Jonathon White

Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis

AIMS Based on randomized trials using first-generation devices, transcatheter aortic valve replacement (TAVR) is well established in the treatment of high-risk (HR) patients with severe aortic stenosis (AS). To date, there is a paucity of adjudicated, prospective data evaluating outcomes with newer generation devices and in lower risk patients. We report early outcomes of a large, multicentre registry of inoperable, HR, and intermediate-risk (IR) patients undergoing treatment with the next-generation SAPIEN 3 transcatheter heart valve (THV). METHODS AND RESULTS Patients with severe, symptomatic AS (583 high surgical risk or inoperable and 1078 IR) were enrolled in a multicentre, non-randomized registry at 57 sites in the USA and Canada. All patients received TAVR with the SAPIEN 3 system via transfemoral (n = 1443, 86.9%) and transapical or transaortic (n = 218, 13.1%) access routes. The rate of 30-day all-cause mortality was 2.2% in HR/inoperable patients [mean Society of Thoracic Surgeons (STS) score 8.7%] and 1.1% in IR patients (mean STS score 5.3%); cardiovascular mortality was 1.4 and 0.9%, respectively. In HR/inoperable patients, the 30-day rate of major/disabling stroke was 0.9%, major bleeding 14.0%, major vascular complications 5.1%, and requirement for permanent pacemaker 13.3%. In IR patients, the 30-day rate of major/disabling stroke was 1.0%, major bleeding 10.6%, major vascular complications 6.1%, and requirement for permanent pacemaker 10.1%. Mean overall Kansas City Cardiomyopathy Questionnaire score increased from 47.8 to 67.8 (HR/inoperable, P < 0.0001) and 54.7 to 74.0 (IR, P < 0.0001). Overall, paravalvular regurgitation at 30 days was none/trace in 55.9% of patients, mild in 40.7%, moderate in 3.4%, and severe in 0.0%. Mean gradients among patients with paired baseline and 30-day or discharge echocardiograms decreased from 45.8 mmHg at baseline to 11.4 mmHg at 30 days, while aortic valve area increased from 0.69 to 1.67 cm(2). CONCLUSIONS The SAPIEN 3 THV system was associated with low rates of 30-day mortality and major/disabling stroke as well as low rates of moderate or severe paravalvular regurgitation. TRIAL REGISTRATION ClinicalTrials.gov #NCT01314313.

Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

Aim We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results We performed an individual patient data pairwise and network meta-analysis comparing short-term (⩽6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ⩽6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98–2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65–1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

Absorb everolimus-eluting bioresorbable scaffolds in coronary bifurcations: a bench study of deployment, side branch dilatation and post-dilatation strategies.

AIMS To provide bench insights which may predict safety and efficacy of side branch dilatation (SB) and kissing balloon post-dilatation (KBPD) in Absorb everolimus-eluting bioresorbable scaffolds deployed in bifurcations. METHODS AND RESULTS Stages of deployment and post-dilatation of scaffolds (3.0 and 3.5 mm diameter) in bifurcation phantoms were imaged by fluoroscopy, light microscopy and micro-computed tomography. Dilatation through the scaffold side displaced struts from the side branch (SB) lumen, but caused main branch (MB) malapposition opposite the SB, MB scaffold narrowing beyond the SB, and protrusion of struts into the SB. Scaffold distortion was corrected by MB post-dilatation or by mini-kissing balloon post-dilatation (mini-KBPD). When 3.0 mm diameter balloons were used for SB dilatation or mini-KBPD in 3.0 mm Absorbs, strut fracture did not occur at or below inflation pressures of 10 and 5 atm, respectively. Above these thresholds, the likelihood of strut fracture increased with increasing pressure. Fractures were usually single without malapposition, but mini-KBPD or post-dilatation with high inflation pressures sometimes caused multiple strut fractures and lumen compromise. CONCLUSIONS SB dilatation of an Absorb caused MB distortion which was corrected by MB post-dilation or low-pressure mini-KBPD without scaffold damage below pressure thresholds. These benchtop insights may help guide the clinical deployment of Absorb scaffolds in bifurcations and might enhance clinical outcomes but need clinical confirmation.

Stent Longitudinal Strength Assessed Using Point Compression Insights From a Second-Generation, Clinically Related Bench Test

Background—Stent longitudinal distortion, while infrequent, can lead to adverse clinical events. Our first bench comparison of susceptibility of different stent designs to distortion applied force to the entire circumference of the proximal stent hoop. The test increased understanding of stent design and led to recommendations for design change in some. Our second-generation test more closely mimics clinical scenarios by applying force to a point on the proximal hoop of a malapposed stent. Methods and Results—Each 3-mm-diameter stent was secured in a test apparatus so that its proximal 5 mm was malapposed in a 3.5-mm tube. An instron applied force to the proximal hoop of each of 5 examples of each of 6 stent designs using a narrow rod so that force applied and distance compressed could be measured. Hoops on the side of the force were pushed together, became malapposed, and obstructed the lumen. In addition, the proximal stent hoop tilted causing malapposition, the contralateral side of the stent from the applied force causing lumen obstruction. Conclusions—This second-generation, more clinically relevant test showed the Biomatrix Flex was the most resistant to deformation and the Element the most easily deformed. The addition of more connectors between the proximal hoops in the Promus Premier design has reduced the potential for distortion when compared with the Element, so that distortion was similar to the Vision, Multi-Link 8, and Integrity designs. The test also provided insight into the way in which stents are likely to distort in clinical practice.

Impact of Coronary Artery Disease Severity Assessed With the SYNTAX Score on Outcomes Following Transcatheter Aortic Valve Replacement

Background The influence of coronary artery disease (CAD) on clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR) is still controversial. We sought to evaluate the impact of CAD severity as measured by the SYNTAX score (SS) on patients undergoing TAVR. Methods and Results A total of 377 patients who underwent TAVR in 2 high‐volume centers in North America were included in our retrospective analysis. A blinded angiographic core laboratory calculated the SS on all available coronary angiograms with the use of quantitative coronary analysis. Patients were stratified into 4 groups: (1) no CAD (SS=0); (2) low SS (SS between 1 and 22); (3) intermediate SS (SS between 23 and 32); and (4) high SS (SS ≥33). Patients who had undergone percutaneous coronary intervention within 6 months prior to TAVR were separated into 2 categories based on their residual SS (<8 and ≥8). Patients with previous coronary artery bypass grafting (CABG) were divided into 2 groups: (1) low CABG SS and (2) high CABG SS. The primary end point was a composite of all‐cause mortality, myocardial infarction, and stroke. At 30 days and 1 year, both the presence and the severity of CAD had no impact on the rate of the combined primary end point and on all‐cause mortality, cardiovascular mortality, and myocardial infarction. Patients with less complete revascularization (residual SS ≥8 versus residual SS <8 and low CABG SS versus high CABG SS, had similar rates of the combined primary end point, all‐cause mortality, cardiovascular mortality, MI, and stroke, at both 30 days and 1 year. Conclusions In our core laboratory–validated study, neither the severity of CAD nor completeness of revascularization after percutaneous coronary intervention or CABG were associated with clinical outcomes after TAVR, at both 30 days and 1 year.

Coronary stent durability and fracture: an independent bench comparison of six contemporary designs using a repetitive bend test.

AIMS Stent fracture is important because it may cause adverse events. The interventional cardiologist needs independent data to aid stent selection. Stent designers need data to improve stent design. We used a repetitive bend test to compare durability and fracture for different stent designs. METHODS AND RESULTS Tested were 15 examples of six designs (BioMatrix Flex, Vision, MULTI-LINK 8, Element, Promus PREMIER and Integrity). One end of a nominally deployed stent was mounted on a fixed mandrel. The other end was translated a distance of ±3.5 mm at a rate of 6 Hz until fracture or 10 million cycles completed. The numbers of cycles to fracture for the Vision design (288,411±193,391) and the MULTI-LINK 8 (314,475±239,869) were significantly greater than for the BioMatrix Flex design (38,904±13,160), p<0.001. The difference between Vision and MULTI-LINK 8 was not significant (p=0.79). The Element, PREMIER, and Integrity designs did not fracture. Most fractures were in the curved portions of connectors between hoops. CONCLUSIONS The stent design which fractured most readily was the BioMatrix Flex. The most flexible designs did not fracture and, in general, stents with three connectors were more likely to fracture than those with two connectors between loops.

Impact of Methodologic Differences in Three-Dimensional Echocardiographic Measurements of the Aortic Annulus Compared with Computed Tomographic Angiography Before Transcatheter Aortic Valve Replacement

Background: Three‐dimensional (3D) echocardiographic (3DE) imaging is an alternative to multi–detector row computed tomography (MDCT) for aortic annular measurement before transcatheter aortic valve replacement (TAVR). A commonly used direct planimetry from a reconstructed short‐axis view has not been compared with semiautomated 3DE methods. Typically accepted optimal cutoffs for percent prosthesis‐area oversizing of the balloon‐expandable SAPIEN or SAPIEN XT valve to native annular size are approximately 5% to 15%. The aim of this study was to compare semiautomated and direct planimetric 3DE methods for aortic annular sizing with a gold standard of MDCT to determine predictive value for paravalvular regurgitation (PVR) and balloon postdilatation. Methods: In this retrospective analysis, aortic annular cross‐sectional area was measured from pre‐TAVR imaging using (1) MDCT (CT_Area), (2) a 3D transesophageal echocardiographic (TEE) semiautomated method (3DE_Area_SA), and (3) a 3D TEE direct planimetric method (3DE_Area_Direct). Annular area percent oversizing was calculated. PVR after TAVR was assessed from intraoperative TEE imaging. Need for balloon postdilatation was recorded. Results: One hundred patients who underwent TAVR with either the SAPIEN or SAPIEN XT balloon‐expandable prosthesis were analyzed. Twenty‐three patients had mild or greater PVR after TAVR. CT_Area was 442 ± 79 mm2, 3DE_Area_SA was 435 ± 81 mm2, and 3DE_Area_Direct was 429 ± 82 mm2. Both 3DE_Area_SA and 3DE_Area_Direct underestimated MDCT (P < .05). All methods were highly correlative (R = 0.88–0.93, P < .0001). Percent oversizing obtained by the three methods significantly predicted mild or greater PVR and need for balloon postdilatation by receiver operating characteristic analysis, with optimal cutoffs for CT_Area (9%–10%) and 3DE_Area_SA (14%) within the recommended ranges for the studied transcatheter valves and for 3DE_Area_Direct higher than the recommended range (18%–19%). Inter‐ and intraobserver reproducibility were lowest for 3DE_Area_Direct. Conclusions: Caution must be used when using 3D TEE direct planimetry of the aortic annulus, as optimal percent oversizing ranges approach the level associated with root injury, and measurements are less reproducible. Therefore, semiautomated 3DE planimetry is preferred to 3DE direct planimetry for aortic annulus sizing.

Meta-analysis of the Impact of Avoiding Balloon Predilation in Transcatheter Aortic Valve Implantation

Balloon predilation (BPD) has been an integral part of transcatheter aortic valve implantation (TAVI) since inception. We sought to investigate the effect of avoiding BPD on outcomes of TAVI across different valve types. Articles were included if outcomes of TAVI without BPD were reported. Pooled meta-analysis used a random effects model and reported odds ratios (ORs). Twenty-one studies with 10,752 patients were pooled for analysis. Age and gender were well matched between NoBPD and BPD groups. There was no difference in mortality, stroke, bleeding, and acute kidney injury. NoBPD showed lower pacemaker rates (OR 0.84, 95% confidence interval [CI] 0.72 to 0.97), vascular complications (OR 0.77, 95% CI 0.62 to 0.95), and early safety at 30 days (OR 0.81, 95% CI 0.66 to 0.99). For balloon-expandable valves, lower rates of aortic regurgitation (OR 0.73, 95% CI 0.53 to 0.99) and early safety (OR 0.68, 95% CI 0.55 to 0.85) were seen. Self-expanding valves showed lower pacemaker (OR 0.80, 95% CI 0.66 to 0.97) and vascular complications (OR 0.70, 95% CI 0.50 to 0.99), with a trend toward higher postdilation (OR 1.51, 95% CI 0.85 to 2.67). TAVI without BPD is safe and effective. NoBPD is associated with fewer vascular complications, less aortic regurgitation, and fewer pacemaker requirements and composite early safety end points.

Meta-Analysis of Usefulness of Anticoagulation After Transcatheter Aortic Valve Implantation

Since the advent of bioprosthetic valves, the implications of long-term anticoagulation after valve replacement are unclear. There are very little data on outcomes of long-term anticoagulation after transcatheter aortic valve implantation (TAVI). Our aim was to conduct a systematic review of literature regarding anticoagulation after TAVI. The existing literature on anticoagulation after bioprosthetic valve replacement was thoroughly reviewed, including the most recent American College of Cardiology/American Heart Association 2017 guidelines for management of valvular disease, which is based on sparse, nonrandomized retrospective data. A systematic review of MEDLINE, EMBASE, and Cochrane CENTRAL databases was conducted to retrieve articles reporting outcomes on anticoagulation after TAVI, and 5 articles were retrieved. Pooled analysis revealed lower bleeding rates in the anticoagulated group (22% vs 35%, p = 0.006). Stroke and mortality were inconsistently reported by the studies. The data regarding outcomes of patients on anticoagulation after TAVI are sparse. Systematic collection of anticoagulation data in the existing registries and future trials should be strongly considered in patients undergoing TAVI.

Choice of Appropriate Endpoints for a Balloon Versus Stent Trial

The recent paper by Latib et al. ([1][1]) compared the efficacy of a paclitaxel-eluting balloon (PEB) with that of a paclitaxel-eluting stent (PES) at preventing restenosis after percutaneous coronary intervention in coronary arteries <2.8 mm in diameter. The prespecified primary endpoint was in-