Olivier Varenne

Risk of Myocardial Infarction and Vascular Death After Transient Ischemic Attack and Ischemic Stroke A Systematic Review and Meta-Analysis

Background— Whether stroke patients should be investigated for asymptomatic coronary artery disease remains matter of debate. Absolute risks of myocardial infarction (MI) and vascular death after a stroke have not been accurately assessed. We performed a systematic review and a meta-analysis to determine the risk of MI and nonstroke vascular death after transient ischemic attack (TIA) and ischemic stroke. Cohort studies of TIA or ischemic stroke patients were included if they were published between 1980 and March 2005, reported risk of MI and nonstroke vascular death, enrolled >100 patients, and had at least 1 year of follow-up. We included 39 studies in a total of 65 996 patients with mean follow-up of 3.5 years. Two reviewers independently carried out data extraction using a standardized form. Absolute annual risks were estimated through weighted meta-regressions with a random effect. To test the predictions of expected event rates derived from our analysis, we used individual patient data. Summary of Review— The annual risks were 2.1% (CI 95%: 1.9 to 2.4) for nonstroke vascular death, 2.2% (1.7 to 2.7) for total MI, 0.9% (0.7 to 1.2) for nonfatal MI and 1.1% (0.8 to 1.5) for fatal MI. The time course of risk was linear. Estimated risks fitted well with observed risks at the individual level. There was no heterogeneity in the absolute risks according to baseline study characteristics. Conclusions— Patients with TIA or stroke have a relatively high risk of MI and nonstroke vascular death. Additional research is needed to identify the determinants of coronary artery disease in stroke patients.

Is Hypothermia After Cardiac Arrest Effective in Both Shockable and Nonshockable Patients? Insights From a Large Registry

Background— Although the level of evidence of improvement is significant in cardiac arrest patients resuscitated from a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia [VF/VT]), the use of therapeutic mild hypothermia (TMH) is more controversial in nonshockable patients (pulseless electric activity or asystole [PEA/asystole]). We therefore assessed the prognostic value of hypothermia for neurological outcome at hospital discharge according to first-recorded cardiac rhythm in a large cohort. Methods and Results— Between January 2000 and December 2009, data from 1145 consecutive out-of-hospital cardiac arrest patients in whom a successful resuscitation had been achieved were prospectively collected. The association of TMH with a good neurological outcome at hospital discharge (cerebral performance categories level 1 or 2) was quantified by logistic regression analysis. TMH was induced in 457/708 patients (65%) in VF/VT and in 261/437 patients (60%) in PEA/asystole. Overall, 342/1145 patients (30%) reached a favorable outcome (cerebral performance categories level 1 or 2) at hospital discharge, respectively 274/708 (39%) in VF/VT and 68/437 (16%) in PEA/asystole (P<0.001). After adjustment, in VF/VT patients, TMH was associated with increased odds of good neurological outcome (adjusted odds ratio, 1.90; 95% confidence interval, 1.18 to 3.06) whereas in PEA/asystole patients, TMH was not significantly associated with good neurological outcome (adjusted odds ratio, 0.71; 95% confidence interval, 0.37 to 1.36). Conclusions— In this large cohort of cardiac arrest patients, hypothermia was independently associated with an improved outcome at hospital discharge in patients presenting with VF/VT. By contrast, TMH was not associated with good outcome in nonshockable patients. Further investigations are needed to clarify this lack of efficiency in PEA/asystole.

Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent.

OBJECTIVES This study sought to compare the safety and efficacy of 2 dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) (Boston Scientific Corp., Natick, Massachusetts) compared with the durable polymer PROMUS Element EES (Boston Scientific Corp.). BACKGROUND Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing. Bioabsorbable polymer-coated drug-delivery systems may reduce the risk of late adverse events, including stent thrombosis, and thus the need for prolonged dual-antiplatelet therapy. METHODS A total of 291 patients with a de novo lesion ≤28 mm in length, in a coronary artery of ≥2.25 to ≤3.5 mm diameter, were enrolled in the EVOLVE study, a prospective, randomized, single-blind, noninferiority trial. Patients were randomly assigned in a 1:1:1 ratio to PROMUS Element, SYNERGY, or SYNERGY half dose. The primary clinical endpoint was the 30-day rate of target lesion failure, defined as cardiac death or myocardial infarction related to the target vessel, or target lesion revascularization. The primary angiographic endpoint was 6-month in-stent late loss measured by quantitative coronary angiography. RESULTS The 30-day primary clinical endpoint of target lesion failure occurred in 0%, 1.1%, and 3.1% of patients in the PROMUS Element, SYNERGY, and SYNERGY half dose groups, respectively. The 6-month in-stent late loss was 0.15 ± 0.34 mm for PROMUS Element, 0.10 ± 0.25 mm for SYNERGY, and 0.13 ± 0.26 mm for SYNERGY half dose (SYNERGY, difference -0.06, upper 95.2% confidence limit: 0.02, p for noninferiority <0.001; SYNERGY half dose, difference -0.03, upper 95.2% confidence limit: 0.05, p for noninferiority <0.001). Clinical event rates remained low and comparable between groups, with no stent thromboses in any group at 6 months. CONCLUSIONS The EVOLVE trial confirms the effective delivery of everolimus by a unique directional bioabsorbable polymer system utilizing the SYNERGY stent. (A Prospective Randomized Multicenter Single-Blind Noninferiority Trial to Assess the Safety and Performance of the Evolution Everolimus-Eluting Monorail Coronary Stent System [Evolution Stent System] for the Treatment of a De Novo Atherosclerotic Lesion [EVOLVE]; NCT01135225).

Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis.

RATIONALE Although frequent, little is known about early-onset pneumonia that occurs in the postresuscitation period. Although induced hypothermia is recommended as a method of improving neurological outcome, its influence on the occurrence of early-onset pneumonia is not well defined. OBJECTIVES To describe the incidence, risk factors, causative agents, and impact on outcome of early-onset pneumonia occurring within 3 days after out-of-hospital cardiac arrest (OHCA). METHODS Retrospective analysis of a large cohort study of all patients successfully resuscitated after OHCA and admitted from July 2002 to March 2008 in two medical intensive care units (ICUs). Patients who presented accidental hypothermia or a known pneumonia before OHCA, or patients who died within the first 24 hours, were excluded. MEASUREMENTS AND MAIN RESULTS During this 6-year period, 845 patients were admitted after OHCA, and 641 consecutive patients were included. A total of 500 patients (78%) were treated with therapeutic hypothermia. In the first 3 days, 419 (65%) presented early-onset pneumonia. Multivariate analysis disclosed therapeutic hypothermia as the single independent risk factor of early-onset pneumonia (odds ratio, 1.90; 95% confidence interval, 1.28-2.80; P = 0.001). Early-onset pneumonia increased length of mechanical ventilation (5.7 ± 5.9 vs. 4.7 ± 6.2 d; P = 0.001) and ICU stay (7.9 ± 7.2 versus 6.7 ± 7.6 d; P = 0.001), but did not influence incidence of ventilator-associated pneumonia (P = 0.25), favorable neurologic outcome (P = 0.35), or ICU mortality (P = 0.26). CONCLUSIONS After OHCA, therapeutic hypothermia is associated with an increased risk of early-onset pneumonia. This complication was associated with prolonged respiratory support and ICU stay, but did not significantly influence ICU mortality.

Four-Year Follow-Up of TYPHOON (Trial to Assess the Use of the CYPHer Sirolimus-Eluting Coronary Stent in Acute Myocardial Infarction Treated With BallOON Angioplasty)

OBJECTIVES The aim of this study was to assess the long-term safety and efficacy of the CYPHER (Cordis, Johnson and Johnson, Bridgewater, New Jersey) sirolimus-eluting coronary stent (SES) in percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND Concern over the safety of drug-eluting stents implanted during PCI for STEMI remains, and long-term follow-up from randomized trials are necessary. TYPHOON (Trial to assess the use of the cYPHer sirolimus-eluting stent in acute myocardial infarction treated with ballOON angioplasty) randomized 712 patients with STEMI treated by primary PCI to receive either SES (n = 355) or bare-metal stents (BMS) (n = 357). The primary end point, target vessel failure at 1 year, was significantly lower in the SES group than in the BMS group (7.3% vs. 14.3%, p = 0.004) with no increase in adverse events. METHODS A 4-year follow-up was performed. Complete data were available in 501 patients (70%), and the survival status is known in 580 patients (81%). RESULTS Freedom from target lesion revascularization (TLR) at 4 years was significantly better in the SES group (92.4% vs. 85.1%; p = 0.002); there were no significant differences in freedom from cardiac death (97.6% and 95.9%; p = 0.37) or freedom from repeat myocardial infarction (94.8% and 95.6%; p = 0.85) between the SES and BMS groups. No difference in definite/probable stent thrombosis was noted at 4 years (SES: 4.4%, BMS: 4.8%, p = 0.83). In the 580 patients with known survival status at 4 years, the all-cause death rate was 5.8% in the SES and 7.0% in the BMS group (p = 0.61). CONCLUSIONS In the 70% of patients with complete follow-up at 4 years, SES demonstrated sustained efficacy to reduce TLR with no difference in death, repeat myocardial infarction or stent thrombosis. (The Study to Assess AMI Treated With Balloon Angioplasty [TYPHOON]; NCT00232830).

Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions The SPIRIT II Trial

Background—This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial. Methods and Results—This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P=0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.33±0.37 mm versus PES, 0.34±0.34 mm; P=0.84) and percentage volume obstruction (EES, 5.18±6.22% versus PES, 5.80±6.31%; P=0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%). Conclusions—Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years.

Prevention of arterial spasm during percutaneous coronary interventions through radial artery: The SPASM study

Aims: Radial artery spasm remains the major limitation of transradial approach for percutaneous coronary interventions. The aim of our study was to evaluate the efficacy of vasodilators in the prevention of radial artery spasm during percutaneous coronary interventions. Methods and results: 1,219 patients were consecutively randomized to receive placebo (n = 198), molsidomine 1 mg (n = 203), verapamil 2.5 mg (n = 409), 5 mg (n = 203) or verapamil 2.5 mg and molsidomine 1 mg (n = 206). All drugs were administered through the arterial sheath. The primary end point was the occurrence of a radial artery spasm defined by the operator as severe limitation of the catheter movement, with or without angiographic confirmation. Main characteristics including age, sex, wrist and arterial sheath diameters and procedure duration were identical across the groups. The rate of radial artery spasm was lowest in patients receiving verapamil and molsidomine (4.9%), compared to verapamil 2.5 mg or 5 mg (8.3 and 7.9%), or molsidomine 1 mg (13.3%); and placebo (22.2%) (P < 0.0001). Conclusion: Radial artery spasm during transradial percutaneous interventions was effectively prevented by the administration of vasodilators. The combination of verapamil 2.5 mg and molsidomine 1 mg provided the strongest relative risk reduction of spasm compared to placebo and should therefore be recommended during percutaneous coronary interventions through the radial approach.

Prevalence of Asymptomatic Coronary Artery Disease in Ischemic Stroke Patients. The PRECORIS Study

Background— Coronary artery disease (CAD) is a significant cause of morbidity and mortality in stroke patients. Some patients with asymptomatic CAD might benefit from specific prevention, but the prevalence of asymptomatic CAD is not well known. We assessed the prevalence of ≥50% asymptomatic CAD in patients with ischemic stroke or transient ischemic attack and whether the prevalence is related to traditional vascular risk factors and cervicocephalic atherosclerosis. Methods and Results— From January 2006 to February 2009, consecutive patients between 45 and 75 years of age with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack and no prior history of CAD were enrolled in the study. All patients had a 64-section computed tomography coronary angiography and a detailed cervicocephalic arterial workup. Risk factors were assessed individually and through the Framingham Risk Score. Among 300 patients included in the study, 274 had computed tomography coronary angiography. The prevalence of ≥50% asymptomatic CAD was 18% (95% confidence interval [CI], 14 to 23; n=50). Asymptomatic CAD was independently associated with traditional risk factors assessed individually and through the Framingham Risk Score (odds ratio [OR], 2.6; 95% CI, 1.0 to 7.6 for a 10-year risk of coronary heart disease of 10% to 19%; and OR, 7.3; 95% CI, 2.8 to 19.1 for a 10 year-risk of coronary heart disease ≥20%), the presence of at least 1 ≥50% cervicocephalic artery stenosis (OR, 4.0; 95% CI, 1.4 to 11.2), excessive alcohol consumption (OR, 3.1; 95% CI 1.3 to 7.3), and ankle brachial index <0.9 (OR, 2.2; 95% CI, 0.9 to 5.2). The prevalence of ≥50% asymptomatic CAD was also related to the extent of cervicocephalic atherosclerosis. Conclusions— About one fifth of patients with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack have ≥50% asymptomatic CAD. In addition to vascular risk factors, the presence of ≥50% cervicocephalic artery stenosis is strongly related to ≥50% asymptomatic CAD.

Benefit of an early and systematic imaging procedure after cardiac arrest: Insights from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry ☆

AIMS Identification of the cause of out-of-hospital cardiac arrest (OHCA) is of paramount importance. We investigated the ability of our imaging strategy to provide an early etiological diagnosis of OHCA and the influence of this strategy on ICU survival. METHODS Retrospective review of a prospectively acquired ICU database (01/2000-12/2010) including all OHCA patients without obvious extracardiac cause, for which an early diagnosis research was conducted (coronary angiography and/or brain and chest CT scan) within 24h after resuscitation. These procedures could be performed separately or be combined, according to a decision algorithm. RESULTS Of the 1274 patients admitted after OHCA during this 10-year period, the imaging strategy was applied in 896 patients. Patients who benefited from coronary angiography and/or CT scan were admitted to our ICU after a median delay of 180 [130-220]min after resuscitation. Seven hundred and forty-five coronary angiographies were performed, of which 452 (61%) identified at least one significant coronary lesion deemed responsible for the OHCA. CT-scan was performed in 355 patients and provided a diagnosis in 72 patients (20%), mainly stroke (n=38) and pulmonary embolism (n=19). Overall, this strategy allowed early diagnosis in 524 patients (59%). ICU survival was significantly higher for patients with a diagnosis identified by coronary angiography as compared with CT-scan (43% vs 10%, p<0.001). CONCLUSION The use of an early diagnosis protocol with immediate coronary angiography and/or CT scan provided the etiology of nearly two thirds of OHCA cases. In this large retrospective database, coronary angiography yielded a better diagnostic value than brain and/or chest CT-scan.

Stent thrombosis: an increased adverse event after angioplasty following resuscitated cardiac arrest.

BACKGROUND The leading cause of sudden cardiac death is myocardial ischemia. As for uncomplicated acute myocardial infarction (AMI), international guidelines plead for early coronary angiography with, in case of culprit lesion, angioplasty and stent implantation. However after cardiac arrest (CA), shock, hypothermia and changes in antiplatelet pharmacokinetic may promote stent thrombosis (ST). Incidence of ST in this situation has never been studied. OBJECTIVE The aim of this study was to investigate incidence and determinants of ST after ischemic CA successfully revascularized. METHODS We analyzed 208 consecutive patients admitted in our institution for AMI and who underwent PCI with stent implantation. Among these patients, 55 presented a resuscitated CA and were compared to 153 without CA (control group). All patients in the CA group received hypothermia (33 °C for 24 h) following resuscitation and PCI. RESULTS There was no difference between the 2 groups for age, gender, cardiovascular risk factors, coronary lesions and type of stent. In the CA group, patients were less frequently pre-treated with heparin (50.9% vs 98.7%, p<0.001) and aspirin (52.7% vs 99%, p<0.001). In the CA group, we observed a significantly higher incidence of confirmed acute or subacute ST than in the control group: 10.9% vs 2.0% (p=0.01). None of CA patients had received a dual antiplatelets therapy (0% vs 99%). LVEF at admission was lower in the CA group (40.3% vs 48%; p<0.001), and shock was more frequent (83.6% vs 8.5%; p<0.001). Survival at 28 days was 50.1% in CA group vs 98.0% (p<0.001). In multivariate analysis, CA before stenting appears to be an independent risk factor for confirmed ST (OR=12.9; 95%CI 1.3-124.6; p=0.027). CONCLUSION In CA patients treated with cooling, stenting for AMI is associated with a high risk of ST. Shock, insufficient antithrombotic treatment, pharmacokinetic changes related to hypothermia may contribute to this higher risk. A strategy aiming to reduce this complication may probably improve prognosis of patients who underwent coronary sudden death.