Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI). AIM: We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor. METHODS: We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding. RESULTS: For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64). CONCLUSION: Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.

Pre-treatment with dual antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Although dual antiplatelet therapy is the standard of care in non-ST-segment elevation acute coronary syndromes (NSTEACS), it remains unclear when a second antiplatelet agent should be initiated. We sought to assess the safety and efficacy of pre-treatment with clopidogrel in patients with NSTEACS undergoing percutaneous coronary intervention (PCI). METHODS: We analysed baseline clinical and procedural characteristics of 6817 patients with NSTEACS who underwent PCI from the Melbourne Interventional Group registry from 2005 to 2012. Patients were included in the pre-treatment group if clopidogrel was administered prior to cardiac catheterisation. We assessed 30-day mortality, myocardial infarction (MI) and major adverse cardiovascular events. The safety endpoint was in-hospital bleeding. RESULTS: Of the 6817 patients, only 2951 (43%) received pre-treatment with clopidogrel. Patients in the pre-treatment group were more likely to present with unstable angina (70.8% vs 68.2%, P = 0.02) and have a history of MI (35.6% vs 23.6%, P < 0.01) but were less likely to have PCI within 24 h of admission (17.2% vs 25.2%, P < 0.01). There was no difference between the groups in 30-day mortality (0.9% vs 1.4%, P = 0.06), MI (2.0% vs 2.2%, P = 0.52) or major adverse cardiovascular event (3.7% vs 4.2%, P = 0.25). There was no difference in bleeding complications (1.9% vs 1.9%, P = 0.94). CONCLUSIONS: Pre-treatment with dual antiplatelet therapy in NSTEACS is not routine clinical practice in Australia. Pre-treatment appears safe but is not associated with improved short-term clinical outcomes.

Interleukin-17 Expression in the Barrett's Metaplasia-Dysplasia-Adenocarcinoma Sequence.

Introduction. This pilot study evaluated the expression of the proinflammatory cytokine IL-17 along the Barrett's metaplasia-dysplasia-adenocarcinoma sequence by establishing the expression levels of IL-17 in columnar epithelium, intestinal metaplastic cells, and dysplastic/glandular neoplastic cells. Immunohistochemical techniques were used to examine the accumulation of the proinflammatory cytokine IL-17 in forty (n = 40) formalin-fixed, paraffin-embedded oesophageal archived specimens across a range of endoscopic diagnostic categories, and a highly significant difference was found, where P ≤ 0.001, in IL-17 expression (Kruskall Wallis and Mann-Whitney U) between all the cell types examined. There was also a strong positive correlation (Spearman's rank correlation) between disease progression and IL-17 expression (r s = 0.883, P < 0.001, n = 29), IL-17 expression was absent or absent/weak in columnar epithelium, weak to moderate in columnar metaplastic cells, and moderate to strong in dysplastic/neoplastic cells, which demonstrated that the elevation of IL-17 expression occurs in the progression of the disease. Understanding the differential expression of IL-17 between benign and malignant tissue potentially has a significant diagnostic, prognostic, and therapeutic value. Ultimately, this selective biomarker may be employed in routine clinical practice for the screening of oesophageal adenocarcinoma.

Five-minute heart rate variability can predict obstructive angiographic coronary disease.

OBJECTIVE: Obstructive coronary artery disease (CAD) is evident in only half of patients referred for diagnostic angiography. Five-minute heart rate variability (HRV) is a non-invasive marker for autonomic control of the vasculature, which this study hypothesised could risk-stratify cardiac patients and reduce unnecessary angiograms. DESIGN: A prospective observational study (the Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study). SETTING: Three cardiac centres in Melbourne, Australia. PATIENTS: 470 consecutive patients undergoing elective angiography (with predominantly normal cardiac rhythm), regardless of co-morbidity. MAIN OUTCOME MEASURES: The presence of obstructive CAD (≥50% stenosis) on angiography. RESULTS: Patients with obstructive CAD had significantly reduced HRV, particularly in the low frequency (LF) range (median 180 vs 267 ms(2) without CAD; p<0.001). There was a linear trend with the severity of CAD; median LF power (IQR) in patients with normal coronaries was 275 (612), with minor coronary irregularities 255 (400), single-vessel CAD 212 (396) and more severe disease 170 (327) ms(2); p value for trend 0.003. There was a similar reduction in LF power regardless of the anatomical location of coronary stenoses. Comparing patients with LF less than 250 and 250 ms(2) or greater, the adjusted OR for obstructive CAD using multivariate regression was 2.42, 95% CI 1.33 to 4.38 (p=0.004). No interactions were noted in subgroup analysis and HRV added to risk prediction irrespective of the baseline Framingham risk (p<0.0001). CONCLUSION: Low HRV is strongly predictive of angiographic coronary disease regardless of other co-morbidities and is clinically useful as a risk predictor in patients with sinus rhythm. CLINICAL TRIAL REGISTRATION INFORMATION: http://clinicaltrials.gov/ct2/show/NCT00403351 www.armcad.com.

Clinical outcomes of drug-eluting stent use in patients with ST elevation myocardial infarction.

AIM: Randomised trials using drug-eluting stents (DES) in ST elevation myocardial infarction (STEMI) have shown mixed results, and excluded patients at the highest risk of adverse outcomes. We aimed to determine the real world clinical outcomes of DES and compare these with bare-metal stents (BMS) in an unrestricted observational study of patients presenting with STEMI. METHODS: 564 consecutive patients undergoing primary PCI for STEMI were prospectively enrolled in the Melbourne Interventional Group registry (August 2004 to May 2006). The choice of using DES was at the operator's discretion, yet restricted to patients considered at highest risk of restenosis [e.g. diabetes, long lesions (>20 mm) and small target vessels (<2.5 mm)]. Clinical, procedural, and 12-month outcomes of patients receiving DES were evaluated and compared to BMS. RESULTS: DES were used in 45% of patients presenting with STEMI. The rates of cardiogenic shock were similar in the DES and BMS groups (10.2 vs. 11%, p=0.71). In-hospital outcomes were not significantly different with respect to death (4.7 vs. 7.2%, p=0.23), major adverse cardiac events (MACE) (10.6 vs. 11.3%, p=0.80) or stent thrombosis (1.7 vs. 0.3%, p=0.71). At 12 months, target vessel revascularisation (TVR) in patients with DES was 10.2% vs. 7.2% in BMS (p=0.22). On propensity score adjusted multivariate analyses, the only independent predictor of 12-month MACE was presentation with cardiogenic shock (OR 2.59, 95% C.I 1.04-6.45), and the only predictor of 12-month TVR was reference vessel diameter ≤2.5 mm (OR 2.16, 95% C.I 1.06-4.33). DES use was not independently predictive of lower TVR, MACE rates or mortality. Late stent thrombosis rates were similar (DES 3.2 vs. BMS 3.8%, p=0.65). CONCLUSIONS: Drug-eluting stents are frequently used in Australia in the high-risk setting of STEMI. While target vessel revascularisation rates were moderate in this high-risk group, there was no increased mortality, reinfarction or stent thrombosis compared to bare-metal stents.

Diagnostic accuracy of 16-slice CT coronary angiography in the evaluation of coronary artery disease.

Multislice CT coronary angiography (CT-CA) has emerged as a potential imaging method for coronary artery disease. This study aimed to ascertain the accuracy of 16-slice CT in the diagnosis of significant coronary stenosis (>or=50% reduction of lumen diameter). This mixed retrospective/prospective observational study compared 95 paired 16-slice CT-CA and fluoroscopic coronary angiography (FCA) sets. A cardiologist and a radiologist blinded to the FCA findings evaluated CT-CA images independently by visual estimation. Disagreement between these reporters was arbitrated by a third CT reporter (a cardiologist). A separate cardiologist blinded to CT-CA findings assessed FCA by visual estimation. Of 1,161 coronary segments assessable on FCA, 1,103 segments (95%) were assessable on CT-CA. The CT-CA correctly diagnosed 147/180 segments with significant stenoses (sensitivity = 82%) and correctly identified 874/923 coronary segments without significant stenoses (specificity = 95%). The positive and negative predictive values of CT-CA in the diagnosis of coronary segment with significant stenosis were 75 and 96%, respectively. On patient-based analysis, CT-CA correctly identified all 68 studies with at least one vessel with significant stenosis (sensitivity = 100%; specificity = 83%). The positive and negative predictive values of CT-CA in identifying patients with significant coronary stenosis were 94 and 100%, respectively. The 16-slice CT-CA showed moderately good sensitivity but very high specificity and negative predictive value in the diagnosis of significant coronary stenosis. The CT-CA would appear to be a useful 'rule-out' test for patients with low-risk profile for ischaemic heart disease.

Determining the proportion of coronary segments assessable on 16-slice CT coronary angiography: a brief report.

Computed tomography coronary angiography (CT-CA) is becoming a popular non-invasive coronary imaging method. We aimed to determine the proportion of coronary segments assessable on a 16-slice CT in comparison with conventional selective coronary angiography (SCA). We identified all patients who had both 16-slice CT-CA and recent SCA (less than 12 months) from March 2004 to July 2005. Two CT reporters blinded to SCA independently classified coronary segment assessability on CT-CA. A cardiologist blinded to CT findings classified assessability of coronary segments on SCA. Data were analysed using descriptive statistics and proportion of agreement. Ninety-five study pairs were included in the analysis. Of those, 1161 coronary segments were deemed assessable on SCA and 1103 segments (95%) were also assessable on CT-CA. Nonassessable segments on CT-CA were predominantly in the distal segments and branches of coronary arteries. Reasons for nonassessability were small calibre (48.3%), motion artefacts (20.7%) and poorly reconstructed segments (22.4%). The 16-slice CT was able to assess a high proportion of but not all coronary segments. Nonassessable segments were predominantly distal segments or branches of coronary arteries. Motion artefacts due to heart-rate changes, small calibre and poorly reconstructed images were main causes of nonassessability on 16-slice CT-CA.

Metformin prolongs the postprandial fall in plasma ghrelin concentrations in type 2 diabetes.

BACKGROUND: Weight loss is difficult to achieve in type 2 diabetes and many therapies are associated with weight gain, an effect attenuated by metformin. We studied the effects of metformin on energy expenditure, appetite and the regulation of PYY and ghrelin in type 2 diabetes. METHODS: Plasma peptide YY (PYY), ghrelin, resting metabolic rate (RMR), postprandial thermogenesis (PPTG), and appetite ratings were measured at baseline and following a mixed meal in 11 type 2 diabetic subjects treated with diet alone (T2D) and 10 treated with metformin monotherapy (T2MF). The groups were similar in age, gender and adiposity. RESULTS: There were no differences in baseline anthropometric, or metabolic variables between the groups. Postprandially, plasma ghrelin fell equally in both groups (23% versus 24.5%, p < 0.05 versus baseline, p = NS between groups) but were reduced for longer in T2MF (below baseline 60-240 min T2MF versus 60-180 min T2D) coincidentally with a prolonged sensation of fullness and suppression of hunger in the metformin-treated group. There were no differences in PYY concentrations, RMR or PPTG. CONCLUSIONS: Metformin prolongs the postprandial fall in ghrelin concentrations. These effects may prolong the inter-meal interval, thereby decreasing snack intake and daily energy intake, promoting weight loss.

The foundation and launch of the Melbourne Interventional Group: a collaborative interventional cardiology project.

The Melbourne Interventional Group (MIG) is a voluntary collaborative venture of interventional cardiologists practicing at 12 major public and private hospitals in Victoria, designed to record data pertaining to percutaneous coronary interventions (PCI) and perform long-term follow-up. The potential advantages of collaboration involve large-scale analysis of current interventional strategies (e.g. drug-eluting stents, evaluation of new technologies and cost-effective analysis), provide a basis for multi-centred clinical trials and allow comparison of clinical outcomes with cardiac surgery. The established registry documents demographic, clinical and procedural characteristics of consecutive patients undergoing PCI and permits analysis of those characteristics at 30 days and 12 months. The registry is co-ordinated by the Centre of Clinical Research Excellence (CCRE), a research body within the Department of Epidemiology and Preventive Medicine (Monash University, Melbourne). The eventual goal of MIG is to provide a contemporary appraisal of Australian interventional cardiology practice, with opportunities to improve in-hospital and long-term outcomes of patients with coronary artery disease.

Results of the study to determine rotablator and transluminal angioplasty strategy (STRATAS).

Rotational atherectomy is used to debulk calcified or complex coronary stenoses. Whether aggressive burr sizing with minimal balloon dilation (<1 atm) to limit deep wall arterial injury improves results is unknown. Patients being considered for elective rotational atherectomy were randomized to either an "aggressive" strategy (n = 249) (maximum burr/artery >0.70 alone, or with adjunctive balloon inflation < or = 1 atm), or a "routine" strategy (n = 248) (maximum burr/artery < or =0.70 and routine balloon inflation > or =4 atm). Patient age was 62 +/- 11 years. Fifty-nine percent routine and 60% aggressive strategy patients had class III to IV angina. Fifteen percent routine and 16% aggressive strategy patients had a restenotic lesion treated; lesion length was 13.6 versus 13.7 mm. Reference vessel diameter was 2.64 mm. Maximum burr size (1.8 vs 2.1 mm), burr/artery ratio (0.71 vs 0.82), and number of burrs used (1.9 vs 2.7) were greater for the aggressive strategy, p <0.0001. Final minimum lumen diameter and residual stenosis were 1.97 mm and 26% for the routine strategy versus 1.95 mm and 27% for the aggressive strategy. Clinical success was 93.5% for the routine strategy and 93.9% for the aggressive strategy. Creatine kinase-myocardial band (CK-MB) was >5 times normal in 7% of the routine versus 11% of the aggressive group. CK-MB elevation was associated with a decrease in rpm of >5,000 from baseline for a cumulative time >5 seconds, p = 0.002. At 6 months, 22% of the routine patients versus 31% of the aggressive strategy patients had target lesion revascularization. Angiographic follow-up (77%) showed minimum lumen diameter to be 1.26 mm in the routine group versus 1.16 mm in the aggressive group, and the loss index 0.54 versus 0.62. Dichotomous restenosis was 52% for the routine strategy versus 58% for the aggressive strategy. Multivariable analysis indicated that left anterior descending location (odds ratio 1.67, p = 0.02) and operator-reported excessive speed decrease >5,000 rpm (odds ratio 1.74, p = 0.01) were significantly associated with restenosis. Thus, the aggressive rotational atherectomy strategy offers no advantage over more routine burr sizing plus routine angioplasty. Operator technique reflected by an rpm decrease of >5,000 from baseline is associated with CK-MB elevation and restenosis.

Impact of early percutaneous coronary intervention on short- and long-term outcomes in patients with cardiogenic shock after acute myocardial infarction.

This study assesses the impact of early percutaneous coronary intervention in patients presenting with cardiogenic shock after acute myocardial infarction. Predictors of in-hospital death include the need for intubation, cardiopulmonary resuscitation, and angiographic failure; long-term outcomes at 2 years in hospital survivors are favorable.

Raised levels of plasma interleukin-1beta in major and postviral depression.

OBJECTIVE: Interleukin-1beta (IL-1beta) is released as part of the acute phase immune response and can directly stimulate the release of corticotrophin-releasing hormone and thus induce hypothalamic pituitary adrenal axis hyperactivity. Major depression has been shown to be accompanied by both an acute phase immune response, including raised IL-1beta production and hypothalamic pituitary adrenal axis hyperactivity. In this study the possible role of IL-1beta in major depression and postviral depression was investigated. METHOD: Plasma IL-1beta levels were measured in four groups; patients suffering from postviral depression (n= 17), patients with major depression (n = 20), subjects who were postviral and euthymic (n= 12) and normal controls (n = 20). RESULTS: IL-1beta serum concentrations were significantly elevated in both groups of depressed patients compared to controls. The serum concentrations of IL-1beta were higher in the postviral group than in the major depression group; this difference was not significant. CONCLUSION: These data confirm previous suggestions of elevated IL-1beta levels in major depression and postviral depression. IL-1beta is known to induce depressive symptoms as well as sickness behaviour and may contribute to the hypothalamic pituitary adrenal axis hyperactivity found in mood disorders.

Cerebral white matter lesions in bipolar affective disorder: relationship to outcome.

BACKGROUND: Twenty per cent of patients with bipolar affective disorder suffer an illness that responds inadequately to treatment and has a poor outcome. Many patients, but not all, with bipolar disorder show white matter abnormalities on T(2)-weighted magnetic resonance imaging (MRI). AIMS: To explore the hypothesis that white matter abnormalities on MRI are seen more frequently in subjects whose illness has a poor outcome compared with those with a good outcome or controls. METHOD: Two groups of age- and gender-matched patients with bipolar disorder (14 with a good outcome and 15 with a poor outcome) and 15 controls, aged 20-65 years, were studied. Axial T(2)-weighted MRI scans were examined for the presence and severity of white matter abnormalities. RESULTS: Significantly more poor outcome group members had deep subcortical punctate, but not periventricular, white matter hyperintensities than the good outcome group (P:=0.035) or controls (P:=0.003) and these abnormalities were of greater severity (P:=0.030 and P:<0.014, respectively). CONCLUSIONS: Subcortical white matter lesions are associated with poor outcome bipolar disorder.

Pancreatic tumour marker anti-mucin antibody CAM 17.1 reacts with a sialyl blood group antigen, probably I, which is expressed throughout the human gastrointestinal tract.

CAM 17.1 is an antimucin monoclonal antibody which has recently been proven valuable as a reagent for serological diagnosis of pancreatic cancer. A series of studies have been performed to characterise its epitope. First it was screened immunohistochemically against a wide range of formalin-fixed normal and neoplastic human tissues and showed widespread binding to mucin throughout the gastro-intestinal tract, in both normal and malignant tissues. In pancreas, strong intracellular staining of acinar and ductal cells was found in normal tissue and in carcinoma cells in tumours. Normal stomach showed only weak staining (n = 6), but gastritis with metaplasia showed strong staining (n = 4). Staining of colonic mucosa from patients of known Lewis phenotype showed Le(a+b-) (7/8) and Le(a-b+) (4/6) samples to be positive, but not Le(a-b-) (0/3) samples. CAM 17. 1 agglutinated all donor erythrocytes tested at 4 degreesC regardless of blood group, whereas cord blood red cells were not agglutinated. Since I antigen is the only antigen known to be present on all adult red blood cells but absent from cord blood, this suggests probable involvement of this antigen in the binding site. The agglutination was abolished by sialidase treatment of the red cells and immunoblotting with slot-blotted mucin showed that binding was both acid and sialidase sensitive indicating the involvement of sialic acid in the binding site. These studies show that CAM 17.1 binds to a sialic-acid-containing determinant of mucin, probably sialyl-I, which epitope shows wide distribution throughout the gastro-intestinal tract.

Ultrasonic coronary angioplasty during coronary artery bypass grafting.

This preliminary study in 20 patients demonstrated that ultrasonic coronary angioplasty in the setting of bypass grafting is feasible, safe, and able to recanalize atherosclerotic vessels. Shorter monorail probes were superior to longer probes without guidewires in terms of success of vessel recanalization; >95% of particle debris was <25 microm in size.

Cost-efficacy modeling of catheter reuse for percutaneous transluminal coronary angioplasty.

OBJECTIVES: Our goal was to provide the range of cost savings associated with various catheter reuse strategies. BACKGROUND: Percutaneous transluminal coronary angioplasty catheters are commonly reused in several countries outside the United States. However, the cost-effectiveness of such reuse strategies has not been evaluated. METHODS: Three theoretical models of catheter reuse were constructed using the actual costs for treating patients with coronary angioplasty at the Cleveland Clinic. Costs were calculated based on the number of balloon catheters, the amount of contrast agent used and the rates for urgent revascularization that were observed in a prospective Canadian study on catheter reuse. RESULTS: The median cost to treat a lesion by means of coronary angioplasty using new catheters was $8,800 per patient. In reuse models, the potential to reduce cost depended on the number of balloon catheters used and the rates of urgent revascularization. The "best care" scenario offered a potential savings of $480 (5.5% of total in-hospital cost), whereas the "worst case" scenario resulted in an increased cost of $1,075 (12.2% of total in-hospital cost) compared with the single-use strategy. Cost of the "likely case" scenario was similar to that of the single-use strategy. Sensitivity analyses identified the different rates of revascularization and cost of balloon catheters required to offset potential savings in each strategy. CONCLUSIONS: Although reusing coronary angioplasty catheters may reduce total in-hospital costs, even a modest increase in complications requiring urgent revascularization may offset any potential savings. However, if an increase in complications and procedure time can be avoided, the reuse strategy has significant economic potential and, ultimately, may be extended to other percutaneous coronary interventional equipment.

Rationale for local drug delivery.

Although advances during the last decade have transformed the management of coronary artery disease, deficiencies in our understanding of the basic processes of arterial thrombosis and restenosis after percutaneous intervention continue to present major challenges to their prevention. While coronary stenting has in selected cases provided the first effective approach to the problem of restenosis, new devices such as atherectomy have largely proven ineffective in this field. Similarly, despite evidence that many pharmacological agents reduce neointimal hyperplasia in experimental models, in clinical trials these agents have failed to attenuate the restenotic process. This may reflect patients' inability to tolerate the high systemic drug concentrations required to achieve adequate levels for sufficient time at the target site, necessitating a shift in the focus of therapeutic agents for the prevention of thrombosis and restenosis to local or site-specific delivery. The major advantage that local drug delivery may potentially provide is the ability to achieve high and sustained local concentrations of drug without large systemic doses, thus minimizing systemic toxicity.