Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization

AIMS: No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. METHODS AND RESULTS: A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). CONCLUSION: ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.

Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization: Fifty Years of Revascularization: Where Are We and Where Are We Heading?

The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, urgent, and emergency settings. The 2014 document updates and extends the effort started in 2010, year of the first edition of these guidelines. Importantly, this latest edition provides a systematic review of all randomized clinical trials performed since 1980, comparing different strategies of myocardial revascularization, including coronary artery bypass graft (CABG), balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first- and second-generation drug-eluting stents (DES). This review aims to highlight the most relevant novelties introduced by the 2014 edition of the ESC/EACTS myocardial revascularization guidelines as compared with the previous edition and to describe similarities and differences with the American societies' guidelines.

Percutaneous coronary revascularization in patients with formerly "refractory angina pectoris in end-stage coronary artery disease" - not "end-stage" after all

BACKGROUND: Patients with refractory angina pectoris in end-stage coronary artery disease represent a severe condition with a higher reduction of life-expectancy and quality of life as compared to patients with stable coronary artery disease. It was the purpose of this study to invasively re-evaluate highly symptomatic patients with formerly diagnosed refractory angina pectoris in end-stage coronary artery disease for feasible options of myocardial revascularization. METHODS: Thirty-four patients formerly characterized as having end stage coronary artery disease with refractory angina pectoris were retrospectively followed for coronary interventions. RESULTS: Of those 34 patients 21 (61.8%) were eventually revascularized with percutaneous interventional revascularization (PCI). Due to complex coronary morphology (angulation, chronic total occlusion) PCI demanded an above-average amount of time (66 +/- 42 minutes, range 25-206 minutes) and materials (contrast media 247 +/- 209 ml, range 50-750 ml; PCI guiding wires 2.0 +/- 1.4, range 1-6 wires). Of PCI patients 7 (33.3%) showed a new lesion as a sign of progression of atherosclerosis. Clinical success rate with a reduction to angina class II or lower was 71.4% at 30 days. Surgery was performed in a total of8 (23.5%) patients with a clinical success rate of 62.5%. Based on an intention-to-treat 2 patients of originally 8 (25%) demonstrated clinical success. Mortality during follow-up (1-18 months) was 4.8% in patients who underwent PCI, 25% in patients treated surgically and 25% in those only treated medically. CONCLUSION: The majority of patients with end-stage coronary artery disease can be treated effectively with conventional invasive treatment modalities. Therefore even though it is challenging and demanding PCI should be considered as a first choice before experimental interventions are considered.

Off-pump coronary artery bypass operation does not increase procoagulant and fibrinolytic activity: preliminary results

BACKGROUND: This study analyzes the effects on coagulation and fibrinolysis comparing off-pump coronary artery bypass (OPCAB) and on-pump CABG operations. METHODS: In a prospective, nonrandomized, comparative evaluation, patients scheduled for elective myocardial revascularization were studied. Due to possible confounding factors patients with postoperative retransfusion of mediastinal shed blood were excluded. Nine patients underwent OPCAB operation and 16 underwent on-pump CABG. Activated clotting time (ACT) was adjusted to 250 seconds in OPCAB (81 +/- 18 [mean +/- SD] IU/kg heparin) and to more than 480 seconds in on-pump CABG (400 IU/kg heparin, additional 10,000 IU in pump prime). Perioperatively blood samples were collected and hematologic and hemostatic variables including fibrinopeptide A (FPA), fibrin monomer (FM), thrombin-antithrombin complex (TAT), and D-dimer were analyzed. RESULTS: Both groups showed comparable demographic variables. Number of grafts per patient was slightly higher in the on-pump group (3.6 +/- 0.6 versus 3.0 +/- 1.1, p = 0.23). The FPA levels did not differ significantly between the groups. The FM, TAT, and D-dimer values were significantly higher in on-pump CABG (p < 0.0001, p < 0.01, and p < 0.0001, respectively), reflecting increased coagulant and fibrinolytic activity. This was also the case when values were corrected for hemodilution. CONCLUSIONS: Despite lower systemic anticoagulation activation of coagulation and fibrinolysis is reduced in OPCAB compared with on-pump CABG. Reduced thrombin generation and reduced fibrinolytic activity in OPCAB indicates better preservation of hemostasis. We suggest the term "preserved hemostasis" instead of "hypercoagulant activity" with respect to OPCAB.

Revascularization Treatment of Emergency Patients with Acute ST-Segment Elevation Myocardial Infarction in Switzerland: Results from a Nationwide, Cross-Sectional Study in Switzerland for 2010-2011

BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide and in Switzerland. When applied, treatment guidelines for patients with acute ST-segment elevation myocardial infarction (STEMI) improve the clinical outcome and should eliminate treatment differences by sex and age for patients whose clinical situations are identical. In Switzerland, the rate at which STEMI patients receive revascularization may vary by patient and hospital characteristics. AIMS: To examine all hospitalizations in Switzerland from 2010-2011 to determine if patient or hospital characteristics affected the rate of revascularization (receiving either a percutaneous coronary intervention or a coronary artery bypass grafting) in acute STEMI patients. DATA AND METHODS: We used national data sets on hospital stays, and on hospital infrastructure and operating characteristics, for the years 2010 and 2011, to identify all emergency patients admitted with the main diagnosis of acute STEMI. We then calculated the proportion of patients who were treated with revascularization. We used multivariable multilevel Poisson regression to determine if receipt of revascularization varied by patient and hospital characteristics. RESULTS: Of the 9,696 cases we identified, 71.6% received revascularization. Patients were less likely to receive revascularization if they were female, and 80 years or older. In the multivariable multilevel Poisson regression analysis, there was a trend for small-volume hospitals performing fewer revascularizations but this was not statistically significant while being female (Relative Proportion = 0.91, 95% CI: 0.86 to 0.97) and being older than 80 years was still associated with less frequent revascularization. CONCLUSION: Female and older patients were less likely to receive revascularization. Further research needs to clarify whether this reflects differential application of treatment guidelines or limitations in this kind of routine data.

Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularization

Coronary artery disease remains the leading cause of mortality in most industrialized countries, although age-standardized mortality related to coronary artery disease (CAD) has decreased by more than 40% during the last two decades. Coronary atherosclerosis may cause angina pectoris, myocardial infarction, heart failure, arrhythmia, and sudden death. Medical management of atherosclerosis and its manifestation aims at retardation of progression of plaque formation, prevention of plaque rupture, and subsequent events and treatment of symptoms, when these occur as well as treatment of the sequelae of the disease. Revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is performed as treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia. In high-risk patients with acute coronary syndromes (ACS), a routine invasive strategy with revascularization in most patients provides the best outcome with a significant reduction in death and myocardial infarction compared with an initial conservative strategy. Conversely, the benefit of revascularization among patients with chronic stable CAD has been called into question. This review will provide information that revascularization exerts favourable effects on symptoms, quality of life, exercise capacity, and survival, particularly in those with extensive CAD and documented moderate-to-severe ischaemia. Accordingly, CABG and PCI should be considered a valuable adjunct rather than an alternative to medical therapy.

Five-Year Clinical and Angiographic Outcomes of a Randomized Comparison of Sirolimus-Eluting and Paclitaxel-Eluting Stents: Results of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization LATE Trial

Background—Long-term comparative data of first-generation drug-eluting stents are scarce. We investigated clinical and angiographic outcomes of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) at 5 years as part of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) LATE study. Methods and Results—A total of 1012 patients were randomly assigned to SES or PES. Repeat angiography was completed in 444 of 1012 patients (43.8%) at 5 years. Major adverse cardiac events occurred in 19.7% of SES- and 21.4% of PES-treated patients (hazard ratio, 0.89; 95% confidence interval, 0.68 to 1.17; P=0.39) at 5 years. There were no differences between SES and PES in terms of cardiac death (5.8% versus 5.7%; P=0.35), myocardial infarction (6.6% versus 6.9%; P=0.51), and target lesion revascularization (13.1% versus 15.1%; P=0.29). Between 1 and 5 years, the annual rate of target lesion revascularization was 2.0% (95% confidence interval, 1.4% to 2.6%) for SES and 1.4% (95% confidence interval, 0.9% to 2.0%) for PES. Among patients undergoing paired angiography at 8 months and 5 years, delayed lumen loss amounted to 0.37±0.73 mm for SES and 0.29±0.59 mm for PES (P=0.32). The overall rate of definite stent thrombosis was 4.6% for SES and 4.1% for PES (P=0.74), and very late definite stent thrombosis occurred at an annual rate of 0.65% (95% confidence interval, 0.40% to 0.90%). Conclusions—Long-term follow-up of first-generation drug-eluting stents shows no significant differences in clinical and angiographic outcomes between SES and PES. The continuous increase in late lumen loss in conjunction with the ongoing risk of very late stent thrombosis suggests that vascular healing remains incomplete up to 5 years after implantation of first-generation drug-eluting stents.

Long-term comparison of everolimus-eluting and sirolimus-eluting stents for coronary revascularization

Objectives This study sought to compare the unrestricted use of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention. Background It is unclear whether there are differences in safety and efficacy between EES and SES during long-term follow-up. Methods Using propensity score matching, clinical outcome was compared among 1,342 propensity score–matched pairs of patients treated with EES and SES. The primary outcome was a composite of death, MI, and target vessel revascularization. Results The median follow-up was 1.5 years with a maximum of 3 years. The primary outcome occurred in 14.9% of EES- and 18.0% of SES-treated patients up to 3 years (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.68 to 1.00, p = 0.056). All-cause mortality (6.0% vs. 6.5%, HR: 0.92, 95% CI: 0.68 to 1.25, p = 0.59) was similar, risks of myocardial infarction (MI) (3.3% vs. 5.0%, HR: 0.62, 95% CI: 0.42 to 0.92, p = 0.017), and target vessel revascularization (7.0% vs. 9.6%, HR: 0.75, 95% CI: 0.57 to 0.99, p = 0.039) were lower with EES than SES. Definite stent thrombosis (ST) (HR: 0.30, 95% CI: 0.12 to 0.75, p = 0.01) was less frequent among patients treated with EES. The reduced rate of MI with EES was explained in part by the lower risk of definite ST and the corresponding decrease in events associated with ST (HR: 0.25, 95% CI: 0.08 to 0.75, p = 0.013). Conclusions The unrestricted use of EES appears to be associated with improved clinical long-term outcome compared with SES. Differences in favor of EES are driven in part by a lower risk of MI associated with ST.

Comparison of titanium-nitride-oxide-coated stents with zotarolimus-eluting stents for coronary revascularization a randomized controlled trial

Objectives This study sought to compare the efficacy of passive stent coating with titanium-nitride-oxide (TiNO) with drug-eluting stents releasing zotarolimus (ZES) (Endeavor, Medtronic, Minneapolis, Minnesota). Background Stent coating with TiNO has been shown to reduce restenosis compared with bare-metal stents in experimental and clinical studies. Methods In an assessor-blind noninferiority study, 302 patients undergoing percutaneous coronary intervention were randomized to treatment with TiNO or ZES. The primary endpoint was in-stent late loss at 6 to 8 months, and analysis was by intention to treat. Results Both groups were well balanced with respect to baseline clinical and angiographic characteristics. The TiNO group failed to reach the pre-specified noninferiority margin for the primary endpoint (in-stent late loss: 0.64 ± 0.61 mm vs. 0.47 ± 0.48 mm, difference: 0.16, upper 1-sided 95% confidence interval [CI]: 0.26; pnoninferiority = 0.54), and subsequent superiority testing was in favor of ZES (psuperiority = 0.02). In-segment binary restenosis was lower with ZES (11.1%) than with TiNO (20.5%; psuperiority = 0.04). A stratified analysis of the primary endpoint found particularly pronounced differences between stents among diabetic versus nondiabetic patients (0.90 ± 0.69 mm vs. 0.39 ± 0.38 mm; pinteraction = 0.04). Clinical outcomes showed a similar rate of death (0.7% vs. 0.7%; p = 1.00), myocardial infarction (5.3% vs. 6.7%; p = 0.60), and major adverse cardiac events (21.1% vs. 18.0%, hazard ratio: 1.19, 95% CI: 0.71 to 2.00; p = 0.50) at 1 year. There were no differences in rates of definite or probable stent thrombosis (0.7% vs. 0%; p = 0.51) at 1 year. Conclusions Compared with TiNO, ZES was superior with regard to late loss and binary restenosis. The concept of passive stent coating with TiNO remains inferior to drug-eluting stent technology in reducing restenosis. ([TIDE] Randomized Trial Comparing Titan Stent With Zotarolimus-Eluting Stent: NCT00492908)

Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial

CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known. OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI. DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin. MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up. RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.