Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients.

BACKGROUND: High on treatment platelet reactivity (HTPR) is common in patients receiving clopidogrel following an acute coronary syndrome (ACS); it's also associated with increased morbidity and mortality. More potent and predictable antiplatelet drugs have addressed this issue at the expense of increased bleeding. Identification of HTPR and the targeted use of more potent antiplatelet drugs has, so far, broadly failed. We investigate this approach in terms of the timing of platelet function testing and how this can impact on the ability of these bedside tests to predict HTPR around the time of coronary intervention. METHODS: High risk ACS patients treated with 5 days of clopidogrel had platelet function assessed using the multiple electrode aggregometry system (MEA) pre, post and 24 h following percutaneous coronary intervention (PCI). Simultaneous detailed analysis of platelet status was undertaken with quantification of platelet bound and soluble p-selectin and mass spectrometry quantification of the eicosanoid 12-HETE. RESULTS: As assessed by MEA 40.5% of patients had HTPR pre-PCI; mean aggregation units (AU) in response to ADP were 499.1 ± 46.3 pre-PCI, 407.6 ± 37.7 post-PCI and 269.1 ± 24.6 AU 24 h post-PCI (pre to post PCI p > 0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet reactivity was contrasted with on-going expression of platelet bound p-selectin, increased soluble p-selectin and rising 12-HETE concentrations. CONCLUSIONS: This study outlines significant changes in ex-vivo platelet aggregation that occur within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there were no changes in antiplatelet therapy during the study period its clear that timing is crucial when assessing high on treatment residual platelet activity.

Interaction between access choice and pharmacotherapy for coronary intervention: the results of a UK survey.

INTRODUCTION: Percutaneous coronary intervention (PCI) has changed significantly over the past decade with the uptake of radial access and the development of newer and more potent antiplatelets and safer antithrombins. This survey examined the default access route and pharmacology choice and their interaction in UK interventional practice. METHODS: An email-based survey invited interventional cardiologists to answer questions regarding arterial access and pharmacology use during PCI. Respondents were categorised into femoral, radial and radial(+) (if the other radial was used rather than femoral if the right radial attempt failed). Data were analysed using χ(2) or the Student t test. RESULTS: 81% of the 204 respondents reported the radial artery as their default access site with a significant interaction between years since qualification and access choice (21.1 years for radial(+) vs 23 years for radial (p=0.027) vs 26.6 years for femoral (p=0.013) vs radial (p=0.0005) vs radial(+)). There were 19 different combinations of access and pharmacology reported. For non-ST elevation myocardial infarction PCI, there was a significant trend for radial(+) and radial operators to favour ticagrelor or tailored therapy versus femoral operators (54.8% vs 47.8% vs 35%, respectively, p=0.018). For primary PCI (PPCI), radial(+) and radial operators were much more likely to choose ticagrelor or prasugrel than femoral operators (77.2% (p<0.001) vs 73.9% (p=0.023) vs 50%, respectively (p<0.0001) for trend). For PPCI, glycoprotein inhibitor use was similar between groups (26.1% vs 25%, not significant); radial operators were much more likely to choose bivalirudin (52.8% vs 10%, p<0.0001) and much less likely to use heparin only (19.8% vs 65%, p<0.0001) than femoral operators. CONCLUSIONS: There is a significant interaction between years since qualification and access choice. Although there is no established consensus on access site or drugs, default radial operators are significantly more likely to utilise new generation antiplatelets and bivalirudin than femoral operators.

Switching from transfemoral to transradial access for PCI: a single-center learning curve over 5 years.

BACKGROUND: Percutaneous coronary intervention (PCI) via the transradial (TR) route is an increasingly popular alternative to the transfemoral (TF) route. However, there are limiting factors to its adoption. We report the learning curve over 5 years in a high-volume PCI center during the crossover from TF to TR access for PCI. OBJECTIVE: To evaluate clinical characteristics, radiation doses, screening times, and subsequent clinical outcomes in subjects with femoral and radial access sites for PCI. DESIGN: We retrospectively analyzed our databases for PCI procedures/outcomes of all patients from 2006-2010. SETTING: A university teaching hospital PCI center performing cases predominantly femorally at the beginning of the study period, and transitioning to a predominantly radial access center at the end of the study period. PATIENTS: All patients undergoing PCI via either femoral or radial approach over a 5-year period. RESULTS: In year 1, TR access was used in 31.4% of cases; this rate increased to 90.1% in year 5. The switch from TF to TR access was observed among all operators and all groups of patients regardless of presentation, gender, age, and lesion complexity. In year 1, fluoroscopy times and radiation doses were higher in the TR group, but equalized in years 2 and 3 and reversed during years 4 and 5 when the TR rate was >90%. Over 5 years, the rates of vascular complications and major bleeding were higher in the TF cohort and were associated with longer hospital stay. In-hospital mortality was lower in the TR group. CONCLUSION: The change from TF to TR approach for PCI in a high-volume center is achievable within 5 years, and results in marked clinical benefits. There was an initial learning curve for fluoroscopy time and radiation dose, but this improved once an operator performed >60% of cases radially.

Saphenous vein graft percutaneous coronary intervention via radial artery access: safe and effective with reduced hospital length of stay.

BACKGROUND: Although percutaneous coronary intervention (PCI) via radial artery access confers many advantages over the femoral artery, PCI to saphenous vein grafts (SVG) is commonly performed via the femoral route. We compared outcomes in patients undergoing SVG PCI from the radial and femoral routes. METHODS: We performed a retrospective analysis of patients who underwent SVG PCI between January 2006 and December 2010 in 2 large interventional centers in the United Kingdom. All radial and femoral operators selected for this analysis performed high-volume (>200 PCIs per year) procedures via either vascular route. RESULTS: Of 305 patients (260 males) who underwent SVG PCI, 208 (68.2%) had the procedure completed from the femoral route and 97 (32.8%) radially. There was no difference between groups in fluoroscopy time (femoral vs radial 1095 vs 1125 seconds, P nonsgnificant), but radiation doses were greater (43.87 ± 2.83 Gy/cm(2) vs 56.92 ± 4.52 Gy/cm(2), P = .012) as was body mass index in the radial group (27.99 ± 0.33 vs 29.05 ± 0.42, P = .048). Three femoral access patients had vascular access complications, whereas the radial route group had none. There were no differences in no flow/slow flow (femoral 3.86% vs radial 2.54%, P nonsignificant). The mean length of hospital stay was significantly shorter in the radial access cohort (1.09 vs 2.09 days, P < .001). Three patients converted from radial to femoral artery, whereas one converted from femoral to radial after technical failure to complete the procedure. CONCLUSION: Saphenous vein graft PCI can be safely and effectively performed via radial artery access with comparable fluoroscopy times but not radiation doses. Of clinical significance, use of the radial artery access was associated with decreased hospital stay and arterial complications. These data suggest that a routine radial approach for SVG PCI is feasible and could offer clinical and economic benefits.

Outcomes following PCI in patients with previous CABG: a multi centre experience.

BACKGROUND: Limited data is available to guide operators as to the optimal revascularisation strategy in patients with previous CABG representing with angina. METHOD: Retrospective analysis of 161 patients with prior CABG undergoing PCI in two centres between September 2005 and April 2008. RESULTS: 161 patients (132 male, 68 ± 8 years) underwent PCI at 126 ± 65 months after index CABG. Clinical presentation of recurrent ischaemia was stable in 59.7% and as an acute coronary syndrome in 40.3% of patients. Mean follow-up after PCI was 13.5 ± 4.8 months. About 62.7% of patients underwent native vessel PCI, 32.9% had a graft only PCI, and 4.4% having a combination of both. Drug eluting stents were used in 84.9% of cases. There was one cardiac death and one case of redo CABG during follow-up. Mean CCS angina class decreased from 2.87 to 0.67 (P < 0.0001) in the follow-up group. About 13.6 % of all patients had a MACE at follow up. This was higher in the graft PCI group (21.6% vs. 8.9%, P = 0.048). About 12.4% of the total cohort underwent repeat PCI although 30% of these required PCI for a de-novo lesion. TVR rate was significantly higher in patients undergoing graft PCI than native vessel PCI (15% vs. 4.9%, P = 0.031). Graft PCI was an independent predictor (HR 3.73, 1.27-10.87 [95%CI], P = 0.016) of MACE in these patients. CONCLUSION: PCI significantly improved angina in these patients with low overall rates of TVR. However TVR rate was significantly higher in patients undergoing graft PCI than those undergoing native vessel PCI.

The potential role of resistin in atherogenesis.

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.

Transesophageal echocardiography to guide pulmonary vein mapping and ablation for atrial fibrillation.

BACKGROUND: This study describes the use and outcomes of transesophageal echocardiography to guide atrial fibrillation (AF) ablation procedures. METHODS: Under general anesthesia, 25 patients with a history of AF underwent multiplane transesophageal echocardiography in conjunction with catheter placement under fluoroscopy. RESULTS: In this series, a combined fluoroscopic/echocardiographic approach obviated the need for angiographic imaging. Anatomic variation in pulmonary veins (PV) was common; the shortest distance between the ostia ranged from 2 to 11 mm. Individual PV diameters did not predict the presence of ectopic foci. The number of radiofrequency pulses delivered per vein was 2.6 +/- 2.3 (range: 0-10). Mean fluoroscopy time per procedure was 31 +/- 13 minutes and mean procedure time was 110 +/- 31 minutes. At follow-up, 68% of patients were free from AF. CONCLUSIONS: Transesophageal echocardiography enables identification and cannulation of the ostia and proximal branches of PV during AF ablation. Fluoroscopy, procedure times, and outcomes compare favorably with series using PV angiography and, as such, suggest that a controlled trial is warranted.

Murine cytomegalovirus infection increases aortic expression of proatherosclerotic genes.

BACKGROUND: The possible etiologic role of infection in cardiovascular disease is still debated. Having previously demonstrated that murine cytomegalovirus (MCMV) infection of apolipoprotein (apo) E-/- mice increases atherosclerotic lesion size, we determined if MCMV infection produces proatherogenic changes in aortic gene expression. Additionally, in cholesterol-fed C57BL/6J mice, we examined the effects of MCMV infection on aortic lesion area. METHODS AND RESULTS: C57BL/6J apoE-/- and wild-type C57BL/6J mice were infected with MCMV. At various time points, aortas were collected and pooled. Total RNA was extracted and hybridized to Affymetrix murine chips or analyzed for specific gene expression using TaqMan reverse transcription-polymerase chain reaction. Data from infected and uninfected mice were compared. A separate group of cholesterol-fed C57BL/6J mice were infected with MCMV, and lesion area in the aortic sinus was assessed using oil red O staining. Acute MCMV infection altered aortic expression of atherogenic genes in young apoE-/- and C57BL/6J mice-specifically, monocyte chemoattractant protein-1, monokine induced by interferon-gamma, and interferon-gamma inducible protein 10. Acute infection in adult 9-month-old apoE-/- mice with well-established lesions increased aortic expression of monocyte chemoattractant protein-1. Atherosclerotic lesion area in cholesterol-fed C57BL/6J mice was increased after infection with MCMV. CONCLUSIONS: MCMV infection significantly increases atherosclerotic lesion area and aortic expression of atherogenic genes. These infection-induced effects indicate mechanisms by which cytomegalovirus may contribute to atherosclerotic disease initiation and progression and to the precipitation of clinical events. These results additionally add to data compatible with the concept that infection does play an important role in atherosclerotic disease.

Edge-to-edge repair for functional mitral regurgitation: an echocardiographic study of the hemodynamic consequences.

BACKGROUND AND AIM OF THE STUDY: The study aim was to characterize changes in mitral valve area and flow, and left ventricular (LV) size and function, following edge-to-edge (E-E) repair for severe functional mitral regurgitation (MR). The possibility that preoperative dobutamine stress echocardiography (DSE) might be used to predict post-repair recovery in LV function was also examined. METHODS: Seventeen patients underwent preoperative transthoracic echocardiography (TTE) and DSE, intraoperative transesophageal echocardiography, and three-month postoperative TTE. RESULTS: After repair, mitral valve area was reduced from 8.5 +/- 1.9 cm2 to 3.8 +/- 0.9 cm2 by planimetry (p < 0.0001) and to 2.9 +/- 0.9 cm2 by pressure half-time. Valve area by pressure half-time correlated with the planimetered area (r = +0.55), but was consistently lower (p = 0.004). Sixxteen of 17 patients had mean transmitral gradients <5 mmHg. Postoperative LV end-diastolic diameter improved from 72 +/- 11 to 64 +/- 10 mm (p < 0.01), and end-systolic diameter from 56 +/- 14 to 46 +/- 12 mm (p < 0.05). Mean ejection fraction improved from 25 +/- 12% before repair to 38 +/- 17% after repair (p < 0.02) in patients with evidence of LV function improvement on DSE, but was unchanged (15 +/- 5% versus 17 +/- 5%, p = NS) in patients without evidence of improvement. Postoperatively, 13 patients had no or mild MR, and two patients had moderate MR. There was one perioperative death. CONCLUSION: E-E repair, in combination with ring annuloplasty, reduces LV cavity dimensions and functional MR severity, without causing significant valve stenosis. Improvement on DSE may predict those patients in whom EF will improve following repair.