Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.</p> <p>Methods/Design</p> <p>The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.</p> <p>Discussion</p> <p>The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.</p> <p>Trial registration</p> <p>trialregister.nl NTR1108.</p

Mechanical circulatory support in cardiogenic shock from acute myocardial infarction: Impella CP/5.0 versus ECMO

BACKGROUND: Short-term mechanical circulatory support devices are increasingly used in cardiogenic shock after acute myocardial infarction. As no randomised evidence is available, the choice between high-output Impella or extra-corporeal membrane oxygenation (ECMO) is still a matter of debate. Real-life data are necessary to assess adverse outcomes and to help guide the treatment decision between the different devices. The purpose of this study was to compare characteristics and clinical outcomes of Impella CP/5.0 with ECMO support in patients with cardiogenic shock from myocardial infarction. METHODS: A retrospective, two-centre study was performed on all cardiogenic shock from myocardial infarction patients with Impella CP/5.0 or ECMO support, from 2006 until 2018. The primary outcome was 30-day mortality. Potential baseline imbalance between the groups was adjusted using inverse probability treatment weighting, and survival analysis was performed with an adjusted log-rank test. Secondarily, the occurrence of device-related complications (limb ischaemia, access site-related bleeding, access site-related infection) was evaluated. RESULTS: A total of 128 patients were included (Impella, N=90; ECMO, N=38). The 30-day mortality was similar for both groups (53% vs. 49%, P=0.30), also after adjustment for potential baseline imbalance between the groups (weighted log-rank P=0.16). Patients with Impella support had significantly fewer device-related complications than patients treated with ECMO (respectively, 17% vs. 40%, P<0.01). CONCLUSIONS: Patients treated with Impella CP/5.0 or ECMO for cardiogenic shock after myocardial infarction did not differ in 30-day mortality. More device-related complications occurred with ECMO compared to Impella support

Performance of currently available risk models in a cohort of mechanically supported high-risk percutaneous coronary intervention--From the PROTECT II randomized trial

BACKGROUND: Procedural risk scores facilitate clinical decision making by using individual patient characteristics to estimate the risk of adverse events. The performance of PCI-based risk scores is not well-described among patients undergoing hemodynamically supported high risk PCI. METHODS AND RESULTS: A total of 427 patients with unprotected left main disease, last remaining vessel or three-vessel disease with severely reduced left ventricular function underwent supported high-risk PCI with an intra-aortic balloon pump (IABP, N = 211) or a left ventricular assist device (Impella 2.5, N = 216) as part of the PROTECT II trial. We examined the performance of the additive Euroscore, logistic Euroscore, STS mortality score, STS morbidity and mortality score, Mayo Clinic risk score and New York state PCI risk score on the endpoint of 90-day mortality in this unique high-risk population. Mean age was 67.2 ± 10.9 years; 65.8% of patients were in NYHA class III/IV, and mean LVEF was 24%. All-cause 90-day mortality was 10.4%. The scores were generally correlated (p \u3c 0.0001 for all comparisons), with R(2) values ranging from 0.28 (STS morbidity/mortality and Mayo Clinic) to 0.68 (logistic Euroscore and STS mortality). However, receiver-operator curves for 90-day all-cause mortality for all risk scores demonstrated poor discriminatory performance with c-statistics of 0.542-0.616. Calibration of the risk scores was not poor, but varied according to the specific score examined. CONCLUSION: The discriminatory capacity of currently available risk models is suboptimal when applied to a cohort of mechanically supported complex high-risk PCI. A risk score designed specifically for this population could help to further refine risk assessment

Continuous postoperative pericardial flushing reduces postoperative bleeding after coronary artery bypass grafting: a randomized trial

Background Prolonged or excessive bleeding after cardiac surgery can lead to a broad spectrum of secondary complications. One of the underlying causes is incomplete wound drainage, with subsequent accumulation of blood and clots in the pericardium. We developed the continuous postoperative pericardial flushing (CPPF) therapy to improve wound drainage and reduce postoperative blood loss and bleeding-related complications after cardiac surgery. This study compared CPPF to standard care in patients after coronary artery bypass grafting (CABG). Methods This is a single center, open label, randomized trial that enrolled patients at the Amsterdam UMC, location AMC, Amsterdam, the Netherlands. The study was registered at the ‘Netherlands Trial Register’, study identifier NTR5200 [[1]]. Adults undergoing CABG were randomly assigned to receive CPPF therapy or standard care, participants and investigators were not masked to group assignment. The primary end point was postoperative blood loss in the first 12-hours after surgery. Findings Between the January 15, 2014 and the March 13, 2017, 169 patients were enrolled and assigned to CPPF therapy (study group; n = 83) or standard care (control group; n = 86). CPPF reduced postoperative blood loss when compared to standard care (median differences -385 ml, reduction 76% p=≤0.001), with the remark that these results are overestimated due to a measurement error in part of the study group. None of patients in the study group required reoperation for non-surgical bleeding versus 3 (4%, 95% CI -0.4% to 7.0%) in the control group. None of the patients in the study group suffered from cardiac tamponade, versus 3 (4%, 95% CI -0,4% to 7.0%) in the control group. The incremental cost-effectiveness ratio was €116.513 (95% bootstrap CI €-882.068 to €+897.278). Interpretation The use of CPPF therapy after CABG seems to reduce bleeding and bleeding related complications. With comparable costs and no improvement in Qualty of Life (QoL), cost consideration for the implementation of CPPF is not relevant. None of the patients in the study group required re-interventions for non-surgical bleeding or acute cardiac tamponade, which underlines the proof of concept of this novel therapy

Plasma glucose and not hemoglobin or renal function predicts mortality in patients with STEMI complicated with cardiogenic shock

Objective To assess the predictive value of three biomarkers for mortality in ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock. Background STEMI complicated by cardiogenic shock accounts for the majority of STEMI related deaths. Patients with STEMI and hyperglycemia, anemia or kidney dysfunction on admission have a poor prognosis. As data on the combination of those three established predictors of mortality are sparse in STEMI with cardiogenic shock, the objective of the current study was to investigate their predictive value in STEMI patients with cardiogenic shock. Methods and results Between 1997 and 2005, a total of 3038 patients presented with STEMI and were treated with percutaneous coronary intervention (PCI). On admission 292 patients presented with cardiogenic shock. Glucose, hemoglobin and creatinine clearance were available in 183 out of 292 patients. Overall 1-year mortality was 34%. In multivariate logistic regression analysis, only glucose remained a strong independent predictor for mortality. The odds for mortality increased by 11% for each 1 mmol/l increase in glucose (OR 1.11, 95% CI 1.02-1.21, P = 0.013). Conclusion Hemoglobin and creatinine clearance bear no prognostic value. Only admission glucose levels strongly and independently predict 1-year mortality in STEMI patients with cardiogenic shock and treated with PCI. J Cardiovasc Med 11:827-831 (C) 2010 Italian Federation of Cardiolog

Primary percutaneous coronary intervention for ST elevation myocardial infarction in octogenarians: trends and outcomes

Objective The general population is gradually ageing in the western world. Therefore, the number of octogenarians undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is increasing. We aim to provide insight into temporal trends in the annual proportions of octogenarians among STEMI patients undergoing primary PCI and their clinical characteristics and outcomes over an 11-year observational period. Design Single-centre observational study. Patients Between 1997 and 2007, 4506 STEMI patients were treated with primary PCI at the authors' institution. Patients aged over 80 years were identified. Main outcome measures Temporal trends in the annual proportion of octogenarian STEMI patients and their baseline characteristics, 30-day and 1-year mortality were analysed. Results A total of 379 octogenarians (8.4% of the total population) was treated with primary PCI between 1997 and 2007. Over time, the annual proportion of octogenarians gradually increased from four of 113 (3.5%) in 1997 to 51 of 579 (8.8%) in 2007 (p for trend <0.01). In the total cohort of 379 patients, 30-day mortality was 21% (81 patients) and 1-year mortality was 28% (107 patients). There was no improvement in survival among octogenarian STEMI patients over the 11-year study period. Conclusion The annual proportion of octogenarian STEMI patients increased significantly over the 11-year study period. Mortality among these high-risk patients was high and did not improve during the study period. Unfortunately, little is known about the optimal treatment of the elderly as they are underrepresented in many randomised clinical trials. Further studies into the optimal STEMI management strategy for the elderly are warrante

Real-life use of left ventricular circulatory support with Impella in cardiogenic shock after acute myocardial infarction: 12 years AMC experience

AIMS: Mortality in cardiogenic shock patients remains high. Short-term mechanical circulatory support with Impella can be used to support the circulation in these patients, but data from randomised controlled studies and 'real-world' data are sparse. The aim is to describe real-life data on outcomes and complications of our 12 years of clinical experience with Impella in patients with cardiogenic shock after acute myocardial infarction and to identify predictors of 6-month mortality. METHODS: We describe a single-centre registry from October 2004 to December 2016 including all patients treated with Impella for cardiogenic shock after acute myocardial infarction. We report outcomes and complications and identify predictors of 6-month mortality. RESULTS: Our overall clinical experience consists of 250 patients treated with Impella 2.5, Impella CP or Impella 5.0. A total of 172 patients received Impella therapy for cardiogenic shock, of which 112 patients had cardiogenic shock after acute myocardial infarction. The mean age was 60.1±10.6 years, mean arterial pressure was 67 (56-77) mmHg, lactate was 6.2 (3.6-9.7) mmol/L, 87.5% were mechanically ventilated and 59.6% had a cardiac arrest before Impella placement. Overall 30-day mortality was 56.2% and 6-month mortality was 60.7%. Complications consisted of device-related vascular complications (17.0%), non-device-related bleeding (12.5%), haemolysis (7.1%) and stroke (3.6%). In a multivariate analysis, pH before Impella placement is a predictor of 6-month mortality. CONCLUSIONS: Our registry shows that Impella treatment in cardiogenic shock after acute myocardial infarction is feasible, although mortality rates remain high and complications occur

Paclitaxel-coated balloon angioplasty vs. drug-eluting stenting for the treatment of coronary in-stent restenosis: a comprehensive, collaborative, individual patient data meta-analysis of 10 randomized clinical trials (DAEDALUS study).

AIMS:Consensus is lacking regarding the best treatment for coronary in-stent restenosis (ISR). The two most effective treatments are angioplasty with paclitaxel-coated balloon (PCB) and repeat stenting with drug-eluting stent (DES) but individual trials were not statistically powered for clinical endpoints, results were heterogeneous, and evidence about comparative efficacy and safety in relevant subsets was limited. METHODS AND RESULTS:The Difference in Anti-restenotic Effectiveness of Drug-eluting stent and drug-coated balloon AngiopLasty for the occUrrence of coronary in-Stent restenosis (DAEDALUS) study was a comprehensive, investigator-initiated, collaborative, individual patient data meta-analysis comparing angioplasty with PCB alone vs. repeat stenting with DES alone for the treatment of coronary ISR. The protocol was registered with PROSPERO (CRD42017075007). All 10 available randomized clinical trials were included with 1976 patients enrolled, 1033 assigned to PCB and 943 to DES. At 3-year follow-up, PCB was associated with a significant increase in the risk of target lesion revascularization (TLR) compared with DES [hazard ratio (HR) 1.32, 95% CI 1.02-1.70, P = 0.035; number-needed-to-harm 28.5]. There was a significant interaction between treatment effect and type of restenosed stent (P = 0.029) with a more marked difference in patients with DES-ISR and comparable effects in patients with bare-metal stent-ISR. At 3-year follow-up, the primary safety endpoint of all-cause death, myocardial infarction, or target lesion thrombosis was comparable between treatments (HR 0.80, 95% CI 0.58-1.09, P = 0.152). A pre-specified subgroup analysis indicated a significant interaction between treatment effect and type of DES used to treat ISR (P = 0.033), with a lower incidence of events associated with PCB compared with first-generation DES and similar effect between PCB and second-generation DES (HR 1.06, 95% CI 0.71-1.60, P = 0.764). Long-term all-cause mortality was similar between PCB and DES (HR 0.81, 95% CI 0.53-1.22, P = 0.310); results were consistent comparing PCB and non-paclitaxel-based DES (HR 1.42, 95% CI 0.80-2.54, P = 0.235). Myocardial infarction and target lesion thrombosis were comparable between treatments. CONCLUSIONS:In patients with coronary ISR, repeat stenting with DES is moderately more effective than angioplasty with PCB at reducing the need for TLR at 3 years. The incidence of a composite of all-cause death, myocardial infarction, or target lesion thrombosis was similar between groups. The rates of individual endpoints, including all-cause mortality, were not significantly different between groups.status: publishe

A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study

<p>Abstract</p> <p>Background</p> <p>Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO.</p> <p>Methods/Design</p> <p>The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clinically driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events.</p> <p>Trial registration</p> <p>Clinical Trials.gov: NCT01516723. Patient recruitment started in February 2012.</p