Miles Dalby

Transfer for Primary Angioplasty Versus Immediate Thrombolysis in Acute Myocardial Infarction A Meta-Analysis

Background—The benefit of primary percutaneous coronary intervention (PCI) over thrombolysis has been clearly demonstrated in acute myocardial infarction (AMI). However, the best therapeutic strategy for a patient with AMI presenting to acute care services without catheterization facilities remains under debate. Our objective was to gather all available information from clinical trials comparing transfer of patients experiencing AMI for angioplasty versus immediate thrombolysis. Methods and Results—We performed a meta-analysis of all data available from published randomized trials and from presentations in scientific sessions of major cardiology congresses comparing the 2 strategies. The primary end point was the combined criteria (CC) of death/reinfarction/stroke as defined in each trial. Relative risk (RR) evaluated the treatment effect. We identified 6 clinical trials including 3750 patients. Transfer time was always <3 hours. The CC was significantly reduced by 42% (95% confidence interval [CI] 29% to 53%, P <0.001) in the group transferred for primary PCI compared with the group receiving on-site thrombolysis. When CC parameters were considered separately, reinfarction was significantly reduced by 68% (95% CI, 34% to 84%; P <0.001) and stroke by 56% (95% CI, −15% to 77%; P =0.015). There was a trend toward reduction in all-cause mortality of 19% (95% CI, −3% to 36%; P =0.08) with transfer for PCI. Conclusion—Even when transfer to an angioplasty center is necessary, primary PCI remains superior to immediate thrombolysis. Organization of ambulance systems, prehospital management, and adequate PCI capacity appear now to be the key issues in providing reperfusion therapy for AMI.

Randomized Trial of Complete Versus Lesion-Only Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI and Multivessel Disease: The CvLPRIT Trial

Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. Objectives CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. Methods After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. Results Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. Conclusions In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

The influence of strut thickness and cell design on immediate apposition of drug-eluting stents assessed by optical coherence tomography

BACKGROUND Stent strut malapposition correlates with poor intimal coverage and this may increase the risk of late stent thrombosis. At present, there is limited data on whether stent strut thickness and stent design impact on acute apposition. We aimed to investigate the influence of stent strut thickness and design on acute stent strut apposition (SSA) immediately following drug-eluting stent (DES) implantation using optical coherence tomography (OCT), a technique with higher resolution and fewer artefacts than intravascular ultrasound. METHODS Thirty-six DES in 23 patients (25 lesions) were studied by OCT. SSA was defined as embedded when a strut was buried in the intima for more than half its thickness, protruding when apposed to the intima but not embedded and malapposed when there was no intimal contact. RESULTS Cypher Select stents were implanted in 52%, Taxus Liberte in 32%, Costar in 12% and Endeavour in 4%. A total of 6402 struts were evaluated. Despite stent optimisation using balloons with a final balloon/artery ratio of 1.26+/-0.19 at a maximum inflation pressure of 17.5+/-3.0 atm, only 57.1+/-20.7% of struts were embedded, whereas 33.8+/-18.4% were protruding and 9.1+/-7.4% were malapposed. Stent type was a strong predictor of malapposition on logistic multilevel analysis (OR 3.95, 95%CI: 1.27-12.23, p=0.017). At 12 months follow-up, there were no adverse clinical events. CONCLUSION Despite angiographic optimisation with high pressures and adequately sized balloons, malapposed stent struts are frequently found in complex coronary lesions and more often following the implantation of Cypher Select stents which have a thicker stent strut and closed cell design. With no adverse clinical events at 12 months follow-up, this likely represents a benign phenomenon at least as long as combined anti-platelet therapy is maintained.

Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non–ST-segment elevation acute myocardial infarction (the ARMADA study)

The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH.

A multicentre evaluation of the safety of intracoronary optical coherence tomography.

AIMS Optical coherence tomography (OCT) is increasingly being applied to the coronary arteries. However, the risks associated with the imaging procedure are not yet well defined. The purpose of the present multicentre registry was to assess the acute complications associated with the clinical use of intra-coronary OCT in a large number of patients. METHODS AND RESULTS Consecutive patients from six centres who had OCT examination were retrospectively included. All adverse events and complications, even if transient, were noted. Risks were categorised into: 1) self-limiting 2) major complications including major adverse cardiac events (MACE) and 3) mechanical device failure. A total of 468 patients underwent OCT examination for evaluation of: plaque (40.0%), percutaneous coronary intervention (28.2%) or follow-up stent tissue coverage (31.8%). OCT was performed using a non-occlusive flush technique in 45.3% with a mean contrast volume of 36.6+/-9.4ml. Transient chest pain and QRS widening/ST-depression/elevation were observed in 47.6% and 45.5% respectively. Major complications included five (1.1%) cases of ventricular fibrillation due to balloon occlusion and/or deep guide catheter intubation, 3 (0.6%) cases of air embolism and one case of vessel dissection (0.2%). There were no cases of coronary spasm or MACE during or within the 24 hour period following OCT examination. CONCLUSIONS OCT is a specialised technique with a relatively steep learning curve. Major complications are uncommon and can be minimised with careful procedural planning and having an awareness of the potential contributory risks, especially deep guide catheter intubation during contrast flushing. Upcoming developments will make OCT more practical and less procedurally demanding, also potentially conserving contrast volume considerably.

A Randomized Optical Coherence Tomography Study of Coronary Stent Strut Coverage and Luminal Protrusion With Rapamycin-Eluting Stents

OBJECTIVES We used optical coherence tomography, which has a resolution of <20 microm, to analyze thin layers of neointima in rapamycin-eluting coronary stents. BACKGROUND Lack of neointimal coverage has been implicated in the pathogenesis of drug-eluting coronary stent thrombosis. Angiography and intracoronary ultrasound lack the resolution to examine this. METHODS We conducted a randomized trial in patients receiving polymer-coated rapamycin-eluting stents (Cypher, Cordis, Johnson & Johnson, Miami, Florida) and nonpolymer rapamycin-eluting stents (Yukon, Translumina, Hechingen, Germany) to examine neointimal thickness, stent strut coverage, and protrusion at 90 days. Twenty-four patients (n = 12 for each group) underwent stent deployment and invasive follow-up at 90 days with optical coherence tomography. The primary end point was binary stent strut coverage. Coprimary end points were neointimal thickness and stent strut luminal protrusion. RESULTS No patient had angiographic restenosis. For polymer-coated and nonpolymer rapamycin-eluting stents, respectively, mean (SD), neointimal thickness was 77.2 (25.6) microm versus 191.2 (86.7) mum (p < 0.001). Binary stent strut coverage was 88.3% (11.8) versus 97.2% (6.1) (p = 0.030). Binary stent strut protrusion was 26.5% (17.5) versus 4.8% (8.6) (p = 0.001). CONCLUSIONS Mean neointimal thickness for the polymer-coated rapamycin-eluting stent was significantly less than the nonpolymer rapamycin-eluting stent but as a result coverage was not homogenous, with >10% of struts being uncovered. High-resolution imaging allowed development of the concept of the protrusion index, and >25% of struts protruded into the vessel lumen with the polymer-coated rapamycin-eluting stent compared with <5% with the nonpolymer rapamycin-eluting stent. These findings may have important implications for the risk of stent thrombosis and, therefore, future stent design. (An optical coherence tomography study to determine stent coverage in polymer coated versus bare metal rapamycin eluting stents. ORCA 1, from the Optimal Revascularization of the Coronary Arteries group; ISRCTN42475919).

Diurnal variation in platelet aggregation with the PFA–100 platelet function analyser

Background: Myocardial infarction is commoner in the morning, and previous small studies suggesting diurnal variation in platelet aggregation have been limited to optical aggregometry with platelet-rich plasma and low shear. This phenomenon was studied using whole blood at high shear rates. Method: Fifteen healthy volunteers were venesected at 0800 hrs supine in bed immediately before rising, at 0830 hrs 30 min after rising, at 1200 hrs and 1700 hrs. Samples underwent the high shear method of PFA-100 using additional chemical agonists of collagen with ADP or collagen with epinephrine. PFA-100 results are reported as closure time of the experimental aperture in seconds, a longer time indicating less platelet aggregation. Results: With both epinephrine and ADP, a non-significant shortening of closure time was seen on rising. Subsequently, with both agonists the closure time lengthened through the day. With ADP the difference was small (medians 0830 hrs: 85 s, 1700 hrs: 87.5 s) but statistically significant (p = 0.03). With epinephrine it was much more marked (medians 0830 hrs: 114.3 s, 1700 hrs: 140.5 s) and highly significant (p = 0.002). Conclusions: These findings demonstrate a diurnal rhythm in platelet function using whole blood at high shear rates. This is likely to be more applicable to the in vivo situation than previously reported optical aggregometry studies.BACKGROUND Myocardial infarction is commoner in the morning, and previous small studies suggesting diurnal variation in platelet aggregation have been limited to optical aggregometry with platelet-rich plasma and low shear. This phenomenon was studied using whole blood at high shear rates. METHOD Fifteen healthy volunteers were venesected at 0800 hrs supine in bed immediately before rising, at 0830 hrs 30 min after rising, at 1200 hrs and 1700 hrs. Samples underwent the high shear method of PFA-100 using additional chemical agonists of collagen with ADP or collagen with epinephrine. PFA-100 results are reported as closure time of the experimental aperture in seconds, a longer time indicating less platelet aggregation. RESULTS With both epinephrine and ADP, a non-significant shortening of closure time was seen on rising. Subsequently, with both agonists the closure time lengthened through the day. With ADP the difference was small (medians 0830 hrs: 85 s, 1700 hrs: 87.5 s) but statistically significant (p = 0.03). With epinephrine it was much more marked (medians 0830 hrs: 114.3 s, 1700 hrs: 140.5 s) and highly significant (p = 0.002). CONCLUSIONS These findings demonstrate a diurnal rhythm in platelet function using whole blood at high shear rates. This is likely to be more applicable to the in vivo situation than previously reported optical aggregometry studies.

Initial evidence for the return of coronary vasoreactivity following the absorption of bioabsorbable magnesium alloy coronary stents.

AIMS To investigate the endothelium independent coronary smooth muscle vasomotor function four months after implantation of magnesium alloy absorbable metal stents (AMS) as part of the Progress-AMS clinical trial (n = 5), compared with a control group of patients implanted with permanent metal stents (PMS) (n = 10) undergoing follow-up angiography, but who were free from angiographic restenosis. METHODS AND RESULTS Quantitative coronary angiogram (QCA) using an automated edge detection system was performed before and after the administration of 2 mg intracoronary isosorbide dinitrate (ISDN). The vessel diameter was measured at 0.2 mm intervals throughout the stented segments and a 1 cm proximal reference segment. The cross sectional area (CSA) was calculated before and after the ISDN, averaged and the percentage change measured. Reference segments demonstrated preserved vasomotor function in all cases: +13.28% (AMS) versus +17.15% (PMS), p = 0.39. The mean percentage increase in CSA for the stented segment was +6.78% for the AMS versus -1.30% for PMS, p = 0.003. CONCLUSION These data demonstrate that four months after AMS implantation vasomotor function in reference segments is no different to that observed with PMS. However in contrast to PMS, within the AMS-stented segments there is demonstrable vasodilatation. These observations may have important implications for future stent design.

Radiation dose reduction without compromise of image quality in cardiac angiography and intervention with the use of a flat panel detector without an antiscatter grid

Objective: To test the hypothesis that replacing the antiscatter grid with an air gap will reduce patient radiation exposure without significant compromise of image quality. Methods: 457 patients having either uncomplicated diagnostic studies or a single vessel angioplasty (percutaneous transluminal coronary angioplasty (PTCA)) on a flat plate system (GE Innova) were studied. For two months their total dose–area product score was recorded on standard gridded images and then for two months on images made with the grid out, with an air gap used to reduce scatter. Detector magnification was reduced one step when an air gap was used to achieve the same final image size. A sample set of studies was reviewed blind by five observers, who scored sharpness and contrast on a non-linear scale. Results: The average dose–area product was significantly reduced, both in the diagnostic group (n  =  276), from a mean (SD) of 26.2 (14.7) Gy·cm2 with the grid in to 16.1 (12) Gy·cm2 with the grid out (p  =  0.01), and in the PTCA group (n  =  181), from 48.2 (36.2) to 37 (27.5) (p  =  0.01). The mean image quality scores of the gridless cohort were not significantly different from those of the gridded cohort. Conclusion: With the use of a flat plate detector, air gap gridless angiography reduces the radiation dose to the patient and, in consequence, to the operator without significantly affecting image quality. It is proposed that gridless imaging should be the default technique for adults and children and in most installations.

Brachial artery low-flow-mediated constriction is increased early after coronary intervention and reduces during recovery after acute coronary syndrome: characterization of a recently described index of vascular function

AIMS The endothelium plays a role in regulating vascular tone. Acute and dynamic changes in low-flow-mediated constriction (L-FMC) and how it changes with regard to traditional flow-mediated dilatation (FMD) have not been described. We aimed to investigate the changes in brachial artery L-FMC following percutaneous coronary intervention (PCI) and during recovery from non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS FMD was performed in accordance with a previously described technique in patients before and after PCI and in the recovery phase of NSTEMI, but in addition, L-FMC data were acquired from the last 30 s of cuff inflation. About 135 scans were performed in 96 participants (10 healthy volunteers and 86 patients). Measurement of brachial L-FMC was reproducible over hours. L-FMC was greater among patients with unstable vs. stable coronary atherosclerosis (-1.33 ±1.09% vs. -0.03 ± 1.26%, P < 0.01). Following PCI, FMD reduced (4.43 ± 2.93% vs. 1.66 ± 2.16%, P < 0.01) and L-FMC increased (-0.33 ± 0.76% vs. -1.63 ± 1.15%, P = 0.02). Furthermore, during convalescence from NSTEMI, L-FMC reduced (-1.37 ± 1.19% vs. 0.01 ± 0.82%, P = 0.02) in parallel with improvements in FMD (2.54 ± 2.19% vs. 5.15 ± 3.07%, P < 0.01). CONCLUSION Brachial L-FMC can be measured reliably. Differences were observed between patients with stable and unstable coronary disease. L-FMC was acutely increased following PCI associated with reduced FMD and, in the recovery from NSTEMI, L-FMC reduced associated with increased FMD. These novel findings characterize acute and subacute variations in brachial L-FMC. The pathophysiological and clinical implications of these observations require further study.