Impact of Post-Procedural Graft Flow on Outcomes Following Chronic Total Occlusion Intervention in Post-Coronary Artery Bypass Graft Patients: a Detailed Angiographic Analysis.

Chronic total occlusions (CTO) are frequent in patients with previous coronary artery bypass graft (CABG) surgery. Percutaneous coronary intervention (PCI) is the usual revascularization strategy. Whether or not the presence of a graft on a CTO vessel and post-PCI graft patency impacts outcomes following CTO-PCI is unknown. We sought to evaluate the impact of post-PCI graft patency on the durability of CTO-PCI. In total, 259 post-CABG patients undergoing CTO-PCI in 12 international centers in 2019-2023 were categorized into "grafted" and "ungrafted" groups based on the presence of graft on a CTO vessel. The grafted group was subdivided into "graft-occluded" and "graft-patent" groups, depending on graft patency. Primary endpoints were (a) technical success rate, (b) target vessel failure and (c) CTO failure rates at 1-year. CTO failure was defined as both target vessel revascularization and/or significant in-stent restenosis. A total of 199 patients (77%) were in the grafted group. Grafted CTOs showed higher complexity and lower technical success rates (70% vs. 80%, P=0.004) than non-grafted CTOs. Among the grafted CTOs, 140 (70%) were in the grafted-occluded group and 59 (30%) were in the grafted-patent group. The technical success was lower in the former group (65% vs. 81%, P=0.022). An occluded graft was an independent predictor of technical failure (OR=2.04; 95%CI: 1.03-4.76, p=0.049) and persistent post-PCI graft patency was a strong independent predictor of CTO failure at 1-year (HR=5.6, 95% CI: 1.2-27.5, log-rank P=0.033). In conclusion, in post-CABG patients undergoing CTO-PCI, post-PCI graft patency was a significant predictor of CTO failure.

Performance of the minimalistic hybrid approach algorithm versus other conventional algorithms in the percutaneous treatment of chronic total occlusions.

BACKGROUND: The "Minimalistic Hybrid Approach" (MHA) has been proposed to reduce the invasiveness of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). AIMS: This study aims to assess whether MHA may also reduce the utilization of PCI resources (devices, radiations, and contrast) by comparing it with other conventional algorithms. METHODS: We aimed to assess the impact of MHA on device, radiation, and contrast usage during CTO-PCI analyzing data from the Belgian Working Group on CTO (BWG-CTO) registry. Patients were divided, depending on the algorithm used, into two groups: Conventional versus Minimalistic. Primary objectives were procedure performance measures such as device usage (microcatheters and guidewires), radiological parameters, and contrast use. At 1-year follow-up, patients were evaluated for target vessel failure (TVF), defined as a composite of cardiac death, new myocardial infarction, and target vessel revascularization. RESULTS: Overall, we analyzed 821 CTO-PCIs (Conventional n = 650, Minimalistic n = 171). The Minimalistic group demonstrated higher complexity of CTO lesions. After adjusting for propensity score, the Minimalistic group had a significantly lower number of microcatheters used (1.49 ± 0.85 vs. 1.24 ± 0.64, p = 0.026), while the number of guidewires was comparable (4.80 ± 3.29 vs. 4.35 ± 2.94, p = 0.30). Both groups had similar rates of success and procedural complications, as well as comparable procedural and fluoroscopic times and contrast volume used. At the 1-year follow-up, both groups showed comparable rates of TVF (hazard ratio: 0.57; 95% confidence interval: 0.24-1.34, p = 0.195). CONCLUSION: The MHA may slightly reduce the number of dedicated devices used during CTO-PCI, without adversely affecting the procedural success or long-term outcome.

ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions: Design and rationale of the SONAR trial.

BACKGROUND: The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction. STUDY DESIGN AND OBJECTIVES: The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events. CONCLUSIONS: The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.

Clinical and Hemodynamic Effects of Percutaneous Edge-to-Edge Mitral Valve Repair in Atrial Versus Ventricular Functional Mitral Regurgitation.

The present study aims to assess the clinical and hemodynamic impact of percutaneous edge-to-edge mitral valve repair with MitraClip in patients with atrial functional mitral regurgitation (A-FMR) compared with ventricular functional mitral regurgitation (V-FMR). Mitral regurgitation (MR) grade, functional status (New York Heart Association class), and major adverse cardiac events (MACE; all-cause mortality or hospitalization for heart failure) were evaluated in 52 patients with A-FMR and in 307 patients with V-FMR. In 56 patients, hemodynamic assessment during exercise echocardiography was performed before and 6 months after intervention. MR reduction after MitraClip implantation was noninferior in A-FMR compared with V-FMR (MR grade ≤2 at 6 months in 94% vs 82%, respectively, p <0.001 for noninferiority) and was associated with improvement of functional status (New York Heart Association class ≤2 at 6 months in 90% vs 80%, respectively, p = 0.2). Hemodynamic assessment revealed that cardiac output at 6 months was higher in A-FMR at rest (5.1 ± 1.5 L/min vs 3.8 ± 1.5 L/min, p = 0.002) and during peak exercise (7.9 ± 2.4 L/min vs 6.1 ± 2.1 L/min, p = 0.02). In addition, the reduction in systolic pulmonary artery pressure at rest was more pronounced in A-FMR: Δ SPAP -13.1 ± 15.1 mm Hg versus -2.2 ± 13.3 mm Hg (p = 0.03). MACE rate at follow-up was significantly lower in A-FMR versus V-FMR, with an adjusted odds ratio of 0.46 (95% confidence interval 0.24 to 0.88), which was caused by a reduction in hospitalization for heart failure. In conclusion, percutaneous edge-to-edge mitral valve repair with MitraClip is at least as effective in A-FMR as in V-FMR in reducing MR. However, the hemodynamic improvement and reduction of MACE were significantly better in A-FMR.

Impact of COVID-19-related public containment measures on the ST elevation myocardial infarction epidemic in Belgium: a nationwide, serial, cross-sectional study.

AIMS: The current study assessed the impact of COVID-19-related public containment measures (i.e. lockdown) on the ST elevation myocardial infarction (STEMI) epidemic in Belgium. METHODS AND RESULTS: Clinical characteristics, reperfusion therapy modalities, COVID-19 status and in-hospital mortality of consecutive STEMI patients who were admitted to Belgian hospitals for percutaneous coronary intervention (PCI) were recorded during a three-week period starting at the beginning of the lockdown period on 13 March 2020. Similar data were collected for the same time period for 2017-2019. An evaluation of air quality revealed a 32% decrease in ambient NO2 concentrations during lockdown (19.5 µg/m³ versus 13.2 µg/m³, p < .001). During the three-week period, there were 188 STEMI patients admitted for PCI during the lockdown versus an average 254 STEMI patients before the lockdown period (incidence rate ratio = 0.74, p = .001). Reperfusion strategy was predominantly primary PCI in both time periods (96% versus 95%). However, there was a significant delay in treatment during the lockdown period, with more late presentations (>12 h after onset of pain) (14% versus 7.6%, p = .04) and with longer door-to-balloon times (median of 45 versus 39 min, p = .02). Although the in-hospital mortality between the two periods was comparable (5.9% versus 6.7%), 5 of the 7 (71%) COVID-19-positive STEMI patients died. CONCLUSION: The present study revealed a 26% reduction in STEMI admissions and a delay in treatment of STEMI patients. Less exposure to external STEMI triggers (such as ambient air pollution) and/or reluctance to seek medical care are possible explanations of this observation.

Adherence to quality indicators for ST-elevation myocardial infarction and its relation to mortality: a hospital network analysis from the Belgian STEMI database.

AIMS: To assess the adherence to established quality indicators (QIs) for ST-elevation myocardial infarction (STEMI) at the hospital-network level and its relation to outcome. METHODS AND RESULTS: The data of 7774 STEMI patients admitted to 32 STEMI networks during the period 2014-18 were extracted from the Belgian STEMI database. Five QIs [primary percutaneous coronary intervention use, diagnosis-to-balloon time (DiaTB) <90 min, door-to-balloon time (DoTB) <60 min, P2Y12 inhibitor and statin prescription at discharge, and a composite QI score ranging from 0 to 10] were correlated with in-hospital mortality adjusted for differences in baseline risk profile (TIMI risk score). The median composite QI score was 6.5 [interquartile range (IQR) 6-8]. The most important gaps in quality adherence were related to time delays: the recommended DiaTB and DoTB times across the different networks were achieved in 68% (IQR 53-71) and 67% (IQR 50-78), respectively. Quality adherence was better in networks taking care of more high-risk STEMI patients. The median in-hospital mortality among the STEMI networks was 6.4% (IQR 4.1-7.9%). There was a significant independent inverse correlation between the composite QI score and in-hospital mortality (partial correlation coefficient: -0.45, P = 0.013). Stepwise regression analysis revealed that among the individual QIs, prolonged DiaTB was the most important independent outcome predictor. CONCLUSION: Among established STEMI networks, the time delay between diagnosis and treatment was the most variable and the most relevant prognostic QI, underscoring the importance of assessing quality of care throughout the whole network.

The evolution of the CTO-PCI landscape in Belgium and Luxembourg: a four-year appraisal.

BACKGROUND: To chart the evolution of the CTO-PCI landscape in Belgium and Luxembourg, the Belgian Working Group on Chronic Total Occlusions (BWGCTO) was established in 2016. METHODS: Between May 2016 and December 2019, patients undergoing a CTO-PCI treatment were prospectively and consecutively enrolled. Twenty-one centres in Belgium and one in Luxembourg participated. Individual operators had mixed levels of expertise in treating CTO lesions. Demographic, angiographic, procedural parameters and incidence of major adverse cardiac and cerebrovascular events (MACCE) were systematically registered. RESULTS: Over a four-year enrolment period, 1832 procedures were performed in 1733 patients achieving technical success in 1474 cases (80%), with an in-hospital MACCE rate of 2.3%. Fifty-nine (3%) cases were re-attempt procedures of which 41 (69%) were successful. High-volume centres treated more complex lesions (mean J-CTO score: 2.15 ± 1.21) as compared to intermediate (mean J-CTO score: 1.72 ± 1.23; p < 0.001) and low-volume centres (mean J-CTO score: 0.99 ± 1.21; p = 0.002). Despite this, success rates did not differ between centres (p = 0.461). Overall success rates did not differ over time (p = 0.810). High-volume centres progressively tackled more complex CTOs while keeping success rates stable. In all centres, the most applied strategy was antegrade wire escalation (83%). High-volume centres more often successfully applied antegrade dissection and re-entry and retrograde techniques in lesions with higher complexity. CONCLUSION: With variable experience levels, operators treated CTOs with high success and relatively few complications. Although AWE remains the most used technique, it is paramount for operators to be skilled in all contemporary techniques in order to be successful in more complex CTOs.

Left Ventricular End-Systolic Dimension and Outcome in Patients With Heart Failure Undergoing Percutaneous MitraClip Valve Repair for Secondary Mitral Regurgitation.

Recent MitraClip heart failure (HF) trials suggest that baseline left ventricular (LV) remodeling may be critical for patient selection. We, therefore, investigated whether baseline LV remodeling affects safety, efficacy, and clinical outcomes in HF patients with symptomatic secondary mitral regurgitation (MR) undergoing percutaneous mitral valve repair using MitraClip. LV remodeling was assessed by LV end-systolic dimension index (LVESDi) on transthoracic baseline echocardiography. Early and late outcome was reported using Mitral Valve Academic Research Consortium-criteria. A total of 107 consecutive HF patients (73 ± 10 years, 70% male) who underwent MitraClip intervention for secondary MR were studied. The study population was stratified by median LVESDi between nonadvanced (<28 mm/m², n = 49) and advanced LV remodeling (≥28 mm/m², n = 58). Both groups had similar acute procedural success, in hospital bleeding and nonbleeding complications and significant improvement in MR severity and symptoms, sustained up to 36 months (all p >0.05). LVESDi, but not LV end-diastolic diameter index nor LV ejection fraction, independently related to HF hospitalization (hazard ratio 1.11, 95% confidence interval 1.05 to 1.16, p <0.001) and mortality (hazard ratio 1.11, 95% confidence interval 1.06 to 1.17, p <0.001). At 1 and 3 years, survival free of HF hospitalization was higher in patients without versus with advanced LV remodeling (89% vs 66% and 65% vs 37%, p = 0.002) and mortality was lower (9% vs 24% and 36% vs 47%, p = 0.074), respectively. Annual HF hospitalization rate only decreased in the nonadvanced LV remodeling group (-43%, p = 0.025). Advanced LV remodeling, assessed by LVESDi, in HF patients who underwent MitraClip therapy does not influence therapeutic safety nor efficacy, but implies increased HF hospitalization and mortality risk. This parameter may be valuable for MitraClip therapy patient selection.

Summary of 2018 ESC Guidelines on definition of myocardial infarction, myocardial revascularisation, cardiovascular disease during pregnancy and on arterial hypertension.

During the ESC congress in September 2018 in Munich, the new ESC guidelines were presented and are now available on the ESC website. The new guidelines describe the definition of myocardial infarction and covers management recommendations on following cardiovascular items: myocardial revascularisaton, cardiovascular disease during pregnancy and arterial hypertension. The present document gives a summary of these guidelines and highlights the most important recommendations and changes in the management of these diseases. It will help to increase awareness about the new guidelines and may stimulate to consult the full document for specific items. Ultimately, the authors hope that this document will enhance the implementation of new ESC guidelines in daily clinical practice.

Vulnerability to cardiac arrest in patients with ST elevation myocardial infarction: Is it time or patient dependent? Results from a nationwide observational study.

AIM: Cardiac arrest is a common complication of ST elevation myocardial infarction and is associated with high mortality. We evaluated whether vulnerability to cardiac arrest follows a circadian rhythm and whether it is related to specific patient characteristics. METHODS: A total of 24,164 ST elevation myocardial infarction patients who were admitted to 60 Belgian hospitals between 2008-2017 were analysed. The proportion of patients with cardiac arrest before initiation of reperfusion therapy was calculated for different time periods (hour of the day, months, seasons) and related to patient characteristics using stepwise logistic regression analysis. RESULTS: Cardiac arrest occurred in 10.8% of the ST elevation myocardial infarction patients at a median of 65 min (interquartile range 33-138 min) after onset of pain. ST elevation myocardial infarction patients with cardiac arrest showed a biphasic pattern with one peak in the morning and one peak in the late afternoon. Multivariate analysis identified the following independent factors associated with cardiac arrest: cardiogenic shock (odds ratio=28), left bundle branch block (odds ratio=3.7), short (<180 min) ischaemic period (odds ratio=2.2), post-meridiem daytime presentation (odds ratio=1.4), anterior infarction (odds ratio=1.3). Overall in-hospital mortality was 30% for cardiac arrest patients versus 3.7% for non-cardiac arrest patients (p<0.0001). CONCLUSION: In the present study population, cardiac arrest in ST elevation myocardial infarction showed an atypical circadian rhythm with not only a morning peak but also a second peak in the late afternoon, suggesting that cardiac arrest and ST elevation myocardial infarction triggers are, at least partially, different. In addition, specific patient characteristics, such as short ischaemic period, cardiogenic shock and left bundle branch block, increase the vulnerability to cardiac arrest.

Left ventricular remodelling patterns after MitraClip implantation in patients with severe mitral valve regurgitation: mechanistic insights and prognostic implications.

AIMS: The effect of MitraClip implantation on left ventricular (LV) remodelling has been shown to be highly variable. The present study wants to assess patterns of LV remodelling and its relationship with outcome. METHODS AND RESULTS: Serial echocardiography before, 1 and 6 months after MitraClip implantation was performed in 79 pts with severe mitral regurgitation (MR) (age 74 ± 10 years, New York Heart Association III/IV 80%, LV ejection fraction 38 ± 13%, logistic EuroSCORE 21 ± 15, and functional MR 81%). LV reverse/adverse remodelling was defined as a >15% decrease/>10% increase in LV end-diastolic volume (LVEDV), respectively. Patients were followed over a period of 32 ± 16 months with all-cause mortality as the primary endpoint. A sustained (6 month) reduction of MR ≤ 2 post-MitraClip implantation was observed in 83% of patients. The average decrease in LVEDV 6 months after intervention was 13% ± 16%. Reverse remodelling at 6 months occurred in 40 patients (51%), and adverse remodelling occurred in 6 patients (8%). Patients with adverse remodelling showed a 38% increase of LVEDV at 1 month vs. no early change in LVEDV in patients with reverse remodelling. During follow-up, a total of 25 patients (32%) died. Patients with adverse remodelling died more frequently than patients with reverse remodelling [67% vs. 27%, adjusted odds ratio of 5.6 (95% CI 1.5-21)]. CONCLUSION: The majority of patients undergoing MitraClip implantation for severe MR showed LV reverse remodelling. However, there was a small group in whom afterload mismatch resulted in sustained adverse remodelling with subsequent high mortality.

Assessing the landscape of percutaneous coronary chronic total occlusion treatment in Belgium and Luxembourg: the Belgian Working Group on Chronic Total Occlusions (BWGCTO) registry.

Background: Important developments in materials, devices, and techniques have improved outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI), and resulted in a growing interest in CTO-PCI. The Belgian Working Group on Chronic Total Occlusions (BWGCTO) working group aims to assess the evolution within the CTO-PCI landscape over the next years. Methods: From May 2016 onwards, patients undergoing CTO-PCI were included in the BWGCTO registry by 15 centres in Belgium and Luxemburg. Baseline, angiographic, and procedural data were collected. Here, we report on the one-year in-hospital outcomes. Results: Over the course of one year, 411 procedures in 388 patients were included with a mean age of 64 ± 11 years. The majority were male (81%). Relatively complex CTOs were treated (Japanese CTO score =2.2 ± 1.2) with a high procedure success rate (82%). Patient- and lesion-wise success rates were 83 and 85%, respectively. Major adverse in-hospital events were acceptably low (3.4%). Antegrade wire escalation technique was applied most frequently (82%). On the other hand, antegrade dissection and re-entry and retrograde strategies were more frequently applied in higher volume centres and successful for lesions with higher complexity. Conclusion: Satisfactory procedural outcomes and a low rate of adverse events were obtained in a complex CTO population, treated by operators with variable experience levels. Antegrade wire escalation was the preferred strategy, regardless of operator volume.

Quality assessment in Belgian ST elevation myocardial infarction patients: results from the Belgian STEMI database.

The present report describes the quality of care, including in hospital mortality for more than 22.000 STEMI patients admitted in 60 Belgian hospitals for the period 2008-2016. We found a strong increase in the use of primary PCI over time, particularly for patients that were admitted first in a non-PCI capable hospital, reaching a penetration rate of >95%. The transition of thrombolysis to transfer for pPCI in the setting of a STEMI network was, however, associated with an increase of the proportion of patients with prolonged (>120 min) diagnosis-to-balloon time (from 16 to 22%), suggesting still suboptimal interhospital transfer. The in-hospital mortality of the total study population was 6.5%. For non-cardiac arrest patients in-hospital mortality decreased from 5.1% to 3.7%, while it increased for cardiac arrest patients from 29 to 37%. The observation that quality indicators (QI's), such as modalities and timing of reperfusion therapy, were associated with lower levels of mortality, underscores the potential of QIs for STEMI to improve care and reduce unwarranted variation and premature death from STEMI.

Mode of admission and its effect on adherence to reperfusion therapy guidelines in Belgian STEMI patients.

OBJECTIVES: Emergency medical services play a key role in the recognition and treatment of ST-segment elevation myocardial infarction (STEMI). This study evaluates the effect of emergency medical services use on adherence to reperfusion therapy guidelines in Belgian STEMI patients and on in-hospital mortality. METHODS: The mode of admission with against without emergency medical services was associated with baseline risk profile, reperfusion modalities and in-hospital mortality in 5692 consecutive STEMI patients from 2012 to 2014. RESULTS: A total of 3896 STEMI patients (68%) were transported to the hospital by emergency medical services, and 1796 patients (32%) arrived at the hospital using their own transport (self-referral). Emergency medical services patients were older than self-referral patients (64 vs. 62 years) and more frequently presented with cardiac arrest (14% vs. 5%) and with cardiogenic shock (10% vs. 4%). Emergency medical services patients received primary percutaneous coronary intervention more often (95% vs. 91%, P<0.0001) and more frequently within 90 minutes (72% vs. 65%, P<0.001). Moreover, the time interval between symptom onset and reperfusion therapy was shorter in the emergency medical services group (median of 195 vs. 255 minutes, P<0.001). Crude in-hospital mortality was higher in the emergency medical services group (7.7% vs. 3.8%, P<0.0001) and was mainly driven by the high prevalence of cardiogenic shock and cardiac arrest in the emergency medical services group. After adjustment, the impact on mortality was no longer significantly different. CONCLUSION: Emergency medical services are used by two-thirds of Belgian STEMI patients and are associated with a better adherence to STEMI reperfusion guidelines. These data favour the use of emergency medical services as the preferred transfer system for patients with chest pain suspicious for STEMI.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.