Prodromos Anthopoulos

Acute Stent Thrombosis After Primary Percutaneous Coronary Intervention : Insights From the EUROMAX Trial (European Ambulance Acute Coronary Syndrome Angiography)

OBJECTIVES This study sought to determine clinical, procedural, and treatment factors associated with acute stent thrombosis (AST) in the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial. BACKGROUND Bivalirudin started during transport for primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction significantly reduced major bleeding compared with heparin with or without glycoprotein IIb/IIIa inhibitors (GPI), but it was associated with an increase in AST. METHODS We compared patients with (n = 12) or without AST (n = 2,184) regarding baseline, clinical, and procedural characteristics and antithrombotic treatment strategies (choice of P2Y12 inhibitor, post-primary PCI bivalirudin infusion dose [0.25 mg/kg/h, or BIV-LOW] vs. [1.75 mg/kg/h, or BIV-PCI] vs. heparin ± GPI). Logistic regression was performed to identify independent correlates of AST. RESULTS The overall AST rate was 0.6% and was higher with bivalirudin than with heparin ± GPI (1.1% vs. 0.2%; p = 0.007). Median time to AST was 2.3 h (interquartile range: 1.9 to 2.8 h). Patients with AST had less hypertension (2 of 14 [14.0%] vs. 961 of 2,182 [44.0%]; p = 0.03), and more frequently received GPI (11 of 14 [78.6%] vs. 880 of 2,183 [40.3%]; p = 0.004). Multivariate analysis using Firth penalized maximum likelihood estimation found hypertension (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.07 to 0.92; p = 0.037) and BIV-LOW (OR: 5.8, 95% CI: 1.5 to 22.2; p = 0.010) predictive of AST. Choice of P2Y12 inhibitor had no impact on AST. Compared with heparin ± GPI, AST rates were higher for BIV-LOW (11 of 670 [1.6%] vs. 2 of 947 [0.2%]; p = 0.008), but not different for BIV-PCI (1 of 244 [0.4%]; p = 0.588). CONCLUSIONS In this post-hoc analysis from EUROMAX, AST occurred very early and was not mitigated by the novel P2Y12 inhibitors. Prolonging the bivalirudin infusion at the PCI dose (but not at a lower dose) appeared to mitigate the risk of AST.

Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial.

BACKGROUND Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting. OBJECTIVES The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR. METHODS A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding. RESULTS Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant. CONCLUSIONS In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).

Double Versus Standard Loading Dose of Ticagrelor : Onset of Antiplatelet Action in Patients With STEMI Undergoing Primary PCI

To the Editor: Early and strong platelet inhibition is highly desirable in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Ticagrelor, which has direct action on the P2Y12 receptor and no need for previous metabolic

CorrespondenceResearch CorrespondenceDouble Versus Standard Loading Dose of Ticagrelor: Onset of Antiplatelet Action in Patients With STEMI Undergoing Primary PCI

To the Editor: Early and strong platelet inhibition is highly desirable in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Ticagrelor, which has direct action on the P2Y12 receptor and no need for previous metabolic

Coronary microcirculation evaluation with transesophageal echocardiography Doppler in type II diabetics

Evaluation of coronary microvascular function can be obtained through coronary flow reserve measurements. The aim of this study was to evaluate the coronary microvascular function by using transesophageal-Doppler echocardiographic assessment of coronary flow reserve. The study included 32 normotensive patients with type II diabetes mellitus (group A) of short duration (6.1+/-3.8 years) aged 55.4+/-9.4 years and 14 healthy volunteers matched for age, gender and BMI (group B). No patients had clinical evidence of coronary artery disease and all of them produced a negative recent stress ECG test. Excluded from the study were patients with anemia, left ventricular hypertrophy, arrhythmia, congenital, or acquired structural heart disease. All subjects underwent transesophageal-Doppler echocardiography. Satisfactory coronary blood flow velocity recordings could be obtained from the initial segment of the left anterior descending coronary artery in healthy volunteers and in 27 patients at baseline and 2 min after dipyridamole infusion (0.56 mg/kg, for 4 min). In the remaining 5 patients no satisfactory recordings were available. The indexes of coronary flow reserve, i.e. the ratios of dipyridamole over basal maximum and mean diastolic velocities were calculated. Dipyridamole/rest maximal coronary reserve (Table 3) was 1.946+/-0.743, while this ratio for the mean diastolic velocity was 1.969+/-0.805 in group A. The respective values for group B, were 2.811+/-0.345 (P=0.000 vs. group A) and 2.914+/-0.303 (P=0.000 vs. group A). Thus, the increase in coronary flow reserve although present in both groups, it was more impressive in the normal group. Multiple regression logistic analysis of: age, sex, smoking, glucosylated hemoglobin, duration of diabetes and type of therapy, did not show any correlation of these parameters with the above ratios. This study shows that coronary flow reserve, as measured with transesophageal echocardiography-Doppler, is severely impaired in normotensive patients with type II diabetes, with relatively short duration of the disease.

Success, safety, and efficacy of implantation of diamond-like carbon-coated stents.

The aim of this study was to evaluate safety and clinically defined efficacy of the implantation of a new stent coated with diamond-like carbon (DLC stent), in a group of patients who underwent percutaneous transluminal coronary revascularization procedures in two hemodynamic centers. This study was an observational prospective nonrandomized study that included 196 patients with a total of 236 significant de novo atheromatous coronary lesions, in which 245 DLC stents were implanted. The primary end point of this study was a composite of major cardiovascular events (death or acute myocardial infarction with or without Q) and need for target lesion revascularization (TLR) or target vessel revascularization (TVR) procedure during the first 48 hours and at 6 months after the DLC stent implantation. All patients had a myocardial perfusion imaging study with Tl201 at 6 months after DLC stent implantation. Only patients with a myocardial perfusion imaging study indicative of myocardial ischemia were then submitted for a new coronary angiogram. No major cardiovascular event or emergency TVR occurred during hospitalization. At 6-month follow-up no major cardiovascular event occurred either, whereas the rate for TLR was 5.6% and that for TVR was 7.65%. This preliminary study provides enough clinical evidence that implantation of intracoronary bare metal stents coated with diamond-like carbon is associated with high success rates, safety, and efficacy, both in the hospital and at the 6-month follow-up after the interventional procedure.

Stress Echocardiography Using Adenosine Combined with Nitroglycerin- Dobutamine in the Detection of Viable Myocardium in Patients with Previous Myocardial Infarction

The aim of this study was to assess the value of adenosine (A) and the combination of nitroglycerin (N) with dobutamine (D) stress echocardiography (SE) in the identification of viable myocardium. The clinical and electrocardiographic (ECG) effects of both tests were also evaluated. Fifty-two coronary artery disease patients, aged 56.4 ±8 years, with left ventricular dysfunction due to a previous myocardial infarction (mean ejection fraction: 49 ±8%) were included in the study. Cardiac catheterization was performed in all patients before A (140 μg/kg/minute for five minutes) and the combination of N with D (5-10 μg/kg/minute) stress echocardiography. On the echocardiogram, the left ventricle was divided into 16 segments and wall motion was graded semiquantitatively from 1 (normal) to 4 (dyskinesia). The echocardiographic index was also estimated. A segment was considered viable during A infusion when resting asynergy showed deterioration of one grade or more. In contrast, segmental viability was considered to be present during the combination of N with D infusion when resting asynergy showed improvement of one grade or more. A thallium 201 single photon emission computed tomography (SPECT) with reinjection was performed as reference standard for the identification of viable myocardium. Stress echocardiography during infusion of A was associated with short-duration angina attacks in 3 (5.8%) patients and transient complete atrioventricular (AV) block in 1 (1.9%), whereas during the combination of N with D infusion, 6 (11.5%) patients expe rienced ventricular bigeminy lasting for a short period. ST segment elevation greater than 1 mm was recorded in those leads having a Q wave, in 19 (36.5%) patients. In 10 of these 19 (52.6%), viable myocardium was present in SPECT, as it was in 33 patients (63.5%) having no ST segment elevation (P=NS). Of a total of 832 segments that were graded during A-SE, 276 exhibited resting asynergy and the remaining 556 had normal motion and thickening at rest. The echocardiographic index during A infusion increased from 1.52 ±0.22 to 1.71 ±0.24 (P < 0.001), whereas during D and N infusion it decreased from 1.53 ±0.31 to 1.30 ±0.42 (P < 0.001). With SPECT considered as the gold standard for the identification of viable myocardium, sensitivity, specificity, and positive and negative predictive values of A-SE in detecting viable myocardium were 54%, 86%, 65% and 80%, respectively. The respective values for the combination of nitroglycerin with D-SE were 91%, 89%, 78%, and 96%, respectively. Stress echocardiography during A, and the combination of N with D, constitute safe methods in the identification of viable myocardium. The detection of ST segment elevation in the ECG leads with a Q wave during the combined infusion of nitroglycerin and dobutamine is not related to the presence of viable myocardial tissue. The A-SE provide moderate diagnostic accuracy, while the combination of N with D during SE is much superior in detecting viable myocardium.

One-Year Mortality for Bivalirudin vs Heparins Plus Optional Glycoprotein IIb/IIIa Inhibitor Treatment Started in the Ambulance for ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of the EUROMAX Randomized Clinical Trial

Importance Uncertainty exists regarding potential survival benefits of bivalirudin compared with heparin with routine or optional use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction (STEMI). Few data are available regarding long-term mortality in the context of contemporary practice with frequent use of radial access and novel platelet adenosine diphosphate P2Y12 receptor inhibitors. Objective To assess the effect of bivalirudin monotherapy compared with unfractionated or low-molecular-weight heparin plus optional GPIs on 1-year mortality. Design, Setting, and Participants This international, randomized, open-label clinical trial (EUROMAX [European Ambulance Acute Coronary Syndrome Angiography]) included 2198 patients with STEMI undergoing transport for primary percutaneous coronary intervention from March 10, 2010, through June 20, 2013, and followed up for 1 year. Patients were randomized (1:1) in ambulance to bivalirudin monotherapy vs unfractionated or low-molecular-weight heparin plus optional GPIs (control group). Analysis was based on intention to treat. Main Outcomes and Measures The primary outcome of this prespecified analysis was 1-year mortality. All deaths were adjudicated as cardiac or noncardiac by an independent, blinded clinical events committee. One-year mortality was assessed and examined across multiple prespecified subgroups. Results Of the 2198 patients enrolled (1675 men [76.2%] and 523 women [23.8%]; median [interquartile range] age, 62 [52-72] years), complete 1-year follow-up data were available for 2164 (98.5%). All-cause 1-year mortality occurred in 118 patients (5.4%). The number of all-cause deaths was the same for both treatment groups (59 deaths; relative risk [RR], 1.02; 95% CI, 0.72-1.45; P = .92). No differences were noted in the rates of 1-year cardiac death (44 [4.0%] for the bivalirudin group vs 48 [4.3%] for the control group; RR, 0.93; 95% CI, 0.63-1.39; P = .74) or noncardiac death (15 [1.4%] for the bivalirudin group vs 11 [1.0%] for the control group; RR, 1.39; 95% CI, 0.64-3.01; P = .40). Results were consistent across the prespecified patient subgroups. The rate of deaths occurring from 30 days to 1 year was also similar (27 [2.5%] in the bivalirudin group vs 25 [2.3%] in the control group; RR, 1.10; 95% CI, 0.64-1.88; P = .73). Conclusions and Relevance In patients with STEMI who were being transported for primary percutaneous coronary intervention, treatment with bivalirudin or with heparin with optional use of GPI resulted in similar 1-year mortality. The reduced composite end point of death and/or major bleeding at 30 days in the bivalirudin arm of the EUROMAX trial did not translate into reduced cardiovascular or all-cause death at 1 year. Trial Registration clinicaltrials.gov Identifier: NCT01087723

Severe accordion effect: Myocardial ischemia due to wire complication during percutaneous coronary intervention: A case report

A mechanical alteration during manoeuvring of stiff guidewires in tortuous coronary arteries frequently induces vessel wall shortening and coronary psedostenosis, referred as accordion phenomenon. Subtraction of the guidewires normally leads to the entire resolution of the lesions. A case of this transient angiographic finding, during percutaneous coronary intervention in a tortuous right coronary artery, which resulted in a flow limiting effect and myocardial ischemia, is described in the present report. Differential diagnosis from potential procedure complications and interventional methodology issues are discussed, while similar reports are reviewed.

Non-invasive evaluation of coronary reserve Assessment of coronary reserve in patients with coronary artery disease by transesophageal-Doppler echocardiography

We assessed coronary flow reserve using transesophageal Doppler echocardiography in patients with coronary artery disease. The study included 33 coronary artery disease patients who were undergoing coronary arteriography. The blood flow velocities of the left anterior descending artery before and after intravenous infusion (0.56 mg/min for 4 min) of dipyridamole were recorded using transesophageal Doppler echocardiography. Fourteen normal healthy individuals, matched for age, served as a control group. The index of coronary flow reserve, i.e. the ratio of dipyridamole to baseline maximum diastolic velocity, was calculated. Maximal coronary flow reserve in coronary artery disease patients was significantly lower than in the control group (1.4+/-0.2 vs. 2.8+/-0.3, P<0.001). The coronary artery disease patients were classified into three groups: Group A included 10 patients with <50% left anterior descending artery stenosis; Group B included seven patients with 50-69% left anterior descending artery stenosis; 16 patients with >70% left anterior descending artery stenosis constituted Group C. The maximum coronary flow reserve was significantly different for A vs. B and A vs. C. (A, 1.77+/-0.18; B, 1.51+/-0.1; C, 1.28+/-0.24). A strong and significant correlation was found between the maximum coronary flow reserve and the degree of proximal left anterior descending artery stenosis (r=0.78, P<0.001). Coronary artery disease patients without left anterior descending artery stenosis on the arteriogram exhibited lower maximum coronary flow reserve compared to the control subjects (1.78+/-0.19 vs. 2.8+/-0.3, P=0.000).