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Biomedical subjects

Blair J O'Neill

Publications and source records attributed to Blair J O'Neill.

11 recordsLinked to original sources
PubMed2006

Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment.

BACKGROUND: Subcutaneous enoxaparin is increasingly employed as the antithrombin of choice in non-ST elevation myocardial infarction and in conjunction with various fibrinolytic regimens in acute ST elevation myocardial infarction (STEMI). Few data exist describing the use of subcutaneous or intravenous enoxaparin as an anticoagulant in the highly thrombotic setting of primary percutaneous coronary intervention (PCI) for STEMI. METHODS: The Which Early ST Elevation Therapy (WEST) study compared fibrinolysis (with and without early cardiac catheterization) with primary PCI in a setting that expedited both strategies on first medical contact. Patients assigned primary PCI are administered acetylsalicylic acid 325 mg, clopidogrel 300 mg and subcutaneous enoxaparin 1 mg/kg before transport to a PCI centre. Of 36 initial patients treated with primary PCI, three patients had procedures that were complicated by extensive thrombosis within coronary catheters and on PCI equipment. RESULTS: Index cases were men aged 43 to 68 years who presented with confirmed STEMI and angiographically proven acute total or subtotal occlusion of a major epicardial coronary segment. During PCI, performed 76 min to 102 min following enoxaparin administration, a clot developed within the guide catheter or on the coronary guidewires and balloon catheter shafts, thus necessitating the replacement of all PCI equipment. In one case, there was evidence of continued intracoronary clot propagation and embolization. CONCLUSION: A single, conventional, weight-adjusted dose of subcutaneous enoxaparin before expedited primary PCI for STEMI may not provide a reliable antithrombotic effect. Supplementary intravenous enoxaparin is now strongly recommended within the WEST study, and a substudy evaluating pre- and postprocedural antifactor Xa activity has been initiated.

Abciximab↗
PubMed2006

Universal access -- but when? Treating the right patient at the right time: access to electrophysiology services in Canada.

The Canadian Cardiovascular Society Access to Care Working Group has published a series of commentaries on access to cardiovascular care in Canada. The present article reviews the evidence for timely access to electrophysiology services. Using the best available evidence along with expert consensus by the Canadian Heart Rhythm Society, the panel proposed a series of benchmarks for access to the full scope of electrophysiology services, from initial consultation through to operative procedures. The proposed benchmarks are presented herein.

Canada↗
PubMed2006

Treating the right patient at the right time: Access to cardiac catheterization, percutaneous coronary intervention and cardiac surgery.

The Canadian Cardiovascular Society Access to Care Working Group was formed with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for cardiac catheterization and revascularization procedures for patients with stable angina, and access benchmarks for cardiac catheterization and surgery for patients with valvular heart disease. Literature on standards of care, wait times and wait list management was reviewed. A survey of cardiac centres in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommends the following medically acceptable wait times for access to cardiac catheterization: 14 days for symptomatic aortic stenosis and six weeks for patients with stable angina and other valvular disease. For percutaneous coronary intervention in stable patients with high-risk anatomy, immediate revascularization or a wait time of 14 days is recommended; six weeks is recommended for all other patients. The target for bypass surgery in those with high-risk anatomy or valve surgery in patients with symptomatic aortic stenosis is 14 days; for all others, the target is six weeks. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. There is an ongoing need to continually reassess current risk stratification methods to limit adverse events in patients on waiting lists and assist clinicians in triaging patients for invasive therapies.

Angioplasty, Balloon, Coronary↗
PubMed2005

Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.

OBJECTIVES: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C]. DESIGN AND METHODS: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years). Differences in the proportion of subjects in each group with the given gene combination were assessed and likelihood ratios (LR) were calculated using logistic regression to combine the results of multiple genes. RESULTS: Early-onset CAD patients had increased, but non-significant, frequencies of PPARgamma2 Pro12/Pro12 (P = 0.39) and ENOS T-786C (P = 0.72), while BChE-K was only significantly higher in early-onset CAD patients compared to controls (P = 0.03). There were significantly more APOE epsilon4 alleles alone (P = 0.02) or in combination with BChE-K (P = 0.02) among early-onset CAD patients compared to late-onset CAD ones or controls. When combined, there was a higher prevalence of all four alleles in early-onset CAD (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls: 2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small (1.08 for PPARgamma2 to 1.70 for APOE epsilon4). This increased to 2.78 (1.44-5.37) when combining all four alleles, therefore increasing the pre-test probability of CAD from 5% to a post-test probability of 12.7%. CONCLUSIONS: While any single mutation causes only a mildly increased LR (none > 1.7), in combination, the likelihood of early-onset CAD increased to 2.78 with four mutations. The genetics of early-onset CAD appear to be multifactorial, requiring polygenic models to elucidate risk.

Age of Onset↗
PubMed2004

The 2004 ACC/AHA Guidelines: a perspective and adaptation for Canada by the Canadian Cardiovascular Society Working Group.

Major changes in acute ST elevation myocardial infarction (STEMI) management prompted a comprehensive rewriting of the American College of Cardiology/American Heart Association Guidelines. The Canadian Cardiovascular Society (CCS) participated in both the writing process and the external review. Subsequently, a Canadian Working Group (CWG), formed under the auspices of the CCS, developed a perspective and adaptation for Canada. Herein, accounting for specific realities of the Canadian cardiovascular health system, is a discussion of the implications for prehospital care and transport, optimal reperfusion therapy and an approach to decision making regarding reperfusion options and invasive therapy following fibrinolytic therapy. Major recent developments regarding indications for implantable cardioverter defibrillator(s) (ICDs) also prompted a review of indications for ICDs and the optimal timing of implantation given the potential for recovery of left ventricular function. At least a 40-day, preferably a 12-week, waiting period was judged to be optimal to evaluate left ventricular function post-STEMI. A recommended algorithm for the insertion of an ICD is provided. Implementation of the new STEMI guidelines has substantial implications for resources, organization and priorities of the Canadian health care system. While on the one hand, the necessary incremental funding to provide tertiary and quaternary care and to support revascularization and device implantation capability is desirable, it is equally or more important to develop enhanced prehospital care, including the capacity for early recognition, risk assessment, fibrinolytic therapy and/or triage to a tertiary care centre as part of an enlightened approach to improving cardiac care.

Canada↗
PubMed2003

Statin therapy and the management of acute coronary syndromes.

The pathophysiology of acute coronary syndromes is related to erosion or rupture of vulnerable plaque leading to intracoronary thrombosis as a result of activation of the coagulation cascade and platelet aggregation. Potential benefit of hypolipidemic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition may be related to the pleiotropic effects such as endothelial function improvement, stabilization of the plaque in relation to reduced macrophage activity and smooth muscle cell proliferation, as well as other anti-inflammatory effects that have been demonstrated in animal models. With the publication of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study, early initiation of statin therapy within 24 to 96 h has been recognized as an important addition to the therapeutic armamentarium in the management of patients with acute coronary syndromes.

Acute Disease↗
PubMed2002

Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease.

OBJECTIVES: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD. DESIGN AND METHODS: To determine whether BChE-K is also associated with premature CAD, we examined the frequency of BChE-K among patients with early-onset CAD (n = 150; < 50 yr) vs. late-onset CAD (n = 150; > 65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups, and explored whether there was synergism between BChE-K and APOE-epsilon 4, BChE-K and PON1-R or PON1-R and APOE-epsilon 4. RESULTS: The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%; p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon 4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon 4. CONCLUSIONS: Our study suggests that there is a minor association between BChE-K and early-onset CAD, especially in the presence of the APOE-epsilon 4 allele.

Age of Onset↗