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.

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.

Staged correction of pulmonary atresia, ventricular septal defect, and collateral arteries.

OBJECTIVES: Pulmonary atresia (PA) with ventricular septal defect (VSD) and systemic-pulmonary collateral arteries (SPCAs) presents with variable anatomy with regard to the pulmonary vasculature, requiring personalized surgical treatment. A protocol consisting of staged unifocalization and correction was employed. METHODS: Since 1989, 39 consecutive patients were included (median age at first operation 13 months). In selected cases, a central aorto-pulmonary shunt was performed as the first procedure. Unifocalization procedures were performed through a lateral thoracotomy. Correction consisted of shunt takedown, VSD closure, and interposition of an allograft between the right ventricle and the reconstructed pulmonary artery. Echocardiographic data were obtained postoperatively and at interval follow-up. RESULTS: In 39 patients 66 unifocalization procedures were performed. Early mortality was 5%. Seven patients were considered not suitable for correction, of which four have since died. One patient is awaiting further correction. A correction was performed successfully in 28 patients. Operative mortality was 3% and late mortality was 11%. Median follow-up after the correction was 19 years. Eleven patients required homograft replacement. Freedom from conduit replacement was 88%, 73%, and 60% at 5, 10, and 15 years respectively. Right ventricular function was reasonable or good in 75% of patients. All but one patient were in NYHA Class I or II. CONCLUSIONS: After complete unifocalization 30/37 patients (81%) were considered correctable. The staged approach of PA, VSD, and SPCAs results in adequate correction and good functional capacity. RV function after correction remains reasonable or good in the majority of patients.

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.

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.

Long-term outcome in patients treated with first- versus second-generation drug-eluting stents for the treatment of unprotected left main coronary artery stenosis.

OBJECTIVE AND BACKGROUND: The study aim is to provide long-term clinical outcome after percutaneous coronary intervention (PCI) for unprotected left main coronary arteries (ULMCA) stenosis with the first-generation (1st -gen) drug-eluting stents (DES) in comparison to 2nd -gen DES, since this is largely unknown. METHODS: Between May 2002, and December 2014, a consecutive series of 656 all-comer patients underwent a PCI for ULMCA stenosis at the Erasmus Medical Center. A total of 235 patients were treated with 1st -gen DES, while a total of 421 patients were treated with 2nd -gen DES. RESULTS: Overall, the population consisted of 73% males and 58% presented with an acute coronary syndrome. Median follow-up time was 1,361 days (range from 0 to 5,031). At 5 years, the cumulative incidence of major adverse clinical events (the primary composite endpoint of all-cause death, any myocardial infarction or target lesion revascularization; MACE) did not differ between 1st - and 2nd -gen DES (36.8 vs. 38.6%, respectively, Log Rank p = .79, adjusted hazard ratio [HR] = 1.28 [95% confidence interval (CI) 0.94-1.74]). No difference was found in the individual endpoints of all-cause mortality (29.5 vs. 29% respectively, p = .88, adjusted HR = 1.19 [95% CI, 0.84-1.68]), target vessel myocardial infarction (5.0 vs. 8.4%, p = 0.17, adjusted HR = 1.75 [95% CI, 0.78-3.96]) and target lesion revascularization (8.1 vs. 9.8%, p = .94, adjusted HR = 1.16 [95% CI, 0.59-2.29]) between the 1st - and 2nd -gen DES cohorts, respectively. CONCLUSIONS: In this large cohort of consecutive patients treated for ULMCA stenosis, no significant differences were found in the safety and efficacy of 1st versus 2nd -gen DES at 5 years follow-up.

Fractional flow reserve guided percutaneous coronary intervention optimization directed by high-definition intravascular ultrasound versus standard of care: Rationale and study design of the prospective randomized FFR-REACT trial.

BACKGROUND: Post percutaneous coronary intervention (PCI) fractional flow reserve (FFR) is a significant predictor of major adverse cardiac events (MACE). The rationale for low post procedural FFR values often remains elusive based on angiographic findings alone, warranting further assessment using an FFR pullback or additional intravascular imaging. It is currently unknown if additional interventions intended to improve the PCI, decrease MACE rates. STUDY DESIGN: The FFR REACT trial is a prospective, single-center randomized controlled trial in which 290 patients with a post PCI FFR <0.90 will be randomized (1:1) to either standard of care (no additional intervention) or intravascular ultrasound (IVUS)-directed optimization of the FFR (treatment arm). Eligible patients are those treated with angiographically successful PCI for (un)stable angina or non-ST elevation myocardial infarction (MI). Assuming 45% of patients will have a post PCI FFR <0.90, approximately 640 patients undergoing PCI will need to be enrolled. Patients with a post PCI FFR ≥ 0.90 will be enrolled in a prospective registry. The primary end point is defined as a composite of cardiac death, target vessel MI and clinically driven target vessel revascularisation (target vessel failure) at 1 year. Secondary end points will consist of individual components of the primary end point, procedural success, stent thrombosis and correlations on clinical outcome, changes in post PCI Pd/Pa and FFR and IVUS derived dimensions. All patients will be followed for 3 years. CONCLUSION: The FFR-REACT trial is designed to explore the potential benefit of HD-IVUS-guided PCI optimization in patients with a post PCI FFR <0.90 (Dutch trial register: NTR6711).

References for left main stem dimensions: A cross sectional intravascular ultrasound analysis.

BACKGROUND: Angiographic assessment of left main coronary artery (LMCA) lesions remains challenging and limited data is available on reference diameters and length of nonobstructive LMCA dimensions. Our aim was to provide insights in the dimensions of nonobstructive LMCA and to find a possible correlation with gender and patient habitus. METHODS: This retrospective single center study was performed in a consecutive cohort of patients who underwent Intravascular Ultrasound (IVUS) guided percutaneous coronary interventions of the left coronary system including complete pullbacks of a non-obstructive LMCA (n = 254). RESULTS: Mean LMCA length as measured with IVUS was 7.37 ± 4.2 mm and mean lumen area (LA) was 15.63 ± 4.76 mm2 corresponding to a mean lumen diameter (LD) of 4.41 ± 0.67 mm. An IVUS derived mean LD of >4 mm was present in 71.7%, >4.5 mm in 43% and > 5 mm in 19% of patients. LMCA mean LA was significantly smaller in women as compared to men (14.1 ± 4.1 mm2 and 16.2 ± 4.8 mm2 , P < 0.01). Multivariable analysis identified weight of the patient as the sole significant predictor for LMCA length while height of the patient and LMCA length were predictors of LMCA mean LA. Correlation coefficients of determination for all independent predictors were low (R2 < 0.1 for all). CONCLUSION: This study demonstrated that the mean LD of a non-obstructive LMCA is 4 mm or greater in the majority of patients, with a mean LMCA length of 7.4 mm. Women have smaller luminal dimension than men. No clinically relevant predictors were found for both LMCA length and mean LA.

Role of Lipid-Lowering and Anti-Inflammatory Therapies on Plaque Stabilization.

Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease.