Ronald Dick

Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non–ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: Results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial

BACKGROUND There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI). METHODS We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography. RESULTS Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome. CONCLUSIONS These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.

Aortic Balloon Valvuloplasty—Review and Case Series

Aortic balloon valvuloplasty (BAV) was initially devised in the 1980s as an alternative procedure to the surgical treatment of aortic stenosis, with the theory behind it being both minimally invasive as well as having a lower complication rate [Hara H, et al. Percutaneous balloon aortic valvuloplasty revisited: time for a renaissance? Circulation 2007 March;115(12):e334-8]. In practice however, the procedure was found to have a higher complication rate with only a modest haemodynamic improvement compared to the surgical approach. Most important of all it had an unacceptably high restenosis rate as a substitute for surgery [Otto CM, et al. 3-year outcome after balloon aortic balloon valvuloplasty: insights into prognosis of valvular aortic stenosis. Circulation 1994;89:642-50]. As a result, the procedure has fallen out of favour and has been abandoned at many health care facilities [Hara H, et al. Percutaneous balloon aortic valvuloplasty revisited: time for a renaissance? Circulation 2007 March;115(12):e334-8]. This article will review the management of patients with severe aortic stenosis that are unsuitable to undergo surgery.

Percutaneous Coronary Intervention in Very Elderly Patients. In-hospital Mortality and Clinical Outcome

BACKGROUND There are very few data about percutaneous coronary intervention (PCI) in very elderly patients. This study was aimed at assessing the demographic, clinical and angiographic features, procedural characteristics and in-hospital results of very elderly patients (VEP), aged ≥85 years undergoing PCI and comparing their results with those of a control group (CG) of patients younger than 85 years undergoing PCI throughout the same period of time. METHODS AND RESULTS Between November 2004 and January 2007, 1699 consecutive PCI procedures were evaluated, 102 (6%) PCI procedures were performed in VEP and 1597 (94%) in patients <85 years. The mean age in the VEP group was 87.4 ± 2.4 years vs. 66.7 ± 11.2 years in the CG (p<0.0001). There were more females in the VEP group 49% vs. 22% than in the CG p<0.0001. Acute coronary syndromes (ACS) were a more frequent indication for PCI in VEP than in the CG: ST segment elevation myocardial infarction (STEMI) 14.7% vs. 8.3%, p = 0.025 and non-ST segment elevation acute coronary syndromes 54.9% vs. 43.5%, p = 0.024. The proportion of drug-eluting stents used, although high in both groups, was lower in VEP than in the CG (86.5% vs. 92.9%, p = 0.005). Angiographic lesion success rates were similar in both groups (95.9%). Global unadjusted in-hospital mortality was higher in the VEP group in comparison with the CG 3.9% vs. 0.68%, p = 0.01. The difference in mortality was due only to PCI in patients presenting with STEMI (26.6% in VEP group vs. 3.7% in the CG p = 0.007). There were no in-hospital deaths in VEP presenting with stable coronary syndromes or other ACS. There were no differences in unadjusted in-hospital myocardial infarction, new revascularisation or stroke between both groups. CONCLUSIONS In patients ≥85 years old, PCI seems effective and carries an acceptable in-hospital mortality rate. The presence of STEMI substantially increases the risk of in-hospital death.

Percutaneous Coronary Intervention in Women: In-Hospital Clinical Outcome: Experience from a Single Private Institution in Melbourne

BACKGROUND Differences in outcome between women and men treated with percutaneous coronary intervention (PCI) have decreased. This study was aimed at assessing the demographic, clinical, and angiographic features, procedural characteristics and in-hospital results of women undergoing PCI and comparing their results with those of a group of men undergoing PCI throughout the same period of time. METHODS AND RESULTS All consecutive PCI procedures performed at Epworth Hospital from November 2004 to January 2007 were analysed. Women and men were compared according to baseline clinical, angiographic and procedural characteristics, angiographic success rates and in-hospital outcomes. A total of 1699 consecutive PCI procedures were performed; of these, 405 PCI (23.8%) were performed in women. Women were older (73.9+/-10 years versus 66.1+/-11.9 years, p<0.0001), had a higher prevalence of hypertension (78% versus 63%, p<0.0001), had lower prevalence of prior myocardial infarction (21% versus 27%, p=0.026), and had less history of prior coronary artery by-pass surgery (13% versus 18%, p=0.023) than men. A greater proportion of women presented with acute coronary syndromes (ACS) to PCI than men (63.7% versus 52.9%, p<0.0001). Women had more complex lesions B2/C (78% versus 74%, p=0.049), a higher proportion of ostial lesions (10.5% versus 5.5%, p<0.0001) and less multivessel disease (48% versus 54% p=0.028) than men. Angiographic lesion success rates were similar in both groups. Total unadjusted in-hospital mortality was higher in women than in men (1.97% versus 0.54%, respectively, p=0.013). This difference in mortality was only at the expense of a higher unadjusted mortality in women presenting with ST segment elevation myocardial infarction (STEMI) than men (17.5% versus 1.87%, p=0.002). No women with a stable coronary syndrome or non-ST-segment elevation acute coronary syndrome (NSTE-ACS) died in hospital. There were no differences in in-hospital myocardial infarction, new revascularisation or stroke between both groups. CONCLUSIONS PCI in women has good results but carries an increased unadjusted mortality than in men. This mortality difference between genders in our study, however, was solely at the expense of a higher unadjusted mortality in women than in men undergoing PCI for STEMI.

Clopidogrel Resistance: case reports of CYP2C19 gene variants in suspected coronary stent thrombosis.

Clopidogrel is a widely used anti-platelet agent for the prevention of arterial thrombosis. Clopidogrel is administered as a pro-drug and metabolised to its active metabolite by the hepatic cytochrome P450 2C19 (CYP2C19) enzyme. The active metabolite is responsible for the anti-platelet activity of clopidogrel. Recent studies demonstrate that single nucleotide polymorphisms, (SNPs), in the gene for CYP2C19 result in significantly reduced production of the active metabolite of clopidogrel. Additional studies demonstrate that patients with SNPs in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5, have reduced production of the active metabolite of clopidogrel, reduced inhibition of platelet aggregation and increased incidence of coronary, cerebrovascular, and coronary stent thrombosis. We have been interested in determining the CYP2C19 genotype in cases of coronary stent thrombosis whilst on clopidogrel treatment and provide two case reports of coronary stent thrombosis whilst taking clopidogrel with subsequent CYP2C19 genotyping. As patients at risk of atherothrombosis in general, and stent thrombosis in particular, may be receiving or considered for anti-platelet therapy including clopidogrel, genotyping for CYP2C19 SNPs may be of benefit in the selection of appropriate anti-platelet therapy.

Clinical-scientific notes

We report a case of varicella-zoster virus (VZV) mye-litis in a woman with relapsing-remitting multiplesclerosis(RRMS)receivingnatalizumab,ahumanizedmonoclonal antibody that induces an immunosup-pression localized to the CNS.Case report. A32-year-oldwomanwastreatedwithna-talizumab for highly active RRMS. After the fourth infu-sion, she complained of a right radicular pain in a L5/S1territory.Afewdayslater,theneurologicexaminationdis-closed a distal weakness (3/5 Medical Research Council[MRC]) in the right leg with signs of pyramidal irritationsuggestingaspinalcordrelapse.ThespinalcordMRIdis-closed focal cervical and dorsal T2 hyperintensities and aT2 hypersignal in the conus region with contrastenhancement (figure). A spinal cord relapse was consid-ered. HighdosesofIVmethylprednisolonewereinitiatedfor3days.Twoweekslater,thepatientdeteriorated,withan increase of leg weakness (2/5 MRC) and bladder dys-function. She received another series of IV methylpred-nisolone for 3 days, without improvement. Because ofthis unusualevolution, weperformedalumbar puncture,which revealed a lymphocytic pleocytosis (18 elements),normal proteins, and glycorrhachia. VZV DNA detectedby PCR amplification was positive in CSF. Cytomegalo-virus and herpes simplex virus (HSV) PCR in the CSFwere negative. HIV screeningwasnegative.VZVimmu-noglobulin G in the blood was positive before this acuteepisode (tested in January 2012). No skin rash was notedor reported by the patient. A second spinal cord MRIshowed progression of lesion size, persistent contrastenhancement in the conus region, and new contrast en-hancementsindorsallesions(figure).AcuteVZVmyelitiswas diagnosed. The patient was treated with IV acyclovir10 mg/kg/8 h for 3 weeks and then switched to valacy-clovir, which resulted in a c linical improvement (4/5MRC in right lower limb and recovery of subnormalbladder function but persistent sensory loss in the leftlower limb). CSF at 1 month was normal (4 elements,negative VZV PCR). Spinal cord MRI at 2 months wasclearly improved (figure). Natalizumab was discontinued.Discussion. If cases of HSV encephalitis and meningi-tis have been previously reported,

Very Late Drug-Eluting Stent Thrombosis Post Exercise Stress Echocardiogram

Stent thrombosis, although a rare event, has been the object of considerable interest because of its attendant morbidity and mortality and has come into focus with the advent of drug-eluting stents. We report a case of very late drug-eluting stent thrombosis occurring immediately after an exercise stress echocardiogram, in a patient who, 2 years earlier, had undergone primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). Similar cases reported in the literature and the possible mechanisms of stent thrombosis associated with exercise testing are reviewed.

Epworth Hospital Interventional Cardiology Audit for 2007

The cardiac catheterisation laboratory interventional audit for 2007 showed that 761 cases were performed, treating at total of 941 lesions. Unstable coronary syndromes accounted for 59% of all cases. Coronary stenting was performed in 93.3% of cases, with drug-eluting stents being utilised 88% of the time. Adjunctive therapies included intra-aortic balloon pumping in 3.1% of cases, & 19.5% of patients received a glycoprotein IIb/IIIa inhibitor. Procedural success was attained in 96.1% of cases, with an overall mortality rate of 0.53%, and a similar 0.53% of patients proceeded to surgical revascularisation in the same admission.

Epworth hospital interventional cardiology report, 2002

In March 2001, the Victorian Heart Centre at Epworth Hospital implemented a database management system to improve the standard of data collection and analysis of procedures performed in our catheter laboratory. A retrospective analysis of procedures undertaken during 2000, together with prospective data collected during 2001/2002, has enabled us to achieve our goals of benchmarking performance and undertaking research on the outcomes of interventional cardiology procedures at Epworth. The figures reported in this years cardiac catheterisation laboratory audit report confirm a continued high standard performance in our laboratory.