Hakim Benamer

Elevated Levels of Shed Membrane Microparticles With Procoagulant Potential in the Peripheral Circulating Blood of Patients With Acute Coronary Syndromes

BACKGROUND Apoptotic microparticles are responsible for almost all tissue factor activity of the plaque lipid core. We hypothesized that elevated levels of procoagulant microparticles could also circulate in the peripheral blood of patients with recent clinical signs of plaque disruption and thrombosis. METHODS AND RESULTS We studied 39 patients with coronary heart disease, including 12 patients with stable angina and 27 patients with acute coronary syndromes (ACS), and 12 patients with noncoronary heart disease. We isolated the circulating microparticles by capture with annexin V and determined their procoagulant potential with a prothrombinase assay. The cell origins of microparticles were determined in an additional 22 patients by antigenic capture with specific antibodies. The level of procoagulant microparticles did not differ between stable angina patients and noncoronary patients (10.1+/-1.6 nmol/L phosphatidylserine [PS] equivalent versus 9.9+/-1.6 nmol/L PS equivalent, respectively). However, procoagulant microparticles were significantly elevated in patients with ACS (22.2+/-2.7 nmol/L PS equivalent) compared with other coronary (P<0.01) or noncoronary (P<0.01) patients. Microparticles of endothelial origin were significantly elevated in patients with ACS (P<0.01), which suggests an important role for endothelial injury in inducing the procoagulant potential. CONCLUSIONS High levels of procoagulant endothelial microparticles are present in the circulating blood of patients with ACS and may contribute to the generation and perpetuation of intracoronary thrombi.

Comparison of the prognostic value of C-Reactive protein and troponin I in patients with unstable angina pectoris

This study assessed the prognostic value of cardiac troponin I (cTnI) and C-reactive protein (CRP) in unstable angina, and specifically in patients with angiographically proven coronary artery disease. These biochemical parameters, which are related to myocardial injury or to systemic inflammation, may help in short-term risk stratification of unstable angina. We prospectively studied 195 patients with unstable angina, 100 of whom had angiographically proven coronary artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum concentrations of cTnI (N < 0.4 ng/ml) and CRP (N < 3 mg/L) were measured at admission, 12, and 24 hours later. The rate of in-hospital major adverse cardiac events (death, myocardial infarction, or emergency revascularization) was higher in patients with increased cTnI within the first 24 hours, regardless of the results of coronary angiography (23% vs 7%; p < 0.001). Conversely, events occurred at similar rates in patients with or without increased CRP. In patients with angiographic evidence of coronary artery disease, multivariate analysis showed that increased cTnI within 24 hours of admission (35 patients) was an independent predictor of major adverse cardiac events (odds ratio 6.7, range 1.7 to 27.3), but not cTnI levels at admission and CRP at 0, 12, and 24 hours. Thus, both in unselected patients with unstable angina and in patients with angiographically proven coronary artery disease, increased cTnI within 24 hours of admission, but not CRP, is a predictor of in-hospital clinical outcome. We also found a temporal link between cTnI increase and late elevation of CRP, suggesting that systemic inflammation may partially be a consequence of myocardial injury.

Elevated cardiac troponin I predicts a high-risk angiographic anatomy of the culprit lesion in unstable angina.

BACKGROUND This study assessed the relation between the angiographic appearance of the culprit lesion and cardiac troponin I (cTnI) or C-reactive protein (CRP) elevations within the first 24 hours in unstable angina. Intracoronary thrombus or a complex morphology, is frequently observed on angiography in patients with unstable angina and is associated with a higher rate of spontaneous or coronary angioplasty-related complications. Biochemical parameters related to myocardial injury (eg, cTnI) or to systemic inflammation (eg, CRP) are known prognostic markers for clinical outcome and may help in angiographic risk stratification to provide new adjunctive therapy. METHODS AND RESULTS We studied 100 patients admitted for unstable angina with angiographically proven coronary artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum concentrations of cTnI (N < 0.4 ng/mL) and CRP (N < 3 mg/L) were measured at admission and 12 and 24 hours later. Multivariate analysis showed that elevated cTnI (>/=0.4 ng/mL) within 24 hours (35 patients) was an independent predictor of an angiographic appearance of the culprit lesion carrying a high risk of major cardiac events in the outcome and whether angioplasty is attempted (coronary thrombus, occlusion, or type C lesions; odds ratio 4.1, 1. 6 to 10.5). cTnI levels at admission and CRP at 0, 12, and 24 hours were not predictive of high-risk angiographic anatomy. CONCLUSIONS In patients with unstable angina and angiographically proven coronary artery disease, increased cTnI within 24 hours of admission but not increased CRP is associated with an angiographic appearance of the culprit lesion carrying a high risk of complication, especially in the event of angioplasty.

Reperfusion Syndrome: Relationship of Coronary Blood Flow Reserve to Left Ventricular Function and Infarct Size

OBJECTIVES We tested the hypothesis that the reperfusion syndrome (RS), defined as an additional elevation of the ST segment upon reperfusion, may be a marker of microcirculatory reperfusion injury during acute myocardial infarction (AMI). BACKGROUND The pathophysiology of the RS is unknown, and its prognostic implications are controversial. METHODS Twenty-one patients with an anterior AMI treated < or =12 h after onset by primary coronary angioplasty (PTCA) were studied. Coronary velocity reserve (CVR), an index of microcirculatory function, was measured using a Doppler guidewire. Left ventricular (LV) ejection fraction, infarct size (percent defect) and LV end-systolic volume index (LVESVi) were evaluated by radionuclide ventriculography, 201T1 single-photon emission computed tomography and contrast ventriculography, respectively. RESULTS Baseline ST elevation and pain-to-TIMI 3 time were similar in patients with and without RS. Patients with RS (10/21) had a lower post-PTCA CVR than patients without RS (median [95% confidence interval]: 1.2 [1-1.3] vs. 1.6 [1.5-1.7], p < 0.005). Even though predischarge CVR was similar in the two groups, infarct size at six weeks (26 [21 to 37] vs. 14 [10-17]% 201T1 defect, p = 0.001) and predischarge LVESVi (45% [40 to 52] vs. 30% [29 to 38] mL/m2, p = 0.001) were larger, and LV ejection fraction at six weeks (40% [37 to 46] vs. 55% [50 to 60], p = 0.004) was lower in patients with RS than in patients without RS. CONCLUSIONS Patients with RS during primary PTCA for an anterior AMI have a transiently lower CVR than patients without RS, but sustained LV dysfunction and larger infarct size, suggesting that RS is a marker of microcirculatory reperfusion injury.

Relation of mortality of primary angioplasty during acute Myocardial Infarction to door-to-thrombolysis In Myocardial Infarction (TIMI) time

For primary angioplasty of acute myocardial infarction (AMI), the relation of treatment benefit and time has been debated. The present study aimed to evaluate, in a single-center cohort of patients with ST-segment elevation AMI, which time intervals were carefully and consistently measured, and the relations among ischemic time, in-hospital delays, and in-hospital survival. We included 499 patients (mean age 59 years; 80% men) who underwent successful primary percutaneous transluminal coronary angioplasty (PTCA) for AMI admitted ≤6 hours after symptom onset. The population was divided into tertiles with respect to time between onset of symptoms and admission, onset of symptoms to Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow, and time from admission to TIMI grade 3 flow. Univariate analysis followed by multiple logistic regression was performed using the variables linked to mortality in the univariate analysis to assess the relation between predictor variables and in-hospital mortality. The in-hospital mortality rate was 3.2%. There was no significant relation between the various tertiles of time intervals and in-hospital mortality. After linear logistic regression, only age (odds ratio [OR] 1.79 per 10 years), female gender (OR 3.56), and door-to-TIMI 3 time (OR 1.27 per 15 minutes) were independently correlated with in-hospital mortality.

A matched comparison of the combination of prehospital thrombolysis and standby rescue angioplasty with primary angioplasty.

This study sought to assess the rate of acute Thrombolysis In Myocardial Infarction (TIMI) trial grade 3 patency that can be achieved with the combination of prehospital thrombolysis and standby rescue angioplasty in acute myocardial infarction. No large angiographic study has been performed after prehospital thrombolysis to determine the 90-minute TIMI 3 patency rate in the infarct-related artery. Hospital outcome and artery patency were compared to 170 matched patients treated with primary angioplasty. Prehospital thrombolysis was applied 151+/-61 minutes after the onset of pain in 170 patients (56+/-12 years, 86% men), using recombinant tissue-type plasminogen activator, streptokinase, or eminase. Emergency 90-minute angiography was performed in every case. All patients in whom thrombolysis failed underwent rescue angioplasty. After thrombolysis alone, TIMI grade 3 flow in the infarct-related artery was observed in 108 patients (64%), TIMI grade 2 in 12 (7%), and TIMI grade 0 or 1 in 50 (29%). Rescue angioplasty was successful in 47 of 50 attempts. Overall, TIMI 3 patency was achieved in 91%, and additionally TIMI 2 flow in 7% of patients, an average of 113+/-39 minutes after thrombolysis and 55+19 minutes after admission. Therefore, < 2 hours after thrombolysis, only 2% of patients had persistent occlusion (TIMI 0 or 1) of the infarct-related artery. In-hospital mortality was 4% overall (7 of 170), and 3% in the 155 patients in whom TIMI 3 was obtained during the acute phase. Severe hemorrhagic complications occurred in 14 patients (8%) with 2 fatal cerebral hemorrhages (7% of patients required transfusions). The matched comparison with primary PTCA showed no significant difference in hospital outcome. Combined prehospital thrombolysis, 90-minute angiography, and rescue angioplasty yield a high rate of acute TIMI 3 patency rate early after thrombolysis and hospital admission. A randomized, prospective comparison between these 2 reperfusion strategies may be now warranted.

A randomized double-blind trial of intravenous trimetazidine as adjunctive therapy to primary angioplasty for acute myocardial infarction

BACKGROUND Despite high patency rates, primary angioplasty for myocardial infarction does not necessarily result in optimal myocardial reperfusion and limitation of infarct size. Experimentally, trimetazidine limits infarct size, decreases platelet aggregation, and reduces leukocyte influx into the infarct zone. To assess trimetazidine as adjunctive therapy to primary angioplasty for acute myocardial infarction a prospective, double-blind, placebo-controlled pilot trial was performed. METHODS 94 patients with acute myocardial infarction were randomized to receive trimetazidine (40 mg bolus followed by 60 mg/day intravenously for 48 h) (n=44) or placebo (n=50), starting before recanalization of the infarct vessel by primary angioplasty. Patients underwent continuous ST-segment monitoring to assess return of ST-segment deviation to baseline and presence of ST-segment exacerbation at the time of vessel recanalization. Infarct size was measured enzymatically from serial myoglobin measurements. Left ventricular angiography was performed before treatment and repeated at day 14. RESULTS Blinded ST segment analysis showed that despite higher initial ST deviation from baseline in the trimetazidine group (355 (32) vs. 278 (29) microV, P=0.07), there was an earlier and more marked return towards baseline within the first 6 h than in the placebo group (P=0.014) (change: 245 (30) vs. 156 (31) microV respectively, P=0.044). There was a trend towards less frequent exacerbation of ST deviation at the time of recanalization in the trimetazidine group (23.3 vs. 42.2%, P=0.11). There was no difference in left ventricular wall motion at day 14, or in enzymatic infarct size. There was no side effect from treatment. Clinical outcomes were similar between groups. CONCLUSION Trimetazidine was safe and led to earlier resolution of ST-segment elevation in patients treated by primary angioplasty for acute myocardial infarction.

Efficacy of Streptokinase, but Not Tissue-Type Plasminogen Activator, in Achieving 90-Minute Patency After Thrombolysis for Acute Myocardial Infarction Decreases With Time to Treatment

OBJECTIVES We sought to examine the relation between time to treatment and 90-min patency rates in patients receiving intravenous streptokinase (SK) or accelerated tissue-type plasminogen activator (t-PA). BACKGROUND Early patency of the infarct-related artery is a major determinant of survival after thrombolysis for acute myocardial infarction. Some data suggest that time to treatment may influence the efficacy of nonfibrin-specific thrombolytic agents in restoring early patency of the infarct-related vessel. METHODS We performed a retrospective analysis of a cohort of 481 patients receiving thrombolytic therapy for acute myocardial infarction <6 h after pain onset, all of whom underwent 90-min coronary angiography. Patency of the infarct-related artery was graded by two observers who had no knowledge of the treatment received or the time between pain and therapy. RESULTS There was no difference in baseline clinical or angiographic characteristics according to the timing or nature of treatment. Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 patency rate after SK correlated negatively with the time between onset of pain and thrombolysis (r = 0.8, p = 0.05), whereas the 90-min patency rate after t-PA appeared stable as a function of time to treatment. When patients were categorized as having received treatment <3 or > or = 3 h after pain onset, the patency rate was similar with t-PA, but significantly higher when SK was administered early rather than late, regardless of whether TIMI flow grades 2 and 3 were pooled (86.9% vs. 59.4%, p = 0.0001) or TIMI flow grade 3 alone was considered to indicate patency (81.7% vs. 53.6%, p = 0.0001). Multivariate logistic regression analysis showed a negative effect of time to treatment on the patency probability for SK (p = 0.0001) but not for t-PA. CONCLUSIONS The efficacy of streptokinase but not t-PA in restoring early coronary patency after intravenous thrombolysis is markedly lower when patients are treated later after onset of pain.

Expert consensus: Renal denervation for the treatment of hypertension

Catheter-based renal denervation is a new method able to disrupt renal sympathetic nerves located in the adventitia of renal arteries. A randomized clinical trial showed a decrease in blood pressure in resistant hypertensive patients. In order to guide clinicians and interventional practitioner for the use of this new approach, different French scientific societies (Hypertension, Cardiology and Radiology) decided to combine their expertise and propose an expert consensus to assess benefit/risk ratio of this technique in the field of arterial hypertension. In 2012, this expert consensus propose to limit renal denervation technique to patients with essential hypertension uncontrolled by four or more antihypertensive therapies with at least one treatment being a diuretic and spironolactone at a dose of 25mg shown to be unable to control blood pressure. Measurement of office BP should be at least with SBP more than 160mmHg and/or DBP more than 100mmHg confirmed by ambulatory BP measurement (home or ABP measurement with SBP more than 135mmHg and DBP more than 85mm during daytime period). Finally, renal artery anatomy and function should allow proper intervention (i.e., two functional kidneys, absence of previous renal angioplasty). Renal enervation is a complex interventional procedure with potentially arterial complications, training is required for practitioners. Antihypertensive treatment should not be interrupted immediately after renal denervation since blood pressure lowering effect are delayed and reached maximum effect after 3 months. Monitoring of blood pressure, renal function and anatomy of renal arteries is required 12 months and 36 months after procedure. The expert consensus requires the inclusion of patients experiencing this procedure in a observational study with record form and follow-up.

A multicentre comparison of transradial and transfemoral approaches for coronary angiography and PTCA in obese patients: the TROP registry

AIMS The incidence of obesity is increasing continuously in industrial countries. Vascular complications after the transfemoral approach (TF) for either coronary angiography (CA) or angioplasty (PCI) are more frequent in this population. The transradial approach may decrease the risk of such complications. METHODS AND RESULTS We undertook a prospective, multicentre, European registry of overweight patients (BMI >/=35), undergoing CA and/or PCI in centres with broad experience in the transradial approach (TR). The vascular approach was left to the operators discretion. The primary end point was the occurrence of access related complications resulting in delayed hospital discharge 555 patients, (age 60.8+/-10.9 years; males 57.3%; BMI: 38.5+/-3.6 kg/m2) were included in the study. Of these, 157 underwent the transfemoral approach and 398 the transradial. Total procedure time was significantly shorter for the transradial approach in these morbidly obese patients (TR: 35.5+/-25.8 min versus TF: 52.4+/-25.2 min, p=0.0001), and hospital stay after CA or PCI was significantly shorter in the transradial group (TR: 1.8+/-2.3 days versus TF: 2.5+/-4.3 days, p=0.04). Vascular complications delaying hospital discharge occurred in 0.8% of TR patients vs 5.1% TF patients. p=0.0009). CONCLUSIONS The rate of vascular complications in overweight patients after CA or PCI can be significantly decreased by the use of the transradial approach in centres with a large experience.