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.

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.

Relationship between stent length and very long-term target lesion failure following percutaneous coronary intervention for ST-elevation myocardial infarction in the drug-eluting stents era: insights from the EXAMINATION-EXTEND study.

BACKGROUND: Little data exist on the relationship between total stent length (TSL) and cardiovascular outcomes at very-long follow-up in patients with ST-elevation myocardial infarction (STEMI) in the 2nd generation drug-eluting stents (DES) era. AIM: To analyze the relationship between TSL and 10-year target-lesion failure (TLF) in STEMI patients treated with percutaneous coronary intervention enrolled in the EXAMINATION-EXTEND. METHODS: The EXAMINATION-EXTEND was an extended-follow-up study of the EXAMINATION trial, which randomized 1:1 STEMI patients to receive DES or bare metal stent (BMS). The primary endpoint was TLF, defined as a composite of target lesion revascularization (TLR), target vessel myocardial infarction (TVMI), or definite/probable stent thrombosis (ST). Relationship between stent length and TLF was evaluated in the whole study group in a multiple-adjusted Cox regression model with TSL as a quantitative variable. Subgroup analysis was also performed according to stent type, diameter, and overlap. RESULTS: A total of 1,489 patients with a median TSL of 23 mm (Q1-Q318-35 mm) were included. TSL was associated with TLF at 10 years (adjusted HR per 5 mm increase of 1.07; 95% CI, 1.01-1.14; P = .02). This effect was mainly driven by TLR and was consistent regardless of stent type, diameter, or overlap. There was no significant relationship between TSL and TV-MI or ST. CONCLUSIONS: In STEMI patients, there is a direct relationship between TSL implanted in the culprit vessel and the risk of TLF at 10 years, mainly driven by TLR. The use of DES did not modify this association.

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.

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.

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.

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.

Diagnostic accuracy of angiography-based vessel fractional flow reserve after chronic coronary total occlusion recanalization.

BACKGROUND: Angiography-based vessel fractional flow reserve (vFFR) demonstrated a strong correlation with invasive fractional flow reserve (FFR) in both a pre- and post-percutaneous coronary intervention (PCI) setting. However, the role of vFFR and its correlation with post-PCI FFR in chronic coronary occlusions (CTO) has not been evaluated yet. We sought to investigate the diagnostic performance of post-PCI vFFR with post-PCI FFR as a reference in patients undergoing successful CTO PCI. METHODS: Between March 2016 and April 2020, a total of 80 patients from the FFR-SEARCH (prospective registry) and FFR REACT (randomized controlled trial) studies underwent successful CTO recanalization with post-PCI FFR measurements. RESULTS: A total of 50 patients (median age 66 (interquartile range [IQR]: 56-74) years, 76% were male) were eligible for the analysis. Median post-PCI FFR was 0.89 (IQR: 0.84-0.94), while median post-PCI vFFR was 0.91 (IQR: 0.85-0.94) (p 0.10). Suboptimal physiological results, defined as FFR and vFFR <0.90, were identified in 26 (52%) and in 21 (42%) patients, respectively. A strong correlation (r = 0.82) was found between vFFR and FFR with a mean bias of 0.013 ± 0.051. Receiver-operating characteristics curve analysis revealed an excellent accuracy of vFFR in predicting FFR <0.90 (area under the curve: 0.97; 95% confidence interval: 0.93-1.00). CONCLUSION: Post-PCI vFFR shows a good correlation with post-PCI FFR and a high diagnostic accuracy for post-PCI FFR ≤0.90 in patients undergoing successful PCI of a CTO lesion.

Impact of thrombus burden on long-term clinical outcomes in patients with either anterior or non-anterior ST-segment elevation myocardial infarction.

Large thrombus burden (LTB) during ST-segment elevation myocardial infarction (STEMI) could translate into worse clinical outcomes. The impact of a LTB in terms of long-term clinical outcomes on different myocardial infarct territories has not yet been fully evaluated. From April 2002 to December 2004, consecutive patients with STEMI undergoing percutaneous coronary intervention with drug eluting stent were evaluated. The study sample was stratified in two groups: anterior STEMI and non-anterior STEMI. LTB was considered as a thrombus larger than or equal to 2-vessel diameters, and small thrombus burden less than 2-vessel diameters. Major adverse cardiac events (MACE) were evaluated at 10-year and survival data were collected up to 15-year. A total of 812 patients were evaluated, 6 patients were excluded due to inadequate angiographic images, 410 (50.9%) had an anterior STEMI and 396 (49.1%) a non-anterior STEMI. Patients with LTB had higher rates of 10-year mortality (aHR 2.27, 95%CI 1.42-3.63; p = 0.001) and 10-year MACE (aHR 1.46, 95%CI 1.03-2.08; p = 0.033) in anterior STEMI, but not in non-anterior STEMI (aHR 0.78, 95%CI 0.49-1.24; p = 0.298; aHR 0.71, 95%CI 0.50-1.02; p = 0.062). LTB was associated with increased 30-day mortality (aHR 5.60, 95%CI 2.49-12.61; p < 0.001) and 30-day MACE (aHR 2.72, 95%CI 1.45-5.08; p = 0.002) in anterior STEMI, but not in non-anterior STEMI (aHR 0.39, 95%CI 0.15-1.06; p = 0.066; aHR 0.67, 95%CI 0.31-1.46; p = 0.316). Beyond 30-day, LTB had no impact on mortality and MACE in both groups. In anterior STEMI, LTB is associated with worse long-term clinical outcomes, this effect was driven by early events.

Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial.

BACKGROUND: Early treatment with a potent oral platelet P2Y12 inhibitor is recommended in patients presenting with ST-segment-elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y12 inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown. METHODS: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment-elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes. RESULTS: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47-70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65-1.30], P=0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78-1.58], P=0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y12 reactivity unit, differed significantly between groups (crushed, 192 [132-245] versus integral, 227 [184-254], P≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days. CONCLUSIONS: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment-elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296540.

Validation of novel 3-dimensional quantitative coronary angiography based software to calculate fractional flow reserve post stenting.

OBJECTIVES: To validate novel dedicated 3D-QCA based on the software to calculate post PCI vessel-FFR (vFFR) in a consecutive series of patients, to assess the diagnostic accuracy, and to assess inter-observer variability. BACKGROUND: Low post percutaneous coronary intervention (PCI) fractional flow reserve (FFR) predicts future adverse cardiac events. However, FFR assessment requires the insertion of a pressure wire in combination with the use of a hyperemic agent. METHODS: FAST POST study is an observational, retrospective, single-center cohort study. One hundred patients presenting with stable angina or non ST-elevation myocardial infarction, who underwent post PCI FFR assessment using a dedicated microcatheter were included. Two orthogonal angiographic projections were acquired to create a 3D reconstruction of the coronary artery using the CAAS workstation 8.0. vFFR was subsequently calculated using the aortic root pressure. RESULTS: Mean age was 65±12 years and 70% were male. Mean microcatheter based FFR and vFFR were 0.91±0.07 and 0.91±0.06, respectively. A good linear correlation was found between FFR and vFFR (r = 0.88; p <.001). vFFR had a higher accuracy in the identification of patients with FFR values <0.90, AUC 0.98 (95% CI: 0.96-1.00) as compared with 3D-QCA AUC 0.62 (95% CI: 0.94-0.74). Assessment of vFFR had a low inter-observer variability (r = 0.95; p <.001). CONCLUSION: 3D-QCA derived post PCI vFFR correlates well with invasively measured microcatheter based FFR and has a high diagnostic accuracy to detect FFR <0.90 with low inter-observer variability.

Correlation between 3D-QCA based FFR and quantitative lumen assessment by IVUS for left main coronary artery stenoses.

OBJECTIVES: We aimed to evaluate the feasibility of using three dimensional-quantitative coronary angiography (3D-QCA) based fractional flow reserve (FFR) (vessel fractional flow reserve [vFFR], CAAS8.1, Pie Medical Imaging) and to correlate vFFR values with intravascular ultrasound (IVUS) for the evaluation of intermediate left main coronary artery (LMCA) stenosis. BACKGROUND: 3D-QCA derived FFR indices have been recently developed for less invasive functional lesion assessment. However, LMCA lesions were vastly under-represented in first validation studies. METHODS: This observational single-center cohort study enrolled consecutive patients with stable angina, unstable angina, or non-ST-segment elevation myocardial infarction and nonostial, intermediate grade LMCA stenoses who underwent IVUS evaluation. vFFR was computed based on two angiograms with optimal LMCA stenosis projection and correlated with IVUS-derived minimal lumen area (MLA). RESULTS: A total of 256 patients with intermediate grade LMCA stenosis evaluated with IVUS were screened for eligibility; 147 patients met the clinical inclusion criteria and had a complete IVUS LMCA footage available, of them, 63 patients (63 lesions) underwent 3D-QCA and vFFR analyses. The main reason for screening failure was insufficient quality of the angiogram (51 patients,60.7%). Mean age was 65 ± 11 years, 75% were male. Overall, mean MLA within LMCA was 8.77 ± 3.17 mm2 , while mean vFFR was 0.87 ± 0.09. A correlation was observed between vFFR and LMCA MLA (r = .792, p = .001). The diagnostic accuracy of vFFR ≤0.8 in identifying lesions with MLA < 6.0 mm2 (sensitivity 98%, specificity 71.4%, area under the curve (AUC) 0.95, 95% confidence interval (CI) 0.89-1.00, p = .001) was good. CONCLUSIONS: In patients with good quality angiographic visualization of LMCA and available complete LMCA IVUS footage, 3D-QCA based vFFR assessment of LMCA disease correlates well to LMCA MLA as assessed by IVUS.

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel.

BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.

Percutaneous complete revascularization strategies using sirolimus-eluting biodegradable polymer-coated stents in patients presenting with acute coronary syndrome and multivessel disease: Rationale and design of the BIOVASC trial.

BACKGROUND: Complete revascularization in patients with an acute coronary syndrome and multivessel disease is superior compared to culprit-only treatment. However, it is unknown whether direct complete or staged complete revascularization should be pursued. METHODS: The BIOVASC study is an investigator-initiated, prospective, multicenter, randomized, 2-arm, international, open-label, noninferiority trial. We will randomize 1,525 patients 1:1 to immediate complete revascularization (experimental arm) or culprit-only plus staged complete revascularization (control arm). Patients will be enrolled in approximately 30 sites in Belgium, Italy, the Netherlands, and Spain. The primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any unplanned ischemia-driven revascularization (excluding staged procedures in the control arm at the predetermined time), and cerebrovascular events (MACCE) at 1 year post index procedure. CONCLUSIONS: The BIOVASC study aims to further refine the treatment algorithm for acute coronary syndrome patients with multivessel disease in terms of optimal timing for complete revascularization (Clinicaltrials.gov NCT03621501).

COMPARison of pre-hospital CRUSHed vs. uncrushed Prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary interventions: Rationale and design of the COMPARE CRUSH trial.

BACKGROUND: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown. HYPOTHESIS: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose. STUDY DESIGN: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours. CONCLUSIONS: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540.

Serial invasive imaging follow-up of the first clinical experience with the Magmaris magnesium bioresorbable scaffold.

OBJECTIVES: To assess the performance of the commercially available Magmaris sirolimus-eluting bioresorbable scaffold (BRS) with invasive imaging at different time points. BACKGROUND: Coronary BRS with a magnesium backbone have been recently studied as an alternative to polymeric scaffolds, providing enhanced vessel support and a faster resorption rate. We aimed to assess the performance of the commercially available Magmaris sirolimus-eluting BRS at different time points. METHODS: A prospective, single-center, nonrandomized study was performed at the Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands. Six patients with stable de novo coronary artery lesions underwent single-vessel revascularization with the Magmaris sirolimus-eluting BRS. Invasive follow-up including intravascular imaging using optical coherence tomography (OCT) was performed at different time points. RESULTS: At a median of 8 months (range 4-12 months) target lesion failure occurred in one patient. Angiography revealed a late lumen loss of 0.59 ± 0.39 mm, a percentage diameter stenosis of 39.65 ± 15.81%, and a binary restenosis rate of 33.3%. OCT showed a significant reduction in both minimal lumen area (MLA) and scaffold area at the site of the MLA by 43.44 ± 28.62 and 38.20 ± 25.74%, respectively. A fast and heterogeneous scaffold degradation process was found with a significant reduction of patent struts at 4-5 months. CONCLUSIONS: Our findings show that the latest iteration of magnesium BRS suffers from premature dismantling, resulting in a higher than expected decrease in MLA.

Assessment of residual thrombus burden in patients with ST-segment elevation myocardial infarction undergoing bivalirudin versus unfractionated heparin infusion: The MATRIX (minimizing adverse hemorrhagic events by transradial access site and angioX) OCT study.

BACKGROUND: Residual stent strut thrombosis after primary percutaneous coronary intervention (PCI), negatively affects myocardial perfusion, may increase stent thrombosis risk, and it is associated with neointima hyperplasia at follow-up. OBJECTIVES: To study the effectiveness of any bivalirudin infusion versus unfractionated heparin (UFH) infusion in reducing residual stent strut thrombosis in patients with ST-elevation myocardial infarction (STEMI). METHODS: Multi-vessel STEMI patients undergoing primary PCI and requiring staged intervention were selected among those randomly allocated to two different bivalirudin infusion regimens in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Those receiving heparin only were enrolled into a registry arm. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of primary PCI and 3-5 days thereafter during a staged intervention. The primary endpoint was the change in minimum flow area (ΔMinFA) defined as (stent area + incomplete stent apposition [ISA] area) - (intraluminal defect + tissue prolapsed area) between the index and staged PCI. RESULTS: 123 patients in bivalirudin arm and 28 patients in the UFH arm were included. Mean stent area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The ΔMinFA in the bivalirudin group was 0.25 versus 0.05 mm2 in the UFH group, which resulted in a between-group significant difference of 0.36 [95% CI: (0.05, 0.71); p = .02]. This was mostly related to a decrease in tissue protrusion in the bivalirudin group (p = .03). There was a trend towards more patients in the bivalirudin group who achieved a 5% difference in the percentage of OCT frames with the area >5% (p = .057). CONCLUSIONS: The administration of bivalirudin after primary PCI significantly reduces residual stent strut thrombosis when compared to UFH. This observation should be considered hypothesis-generating since the heparin-treated patients were not randomly allocated.