Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial.

BACKGROUND: In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. METHODS: This prospective, open-label, non-inferiority, randomised trial was done at 29 hospitals across Belgium, Italy, the Netherlands, and Spain. We included patients aged 18-85 years presenting with ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndrome and multivessel (ie, two or more coronary arteries with a diameter of 2·5 mm or more and ≥70% stenosis based on visual estimation or positive coronary physiology testing) coronary artery disease with a clearly identifiable culprit lesion. A web-based randomisation module was used to randomly assign patients (1:1), with a random block size of four to eight, stratified by study centre, to undergo immediate complete revascularisation (PCI of the culprit lesion first, followed by other non-culprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularisation (PCI of only the culprit lesion during the index procedure and PCI of all non-culprit lesions deemed to be clinically significant by the operator within 6 weeks after the index procedure). The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1 year after the index procedure. Secondary outcomes included all-cause mortality, myocardial infarction, and unplanned ischaemia-driven revascularisation at 1 year after the index procedure. Primary and secondary outcomes were assessed in all randomly assigned patients by intention to treat. Non-inferiority of immediate to staged complete revascularisation was considered to be met if the upper boundary of the 95% CI of the hazard ratio (HR) for the primary outcome did not exceed 1·39. This trial is registered with ClinicalTrials.gov, NCT03621501. FINDINGS: Between June 26, 2018, and Oct 21, 2021, 764 patients (median age 65·7 years [IQR 57·2-72·9] and 598 [78·3%] males) were randomly assigned to the immediate complete revascularisation group and 761 patients (median age 65·3 years [58·6-72·9] and 589 [77·4%] males) were randomly assigned to the staged complete revascularisation group, and were included in the intention-to-treat population. The primary outcome at 1 year occurred in 57 (7·6%) of 764 patients in the immediate complete revascularisation group and in 71 (9·4%) of 761 patients in the staged complete revascularisation group (HR 0·78, 95% CI 0·55-1·11, pnon-inferiority=0·0011). There was no difference in all-cause death between the immediate and staged complete revascularisation groups (14 [1·9%] vs nine [1·2%]; HR 1·56, 95% CI 0·68-3·61, p=0·30). Myocardial infarction occurred in 14 (1·9%) patients in the immediate complete revascularisation group and in 34 (4·5%) patients in the staged complete revascularisation group (HR 0·41, 95% CI 0·22-0·76, p=0·0045). More unplanned ischaemia-driven revascularisations were performed in the staged complete revascularisation group than in the immediate complete revascularisation group (50 [6·7%] patients vs 31 [4·2%] patients; HR 0·61, 95% CI 0·39-0·95, p=0·030). INTERPRETATION: In patients presenting with acute coronary syndrome and multivessel disease, immediate complete revascularisation was non-inferior to staged complete revascularisation for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischaemia-driven revascularisation. FUNDING: Erasmus University Medical Center and Biotronik.

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a meta-analysis of randomized trials.

AIMS: Additional randomized clinical trial (RCT) data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) is available, including longer term follow-up. A meta-analysis comparing TAVI to SAVR was performed. A pragmatic risk classification was applied, partitioning lower-risk and higher-risk patients. METHODS AND RESULTS: The main endpoints were death, strokes, and the composite of death or disabling stroke, occurring at 1 year (early) or after 1 year (later). A random-effects meta-analysis was performed. Eight RCTs with 8698 patients were included. In lower-risk patients, at 1 year, the risk of death was lower after TAVI compared with SAVR [relative risk (RR) 0.67; 95% confidence interval (CI) 0.47 to 0.96, P = 0.031], as was death or disabling stroke (RR 0.68; 95% CI 0.50 to 0.92, P = 0.014). There were no differences in strokes. After 1 year, in lower-risk patients, there were no significant differences in all main outcomes. In higher-risk patients, there were no significant differences in main outcomes. New-onset atrial fibrillation, major bleeding, and acute kidney injury occurred less after TAVI; new pacemakers, vascular complications, and paravalvular leak occurred more after TAVI. CONCLUSION: In lower-risk patients, there was an early mortality reduction with TAVI, but no differences after later follow-up. There was also an early reduction in the composite of death or disabling stroke, with no difference at later follow-up. There were no significant differences for higher-risk patients. Informed therapy decisions may be more dependent on the temporality of events or secondary endpoints than the long-term occurrence of main clinical outcomes.

Treatment of late paravalvular regurgitation after transcatheter aortic valve implantation: prognostic implications.

AIMS: Paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) is associated with increased morbidity and mortality. The effect of transcatheter interventions to treat PVR after the index TAVI was investigated. METHODS AND RESULTS: A registry of consecutive patients who underwent transcatheter intervention for ≥ moderate PVR after the index TAVI at 22 centers. The principal outcomes were residual aortic regurgitation (AR) and mortality at 1 year after PVR treatment. A total of 201 patients were identified: 87 (43%) underwent redo-TAVI, 79 (39%) plug closure, and 35 (18%) balloon valvuloplasty. Median TAVI-to-re-intervention time was 207 (35; 765) days. The failed valve was self-expanding in 129 (63.9%) patients. The most frequent devices utilized were a Sapien 3 valve for redo-TAVI (55, 64%), an AVP II as plug (33, 42%), and a True balloon for valvuloplasty (20, 56%). At 30 days, AR ≥ moderate persisted in 33 (17.4%) patients: 8 (9.9%) after redo-TAVI, 18 (25.9%) after plug, and 7 (21.9%) after valvuloplasty (P = 0.036). Overall mortality was 10 (5.0%) at 30 days and 29 (14.4%) at 1 year: 0, 8 (10.1%), and 2 (5.7%) at 30 days (P = 0.010) and 11 (12.6%), 14 (17.7%), and 4 (11.4%) at 1 year (P = 0.418), after redo-TAVI, plug, and valvuloplasty, respectively. Regardless of treatment strategy, patients in whom AR was reduced to ≤ mild had lower mortality at 1 year compared with those with AR persisting ≥ moderate [11 (8.0%) vs. 6 (21.4%); P = 0.007]. CONCLUSION: This study describes the efficacy of transcatheter treatments for PVR after TAVI. Patients in whom PVR was successfully reduced had better prognosis. The selection of patients and the optimal PVR treatment modality require further investigation.

Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).

Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction.

BACKGROUND: The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. METHODS: The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. RESULTS: Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04). CONCLUSIONS: In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation.

BAlloon expandable vs. SElf expanding transcatheter vaLve for degenerated bioprosthesIs: design and rationale of the BASELINE trial.

BACKGROUND: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis. METHODS: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies. CONCLUSIONS: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072).

Transcatheter Left Ventricular Restoration in Patients With Heart Failure.

BACKGROUND: Left ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in patients with heart failure with reduced ejection fraction. The AccuCinch Transcatheter Left Ventricular Restoration system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to the basal free wall radius. We evaluated the echocardiographic and clinical outcomes following transcatheter left ventricular restoration. METHODS AND RESULTS: We analyzed 51 heart failure patients with a left ventricular ejection fraction between 20% and 40%, with no more than 2+ mitral regurgitation treated with optimal medical therapy, who subsequently underwent transcatheter left ventricular restoration. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire scores, and 6-minute walk test distances were measured at baseline through 12 months. Primary analysis end point was change in end-diastolic volume at 12 months compared with baseline. Patients (n = 51) were predominantly male (86%) with a mean age of 56.3 ± 13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% decrease in the free wall arc length. At 12 months, the LV end-diastolic volume decreased by 33.6 ± 34.8 mL (P < .01), with comparable decreases in the LV end-systolic volume. These decreases were associated with significant improvements in the overall Kansas City Cardiomyopathy Questionnaire score (16.4 ± 18.7 points; P < .01) and 6-minute hall walk test distance (45.9 ± 83.9 m; P < .01). There were no periprocedural deaths; through the 1-year follow-up, 1 patient died (day 280) and 1 patient received a left ventricular assist device (day 13). CONCLUSIONS: In patients with heart failure with reduced ejection fraction without significant mitral regurgitation receiving optimal medical therapy, the AccuCinch System resulted in decreases of LV volume, as well as improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).

Clinical value of CT-derived simulations of transcatheter-aortic-valve-implantation in challenging anatomies the PRECISE-TAVI trial.

BACKGROUND: Preprocedural computed tomography planning improves procedural safety and efficacy of transcatheter aortic valve implantation (TAVI). However, contemporary imaging modalities do not account for device-host interactions. AIMS: This study evaluates the value of preprocedural computer simulation with FEops HEARTguideTM on overall device success in patients with challenging anatomies undergoing TAVI with a contemporary self-expanding supra-annular transcatheter heart valve. METHODS: This prospective multicenter observational study included patients with a challenging anatomy defined as bicuspid aortic valve, small annulus or severely calcified aortic valve. We compared the heart team's transcatheter heart valve (THV) planning decision based on (1) conventional multislice computed tomography (MSCT) and (2) MSCT imaging with FEops HEARTguideTM simulations. Clinical outcomes and THV performance were followed up to 30 days. RESULTS: A total of 77 patients were included (median age 79.9 years (IQR 74.2-83.8), 42% male). In 35% of the patients, preprocedural planning changed after FEops HEARTguideTM simulations (change in valve size selection [12%] or target implantation height [23%]). A new permanent pacemaker implantation (PPI) was implanted in 13% and >trace paravalvular leakage (PVL) occurred in 28.5%. The contact pressure index (i.e., simulation output indicating the risk of conduction abnormalities) was significantly higher in patients with a new PPI, compared to those without (16.0% [25th-75th percentile 12.0-21.0] vs. 3.5% [25th-75th percentile 0-11.3], p < 0.01) The predicted PVL was 5.7 mL/s (25th-75th percentile 1.3-11.1) in patients with none-trace PVL, 12.7 (25th-75th percentile 5.5-19.1) in mild PVL and 17.7 (25th-75th percentile 3.6-19.4) in moderate PVL (p = 0.04). CONCLUSION: FEops HEARTguideTM simulations may provide enhanced insights in the risk for PVL or PPI after TAVI with a self-expanding supra-annular THV in complex anatomies.

Stent expansion in calcified coronary chronic total occlusions: The impact of different stent platforms.

OBJECTIVES: To evaluate the stent expansion of the durable-polymer Zotarolimus-eluting stent (dp-ZES), the durable-polymer Everolimus-eluting stent (dp-EES), and the bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in calcified coronary chronic total occlusions (CTO). BACKGROUND: The newer generation stents with ultrathin struts might raise concerns regarding reduced radial strength and higher stent recoil (SR) when implanted in calcified CTOs. METHODS: Between January 2017 and June 2021 consecutive patients with CTO undergoing percutaneous coronary intervention with dp-ZES, dp-EES, or bp-SES were evaluated. The analysis was performed in calcific and in noncalcific CTOs. Quantitative coronary angiography analysis was used to assess diameter stenosis (DS), absolute and relative SR, absolute and relative focal SR, absolute and relative balloon deficit (BD), and absolute and relative focal BD. The primary endpoint was DS. RESULTS: A total of 213 CTOs were evaluated, 115 calcific CTOs (dp-ZES:25, dp-EES:29, bp-SES:61) and 98 non-calcific CTOs (dp-ZES:41, dp-EES:11, bp-SES:46). In calcific CTOs, residual DS was lower in dp-ZES than in dp-EES and bp-SES (-1.00% [-6.50-6.50] vs. 13.00% [7.0-19.00] vs. 15.00% [5.00-20.00]; p < 0.001). Dp-ZES was also an independent predictor of residual DS ≤ 10% (OR 11.34, 95% CI 2.6-49.43, p = 0.001). Absolute and relative focal SR and absolute and relative SR were similar between dp-ZES, dp-EES, and bp-SES (p = 0.913, p = 0.890, p = 0.518, p = 0.426, respectively). In noncalcified CTOs, the residual DS was similar in the three groups (p = 0.340). High relative focal SR was less frequent in dp-ZES than in dp-EES and in bp-SES (19.5% vs. 54.5% vs. 37.0%; p < 0.048). CONCLUSIONS: The three stent platforms demonstrated an overall low residual DS when implanted in CTOs. However, dp-ZES was associated with the lowest residual DS and identified as independent predictor of residual DS ≤ 10% in patients with calcific CTOs. Dp-ZES was associated with a lower incidence of high relative focal stent recoil, in noncalcific CTOs. Balloon deficit might be considerate as a surrogate for stent expansion in calcified CTOs.

Prosthesis-patient mismatch after transcatheter implantation of contemporary balloon-expandable and self-expandable valves in small aortic annuli.

BACKGROUND: Evidence of clinical impact of PPM after TAVI is conflicting and might vary according to the type of valve implanted. AIMS: To assess the clinical impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) with balloon-expandable (BEV) and self-expandable valves (SEV) in patients with small annuli. METHODS: TAVI-SMALL 2 enrolled 628 patients in an international retrospective registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm2 ) treated with transfemoral TAVI at 16 high-volume centers between 2011 and 2020. Analyses were performed comparing patients with less than moderate (n = 452), moderate (n = 138), and severe PPM (n = 38). Primary endpoint was incidence of all-cause mortality. Predictors of all-cause mortality and PPM were investigated. RESULTS: At a median follow-up of 380 days (interquartile range: 210-709 days), patients with severe PPM, but not moderate PPM, had an increased risk of all-cause mortality when compared with less than moderate PPM (log-rank p = 0.046). Severe PPM predicted all-cause mortality in patients with BEV (hazard ratio [HR]: 5.20, 95% confidence interval [CI]: 1.27-21.2) and intra-annular valves (IAVs, HR: 4.23, 95% CI: 1.28-14.02), and it did so with borderline significance in the overall population (HR: 2.89, 95% CI: 0.95-8.79). Supra-annular valve (SAV) implantation was the only predictor of severe PPM (odds ratio: 0.33, 95% CI: 0.13-0.83). CONCLUSIONS: Patients with small aortic annuli and severe PPM after TAVI have an increased risk of all-cause mortality at early term follow-up, especially after IAV or BEV implantation. TAVI with SAV protected from severe PPM.

Culprit lesion plaque characterization and thrombus grading by high-definition intravascular ultrasound in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Dedicated prospective studies investigating high-definition intravascular ultrasound (HD-IVUS)-guided primary percutaneous coronary intervention (PCI) are lacking. The aim of this study was to qualify and quantify culprit lesion plaque characteristics and thrombus using HD-IVUS in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: The SPECTRUM study is a prospective, single-center, observational cohort study investigating the impact of HD-IVUS-guided primary PCI in 200 STEMI patients (NCT05007535). The first 100 study patients with a de novo culprit lesion and a per-protocol mandated preintervention pullback directly after vessel wiring were subject to a predefined imaging analysis. Culprit lesion plaque characteristics and different thrombus types were assessed. An IVUS-derived thrombus score, including a 1-point adjudication for a long total thrombus length, long occlusive thrombus length, and large maximum thrombus angle, was developed to differentiate between low (0-1 points) and high (2-3 points) thrombus burden. Optimal cut-off values were obtained using receiver operating characteristic curves. RESULTS: The mean age was 63.5 (±12.1) years and 69 (69.0%) patients were male. The median culprit lesion length was 33.5 (22.8-38.9) mm. Plaque rupture and convex calcium were appreciated in 48 (48.0%) and 10 (10.0%) patients, respectively. Thrombus was observed in 91 (91.0%) patients (acute thrombus 3.3%; subacute thrombus 100.0%; organized thrombus 22.0%). High IVUS-derived thrombus burden was present in 37/91 (40.7%) patients and was associated with higher rates of impaired final thrombolysis in myocardial infarction flow (grade 0-2) (27.0% vs. 1.9%, p < 0.001). CONCLUSIONS: HD-IVUS in patients presenting with STEMI allows detailed culprit lesion plaque characterization and thrombus grading that may guide tailored PCI.

Optical coherence tomography-derived predictors of stent expansion in calcified lesions.

BACKGROUND: Severe coronary artery calcification is associated with stent underexpansion and subsequent stent failure. AIMS: We aimed to identify optical coherence tomography (OCT)-derived predictors of absolute (minimal stent area [MSA]) and relative stent expansion in calcified lesions. METHODS: This retrospective cohort study included patients who underwent percutaneous coronary intervention (PCI) with OCT assessment before and after stent implantation between May 2008 and April 2022. Pre-PCI OCT was used to assess calcium burden and post-PCI OCT was used to assess absolute and relative stent expansion. RESULTS: A total of 361 lesions in 336 patients were analyzed. Target lesion calcification (defined as OCT-detected maximum calcium angle ≥ 30°) was present in 242 (67.0%) lesions. Following PCI, median MSA was 5.37 mm2 in calcified lesions and 6.24 mm2 in noncalcified lesions (p < 0.001). Median stent expansion was 78% in calcified lesions and 83% in noncalcified lesions (p = 0.325). In the subset of calcified lesions, average stent diameter, preprocedural minimal lumen area, and total calcium length were independent predictors of MSA in multivariable analysis (mean difference 2.69 mm2 /mm2 , 0.52 mm2 /mm, and -0.28 mm2 /5 mm, respectively, all p < 0.001). Total stent length was the only independent predictor of relative stent expansion (mean difference -0.465% per mm, p < 0.001). Calcium angle, thickness, and the presence of nodular calcification were not significantly associated with MSA or stent expansion in multivariable analyses. CONCLUSION: Calcium length appeared to be the most important OCT-derived predictor of MSA, whereas stent expansion was mainly determined by total stent length.

Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study.

AIMS: The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial. METHODS AND RESULTS: SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35). CONCLUSIONS: Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.

Changing haemodynamic status of patients referred for transcatheter aortic valve intervention during the COVID-19 pandemic.

INTRODUCTION: Delays in the diagnosis and referral of aortic stenosis (AS) during the coronavirus disease 2019 (COVID-19) pandemic may have affected the haemodynamic status of AS patients. We aimed to compare clinical and haemodynamic characteristics of severe AS patients referred for transcatheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) before the pandemic versus two subsequent periods. METHODS: This study compared three 1­year historical cohorts: a pre-COVID-19 group (PCOV), a 1st-year COVID-19 group (COV-Y1) and a 2nd-year COVID-19 group (COV-Y2). The main parameters were baseline New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Demographics, procedural characteristics and 30-day clinical outcomes were assessed. The transition time between heart team decision and TAVI was examined. Pairwise group comparisons were performed (PCOV vs COV-1Y and COV-1Y vs COV-2Y). RESULTS: A total of 720 patients were included with 266, 249 and 205 patients in the PCOV, COV-Y1 and COV-Y2 groups, respectively. BAV was performed in 28 patients (4%). NYHA class did not differ across the cohorts. Compared to PCOV, LVEF was slightly lower in COV-Y1 (58% (49-60%) vs 57% (45-60%), p = 0.03); no difference was observed when comparing COV-Y1 and COV-Y2. LVEDP was higher in COV-Y1 than in PCOV (20 mm Hg (16-26 mm Hg) vs 17 mm Hg (13-24 mm Hg), p = 0.01). No difference was found when comparing LVEDP between COV-Y1 and COV-Y2. Thirty-day mortality did not differ between groups. Transition time was reduced in the COVID era. Duration of hospital stay declined over the study period. CONCLUSIONS: Patients undergoing TAVI during the COVID-19 pandemic had more advanced AS illustrated by lower LVEF and higher LVEDP, but there were no differences in clinical outcome. The TAVI pathway became more efficient.

Initial experience with orbital atherectomy in a tertiary centre in the Netherlands.

BACKGROUND: In January 2021, the Diamondback 360 orbital atherectomy (OA) system received CE mark approval and became available in Europe. The first procedure in Europe was performed at the Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands. AIMS: To report the procedural safety and efficacy of the initial experience with OA in a tertiary care institution in the Netherlands. METHODS: Patients with de novo severely calcified coronary artery disease who were treated with intended invasive imaging-guided OA were included in a prospective single-centre registry. Device success, defined as less than 50% stenosis after OA, and procedural success, defined as successful stent implantation with less than 50% residual stenosis, were evaluated. Calcium debulking effects were assessed by invasive imaging. Safety was assessed up to 30 days after the index procedure. RESULTS: Between February 2021 and June 2021, 29 patients with a total of 39 coronary arteries underwent OA. Target lesions were heavily calcified with a mean length of 32 mm and a calcium arc of 320 degrees. Invasive imaging was applied in all but one patient and 36 vessels. Superficial sanding was observed in almost all vessels (90%) and fracturing of deeper medial calcium in more than half of the vessels (63%), with a device success of 66% and procedural success of 94%. The mean stent symmetry index was 0.84, indicating good circular stent expansion. No primary safety events occurred during 30 days of follow-up. CONCLUSION: Our initial experience with OA for heavily calcified coronary lesions demonstrated favourable debulking effects and plaque modification, with high procedural success and clinical safety.

Pre-hospital treatment with crushed versus integral tablets of prasugrel in patients presenting with ST-Segment Elevation Myocardial Infarction-1-year follow-up results of the COMPARE CRUSH trial.

The present research letter reports the 1-year clinical outcomes of the randomized COMPARE CRUSH trial, which allocated STEMI patients at first medical contact in the ambulance to receive either crushed or integral tablets of prasugrel loading dose. This trial aimed to investigate whether early enhanced antiplatelet effect constituted by the crushed potent oral P2Y12 inhibitor prasugrel could lead to improved early myocardial reperfusion and clinical outcomes.

COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy".

BACKGROUND: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking. STUDY OBJECTIVES: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. STUDY DESIGN: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA2DS2-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. SUMMARY: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. NCT TRIAL NUMBER: NCT04676880.

Elastic stent recoil in coronary total occlusions: Comparison of durable-polymer zotarolimus eluting stent and ultrathin strut bioabsorbable-polymer sirolimus eluting stent.

OBJECTIVES: To compare stent recoil (SR) of the thin-strut durable-polymer Zotarolimus-eluting stent (dp-ZES) and the ultrathin-strut bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in chronic total occlusions (CTOs) and to investigate the predictors of high SR in CTOs. BACKGROUND: Newer ultrathin drug eluting stent might be associated with lower radial force and higher elastic recoil due to the thinner strut design, possibly impacting on the rate of in-stent restenosis and thrombosis. METHODS: Between January 2017 and November 2019, consecutive patients with CTOs undergoing percutaneous coronary intervention were evaluated. Only patients treated with dp-ZES or bp-SES were included and stratified accordingly. Quantitative coronary angiography analysis was used to assess absolute SR, relative SR, absolute focal SR, relative focal SR, high absolute, and high relative focal SR. RESULTS: A total of 128 lesions (67 treated with dp-ZES and 61 with bp-SES) in 123 patients were analyzed. Between bp-SES and dp-ZES no differences were found in absolute SR (p = .188), relative SR (p = .138), absolute focal SR (p = .069), and relative focal SR (p = .064). High absolute and high relative focal SR occurred more frequently in bp-SES than in dp-ZES (p = .004 and p = .015). Bp-SES was a predictor of high absolute focal SR (Odds ratio [OR] 3.29, 95% confidence interval [CI] 1.50-7.22, p = .003]. High-pressure postdilation and bp-SES were predictors of high relative focal SR (OR 2.22, 95% CI 1.01-4.86, p = .047; OR 2.74, 95% CI 1.24-6.02, p = .012, respectively). CONCLUSIONS: Both stents showed an overall low SR. However, ultra-thin strut bp-SES was a predictor of high absolute and high relative focal SR.

Final 3-year clinical outcomes following transcatheter aortic valve implantation with a supra-annular self-expanding repositionable valve in a real-world setting: Results from the multicenter FORWARD study.

OBJECTIVES: The Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3-year clinical follow up of the FORWARD study. BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long-term clinical outcome data with the Evolut R platform are scarce. METHODS: FORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart-Team assessment. TAVR was attempted in 1039 patients. RESULTS: Mean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all-cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all-cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all-cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low. CONCLUSIONS: The Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve-related adverse events were low.