Individualised assessment of response to clopidogrel in patients presenting with acute coronary syndromes: a role for short thrombelastography?

INTRODUCTION: There is considerable interindividual variation in response to the antiplatelet agent clopidogrel. Hyporesponse predicts negative outcomes in patients presenting with a variety of ischemic cardiac conditions and following intracoronary stent placement. Many tests of clopidogrel activity are time consuming and complex. Short thromboelastography (s-TEG) allows rapid measurement of platelet clopidogrel response. AIMS: We initiated this study to investigate the utility of s-TEG in assessing the response to clopidogrel in patients presenting with acute coronary syndromes (ACS) and to compare these results with established clopidogrel monitoring techniques. METHODS: Patients admitted with unstable angina (UA) or Non ST elevation myocardial infarction (NSTEMI) undergoing coronary angiography were recruited. After routine loading with clopidogrel, all patients were tested with s-TEG and Accumetrics Verify-Now rapid platelet function analyzer (VN-RPFA). We used the modified TEG technique of measuring area under the curve at 15 min (AUC15), which allows a rapid estimation of antiplatelet response. Vasodilator-stimulated phosphoprotein phosphorylation (VASP) was also tested in a subgroup of patients. Clinical follow-up was obtained at 1 year. s-TEG results were correlated with VN-RPFA and VASP findings. RESULTS: A total of 49 patients (33 male, mean age 63) were recruited and tested with s-TEG and VN-RPFA and a total of 39 patients were also assessed with VASP. s-TEG readings correlated well with VN-RPFA (r(2)= 0.54, P < 0.0001) and VASP (r(2)= 0.26, P= 0.001). CONCLUSION: s-TEG provides timely results which compare to current tests of clopidogrel activity. This technique can also be used to measure a variety of other clotting parameters and as such could develop into a valuable near patient test for the interventional cardiologist.

Direct coronary stenting compared with stenting after predilatation is feasible, safe, and more cost-effective in selected patients: evidence to date indicating similar late outcomes.

OBJECTIVES: To review the currently available data from studies assessing feasibility, safety, clinical outcome and cost-effectiveness of direct stenting. BACKGROUND: With technical advances of stent designs and their delivery systems a new strategy has become increasingly popular: direct stent implantation without prior balloon dilatation. METHODS: The Medline database was searched from January 1996 to March 2001 for clinical trials investigating direct stenting using the index terms direct stenting, coronary intervention, percutaneous transluminal coronary angioplasty (PTCA), PCI, angioplasty and ischemic heart disease. Studies were chosen based on the number of patients involved and endpoints mentioned. Data not yet published but presented at recent international meetings were also included. A comparison between direct stenting and stenting with predilatation was performed using for the latter results of the randomized trials supplemented with Benestent II data. RESULTS: At least 26 studies have investigated direct stenting, showing high primary and final success rates with few complications. Direct stenting provides a way to reduce costs, shorten procedural and fluoroscopy times and lower material consumption. Immediate and long-term clinical outcomes appear to be similar to stenting with predilatation. Preliminary results of large randomized trials with angiographic follow-up indicate that restenosis rates are similar to those of conventional stenting strategies. CONCLUSIONS: Direct stenting compared with stenting with predilatation is feasible, safe, faster and more cost-effective. The evidence to date shows similar late outcomes.

Nitric oxide and myocardial function in heart failure: friend or foe?

There is good evidence that nitric oxide has important autocrine/paracrine effects in the myocardium, serving to optimise and fine tune cardiac function

Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery.

AIMS: Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and vasoprotective molecule whose expression is modulated by hypoxia and inflammatory mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are influenced by pre-existing coronary artery disease and by changes in circulating interleukin-6 (IL-6). METHODS AND RESULTS: Plasma VEGF-A and IL-6 were measured prior to and at various time intervals following surgery in individuals with angiographically normal coronary arteries requiring cardiac valve replacement (N group) and in patients with coronary artery disease and stable angina undergoing coronary artery bypass grafting (CAD group). Baseline VEGF-A levels were not significantly different in CAD (22.3+/-2.6 pg x ml(-1)) compared to the N group (14.9+/-2.9 pg x ml(-1)). Following cardiac surgery there was a significant rise of VEGF-A in CAD (P<0.0005 vs baseline), but not in the N group, reaching a maximum (approximately 2 fold increase) after 24 h. Surgery caused a rapid increase of plasma IL-6 in both groups, but the rise was significantly larger in CAD patients (P<0.0005 vs N) where it preceded the increase in VEGF-A. Furthermore, in patients with CAD there was a significant correlation between the change in VEGF-A and the change in IL-6 (P<0.04). CONCLUSION: These findings demonstrate that in patients with coronary artery disease cardiothoracic surgery leads to an acute rise in VEGF-A. We suggest that this rise may result from an interaction between the pre-existing atheromatous process and a systemic increase of inflammatory mediators.

Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.

BACKGROUND: Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. METHODS AND RESULTS: We compared the effects of intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt(max) (from 1826 to 1578 mm Hg/s; P<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt(max) were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS). The blunted pacing-induced rise in LV dP/dt(max) in these patients was unaltered by L-NMMA. CONCLUSION: Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.

Treatment of intractable angina in a nonagenarian patient by direct coronary stenting.

BACKGROUND: A 91-year-old man presented with a 6-month history of exertional angina. As he was already on maximally tolerated medical therapy, we decided to perform coronary angiography, which revealed severe stenosis of the distal main stem coronary artery, OUTCOME: The lesion was crossed with an intra-coronary wire, and a stent placed to cover the distal main stem lesion, without prior balloon dilatation. The result was satisfactory and he remains symptom-free at 6-month follow-up. CONCLUSION: Treatment of left main stem lesions with percutaneous intervention may be an acceptable alternative to surgery in high-risk elderly patients. Since percutaneous coronary angioplasty can be performed on very elderly patients with a high degree of success, the decision to investigate and treat should not be based solely on biological age.

Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management.

Viral infection of the heart is relatively common and usually of little consequence. It can, however, lead to substantial cardiac damage and severe acute heart failure. It can also evolve into the progressive syndrome of chronic heart failure. Recent studies have gone some way towards unravelling the complex mechanisms underlying the heart muscle damage that occurs after viral infection. These studies have lent support to both immune and viral mediated (independent of an immune response) cardiac damage. Acute myocarditis can present in various ways, and it may be a cause of sudden death in an otherwise healthy young adult. New treatments for viral heart disease are awaited. In the meanwhile, the haemodynamic support of patients with acute left ventricular failure caused by myocarditis should be aggressive, to allow for the possibility of spontaneous recovery. Contemporary trials of treatment in chronic heart failure secondary to dilated cardiomyopathy support the use of angiotensin converting enzyme inhibitors, beta adrenoceptor blockers, and spironolactone in such patients.

Forensic echocardiography: a case in point.

Transthoracic echocardiography (TTE) has an important role in the assessment of patients with acute penetrating chest trauma. We report the case of a 36-year-old man who sustained a stab wound to the chest. After admission, he required emergency pericardiocentesis. TTE revealed a traumatic ventricular septal defect and a defect in the anterior mitral valve leaflet. To assess whether these lesions were related to the initial stab wound or the pericardiocentesis, the transducer was positioned over the stab wound, and the lesions were shown to be in the same plane as the entry site, thus ruling out iatrogenic trauma.

Should all children receive two measles vaccinations? A study of measles susceptibility in a suburban New Jersey private practice.

Because of the rising incidence of rubeola, we tested all our patients who were vaccinated prior to 15 months of age and those vaccinated after 15 months, if requested, for susceptibility to measles (IgG, ELISA). Those found to be susceptible were revaccinated. Of 1,228 tested, 264 (21.5%) were susceptible. In the group vaccinated before 1980, 237 of 901 (26.3%) were susceptible, whereas only 27 of 327 (8.3%) vaccinated after 1980 were not immune. Susceptibility was sharply divided by month of age at vaccination at the 14-month mark. Less than 5% of those vaccinated after age 15 months in the 1980s (one of 22, or 4.5%) were susceptible. Waning immunity (secondary vaccine failure) was not found to be a factor in our patients. Despite outbreaks of measles in surrounding communities and in our area, none of our patients developed measles. Identification of high-risk groups and selective measles revaccination should be considered as an alternative to universal revaccination in populations such as ours, since it is more cost-effective and may prove equally successful.