 ± 8.18 years) who underwent TAVI between March 2010 and October 2014 were in-cluded in the study. Thirty-day follow-up was performed and available in each patient. Base-line risk was calculated according to EuroSCORE I, EuroSCORE II, STS, ACEF, Amblers, OBSERVANT and SURTAVI scores. RESULTS In receiver operating characteristics analysis, neither of the investigated scales was able to distinguish between patients with or without an endpoint with areas under the curve (AUC) not exceeding 0.6, as follows: EuroSCORE I, AUC 0.55; 95% confidence intervals (CI) 0.47-0.63, p = 0.59; EuroSCORE II, AUC 0.59; 95% CI 0.51-0.67, p = 0.23; STS, AUC 0.55; 95% CI 0.47-0.63, p = 0.52; ACEF, AUC 0.54; 95% CI 0.46-0.62, p = 0.69; Amblers, AUC 0.54; 95% CI 0.46-0.62, p = 0.70; OBSERVANT, AUC 0.597; 95% CI 0.52-0.67, p = 0.21; SURTAVI, AUC 0.535; 95% CI 0.45-0.62, p = 0.65. SURTAVI model was calibrated best in high-risk patients showing coherence between expected and observed mortality (10.8% vs. 9.4%, p = 0.982). ACEF demonstrated best classification accuracy (17.5% vs. 6.9%, p = 0.053, observed mortality in high vs. non-high-risk cohort, respectively). CONCLUSIONS None of the investigated risk scales proved to be optimal in predicting 30-day mortality in unselected, real-life population with aortic stenosis referred to TAVI. This data supports primary role of heart team in decision process of selecting patients for TAVI.

Inflammatory activity of pericoronary adipose tissue may affect plaque composition in patients with acute coronary syndrome without persistent ST-segment elevation: preliminary results

BACKGROUND The extravascular expression of inflammatory mediators may adversely influence coronary lesion formation and plaque stability through outside-to-inside signalling. It has been shown that the maximal standardised uptake value (SUV) of 18-fluorodeoxyglucose detected by positron emission tomography (PET/CT) is proportional to macrophage density. AIM To investigate whether the inflammatory activity of pericoronary adipose tissue (PVAT) may influence plaque composition in acute coronary syndrome without persistent ST-segment elevation (NSTE-ACS) patients. METHODS In a prospective study, 36 coronary arteries (LM, RCA, LCX, LAD) were investigated in non-diabetic patients with a low or intermediate risk of NSTE-ACS (GRACE ≤ 140). SUV was measured in fat surrounding coronary arteries on the sections corresponding to proximal and medial segments (Siemens biograph 64-PET/CT system). Additionally, SUV was measured in subcutaneous fat (SC), visceral thoracic fat (VS), and epicardial fat over the right ventricle (EPI). Virtual histology intravascular ultrasound (VH-IVUS) was performed to assess plaque composition (Volcano, USA). PET/CT sections were further examined in segments corresponding to coronary plaques. RESULTS PVAT SUV in NSTE-ACS patients was significantly greater than in other fat locations (LM SUV: 1.60; RCA SUV: 1.54; LCX SUV: 1.94; LAD SUV: 2.37 vs. SC SUV 0.57; VS SUV: 0.77; EPI SUV: 0.98; p < 0.001; ANOVA). PVAT SUV positively correlated with plaque burden (r = 0.49, p < 0.05) and necrotic core plaque rate (r = 0.68, p < 0.05), and negatively correlated with fibrous plaque rate (r = -0.52, p < 0.05). CONCLUSIONS The inflammatory activity of PVAT reflected by SUV is greater than in subcutaneous, visceral thoracic, or epicardial tissue in NSTE-ACS patients; PVAT SUV correlates with the plaque burden and necrotic core component of coronary plaque.

Direct transcatheter aortic valve implantation – one-year outcome of a case control study

Introduction Transaortic valve implantation (TAVI) has a well-established position in the treatment of high-risk and inoperable patients with severe aortic stenosis (AS). The TAVI protocol requires a pre-dilatation for native valve preparation. Aim To assess the safety and feasibility of TAVI without pre-dilatation and to compare it with the procedure with pre-dilatation. Material and methods Out of 101 TAVI patients, in 10 the procedure was performed without balloon predilatation, and 8 patients were included in the analysis. The procedural, echocardiographic, and clinical outcomes were compared with a case control matched cohort (1: 2 ratio). A 12-month follow-up was done in all cases. Results The procedure was successfully completed in all patients in the study group (SG), but there was one procedural failure in the control group (CG). All patients received a CoreValve (Medtronic) bioprosthesis. There was a significant immediate decrease in transvalvular gradients (TG) in both study arms after the procedure (SG: mean TG: from 46.0 ±14.0 mm Hg to 10.0 ±4.8 mm Hg, p < 0.001; CG: mean TG: from 55.9 ±12.0 mm Hg to 9.9 ±2.9 mm Hg, p < 0.001). A marked increase in the effective orifice areas was observed in both cohorts (SG: 1.63 ±0.13 cm2 and CG: 1.67 ±0.25 cm2, p = 0.75). The periprocedural complication rate was equally distributed in both arms. The 12-month all-cause mortality was 12.5% in both groups. Conclusions The direct TAVI approach seams to be safe and feasible. The clinical and echocardiographic results are not different from those achieved in patients treated with standard TAVI protocol with pre-dilatation.

Pre-procedural dual antiplatelet therapy and bleeding events following transcatheter aortic valve implantation (TAVI)

INTRODUCTION Transcatheter aortic valve implantation (TAVI) is associated with bleeding that increases mortality. Dual antiplatelet therapy (DAPT) is recommended in TAVI, however little is known about pre-procedural DAPT use and its impact on hemostasis. We sought to determine the frequency, predictors and bleeding events in patients receiving DAPT before TAVI. METHODS Three-hundred-and-three (n=303, 78.6±7.6years, 49% female, EuroScore 23.1±16.9) consecutive patients undergoing TAVI were prospectively analyzed and followed for in-hospital events. According to pre-procedural antiplatelet status study population was divided into 2 groups: patients receiving aspirin and clopidogrel (DAPT) and those on aspirin only or no antiplatelet therapy (noDAPT). RESULTS Pre-procedural DAPT was used in 139 cases (46%). Previous PCI (OR 4.8, [2.8-8.3], p<0.0001), implantation of self-expandable prosthesis (OR 2.2, [1.2-4], p=0.007) femoral access (OR 2.2, [1.1-4.5], p=0.029) and platelet count (OR 1.006, [1.002-1.01], p=0.002) were identified as independent predictors of pre-procedural DAPT. No difference was observed in the rates of any bleeding (23% in DAPT vs. 24.4% in noDAPT, p=0.930) or major/life-threatening bleeding (12.2% in DAPT vs. 14.7% in noDAPT, p=0.715). Propensity-score matching analysis did not alter the results. GFR <30ml/min was the strongest predictor of bleeding (OR 4.3, [1.9-9.9], p=0.0005). There was a trend towards lower frequency of MI and stroke/TIA in DAPT as compared with noDAPT (3.6% vs. 9.8%, p=0.082). CONCLUSIONS Pre-procedural DAPT is frequent and does not increase short-term bleeding complications or need for transfusion following TAVI. Possible impact of DAPT use before TAVI on ischemic complications needs to be investigated in larger populations.

Common carotid artery access for transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) is an alternative method of treatment for severe symptomatic aortic stenosis in patients who are at high risk of surgical aortic valve replacement (AVR). In randomised clinical trials TAVI was shown to be superior to standard medical therapy in a cohort of inoperable patients and non-inferior to AVR in high-risk operable patients. Additionally, in a recent trial with self-expandable prosthesis use, TAVI was associated with lower mortality compared with surgery. Usually, femoral arteries are the most common vascular access to deliver the bioprosthesis; however, in some cases (up to 20%) this route may not be applied because of significant peripheral artery disease or tortuosity. In this article, we present the first two TAVI procedures in Poland performed via the left common carotid artery.

Baseline platelet indices and bleeding after transcatheter aortic valve implantation.

Bleeding complications are frequent and independently predict mortality after transcatheter aortic valve implantation (TAVI). It has been demonstrated that certain platelet parameters are indicative of platelet reactivity. We sought to determine the possible correlation between simple platelet indices and bleeding complications in patients undergoing TAVI. Platelet indices – platelet count, mean platelet volume (MPV), platelet distribution width and plateletcrit – were measured in 110 consecutive patients on the day preceding TAVI. In-hospital bleeding events after TAVI were assessed according to the Valve Academic Research Consortium-2 classification as any bleeding, major and life-threatening bleeding (MLTB) and need for transfusion. By receiver-operating characteristic analysis, only MPV was able to distinguish between patients with and without any bleeding [area under the curve (AUC) 0.629, 95% confidence interval (CI) 0.531–0.719, P = 0.0342], MLTB (AUC 0.730, 95% CI 0.637–0.811, P = 0.0004) and need for transfusion (AUC 0.660, 95% CI 0.563–0.747, P = 0.0045). By multivariate logistic regression, high MPV (>10.6) and low platelet distribution width (<14.8) were associated with increased risk of any bleeding [odds ratio (OR) 4.08, 95% CI 1.66–10.07, P = 0.0022; and OR 3.82, 95% CI 1.41–10.36, P = 0.0084, respectively] and MLTB (OR 10.76, 95% CI 3.05–38, P = 0.0002; and OR 8.46, 95% CI 1.69–42.17, P = 0.0092, respectively). Additionally, high MPV independently correlated with the need for transfusion (OR 4.11, 95% CI 1.71–9.86, P = 0.0016). Larger and less heterogenic platelets may be associated with increased risk of short-term bleeding complications after TAVI.

Next-generation re-sequencing of genes involved in increased platelet reactivity in diabetic patients on acetylsalicylic acid

Abstract The objective of this study was to investigate whether rare missense genetic variants in several genes related to platelet functions and acetylsalicylic acid (ASA) response are associated with the platelet reactivity in patients with diabetes type 2 (T2D) on ASA therapy. Fifty eight exons and corresponding introns of eight selected genes, including PTGS1, PTGS2, TXBAS1, PTGIS, ADRA2A, ADRA2B, TXBA2R, and P2RY1 were re-sequenced in 230 DNA samples from T2D patients by using a pooled PCR amplification and next-generation sequencing by Illumina HiSeq2000. The observed non-synonymous variants were confirmed by individual genotyping of 384 DNA samples comprising of the individuals from the original discovery pools and additional verification cohort of 154 ASA-treated T2DM patients. The association between investigated phenotypes (ASA induced changes in platelets reactivity by PFA-100, VerifyNow and serum thromboxane B2 level [sTxB2]), and accumulation of rare missense variants (genetic burden) in investigated genes was tested using statistical collapsing tests. We identified a total of 35 exonic variants, including 3 common missense variants, 15 rare missense variants, and 17 synonymous variants in 8 investigated genes. The rare missense variants exhibited statistically significant difference in the accumulation pattern between a group of patients with increased and normal platelet reactivity based on PFA-100 assay. Our study suggests that genetic burden of the rare functional variants in eight genes may contribute to differences in the platelet reactivity measured with the PFA-100 assay in the T2DM patients treated with ASA.

Complete percutaneous approach versus surgical access in transfemoral transcatheter aortic valve implantation: results from a multicentre registry

BACKGROUND Although the femoral approach is the most common route utilised in transcatheter aortic valve implantation (TAVI), it still carries a substantial risk of severe bleeding and vascular complications. AIM The aim of our study was to compare the safety and efficacy of the complete percutaneous (CPC) approach with surgical cut-down and closure (SCC) in TAVI patients. METHODS The study population comprised 683 patients with severe aortic stenosis, who underwent transfemoral TAVI. Bleeding and vascular complications were defined according to the Valve Academic Research Consortium (VARC-2) criteria. Propensity-matched cohorts were created to reduce the potential bias of non-random assignment to the type of vascular access technique (SSC, n = 203 vs. CPC, n = 203). RESULTS The rate of minor vascular complications was higher in the CPC cohort (18.2% vs. 9.9%, p = 0.02). There were no differences in major vascular complications or in any type of bleedings between the two groups. Age (odds ratio [OR] 1.044; 95% confidence interval [CI] 1.003-1.09, p = 0.046), preprocedural haemoglobin (OR 0.849; 95% CI 0.760-0.944, p = 0.03), and baseline estimated glomerular filtration rate < 30 mL/min (OR 3.216; 95% CI 1.176-8.741, p = 0.021) were independent predictors of life-threatening/disabling and major bleedings. Diabetes remained the only independent predictor of major vascular complications (OR 1.695; 95% CI 1.014-3.156, p = 0.046). CONCLUSIONS In this retrospective analysis both vascular access and closure techniques were associated with a similar risk of severe bleeding and major vascular events. However, these findings should be further confirmed in a multicentre, randomised study.

Transcatheter aortic valve-in-valve implantation in failed stentless bioprostheses

OBJECTIVE To compare the safety and efficacy of transcathether aortic valve-in-valve implantation (ViV-TAVI) in degenerated stentless bioprostheses with failed stented valves and degenerated native aortic valves. INTRODUCTION Little is known about ViV-TAVI in degenerated stentless valves. METHODS Out of 45 ViV-TAVI procedures reported in the POL-TAVI registry, 20 failed stentless valves were compared with 25 stented prostheses and propensity-matched with 45 native TAVI cases. The mean follow-up was 633 (95% confidence interval [CI], 471-795) days and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. RESULTS Patients with degenerated stentless valves were younger (65.6, CI 58-73.1 years vs 75.6, CI 72.2-78 [stented] vs 80.1, CI 78.7-81.6 y. [native], P < 0.001). Implantation was required later after surgery (11.5, CI 8-14.9 years) in the stentless cohort as compared with the stented one (6.2, CI 4.7-7.6 years, P = 0.006). ViV-TAVI in the stentless group was also associated with larger amount of contrast (211, CI 157-266 mL vs 135, CI 104-167 mL [stented] vs 132 (119-145) mL [native], P = 0.022). Using VARC-2 composite endpoints, ViV-TAVI in stentless prostheses was characterized by a lower device success (50% vs 76% in stented vs 88.9% in native TAVI, P < 0.001), but comparable early safety up to 30 days (73.7% vs 84% vs 81.8%, respectively, log-rank P = 0.667) and long-term clinical efficacy beyond 30 days (72.2% vs 72% vs 73.8%, respectively, log-rank P = 0.963). CONCLUSIONS Despite technical challenges and a lower device success, ViV-TAVI in stentless aortic bioprostheses achieves similar safety, efficacy, and functional improvement as in stented or degenerated native valves.