Olivier F. Bertrand

Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.

CONTEXT High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. OBJECTIVE To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. INTERVENTIONS High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. MAIN OUTCOME MEASURES The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. RESULTS At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). CONCLUSIONS Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00645918.

Acute kidney injury following transcatheter aortic valve implantation : predictive factors, prognostic value, and comparison with surgical aortic valve replacement

Aims Very few data exist on the occurrence of acute kidney injury (AKI) associated with transcatheter aortic valve implantation (TAVI). The objectives of the present study were (i) to determine the incidence, predictive factors, and prognostic value of AKI following TAVI, and (ii) to compare the occurrence of AKI in TAVI vs. surgical aortic valve replacement (SAVR) in patients with pre-procedural chronic kidney disease (CKD). Methods and results A total of 213 patients (mean age 82 ± 8 years) undergoing TAVI for the treatment of severe aortic stenosis were included in the study. Acute kidney injury was defined as a reduction of >25% in estimated glomerular filtration rate (eGFR) within 48 h following the procedure or the need for haemodialysis during index hospitalization. Those patients with pre-procedural CKD (eGFR <60 mL/min/1.73 m2, n = 119) were compared with 104 contemporary patients with CKD who underwent isolated SAVR. The incidence of AKI following TAVI was 11.7%, with 1.4% of the patients requiring haemodialysis. Predictive factors of AKI were hypertension (OR: 4.66; 95% CI: 1.04–20.87), chronic obstructive pulmonary disease (OR: 2.64, 95% CI: 1.10–6.36), and peri-operative blood transfusion (OR: 3.47, 95% CI: 1.30–9.29). Twenty-one patients (9.8%) died during index hospitalization, and the logistic EuroSCORE (OR: 1.03 for each increase of 1%; 95% CI: 1.01–1.06) and occurrence of AKI (OR: 4.14, 95% CI: 1.42–12.13) were identified as independent predictors of postoperative mortality. Patients with CKD who underwent TAVI were older, had a higher logistic EuroSCORE and lower pre-procedural eGFR values compared with those who underwent SAVR (P < 0.0001 for all). The incidence of AKI was lower (P = 0.001; P = 0.014 after propensity score adjustment) in CKD patients who underwent TAVI (9.2%, need for haemodialysis: 2.5%) compared with those who underwent SAVR (25.9%, need for haemodialysis: 8.7%). Conclusion Acute kidney injury occurred in 11.7% of the patients following TAVI and was associated with a greater than four-fold increase in the risk of postoperative mortality. Hypertension, chronic obstructive pulmonary disease, and blood transfusion were predictive factors of AKI. In those patients with pre-procedural CKD, TAVI was associated with a significant reduction of AKI compared with SAVR.

Comparison of the hemodynamic performance of percutaneous and surgical bioprostheses for the treatment of severe aortic stenosis.

OBJECTIVES This study was undertaken to compare the hemodynamic performance of a percutaneous bioprosthesis to that of surgically implanted (stented and stentless) bioprostheses for the treatment of severe aortic stenosis. METHODS Fifty patients who underwent percutaneous aortic valve implantation (PAVI) with the Cribier-Edwards or Edwards SAPIEN bioprosthetic valve (Edwards Lifesciences, Inc., Irvine, California) were matched 1:1 for sex, aortic annulus diameter, left ventricular ejection fraction, body surface area, and body mass index, with 2 groups of 50 patients who underwent surgical aortic valve replacement (SAVR) with a stented valve (Edwards Perimount Magna [SAVR-ST group]), or a stentless valve (Medtronic Freestyle, Medtronic, Minneapolis, Minnesota [SAVR-SL group]). Doppler echocardiographic data were prospectively obtained before the intervention, at discharge, and at 6- to 12-month follow-up. RESULTS Mean transprosthetic gradient at discharge was lower (p < 0.001) in the PAVI group (10 +/- 4 mm Hg) compared with the SAVR-ST (13 +/- 5 mm Hg) and SAVR-SL (14 +/- 6 mm Hg) groups. Aortic regurgitation (AR) occurred more frequently in the PAVI group (mild: 42%, moderate: 8%) compared with the SAVR-ST (mild: 10%, moderate: 0%) and SAVR-SL (mild: 12%, moderate: 0%) groups (p < 0.0001). At follow-up, the mean gradient in the PAVI group remained lower (p < 0.001) than that of the SAVR-ST group, but was similar to that of the SAVR-SL group. The incidence of severe prosthesis-patient mismatch was significantly lower (p = 0.007) in the PAVI group (6%) compared with the SAVR-ST (28%) and SAVR-SL (20%) groups. However, the incidence of AR remained higher (p < 0.0001) in the PAVI group compared with the 2 other groups. CONCLUSIONS PAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR.

Transradial Approach for Coronary Angiography and Interventions: Results of the First International Transradial Practice Survey

OBJECTIVES The aim of this study was to evaluate practice of transradial approach (TRA). BACKGROUND TRA has been adopted as an alternative access site for coronary procedures. METHODS A questionnaire was distributed worldwide with Internet-based software. RESULTS The survey was conducted from August 2009 to January 2010 among 1,107 interventional cardiologists in 75 countries. Although pre-TRA dual hand circulation testing is not uniform in the world, >85% in the U.S. perform Allen or oximetry testing. Right radial artery is used in almost 90%. Judkins catheters are the most popular for left coronary artery angiographies (66.5%) and right coronary artery angiographies (58.8%). For percutaneous coronary intervention (PCI), 6-F is now standard. For PCI of left coronary artery, operators use standard extra back-up guiding catheters in >65% and, for right coronary artery 70.4% use right Judkins catheters. Although heparin remains the routine antithrombotic agent in the world, bivalirudin is frequently used in the U.S. for PCI. The incidence of radial artery occlusion before hospital discharge is not assessed in >50%. Overall, approximately 50% responded that their TRA practice will increase in the future (68.4% in the U.S.). CONCLUSIONS TRA is already widely used across the world. Diagnostic and guiding-catheters used for TRA remain similar to those used for traditional femoral approach, suggesting that specialized radial catheters are not frequently used. However, there is substantial variation in practice as it relates to specific aspects of TRA, suggesting that more data are needed to determine the optimal strategy to facilitate TRA and optimize radial artery patency after catheterization.

The Transradial Approach to Percutaneous Coronary Intervention: Historical Perspective, Current Concepts, and Future Directions

Periprocedural bleeding complications after percutaneous coronary intervention (PCI) are associated with increased short- and long-term morbidity and mortality. Although clinical trials have primarily assessed pharmacological strategies for reducing bleeding risk, there is a mounting body of evidence suggesting that adoption of a transradial rather than a transfemoral approach to PCI may permit greater reductions in bleeding risk than have been achieved with pharmacological strategies alone. However, despite a long history of use, a lack of widespread uptake by physicians coupled with the technological limitations of available devices has in the past confined transradial PCI to the status of a niche procedure, and many operators lack experience in this technique. In this review, we examine the history of the transradial approach to PCI and discuss some of the circumstances that have hitherto limited its appeal. We then review the current state of the peer-reviewed literature supporting its use and summarize the unresolved issues affecting broader application of this technique, including lack of operator familiarity and an insufficient evidence base for guiding practice. Finally, we describe potential directions for future investigation in the transradial realm.

Effects of the Acyl Coenzyme A:Cholesterol Acyltransferase Inhibitor Avasimibe on Human Atherosclerotic Lesions

Background—Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis. Methods and Results—This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level <125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was ≈200 mm3, and the least squares mean change at end of treatment was 0.7 mm3 for placebo and 7.7, 4.1, and 4.8 mm3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted P=0.17 [unadjusted P=0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (P=NS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (P<0.05 in all groups). Conclusions—Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol.

A Randomized Study Comparing Same-Day Home Discharge and Abciximab Bolus Only to Overnight Hospitalization and Abciximab Bolus and Infusion After Transradial Coronary Stent Implantation

Background— Systematic use of coronary stents and optimized platelet aggregation inhibition has greatly improved the short-term results of percutaneous coronary interventions. Transradial percutaneous coronary interventions have been associated with a low risk of bleeding complications. It is unknown whether moderate- and high-risk patients can be discharged safely the same day after uncomplicated transradial percutaneous coronary interventions. Methods and Results— We randomized 1005 patients after a bolus of abciximab and uncomplicated transradial percutaneous coronary stent implantation either to same-day home discharge and no infusion of abciximab (group 1, n=504) or to overnight hospitalization and a standard 12-hour infusion of abciximab (group 2, n=501). The primary composite end point of the study was the 30-day incidence of any of the following events: death, myocardial infarction, urgent revascularization, major bleeding, repeat hospitalization, access site complications, and severe thrombocytopenia. The noninferiority of same-day home discharge and bolus of abciximab only compared with overnight hospitalization and abciximab bolus and infusion was evaluated. Two thirds of patients presented with unstable angina and ≈20% presented with high-risk acute coronary syndrome prior to the procedure. The incidence of the primary end point was 20.4% in group 1 and 18.2% in group 2 (P=0.017 for noninferiority) with a troponin T–based definition of myocardial infarction; the incidence of the primary end point was 11.1% in group 1 and 9.6% in group 2 (P=0.0004 for noninferiority) with a creatinine kinase myocardial band–based definition of myocardial infarction. No death occurred. Rate of major bleeding in both groups was extremely low at 0.8% and 0.2%, respectively. From 504 patients randomized in group 1, 88% were discharged home the same day. Conclusion— Our data suggest that same-day home discharge after uncomplicated transradial coronary stenting and bolus only of abciximab is not clinically inferior, in a wide spectrum of patients, to the standard overnight hospitalization and a bolus followed by a 12-hour infusion. This novel approach offers a safe strategy for same-day home discharge after uncomplicated coronary intervention.

Predicting Late Myocardial Recovery and Outcomes in the Early Hours of ST-Segment Elevation Myocardial Infarction : Traditional Measures Compared With Microvascular Obstruction, Salvaged Myocardium, and Necrosis Characteristics by Cardiovascular Magnetic Resonance

OBJECTIVES The aim of this study was to determine whether a very early imaging strategy improves the prediction of late systolic dysfunction and poor outcomes in ST-segment elevation myocardial infarction (STEMI) compared with traditional predictors. BACKGROUND Earlier prediction of poor outcomes after STEMI is desirable, because it will allow tailored therapy at the earliest possible time, when benefits might be greatest. METHODS One hundred and three patients with acute STEMI were studied by contrast-enhanced cardiovascular magnetic resonance within 12 h of primary angioplasty and at 6 months and followed >2 years. The primary end point was left ventricular (LV) dysfunction, whereas poor outcomes were a key secondary end point. RESULTS Traditional risk factors were only modest predictors of late LV dysfunction. Late gadolinium enhancement (LGE) volume maintained a stronger association to LV ejection fraction change than infarct transmurality, microvascular obstruction, or myocardial salvage during STEMI (p = 0.02). Multivariable logistic regression identified LGE volume during STEMI as the best predictor of late LV dysfunction (odds ratio: 1.36, p = 0.03). An LGE >or=23% of LV during STEMI accurately predicted late LV dysfunction (sensitivity 89%, specificity 74%). The LGE volume provided important incremental benefit for predicting late dysfunction (area under the curve = 0.92, p <or= 0.03 vs. traditional risk factors). Twenty-three patients developed poor outcomes (1 death, 2 myocardial infarctions, 5 malignant arrhythmias, 4 severe LV dysfunction <35%, 11 hospital stays for heart failure) over 2.6 +/- 0.9 years; LGE volume remained a strong independent predictor of poor outcomes, whereas LGE >or=23% carried a hazard ratio of 6.1 for adverse events (p < 0.0001). CONCLUSIONS During the hyperacute phase of STEMI, LGE volume provides the strongest association and incremental predictive value for late systolic dysfunction and discerns poor late outcomes.

Biocompatibility aspects of new stent technology

Stent implantation represents a major step forward since the introduction of coronary angioplasty. As indications continue to expand, better understanding of the early and late biocompatibility issues appears critical. Persisting challenges to the use of intracoronary stents include the prevention of early thrombus formation and late neointima development. Different metals and designs have been evaluated in animal models and subsequently in patients. Polymer coatings have been proposed to improve the biocompatibility of metallic stents or to serve as matrix for drug delivery and they are currently undergoing clinical studies. The promises of a biodegradable stent have not yet been fulfilled although encouraging results have recently been reported. Continuous low dose-rate brachytherapy combining the scaffolding effect of the stent with localized radiation therapy has witnessed the development and early clinical testing of radioactive stents. The combined efforts of basic scientists and clinicians will undoubtedly contribute to the improvement of stent biocompatibility in the future.

Transradial arterial access for coronary and peripheral procedures: executive summary by the Transradial Committee of the SCAI.

In response to growing U.S. interest, the Society for Coronary Angiography and Interventions recently formed a Transradial Committee whose purpose is to examine the utility, utilization, and training considerations related to transradial access for percutaneous coronary and peripheral procedures. With international partnership, the committee has composed a comprehensive overview of this subject presented herewith.