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.).

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.).

Long-term follow-up of contemporary drug-eluting stent implantation in diabetic patients: Subanalysis of a randomized controlled trial.

OBJECTIVE: The elevated risk of adverse events following percutaneous coronary intervention in diabetic patients persists with newer-generation DES. The polymer-free amphilimus-eluting stent (PF-AES) possesses characteristics with a potentially enhanced performance in patients with diabetes. Data from the 1-year follow-up period has been previously published. The aim of this subanalysis was to assess long-term performance of two contemporary drug-eluting stents (DES) in a diabetic population. METHODS: In the ReCre8 trial, patients were stratified for diabetes and troponin status, and randomized to implantation of a permanent polymer zotarolimus-eluting stent (PP-ZES) or PF-AES. The primary endpoint was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Clinical outcomes between discharge and 3 years follow-up were assessed. RESULTS: A total of 302 patients with diabetes were included in this analysis. After 3 years, TLF occurred in 12.5% of PP-ZES patients versus 10.0% in PF-AES patients (p = 0.46). Similarly, the separate components of TLF were comparable between the two study arms. The secondary composite endpoint of NACE was higher in the PP-ZES arm with 45 cases (29.6%) versus 30 cases (20.0%) in the PF-AES arm (p = 0.036). In the insulin-dependent diabetic population, TLF occurred in 19.1% of PP-ZES patients versus 10.4% of PF-AES patients (p = 0.21). NACE occurred in 40.4% of PP-ZES patients versus 27.1% of PF-AES patients (p = 0.10). CONCLUSIONS: This subanalysis shows that the use of PF-AES results in similar clinical outcomes as compared to PP-ZES, yet some benefits of use of PF-AES in diabetic patients may prevail. Future dedicated trials should confirm these findings.

Anatomical predictors for suture-based closure of the patent foramen ovale: A multicenter experience.

BACKGROUND: NobleStitch EL is a novel suture-based technique used for patent foramen ovale (PFO) closure and an alternative to traditional double-disc devices without the need for antithrombotic therapy. However, successful closure rates are still unknown, and certain anatomies may be unfavorable for successful closure. AIMS: We assessed the efficacy of the NobleStitch EL and sought to identify patient-related anatomical features associated with successful suture-based closure. METHODS: We included 55 patients who underwent PFO closure with the NobleStitch EL in The Netherlands and Switzerland. Successful closure was defined as residual right-to-left shunt grade ≤1 with Valsalva maneuver at a cardiac ultrasound. Predefined possible anatomical determinants for effective closure included PFO length, atrial septal aneurysm, PFO entry- and exit diameter. RESULTS: Successful closure was achieved in 33 patients (60%). The PFO length was shorter in patients with successful closure compared to unsuccessful closure with a median length of 9.6 mm (IQR 8.0-15.0) versus 13.3 mm (IQR 11.4-18.6) on preprocedural ultrasound (p = 0.041) and 9.9 mm (IQR 8.0-13.1) versus 12.5 mm (IQR 9.7-15.4) on angiography (p = 0.049). Additionally, the PFO exit diameter and PFO volume were smaller in patients with successful closure than unsuccessful closure, with a mean diameter of 7.0 ± 3.1 mm versus 9.5 ± 3.8 mm (p = 0.015) and a median volume of 381 mm3 (IQR 286-894) versus 985 mm3 (IQR 572-1550) (p = 0.016). CONCLUSION: In our study cohort, the successful PFO closure rate using NobleStitch EL was relatively low (60%). With this alternative procedure, patients with a small PFO driven by a short PFO tunnel length and small exit diameter seem to be eligible for successful suture-based closure.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

The impact of frailty on adverse outcomes after transcatheter aortic valve replacement in older adults: A retrospective cohort study.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement for patients who are at increased surgical risk. Consequently, frailty is common in patients undergoing TAVR. OBJECTIVES: This study aims to investigate the impact of frailty on outcomes following TAVR. METHODS: A retrospective cohort study was conducted, including all TAVR candidates who visited the geriatric outpatient clinic for preoperative screening. Frailty status was assessed according to the Groningen Frailty Indicator. The primary outcome of the study was defined as the occurrence of postoperative complications, and this was evaluated according to the Clavien-Dindo classification. An additional analysis was performed to assess the impact of frailty on 1-year all-cause mortality and complications within 30 days of TAVR according to the Valve Academic Research Consortium (VARC-2) criteria. The VARC-2 criteria provide harmonized endpoint definitions for TAVR studies. RESULTS: In total, 431 patients with a mean age of 80.8 ± 6.2 years were included, of whom 56% were female. Frailty was present in 36% of the participants. Frailty was associated with a higher risk of the composite outcome of complications [adjusted odds ratio (OR): 1.55 (95% confidence interval, CI: 1.03-2.34)], 30-day mortality [adjusted OR: 4.84 (95% CI: 1.62-14.49)], 3-month mortality [adjusted OR: 2.52 (95% CI: 1.00-6.28)] and 1-year mortality [adjusted OR: 2.96 (95% CI: 1.46-6.00)]. CONCLUSIONS: Frailty is common in TAVR patients and is associated with an increased overall risk of postoperative complications, particularly mortality. Increased optimization of screening and treatment of frailty in the guidelines for valvular heart diseases is recommended.

Clinical outcomes after permanent polymer or polymer-free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy.

OBJECTIVES: The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics. BACKGROUND: The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics. METHODS: In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. RESULTS: In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022). CONCLUSIONS: Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.

Comparison of the Sapien 3 versus the ACURATE neo valve system: A propensity score analysis.

OBJECTIVES: To compare the outcomes of transfemoral ACURATE neo (NEO) and Sapien 3 (S3) patients in terms of device success and clinical safety outcomes using a propensity score analysis. BACKGROUND: Differences in clinical outcomes between the latest-generation balloon-expandable S3 and self-expanding NEO in a "real-world transfemoral TAVI population" are still unclear. METHODS: We compared up to 6 months clinical outcomes using a propensity score analysis (inverse probability of treatment weighting [IPTW]) to account for differences in baseline characteristics. RESULTS: A total of 345 patients underwent transfemoral transcatheter aortic valve implantation (TAVI) with either NEO or S3 at two centers in the Netherlands. Composite device success and early safety endpoints were comparable between NEO and S3 (Device success: IPTW-adjusted OR: 0.35 [95% CI: 0.12-1.18], and early safety: IPTW-adjusted OR: 0.51 [95% CI: 0.19-1.38]). Six-months mortality was 5.3 versus 3.6%, stroke was 2.8 versus 3.3%, and pacemaker rate was 6.1 versus 8.6%, respectively with p = NS. Mean aortic gradient was lower in the NEO group (5.72 ± 2.47 vs. 9.05 ± 3.48; p = <.001), with a comparable rate of moderate or severe paravalvular leak (0 versus 2.1%; p = NS). CONCLUSIONS: Device success and clinical safety outcomes were comparable for both valves. Up to 6-months follow-up clinical outcomes and mortality rate remained excellent. Mean aortic gradient was lower after ACURATE neo implantation.

Impact of anemia on short-term outcomes after TAVR: A subgroup analysis from the BRAVO-3 randomized trial.

OBJECTIVES: To determine the prognostic impact of anemia in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: Whether the periprocedural use of bivalirudin as compared with UFH in anemic patients undergoing TAVR has an impact on outcomes remains unknown. METHODS: The BRAVO-3 trial compared the use of bivalirudin versus UFH in 802 high risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence (defined as hemoglobin levels <13 g/dl in men and <12 g/dl in women) or absence of anemia. The primary outcomes were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or bleeding) and major bleeding (Bleeding Academic Research Consortium ≥3b) at 30 days. RESULTS: Among 798 patients with available baseline hemoglobin levels, 427 (54%) were anemic of whom 221 (52%) received bivalirudin. There were no significant differences in NACE and major bleeding at 30 days between patients with and without anemia, irrespective of the type of anticoagulant used (pinteraction  = 0.71 for NACE, pinteraction  = 1.0 for major bleeding). However, anemic patients had a higher risk of major vascular complications (adjusted OR 2.43, 95% CI 1.42-4.16, p = 0.001), and acute kidney injury (adjusted OR 1.74, 95% CI 1.16-2.59, p = 0.007) compared to non-anemic patients at 30 days. CONCLUSIONS: Anemia was not associated with a higher risk of NACE or major bleeding at 30 days after TAVR without modification of the treatment effects of periprocedural anticoagulation with bivalirudin versus UFH.

The effect of transcatheter aortic valve implantation approaches on mortality.

OBJECTIVES: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality. BACKGROUND: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF). METHODS: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models. RESULTS: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches. CONCLUSIONS: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.

Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial. METHODS: In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin). RESULTS: In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%; Pnoninferiority=0.0086). Cardiac death occurred in 10 (1.3%) versus 10 patients (1.3%; P value for difference, 1.00), target-vessel myocardial infarction occurred in 18 (2.4%) versus 17 patients (2.3%; P value for difference, 0.87), and target-lesion revascularization occurred in 22 (2.9%) versus 20 patients (2.6%; P value for difference, 0.75) for PF-AES as compared with PP-ZES. Overall, definite or probable stent thrombosis occurred in 1.0%. CONCLUSIONS: PF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02328898.

Laparoscopic based renal denervation in a canine neurogenic hypertension model.

BACKGROUND: Previous renal denervation (RDN) studies showed controversial results in reducing blood pressure. The aim of this study was to provide evidence supporting the effectiveness of laparoscopic-based renal denervation (L-RDN) in treating hypertension. METHODS: Sixteen Beagle dogs were randomly divided into RDN group (n = 12) and sham group (n = 4). Neurogenic hypertension was generated in all dogs via carotid artery route. L-RDN was performed in the RDN group, with sham operation performed as a control. Blood pressure (BP) changes were recorded at 2, 4, 6, and 8 weeks after the procedure. Changes in serum creatinine (sCr), blood urea nitrogen (BUN) and level of norepinephrine (NE) were analyzed. Histological changes of kidney and renal arteries were also evaluated. RESULTS: BP and NE levels were significantly elevated after hypertension induction (p < 0.01). Systolic and diastolic BP of RDN group were decreased by 15.5 mmHg and 7.3 mmHg (p < 0.0001 and p = 0.0021, respectively) at the eighth week after L-RDN. Invasive systolic and diastolic BP of RDN group were significantly decreased by 14.5 mmHg and 15.3 mmHg (p < 0.0001). In contrast, there was no significant decrease in blood pressure in the sham group. In addition, RDN group but not the sham group showed a significant decrease in NE levels (p < 0.001), while no significant changes in sCr and BUN were observed in both groups. Pathological examinations showed no discernible damage, tear, or dissection to the renal arteries in RND group. CONCLUSIONS: L-RDN lowered BP and NE levels in hypertensive dogs without affecting renal artery morphology and kidney function.

General Anesthesia or Conscious Sedation for Transfemoral Aortic Valve Replacement with the SAPIEN 3 Transcatheter Heart Valve.

Differences in the benefits of conscious sedation (CS) and general anesthesia (GA) during transfemoral aortic valve implantation (TAVI) are unclear.We aimed to assess differences in procedural and clinical outcomes based on the type of anesthesia received during TAVI.We analyzed SOURCE 3 Registry data for patients who received the SAPIEN 3 valve by type of anesthesia used during TAVI.Of the 1694 TAVI patients, 1027 received CS and 667 received GA. Patients were similar at baseline (81.5 years; Society of Thoracic Surgeons risk score 7.0). Compared with the GA group, the CS group had fewer intra-procedural transesophageal echocardiography (TEE) and post implantation dilatations performed, and less contrast medium was used. The CS group had significantly less kidney injury at 7 days post-procedure than the GA group (0.4% versus 1.5%, P = 0.014). Moderate paravalvular leaks (PVL) occurred more frequently in the CS group versus the GA group (2.2% versus 0.8%; P = 0.041). No severe PVL were reported. Median total hospital length of stay (LOS) after TAVI was 10 days in the CS group and 11 days in the GS group. At 30 days, all-cause death was 2.1% in CS and 1.7% in GS (P = 0.47), and myocardial infarction was 0.2% in CS and 0.1% in GS (P = 0.83).Our analyses found no significant major outcome differences between CS and GA during TAVI.

One-year clinical outcomes of patients treated with polymer-free amphilimus-eluting stents or zotarolimus-eluting stents: A propensity-score adjusted analysis.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution-technology in coronary stenting. We aimed to assess 1-year clinical outcomes of PF-AES as compared to latest-generation permanent polymer zotarolimus-eluting stents (PP-ZES) in a real-world all-comers setting. METHODS: A prospective registry of patients treated with either PF-AES or PP-ZES between 2014 and 2016 was conducted. The primary outcome was defined as major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcome was defined as target-lesion failure (TLF) at 1 year. To account for measured confounders, a propensity-score adjusted Cox proportional-hazard model was built to evaluate clinical outcomes. RESULTS: A total of 734 consecutive patients with 1,269 DES implantations were enrolled. The population was characterized by 28% diabetes, 24% ST-segment elevation myocardial infarction, and a high number of complex lesions (69%). The rate of MACCE was 11.5% for PF-AES and 13.6% for PP-ZES, plog-rank = 0.11. TLF was numerically lower in PF-AES as compared to PP-ZES (5.4 vs. 6.1%, plog-rank = 0.68). After propensity-score adjustment, PF-AES showed a trend toward a lower rate of MACCE and a favorable rate of TLF as compared to PP-ZES (HR 0.70; 95%CI 0.45 to 1.10, P = 0.12; and HR 0.88; 95%CI 0.47 to 1.65, P = 0.68, respectively). Rates of definite ST were low (0.8 vs. 0.3%, plog-rank = 0.62). CONCLUSIONS: Our study suggests that implantation of PF-AES was safe and effective in real-world patients, with low-rates of MACCE and TLF at 1 year. Our data needs to be confirmed by a large trial to evaluate the clinical outcomes of this novel polymer-free, eluting-technology used in PF-AES.

Impact of baseline cigarette smoking status on clinical outcome after transcatheter aortic valve replacement.

OBJECTIVES: To explore the prevalence of smoking, and its association with clinical and mortality outcome among patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Less data exist regarding the effect of baseline smoking status on clinical and mortality outcome among patients undergoing TAVR. METHODS: Consecutive patients who underwent TAVR at two high volume Dutch centers were included. Smoking status was prospectively questioned by a structured interview at admission. Primary endpoint was 1-year all-cause mortality after TAVR. RESULTS: A total of 913 consecutive patients (80.1 ± 7.6 years; logistic EuroSCORE: 16.5 ± 9.9%) who underwent TAVR for severe aortic valve stenosis were included. There were 47% (n = 432) males, and 57% (n = 522) never-smokers, and 35% (n = 317) prior-smokers, and 8% (n = 74) current-smokers. Smokers (i.e., prior-smokers or current-smokers) were younger compared to never-smokers (78.9 ± 7.9 and 76.4 ± 8.0 vs. 81.3 ± 7.1, P < 0.000, respectively). Median follow-up time was 365 (interquartile range [IQR]: 280-365) days. Overall, prior-smoking was not associated with all-cause mortality at 1-year following TAVR (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.55-1.23). After stratification according to sex, male prior-smokers showed better 1-year survival after TAVR than male never-smokers (12% vs. 20%; P = 0.018, respectively, HR 0.52, 95% CI 0.29-0.89), while this reversed effect was not observed among female prior-smokers versus female never-smokers after TAVR (HR 1.70, 95% CI 0.95-3.05). CONCLUSIONS: Overall, baseline prior-smokers had similar 1-year mortality outcome after TAVR compared with baseline never-smokers. However, there was a reversed association between baseline prior-smoking status and 1-year mortality after TAVR among males, which could partially be explained due to the favorable baseline characteristics.

Rationale and design of amphilimus sirolimus-eluting stents versus zotarolimus-eluting stents in all-comers requiring percutaneous coronary intervention (ReCre8): A multicenter randomized clinical trial.

BACKGROUND: Amphilimus sirolimus-eluting stents (A-SES) represent a novel elution technology in the current era of drug-eluting stents with promising results in patients with diabetes mellitus. At present no large trial has been designed to evaluate clinical outcomes of A-SES as compared to new-generation drug-eluting stents in unselected patients. Accordingly, we designed this trial to evaluate clinical noninferiority of A-SES as compared with zotarolimus-eluting stents (ZES) in a real-world, all-comers setting. STUDY DESIGN: ReCre8 is a prospective multicenter randomized clinical trial evaluating the clinical outcomes of A-SES as compared with ZES in all-comers requiring percutaneous coronary intervention. Patients are randomized 1:1 to receive either A-SES or ZES. On-site block-randomization is stratified by diabetes mellitus, and troponin status to perform prespecified subanalyses. Patients receive 1-month of dual antiplatelet therapy (DAPT) when troponin-negative, or 12-months of DAPT when troponin-positive. The primary endpoint is target-lesion failure at 1-year follow-up. A total of 1,532 patients will be enrolled to demonstrate clinical noninferiority of A-SES with at least 80% power, a noninferiority margin of 3.5% and a type-I-error of 0.05. CONCLUSIONS: ReCre8 (NCT02328898) is the first randomized multicenter trial with a head-to-head comparison of A-SES as compared with ZES to investigate the clinical safety and efficacy of these new-generation DES in a real-world, all-comers population.

Anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS), fractional flow reserve- and intravascular ultrasound-guided management in adult patients.

OBJECTIVES: To describe the use of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) in the evaluation of patients with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS). BACKGROUND: ACAOS of the right and left coronary are rare, but may lead to symptoms and impose a risk for sudden cardiac death, depending on several anatomical features. Assessment and risk estimation is challenging in (nonathlete) adults, especially if they present without symptoms or with atypical complaints. METHODS: The team retrospectively studied 30 consecutive patients with ACAOS with interarterial course, who received IVUS- and FFR-guided treatment at our institution between October 2010 and September 2017. RESULTS: FFR was abnormal in only seven patients. IVUS showed the typical slit-like anatomy of the orifice in 23 patients. Based on FFR and/or IVUS results, in conjunction with the clinical presentation, clinical decision was made. A decision for intervention was made if at least two out of three entities were abnormal. Intervention implied unroofing of the coronary artery (n = 10) or coronary artery bypass grafting (n = 1). In all other patients a conservative strategy was followed. No adverse events occurred in the total population after a median of 37 (0-62) months of follow-up. CONCLUSIONS: Conservative treatment may be justifiable in adult patients with ACAOS in the presence of normal FFR and nonsuspicious symptoms, despite the presence of an interarterial course and/or slitlike orifice on IVUS. We recommend the use of FFR and IVUS in the standard work-up for adult patients with ACAOS and propose the use of a flowchart to aid in decision-making.

Evaluation of Cognitive Function Following Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is associated with procedural-related neurological events and acute cognitive decline. However, data on the effect of TAVR on mid-term cognitive outcome are scarce. Therefore, we aimed to assess the impact of TAVR on mid-term cognitive outcome using different neurocognitive test batteries. METHODS: Patients with severe aortic valve stenosis scheduled for TAVR were enrolled. Cognitive assessment was performed at baseline and 4 months post-TAVR using an eight-word verbal-learning test ("Immediate Recall Memory Test" [IRMT], "Delayed Recall Memory Test" [DRMT], "Recognition of Verbal Information Test" [RVIT]), global cognitive function ("Mini Mental State Examination" [MMSE]), and executive function ("Trail Making Test" [TMT], "Clock-Drawing Test" [CDT]). RESULTS: A total of 30 patients (age: 81±6years, logistic EuroSCORE: 19±10%) completed the follow-up cognitive assessments. Postoperatively, 17% (n=5) developed delirium, 13% (n=4) received permanent pacemaker, and there were no cerebrovascular events. Mean hospital duration time was 5±2 days. Patients (n=22) who did not complete the follow-up cognitive assessments had comparable baseline, procedural and hospital outcome. At follow-up there was a significant improvement in IRMT (27±5 vs. 30±4, p=0.016), with a trend toward improved DRMT (4±2 vs. 5±2, p=0.079). Moreover, patients with lower baseline MMSE and IRMT improved significantly during the follow-up. CONCLUSIONS: Transcatheter aortic valve replacement was associated with an improved IRMT during follow-up. Both MMSE and IRMT were significantly improved among those with lower baseline scores.

TriGuard™ HDH embolic deflection device for cerebral protection during transcatheter aortic valve replacement.

OBJECTIVES: This study aims to evaluate the safety and performance of the new embolic deflection device TriGuard™HDH in patients undergoing TAVR. BACKGROUND: Transcatheter aortic valve replacement (TAVR) is associated with a high incidence of new cerebral ischemic lesions. The use of an embolic protection device may reduce the frequency of TAVR-related embolic events. METHODS: This prospective, single arm feasibility pilot study included 14 patients with severe symptomatic aortic stenosis scheduled for TAVR. Cerebral diffusion weighted magnetic resonance imaging (DWI) was planned in all patients one day before and at day 4 (±2) after the procedure. Major adverse cerebral and cardiac events (MACCEs) were recorded for all patients. Primary endpoints of this study were I) device performance success defined as coverage of the aortic arch takeoffs throughout the entire TAVR procedure and II) MACCE occurrence. Secondary endpoints included the number and the volume of new cerebral ischemic lesions on DWI. RESULTS: Thirteen patients underwent transfemoral TAVR and one patient a transapical procedure. Edwards SAPIEN valve prosthesis was implanted in 8 (57%) patients and Medtronic CoreValve prosthesis in the remaining 6 (43%). Predefined performance success of the TriGuard™HDH device was achieved in 9 (64%) patients. The composite endpoint MACCE occurred in none of the patients. Post-procedural DWI was performed in 11 patients. Comparing the DWI of these patients to a historical control group showed no reduction in number [median 5.5 vs. 5.0, P = 0.857], however there was a significant reduction in mean lesion volume per patient [median 13.8 vs. 25.1, P = 0.049]. CONCLUSION: This study showed the feasibility and safety of using the TriGuard™HDH for cerebral protection during TAVR. This device did not decrease the number of post-procedural new cerebral DWI lesions, however its use showed decreased lesion volume as compared to unprotected TAVR. © 2016 Wiley Periodicals, Inc.

Segmental comparison between a dedicated bifurcation stent and balloon angioplasty using intravascular ultrasound and three-dimensional quantitative coronary angiography: A subgroup analysis of the Tryton IDE randomized trial.

OBJECTIVE: Randomized comparison between the Tryton Side Branch Stent (Tryton Medical, Durham, NC), used in combination with a main branch drug-eluting stent (DES), and side branch balloon angioplasty (SBBA, in combination with a main branch DES) using intravascular ultrasound (IVUS), and three-dimensional quantitative coronary angiography (3D-QCA). BACKGROUND: The Tryton stent has been developed to improve clinical outcomes after percutaneous coronary intervention (PCI) of bifurcation lesions. METHODS: We present the pre-specified IVUS (n = 159) and 3D-QCA (n = 190) sub-group analyses of the Tryton coronary bifurcation trial (randomizing Tryton vs. SBBA). RESULTS: There were no differences in the main branch with regard to minimal lumen area (MLA) (5.33 ± 1.37 in Tryton vs. 5.69 ± 1.72 mm2 in SBBA, P = 0.235) with low neo-intima area in both groups. In the side branch, there were also no statistical significant differences between both groups (3.04 ± 1.02 in Tryton vs. 3.46 ± 1.15 mm2 in SBBA, P = 0.072). On 3D-QCA, no differences in minimal lumen diameter (MLD) and percentage diameter stenosis (%DS) were observed in the proximal and distal main branches. In the side branch, there were also no differences found in %DS and MLD (MLD: 1.34 ± 0.043 mm [Tryton] vs. 1.45 ± 0.31 mm [SBBA], P = 0.090). CONCLUSIONS: There were no differences in 9-month luminal dimensions of the side branch between the Tryton Stent and Side Branch Balloon Angioplasty, as assessed with IVUS (MLA) and 3D QCA (MLD). Angiographic and ultrasound results of the main branch were not negatively influenced by the Tryton stent. © 2016 Wiley Periodicals, Inc.