Michael Koutouzis

Unfractionated heparin administration in patients treated with bivalirudin during primary percutaneous coronary intervention is associated lower mortality and target lesion thrombosis: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

Background Bivalirudin reduces bleeding events and is associated with a lower mortality than the combination of unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitor during primary percutaneous coronary intervention (PCI). However, the effect of adding UFH in patients with ST elevation myocardial infarction (STEMI) treated with bivalirudin during primary PCI is unknown. Methods Patients enrolled in the national Swedish Coronary Angiography and Angioplasty Registry who underwent primary PCI due to STEMI with bivalirudin as anticoagulant were evaluated. Patients were divided into two groups: those treated with bivalirudin only and those treated with bivalirudin plus a bolus dose of UFH. Results 2996 patients were included in the study: 1928 (64%) received only bivalirudin and 1068 (36%) received bivalirudin plus a bolus dose of UFH. The primary combined endpoint of death or target lesion thrombosis at 30 days occurred more often in the bivalirudin group (11.3% vs 6.5%, OR 0.55, 95% CI 0.41 to 0.72, p<0.001). This difference remained significant after adjustment (HR 0.64, 95% CI 0.44 to 0.95, p=0.03). Death at 30 days and definite target lesion thrombosis at 30 days did not differ between the two groups after adjustment (9.2% vs 5.1%, adjusted HR 0.66, 95% CI 0.42 to 1.03, p=0.07 and 2.3% vs 1.5%, adjusted HR 0.59, 95% CI 0.27 to 1.33, p=0.21, respectively). Conclusion An additional bolus dose of UFH is associated with a lower rate of death or definite target lesion thrombosis at 30 days in patients undergoing primary PCI with bivalirudin as anticoagulant.

Primary Percutaneous Coronary Interventions in Nonagenarians

The optimal treatment of very elderly patients with ST elevation myocardial infarction (STEMI) is not yet defined. The aim of this study is to present the feasibility and safety of primary percutaneous coronary interventions (PCI) in nonagenarians.

Radial vs. femoral approach for primary percutaneous coronary intervention in octogenarians

BACKGROUND The transradial approach is associated with fewer bleeding complications during percutaneous coronary interventions (PCIs) but is more technically challenging and associated with prolonged times during intervention. The aim of this study is to retrospectively compare the results of radial vs. femoral approach in patients >or=80 years old undergoing primary or rescue PCI. METHODS Between January 2002 and December 2007, 354 interventions were performed in our institution with the indication of primary or rescue PCI in patients over 80 years old, without history of previous bypass operation or cardiogenic shock on presentation. Thirteen patients required a change of the approach during the procedure and were not enrolled in the final analysis. Forty (12%) interventions were performed through the transradial approach and 301 (88%) through the femoral approach. In-hospital major adverse cerebral and cardiac events and access site bleeding complications as well as 30- and 365-day mortality, procedural times, and contrast volume were evaluated. RESULTS The two groups had similar clinical characteristics, with the exception of serum creatinine that was higher in the transfemoral approach group. There were no differences in procedural times and clinical outcomes, although the transfemoral group had numerically more access site bleeding complications (12/301 vs. 0/40, P=.41). The transradial approach had a higher conversion rate compared with the transfemoral approach (18.3% vs. 1.3%, P<.001). CONCLUSION The transradial approach is feasible and safe in the octogenarians undergoing primary and rescue PCI, but it is associated with a high conversion rate to another approach.

Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart

Objectives Sildenafil may be beneficial during myocardial ischaemia/reperfusion, but this effect may be dose‐dependent, accounting for previous conflicting results. We have explored the effects of two acute and one chronic administration regimen on left ventricular function.

Statin treatment, carotid atherosclerotic plaque macrophage infiltration and circulating inflammatory markers.

Backround Statin treatment is considered as first line therapy in patients with atherosclerotic disease. We evaluated the effect of pre-treatment with statins on carotid plaque infiltration by macrophages and on the circulating levels of proinflammatory cytokines in patients who underwent carotid endarterectomy. Patients and Methods One hundred fourteen patients were enrolled; 89 men and 25 women (mean age 67±8 years; range 42-83 years). Fifty three patients (46%) were on statin treatment at least 3 months before endarterectomy and 61 (54%) had never received statin treatment. The serum levels of high sensitivity C reactive protein (hsCRP), serum amyloid A (SAA), tumor necrosis factor α (TNFα), interleukin (IL)-1β and IL-6 were evaluated preoperatively. The intensity of macrophage infiltration was evaluated by immunochemistry, using the monoclonal antibody CD 68. The area of the plaque covered by macrophages was measured as a proportion of the whole plaque area, using a custom designed image tool analysis. Results Patients on statins had lower serum total cholesterol levels (172±50 vs 194±35 mg/dl, p= 0.014), lower low density cholesterol levels (103±44 vs 123±31 mg/dl, p= 0.010) and lower serum hsCRP levels (1.8 [1.1-3.4] vs 3.4 [1.3-4.9] mg/l, p= 0.03), while SAA, TNFα, IL-6 and IL-1β levels did not differ between the 2 groups. The infiltration of atherosclerotic plaque by macrophages was similar in statin treated patients and in controls (0.55±0.15% vs 0.49±0.19%, p= 0.21). Conclusion Patients on statins have similar macrophage accumulation in their carotid atherosclerotic plaques compared with patients not on statins. Inflammatory markers were also similar in both groups except for hsCRP which was significantly lower in those taking statins.

Serum leptin levels in patients undergoing carotid endarterectomy: a pilot study.

Introduction: Elevated serum leptin levels are associated with cardiovascular events. We investigated the role of serum leptin in patients undergoing carotid endarterectomy (CEA). Methods: A total of 74 patients (55 men; 38 symptomatic and 36 asymptomatic; mean age 66.9 ± 8.2 years) undergoing CEA for >70% carotid artery stenosis were enrolled. Results: Serum leptin levels were lower in symptomatic compared with asymptomatic patients (7.1 ± 1.3 vs 14.4 ± 4.7 ng/dL; P < .001). Interleukin-6 (IL-6) levels were higher in symptomatic compared with asymptomatic patients (4.3 ± 1.7 vs 3.3 ± 1.1 pg/dL; P = .017). Symptomatic patients had more intense macrophage accumulation (0.7% ± 0.1% vs 0.3% ± 0.1%; P < .001). Serum leptin and serum IL-6 levels were independently associated with the presence of symptoms in multivariate analysis. Conclusion: Serum leptin levels were decreased in symptomatic carotid artery disease. This finding requires further investigation in larger studies.

Chronic skeletal muscle ischemia preserves coronary flow in the ischemic rat heart

Chronic skeletal muscle ischemia confers cytoprotection to the ventricular myocardium during infarction, but the underlying mechanisms remain unclear. Although neovascularization in the left ventricular myocardium has been proposed as a possible mechanism, the functional capacity of such vessels has not been studied. We examined the effects of chronic limb ischemia on infarct size, coronary blood flow, and left ventricular function after ischemia-reperfusion. Hindlimb ischemia was induced in 65 Wistar rats by excision of the left femoral artery, whereas 65 rats were sham operated. After 4 wk, myocardial infarction was generated by permanent coronary artery ligation. Infarct size was measured 24 h postligation. Left ventricular function was evaluated in isolated hearts after ischemia-reperfusion, 4 wk after limb ischemia. Neovascularization was assessed by immunohistochemistry, and coronary flow was measured under maximum vasodilatation at different perfusion pressures before and after coronary ligation. Infarct size was smaller after limb ischemia compared with controls (24.4 ± 8.1% vs. 46.2 ± 9.5% of the ventricle and 47.6 ± 8.7% vs. 80.1 ± 9.3% of the ischemic area, respectively). Indexes of left ventricular function at the end of reperfusion (divided by baseline values) were improved after limb ischemia (developed pressure: 0.68 ± 0.06 vs. 0.59 ± 0.05, P = 0.008; maximum +dP/dt: 0.70 ± 0.08 vs. 0.59 ± 0.04, P = 0.004; and maximum -dP/dt: 0.86 ± 0.14 vs. 0.72 ± 0.10, P = 0.041). Coronary vessel density was markedly higher (P = 0.00021) in limb ischemic rats. In contrast to controls (F = 5.65, P = 0.00182), where coronary flow decreased, it remained unchanged (F = 1.36, P = 0.28) after ligation in limb ischemic rats. In conclusion, chronic hindlimb ischemia decreases infarct size and attenuates left ventricular dysfunction by increasing coronary collateral vessel density and blood flow.

CD36 Is Significantly Correlated with Adipophilin in Human Carotid Lesions and Inversely Correlated with Plasma ApoAI

OxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study investigates genes implicated in OxLDL uptake (CD36, SRA), cholesterol efflux inhibition (adipophilin, ADFP), and inflammatory recruitments of leukocytes (IL-8) in plaque lesion areas (PLAs) compared to nonplaque lesion areas (NPLAs) in human carotid endarterectomy specimens. Gene and protein expressions were assayed using quantitative PCR and quantitative immunohistochemistry. Pearson tests were used to investigate potential correlation between (a) different gene expressions and (b) gene expression and patients plasma constituents. CD36, SRA, ADFP, and IL-8 were shown to be significantly more expressed in PLA compared to NPLA. In PLA, a significant correlation was observed between CD36, SRA, ADFP, and IL-8 mRNA levels. Moreover, CD36 expression level was significantly inversely correlated to plasma marker ApoAI. The above investigated genes/proteins may play a key role in the maturation of atherosclerotic lesions.

Long-term results following switch from abciximab to eptifibatide during percutaneous coronary intervention.

The usage of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors improves the outcome during high‐risk percutaneous coronary interventions (PCI). The aim of this study was to evaluate the long‐term effects after a planned switch from abciximab to eptifibatide during PCI.

Intravenous Esmolol is Well Tolerated in Elderly Patients with Heart Failure in the Early Phase of Non-ST Elevation Myocardial Infarction

AimTo investigate the haemodynamic response to and clinical safety and tolerability of intravenous esmolol (Brevibloc®, Baxter Healthcare Corporation, Deerfield, Illinois, USA) in elderly and younger patients with acute non-ST elevation myocardial infarction (NSTEMI) and heart failure.Patients and methodsWe studied 24 consecutive patients, 12 of them elderly (≥75 years old) and 12 younger (32–74 years old), with NSTEMI and symptoms of heart failure on presentation. After stabilisation of the patient’s condition with standard therapy, intravenous esmolol was administered. An infusion rate of 0.05 mg/kg/min for 30 minutes was instituted and, if no adverse effects developed, this was increased to 0.20 mg/kg/min. All haemodynamic parameters were measured before and at the end of each administration using a Swan-Ganz catheter.ResultsOnly one patient in the elderly subgroup did not tolerate the augmented infusion rate (because of severe bradycardia) and so had to return to the initial lower infusion rate. The cardiac index (mean ± SD) was 2.4 ± 0.9 L/min/m2 at baseline and decreased to 1.9 ± 0.4 L/min/m2 (p < 0.05 vs baseline) at the end of the administration of the second dose of esmolol in the elderly patients and 2.6 ± 0.5 L/min/m2 and 2.2 ± 0.5 L/min/m2 (p < 0.05 vs baseline), respectively, in the younger patients. Mean pulmonary wedge pressure was 17 ± 6mm Hg at baseline and increased to 19 ± 4mm Hg (p < 0.05 vs baseline) at the end of the second dose of esmolol in the elderly patients and 16 ± 10mm Hg and 18 ± 10mm Hg (p < 0.05 vs baseline), respectively, in the younger patients. The response of both age groups to esmolol was the same for all of the parameters examined.ConclusionIntravenous esmolol was safe and well tolerated in the early phase of NSTEMI in patients presenting with symptoms of heart failure and ongoing ischaemia, regardless of their age.