Papers by Christopher Glover
Circulation, Nov 20, 2012
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The Canadian journal of cardiology
Gene therapy for the treatment of vascular disease is limited by a low transfection efficiency an... more Gene therapy for the treatment of vascular disease is limited by a low transfection efficiency and/or undesired biological responses. To determine the transfection efficiency of delivering a liposome/DNA complex into balloon-injured rabbit arteries systematically or using a local delivery catheter. The cationic liposomes N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl-sulphate and dioleoyl-phosphatidylethanolamine were mixed 1:1 (wt/wt) and combined with the plasmid pCMV-AP containing the human placental alkaline phosphatase (AP) reporter gene. Before initiating the in vivo experiments, the optimal ratio of liposome to DNA complex and the persistence of transgene expression were determined in cultured vascular smooth muscle cells (SMC). In vivo, a Dispatch catheter was used for local delivery of the liposome/DNA complex into rabbit iliac arteries that had been balloon injured five days previously. The contralateral iliac or renal artery was also balloon injured, and liposomes with normal saline were delivered as a negative control. For the systemic delivery group, the liposome/DNA complex was delivered through an ear vein. AP expression in transfected SMC persisted for 28 days in vitro, although the percentage of transfected cells declined with time (eg, at 24 h it was 27.3%+/-2.9%, at 28 days it was 0.4%+/-0.1%). SMC proliferation in vitro enhanced the transfection efficiency 12-fold. In vivo, local delivery resulted in low levels of transfection in arteries harvested one day postdelivery; however, six of seven arteries harvested three days postdelivery had multiple regions of focal transgene expression involving all three arterial layers. For the systemic delivery group, two of nine arteries expressed the transgene. No transgene expression was found in uninjured arteries in either the local or systemic delivery groups. However, with both local and systemic delivery, balloon-injured arteries that received liposomes and saline showed low levels of AP expression in either the neointima, media or adventitia, presumably due to systemic recirculation of the liposome/AP construct. Liposome-mediated gene transfection can be successfully performed to all vessel layers in vivo by using a local delivery catheter, and may provide a therapeutic opportunity for modulating atherosclerosis and restenosis. Unwanted transfection at a distance may occur with catheter-based local delivery and requires further refinement.
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The Canadian journal of cardiology
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Seminars in interventional cardiology : SIIC, 2000
Coronary atherectomy offers the intuitive advantage of removing tissue mass in order to improve b... more Coronary atherectomy offers the intuitive advantage of removing tissue mass in order to improve blood flow. A second major benefit of atherectomy is the opportunity to study lesion tissue and make pathophysiological insights. The value of the latter cannot be over emphasized, as current animal models for the study of atherosclerosis and restenosis are fraught with limitations. In this review, we outline some of the key descriptive findings that have emerged from the study of atherectomy specimens. Specifically, we will focus on the role of smooth muscle cell proliferation, thrombus organization and matrix formation in primary atherosclerotic lesions, as well as restenotic lesions after balloon angioplasty and stenting.
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Canadian Journal of Cardiology, 2014
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International Journal of Eating Disorders, 2010
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International Journal of Cardiology, 2012
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Current Opinion in Cardiology, 2007
Cardiac transplantation is a complex undertaking and an imperfect solution to end-stage heart fai... more Cardiac transplantation is a complex undertaking and an imperfect solution to end-stage heart failure. Cellular transplantation has been proposed as an alternative solution; however, clinical trials at present are small and show variable results. The mechanisms behind stem cell therapy have not yet been elucidated. Several large trials have been presented that address the question of bone marrow stem cells as therapy for acute myocardial infarction, and also the possible benefits of therapy with granulocyte colony-stimulating factor. Although some trials show a modest improvement in ejection fraction or reduction of infarct size, other trials show no change with treatment. Fewer clinical data are available on the treatment of chronic left ventricular systolic function. Many questions remain such as what cell type to use, dosing, the ideal timing for therapy, and the technique of cell delivery. Finally, further research continues on the cellular milieu, enhancement of cell engraftment, proliferation, and survival. This review briefly examines the background for stem cell therapy, as well as the larger clinical trials of stem cell therapy for acute myocardial infarction and chronic left ventricular systolic dysfunction, and possible pharmacologic enhancement options.
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Atherosclerosis, 2000
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Circulation, Oct 31, 2007
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Circulation, Nov 22, 2011
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Circulation, Nov 25, 2014
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ABSTRACT BACKGROUND. Reperfused myocardium post acute myocardial infarction (AMI) may have altere... more ABSTRACT BACKGROUND. Reperfused myocardium post acute myocardial infarction (AMI) may have altered metabolism with implications for therapy response and function recovery. We explored glucose metabolism and the ‘reverse mismatch’ (RMM) pattern (decreased F-18-fluorodeoxyglucose (FDG) uptake relative to perfusion) in patients who underwent mechanical reperfusion with percutaneous coronary intervention (PCI) for AMI. METHODS AND RESULTS. Thirty-two patients with anterior wall AMI treated with acute reperfusion, with left ventricular ejection fraction ≤ 45%, underwent rest Rb-82 and FDG PET 2-10 days post-AMI. Resting echocardiograms were used to assess wall motion abnormalities. Significant RMM occurred in 15 (47%) patients and was associated with a shorter time to PCI of 2.9h (2.2h, 13.3h) compared to patients without significant RMM: 9.8h (4.2h, 19.8h) (p = 0.03). Within the peri-infarct regions, significant RMM occurred more frequently (p < 0.001) and these segments were more likely to have wall motion abnormalities (OR = 3.2 (1.1, 9.2,), p = 0.03) compared to segments without significant RMM. CONCLUSIONS. RMM is a common pattern on perfusion/FDG PET during the sub-acute phase following reperfusion of AMI. RMM is associated with shorter times to PCI, increased wall motion abnormalities, and occurs more frequently in peri-infarct regions. These findings support the hypothesis of a myocardial metabolic shift during the sub-acute phase of recovery.
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Clinical cardiology, Jan 8, 2016
Patients on dual antiplatelet therapy following percutaneous coronary intervention often have ind... more Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). Although TT may decrease ischemic complications, it may confer increased bleeding risk. We hypothesize that the use of ticagrelor in TT is associated with higher risk of complications; accordingly, we sought to determine predictors of complications in patients on TT. Patients discharged on TT after percutaneous coronary intervention were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and major bleeding complications or net adverse clinical event (NACE). A major secondary endpoint was BARC (Bleeding Academic Research Consortium) types 2, 3, or 5 bleeding. Outcomes were compared between ticagrelor- and clopidogrel-treated patients. Multivariable analyses were performed to elucidate predictors of complications. Twenty-seven of 152...
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The Journal of invasive cardiology
In-stent restenosis (ISR) is a growing problem that is without a practical, efficacious treatment... more In-stent restenosis (ISR) is a growing problem that is without a practical, efficacious treatment strategy. The purpose of this study was to determine the acute outcome of 17 patients with coronary ISR who were treated with the new 8 French (Fr), guide-catheter compatible Flexicut directional atherectomy catheter (Guidant Corporation, Santa Clara, California). Failure to deliver the device occurred in 2/17 ISR lesions. The remaining 15 ISR lesions were successfully debulked (e.g., minimum lumen diameter pre-procedure: 0.30 +/- 0.16 mm; post-atherectomy plus adjuvant therapy: 2.16 +/- 0.57 mm). Of note, the reference vessel diameter was only 2.62 +/- 0.63 mm. In 11/15 tissue specimens, macroscopic or microscopic particles consistent with stent material were found. There was an absence of acute closure or elevations of creatinine phosphokinase levels. Apart from 1 patient who developed recurrent restenosis, all other patients demonstrated either clinical improvement or lack of restenosis during early clinical follow-up (mean, 5 months). We conclude that use of the Flexicut catheter provides satisfactory debulking and early clinical outcomes in patients with ISR. Long-term follow-up of these and additional patients will be helpful in determining the efficacy of the Flexicut atherectomy catheter for the treatment of ISR.
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The Journal of invasive cardiology
Dual antiplatelet therapy, with aspirin and a thienopyridine, is the accepted treatment after per... more Dual antiplatelet therapy, with aspirin and a thienopyridine, is the accepted treatment after percutaneous coronary intervention (PCI). No clear evidence exists regarding the ideal dosage of aspirin. Recent guidelines recommend higher-dose aspirin because of the possible decrease in stent thrombosis. The purpose of this study was to test the hypothesis that high-dose aspirin of 325 mg decreases death and myocardial infarction (MI) compared to a lower dose of 81 mg in patients undergoing PCI. An observational cohort study of 1,840 consecutive patients who underwent PCI was conducted. Patients who did not survive to discharge were excluded. The primary endpoint was a composite of all-cause mortality and MI at 1 year. Nine-hundred and thirty patients (50.5%) were discharged on 325 mg of aspirin and 910 (49.5%) were discharged of 81 mg. The risk of all-cause mortality or MI was not significantly different between patients: low-dose 5.49% (50/910) vs. high-dose 4.19% (39/930); adjusted odds ratio [OR], 1.16; 95% confidence interval [CI], 0.73-1.85). In a multivariable analysis, the Charlson comorbidity score (OR, 1.37; 95% CI, 1.18-1.58) and urgent PCI (OR, 1.75; 95% CI, 1.03-3.00) were associated with increased death or MI. Among patients with drug-eluting stents, the use of low-dose aspirin did not predispose them to death or MI (adjusted OR, 1.12, 95% CI, 0.53-2.34). In this large contemporary analysis of PCI patients, no differences in death or MI were observed at 1 year between patients discharged on low-dose aspirin 81 mg compared to patients on a higher dose.
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The Journal of invasive cardiology
The accurate assessment of a target coronary lesion and appropriate stent selection is important ... more The accurate assessment of a target coronary lesion and appropriate stent selection is important in ensuring procedural success during percutaneous coronary intervention (PCI). Though quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) are available, stent selection is most commonly performed by visual estimation alone. Computed tomographic coronary angiography (CTA) has been shown to correlate well with QCA and IVUS in the assessment of coronary stenoses and may also have a role in stent guidance. Patients awaiting elective PCI underwent CTA. Blinded observers assessed lesion characteristics using: CTA, QCA, IVUS and visual estimation. Luminal diameters, lesion lengths, ACC/AHA lesion types and CTA-suggested stent sizes were compared. A total of 17 patients (26 lesions) were evaluated. There was good correlation between CTA and IVUS for luminal diameter and for lesion length (r = 0.86 and 0.71, respectively). Similarly, the inter-test variability between the...
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Canadian Journal of Cardiology, 2015
Transcatheter aortic valve implantation (TAVI) is the definitive therapy for high-risk patients w... more Transcatheter aortic valve implantation (TAVI) is the definitive therapy for high-risk patients with severe aortic stenosis. The aim of this study was to determine the effect of non-transfemoral access on clinical outcomes in TAVI. We conducted a computerized literature search on SCOPUS and selected all studies published in the English language, from 2002 until March 12 2014, that compared transfemoral access with a non-transfemoral access cohort. Two independent reviewers evaluated the studies and extracted data for analysis. A total 17,020 patients (11,079 transfemoral, 5941 non-transfemoral) encompassing 28 studies underwent TAVI between 2007 to 2013. Overall, the 30-day mortality was 4.7% with the transfemoral approach and 8.1% with a non-transfemoral approach (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.49-0.64; P < 0.01). The 1-year mortality was 16.4% with transfemoral access and 24.8% with non-transfemoral access (OR, 0.68; 95% CI, 0.60-0.75; P < 0.01). Transfemoral access was associated with a greater incidence of vascular complications (OR, 2.1; 95% CI, 1.48-2.99; P < 0.01) but a lower rate of surgical conversion (OR, 0.59; 95% CI, 0.42-0.81; P < 0.01) and similar bleeding (OR, 1.01; 95% CI, 0.81-1.27; P = 0.91) compared with non-transfemoral access. The incidence of cerebrovascular events was similar in both groups (1.6% vs 2.1%; OR, 0.86; 95% CI, 0.64-1.15; P = 0.31). Transfemoral access was associated with lower rate of 30-day and 1-year mortality compared with non-transfemoral access for TAVI. Randomized studies are needed to ascertain the effect of alternative access sites on clinical outcomes in prohibitive-risk, high-risk, and intermediate-risk populations, using currently available technologies.
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Papers by Christopher Glover