S E Fremes

University of Toronto, Toronto, Ontario, Canada

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Publications (192)1042.5 Total impact

  • Saswata Deb, Stephen E. Fremes
    Seminars in Thoracic and Cardiovascular Surgery. 11/2014;
  • Saswata Deb, Stephen E Fremes
    The Journal of thoracic and cardiovascular surgery. 11/2014;
  • Saswata Deb, Stephen E Fremes
    The Journal of thoracic and cardiovascular surgery. 10/2014;
  • Canadian Medical Association Journal 09/2014; · 6.47 Impact Factor
  • Source
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    ABSTRACT: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction.
    Trials. 08/2014; 15(1):339.
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    ABSTRACT: Much is known about the short-term risks of stroke following cardiac surgery. We examined the rate and predictors of long-term stroke in a cohort of patients who underwent cardiac surgery.
    07/2014;
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    ABSTRACT: The study objective was to determine the impact of diabetes on radial artery and saphenous vein graft occlusion and clinical outcomes more than 5 years after coronary artery bypass surgery in the multicenter Radial Artery Patency Study (NCT00187356).
    The Journal of thoracic and cardiovascular surgery. 07/2014;
  • European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2014; · 2.40 Impact Factor
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    ABSTRACT: Background There is increasing demand for transcatheter aortic valve replacement (TAVR) as the primary treatment option for patients with severe aortic stenosis (AS) who are high risk surgical candidates or inoperable. We used mathematical simulation models to estimate the hypothetical effectiveness of TAVR with increasing wait-times. Methods We applied discrete event modelling, using data from the Placement of Aortic Transcatheter Valves (PARTNER) trials. We compared TAVR to medical therapy in the inoperable cohort, and compared TAVR to conventional aortic valve surgery in the high risk cohort. One-year mortality and wait-time deaths were calculated in different scenarios by varying TAVR wait-times from 10 days to 180 days, while maintaining a constant wait-time for surgery at a mean of 15.6 days Results In the inoperable cohort, the 1-year mortality for medical therapy was 50%. When the TAVR wait-time was 10 days, the TAVR wait-time mortality was 1.9% with a 1 year mortality of 31.5%. TAVR wait-time deaths increased to 28.9% with a 180-day wait, with a 1-year mortality of 41.4%. In the high risk cohort, the wait-time deaths and 1-year mortality for the surgical patients were 2.5% and 27% respectively. The TAVR wait-time deaths increased from 2.2% with a 10-day wait to 22.4% with a 180-day wait, and a corresponding increase in 1-year mortality from 24.5% to 32.6%. Mortality with TAVR exceeded surgery when TAVR wait-times exceeded 60 days. Conclusion Modest increases in TAVR wait-times have substantial impact on the effectiveness of TAVR in both inoperable patients and high risk surgical candidates.
    The Canadian journal of cardiology 01/2014; · 3.12 Impact Factor
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    ABSTRACT: Neointimal hyperplasia secondary to vascular smooth muscle cell (VSMC) activation limits the long-term patency of saphenous vein grafts (SVGs). We compared markers of vascular injury and VSMC activation in SVGs harvested using the pedicled 'no-touch' (NT) vs the conventional (CON) technique. Patients undergoing coronary artery bypass surgery were enrolled in the PATENT SVG trial (clinicaltrials.gov NCT01488084). Patients were randomly allocated to have SVGs harvested with the NT technique from one leg and the CON method from the other. SVG segments underwent morphometry, histological and electron microscopy assessments and transcript measurements of VSMC activation and differentiation markers. Leg wound functional recovery and harvest site complications were assessed using a quality-of-life questionnaire. A total of 17 patients (65.3 ± 7.3 years) were enrolled. SVGs harvested using the NT vs CON technique exhibited preserved intimal, medial and adventitial architecture. CON harvest was associated with greater medial Kruppel-like factor 4 transcript levels (0.26 ± 0.05 vs 0.11 ± 0.02, P < 0.05). CON samples had significantly lower medial serum response factor (0.53 ± 0.11 vs 1.44 ± 0.50, P < 0.05) and myocardin (0.59 ± 0.08 vs 1.33 ± 0.33, P < 0.05) transcript levels. MicroRNA-145, an inhibitor of VSMC activation and differentiation, was higher in the NT vs CON samples (1.84 ± 1.03 vs 0.50 ± 0.19, P < 0.05). Leg assessment scores were worse in the NT legs at 3 months, but similar to CON scores at 12 months. SVGs harvested using the 'NT' technique exhibit an early molecular and morphological pattern consistent with decreased VSMC activation compared with CON harvesting. Functional leg recovery was similar in both groups at 12 months. Larger studies are required to corroborate these findings.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2013; · 2.40 Impact Factor
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    ABSTRACT: To identify novel predictors for coronary artery bypass grafting failure, we probed for associations with known clinical and biochemical risk factors for atherosclerosis. We also used microarray analysis to identify novel single nucleotide polymorphisms to better understand the genetics and pathogenesis of graft occlusion. The present study was a nested case-control substudy of the Radial Artery Patency Study 5-year follow-up data. From 1996 to 2001, 87 patients underwent coronary artery bypass grafting. Of these, 26 patients (29.9%) had an occluded study graft (saphenous vein or radial artery) at 8.0 ± 1.1 years. The clinical parameters, late angiography, blood biomarker levels, and surgical outcomes data were included in a multivariate analysis to determine the independent predictors of graft failure. The risk factors of graft failure were fibrinogen (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.33-11.63; P = .01), creatinine (OR, 1.06; 95% CI, 1.02-1.10; P = .006), and diabetes mellitus (OR, 5.15; 95% CI, 1.08-24.59; P = .04). High-density lipoprotein (OR, 0.74; 95% CI, 0.53-1.02; P = .06) was weakly protective; however, low-density lipoprotein and total cholesterol were not predictors. We then identified the association of several human single nucleotide polymorphisms with graft failure, including mutations in glutathione-S-transferase α3. Human coronary arteries and bypass grafts demonstrated increased protein expression of glutathione-S-transferase α3, a known cardioprotective factor, in the atherosclerotic regions and surrounding adventitial tissues. We identified diabetes as a potential clinical predictor and plasma fibrinogen, creatinine, and high-density lipoprotein as potential novel biomarkers. These might help risk stratify patients for the development of graft failure. We also demonstrated a novel association between glutathione-S-transferase α3 and graft failure.
    The Journal of thoracic and cardiovascular surgery 12/2013; · 3.41 Impact Factor
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    ABSTRACT: IMPORTANCE Ischemic heart disease is the leading cause of death globally. Coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) are the revascularization options for ischemic heart disease. However, the choice of the most appropriate revascularization modality is controversial in some patient subgroups. OBJECTIVE To summarize the current evidence comparing the effectiveness of CABG surgery and PCI in patients with unprotected left main disease (ULMD, in which there is >50% left main coronary stenosis without protective bypass grafts), multivessel coronary artery disease (CAD), diabetes, or left ventricular dysfunction (LVD). EVIDENCE REVIEW A search of OvidSP MEDLINE, EMBASE, and Cochrane databases between January 2007 and June 2013, limited to randomized clinical trials (RCTs) and meta-analysis of trials and/or observational studies comparing CABG surgery with PCI was performed. Bibliographies of relevant studies were also searched. Mortality and major adverse cardiac and cerebrovascular events (MACCE, defined as all-cause mortality, myocardial infarction, stroke, and repeat revascularization) were reported wherever possible. FINDINGS Thirteen RCTs and 5 meta-analyses were included. CABG surgery should be recommended in patients with ULMD, multivessel CAD, or LVD, if the severity of coronary disease is deemed to be complex (SYNTAX >22) due to lower cardiac events associated with CABG surgery. In cases in which coronary disease is less complex (SYNTAX ≤22) and/or the patient is a higher surgical risk, PCI should be considered. For patients with diabetes and multivessel CAD, CABG surgery should be recommended as standard therapy irrespective of the severity of coronary anatomy, given improved long-term survival and lower cardiac events (5-year MACCE, 18.7% for CABG surgery vs 26.6% for PCI; P = .005). Overall, the incidence of repeat revascularization is higher after PCI, whereas stroke is higher after CABG surgery. Current literature emphasizes the importance of a heart-team approach that should consider coronary anatomy, patient characteristics, and local expertise in revascularization options. Literature pertaining to revascularization options in LVD is scarce predominantly due to LVD being an exclusion factor in most studies. CONCLUSIONS AND RELEVANCE Both CABG surgery and PCI are reasonable options for patients with advanced CAD. Patients with diabetes generally have better outcomes with CABG surgery than PCI. In cases of ULMD, multivessel CAD, or LVD, CABG surgery should be favored in patients with complex coronary lesions and anatomy and PCI in less complicated coronary disease or deemed a high surgical risk. A heart-team approach should evaluate coronary disease complexity, patient comorbidities, patient preferences, and local expertise.
    JAMA The Journal of the American Medical Association 11/2013; 310(19):2086-95. · 29.98 Impact Factor
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    ABSTRACT: Purpose: There is increasing demand for transcatheter aortic valve replacement (TAVR) as the primary treatment option for patients with severe aortic stenosis (AS) who are high risk surgical candidates or inoperable. TAVR is typically limited to centers of excellence with restricted capacity, thereby causing prolonged wait-times. Our objective was to use mathematical simulation models to estimate the hypothetical effectiveness of TAVR with increasing wait-times, when compared to either conservative medical therapy in inoperable candidates or conventional surgical aortic valve surgery in high risk candidates. Methods: We developed a fully probabilistic discrete event model, using input data from the randomized controlled Placement of Aortic Transcatheter Valves (PARTNER) trials. We evaluated two populations separately: a) in the high risk surgical cohort, we compared TAVR to conventional aortic valve surgery; b) in the inoperable cohort, we compared TAVR to conservative medical therapy. We evaluated 7 scenarios with hypothetical TAVR wait-times ranging from 10 days to 180 days. The main outcome was 1-year mortality and wait-time deaths. Results: In the inoperable cohort, the mean 1-year mortality for the conservative medical therapy arm was approximately 50%. When the TAVR wait-time was 10 days, the mean TAVR wait-time mortality was 1.9% with a 1 year mortality of 31.5%. Mean TAVR wait-time deaths increased to 28.9% with a 180-day wait, with a corresponding mean 1-year mortality of 41.4%. In the high risk cohort, the wait-time deaths and mean 1-year mortality for the surgical patients were 2.5% and 27% respectively in all scenarios. The TAVR wait-time deaths increased from 2.2% at a 10-day wait to 22.4% at a 180-day wait, with a corresponding increase in 1-year mortality from 24.5% to 32.6%. The 1-year mortality in the TAVR group exceeded that in the surgical group at wait-times greater than 60 days. Conclusion: We found that modest increases in TAVR wait-times would have substantial impact on the effectiveness of TAVR in both inoperable patients and high risk surgical candidates. In the high-risk surgical candidates, at wait-times beyond 60 days, TAVR was less effective on average compared to conventional surgery. Our results highlight the importance of aggressive wait-time management for TAVR in severe AS.
    The 35th Annual Meeting of the Society for Medical Decision Making; 10/2013
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    ABSTRACT: Occlusion of the left atrial appendage (LAA) is a potential alternative to anticoagulation for patients with atrial fibrillation (AF); however, evidence of its safety and efficacy is lacking. The Left Atrial Appendage Occlusion Study II (LAAOS II) explored the feasibility of a definitive trial of LAA occlusion for stroke prevention in AF. A cross-sectional study of 1889 consecutive patients undergoing cardiac surgery was performed to determine the prevalence of AF and risk factors for stroke. We also randomized 51 patients with AF and increased stroke risk to LAA occlusion (n = 26) or no occlusion and oral anticoagulation (n = 25) to assess the rate of recruitment and the safety of LAA amputation. In the cross-sectional study, 204 patients (10.8%) had AF and 98 (5.2%) met trial eligibility. Fifty-one patients were recruited into the trial at a rate of 1.6 patients per centre per month. No patient with occlusion had significant bleeding at the LAA site. At 1 year, 4 patients (15.4%) in the occlusion arm and 5 patients (20.0%) in the no-occlusion arm experienced death, myocardial infarction (MI), stroke, noncerebral systemic emboli, or major bleeding (relative risk [RR], 0.71; 95% confidence interval [CI], 0.19-2.66; P = 0.61). The predominant component of the composite was stroke, with 1 in the occlusion arm and 3 in the no-occlusion arm. LAA occlusion can be safely performed at the time of cardiac surgery. A large trial to evaluate the clinical efficacy of LAA occlusion in patients undergoing cardiac surgery is possible in motivated centres with some modifications to the design of LAAOS II.
    The Canadian journal of cardiology 09/2013; · 3.12 Impact Factor
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    ABSTRACT: Transcatheter aortic valve implantation with the self-expandable CoreValve (CV) and the balloon-expandable Edwards SAPIEN (ES) bioprostheses has been widely used for the treatment of severe aortic stenosis. However, a direct comparison of the hemodynamic results associated with these 2 prostheses is lacking. The aim of the present study was to compare the hemodynamic performance of both bioprostheses. A total of 41 patients who underwent transcatheter aortic valve implantation with the CV prosthesis were matched 1:1 for prosthesis size (26 mm), aortic annulus size, left ventricular ejection fraction, body surface area, and body mass index with patients who underwent transcatheter aortic valve implantation with the ES prosthesis. Doppler-echocardiographic data were prospectively collected before the intervention and at hospital discharge, and all examinations were sent to, and analyzed in, a central echocardiography core laboratory. The mean transprosthetic residual gradient was lower (p = 0.024) in the CV group (7.9 ± 3.1 mm Hg) than in the ES group (9.7 ± 3.8 mm Hg). The effective orifice area tended to be greater in the CV group (1.58 ± 0.31 cm(2) vs 1.49 ± 0.24 cm(2), p = 0.10). The incidence of severe prosthesis-patient mismatch was, however, similar between the 2 groups (effective orifice area indexed to the body surface area ≤0.65 cm(2)/m(2); CV 9.8%, ES 9.8%, p = 1.0). The incidence of paravalvular aortic regurgitation was greater with the CV (grade 1 or more in 85.4%, grade 2 or more in 39%) than with the ES (grade 1 or more in 58.5%, grade 2 or more in 22%; p = 0.001). The number and extent of paravalvular leaks were greater in the CV group (p <0.01 for both comparisons). In conclusion, transcatheter aortic valve implantation with the CV prosthesis was associated with a lower residual gradient but a greater rate of paravalvular aortic regurgitation compared to the ES prosthesis. The potential clinical consequences of the differences in hemodynamic performance between these transcatheter heart valves needs to be addressed in future studies.
    The American journal of cardiology 01/2013; · 3.58 Impact Factor
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    ABSTRACT: Transcatheter aortic valve implantation (TAVI) has emerged as an important treatment for patients with severe symptomatic aortic stenosis who are at high operative risk, but accurate estimates of serious adverse effects in contemporary practice are not available. To quantify the adverse effects associated with TAVI, and to evaluate whether the type of transcatheter valve and the route of valve implantation are associated with differences in adverse outcomes. PubMed to 5 May 2012. All studies that included at least 100 patients who had TAVI and reported at least 1 outcome of interest. Two reviewers abstracted the data independently. A random-effects model was used to combine data on adverse outcomes and conduct stratified analyses. A total of 49 studies enrolling 16 063 patients met the inclusion criteria. Overall 30-day and 1-year survival after TAVI were 91.9% (95% CI, 91.1% to 92.8%) and 79.2% (CI, 76.9% to 81.4%), respectively. Heart block requiring permanent pacemaker implantation was the most common adverse outcome (13.1%) and was 5 times more common with the CoreValve (Medtronic, Minneapolis, Minnesota) than the Sapien valve (Edwards Lifesciences, Irving, California) implanted using the transarterial route (25.2% vs. 5.0%, respectively). The overall rate of vascular complications was 10.4% and was highest with transarterial implantation of the Sapien valve (22.3%). Acute renal failure requiring renal replacement therapy was the third most common complication, occurring in 4.9% of patients. Rates of major vascular complications may be overestimated owing to rapidly evolving TAVI technology. The most common adverse effects associated with TAVI are heart block, vascular complications, and renal failure. The type of transcatheter valve and the route of implantation are associated with observed variations in the risks for some adverse effects. Heart and Stroke Foundation of Canada.
    Annals of internal medicine 01/2013; 158(1):35-46. · 13.98 Impact Factor
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    The American Journal of Cardiology 01/2013; · 3.21 Impact Factor
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    ABSTRACT: BACKGROUND: Graft Imaging to Improve Patency (GRIIP), a single-center, randomized blinded clinical trial, reported that intraoperative graft assessment with graft revision according to a priori criteria of transit time flowmetry (TTF) and intraoperative fluorescent angiography did not improve graft patency at one year after coronary artery bypass grafting (CABG) when compared with standard intraoperative management. The objective of this study is to investigate whether other TTF values are more predictive of the saphenous vein graft (SVG) failure and/or clinical outcomes. METHODS: This is a case control retrospective study of 65 SVGs from 44 patients from GRIIP. Study outcomes were graft patency at 12 months and major adverse cardiac events (MACE; death, myocardial infarction, repeat revascularization). RESULTS: Twenty-two SVGs were occluded. In receiver operating characteristic curve analysis, TTF mean flow was significantly predictive of one-year SVG failure (area under the curve = 0.698, p < 0.01), and 31 mL/min was the best cut-off value (p = 0.017, sensitivity 63.6%, specificity 67.4%). The risk of graft occlusion was 14/28, 50% for grafts with mean flow <31 mL/min and 8/37, 21.6% for grafts with mean flow ≥31 mL/min. In logistic regression models, mean flow was a significant predictor of early SVG failure (Odds Ratio 0.95 [0.91-0.99] per mL/min, p = 0.014) whereas other TTF values, patient comorbidities, and/or medication at discharge were not. However, TTF values were not predictive of MACE. CONCLUSIONS: TTF can identify non-functional grafts during CABG, but is of questionable value to improve one-year graft patency.
    Journal of Cardiac Surgery 11/2012; · 1.35 Impact Factor
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    ABSTRACT: The purpose of this study was to present radial and saphenous vein graft (SVG) occlusion results more than 5 years following coronary artery bypass surgery. In the RAPS (Radial Artery Patency Study) study, complete graft occlusion was less frequent in radial artery compared with SVG 1 year post-operatively while functional occlusion (Thrombolysis In Myocardial Infarction flow grade 0, 1, 2) was similar. A total of 510 patients <80 years of age undergoing primary isolated nonemergent coronary artery bypass grafting with 3-vessel disease were initially enrolled in 9 Canadian centers. Target vessels for the radial artery and study SVG were the right and circumflex coronary arteries, which had >70% proximal stenosis. Within-patient randomization was performed; the radial artery was randomized to either the right or circumflex territory and the study SVG was used for the other territory. The primary endpoint was functional graft occlusion by invasive angiography at least 5 years following surgery. Complete graft occlusion by invasive angiography or computed tomography angiography was a secondary endpoint. A total of 269 patients underwent late angiography (234 invasive angiography, 35 computed tomography angiography) at a mean of 7.7 ± 1.5 years after surgery. The frequency of functional graft occlusion was lower in radial arteries compared with SVGs (28 of 234 [12.0%] vs. 46 of 234 [19.7%]; p = 0.03 by McNemar's test). The frequency of complete graft occlusion was also significantly lower in radial compared with SVGs (24 of 269 [8.9%] vs. 50 of 269 [18.6%]; p = 0.002). Radial arteries are associated with reduced rates of functional and complete graft occlusion compared with SVGs more than 5 years following surgery. (Multicentre Radial Artery Patency Study: 5 Year Results; NCT00187356).
    Journal of the American College of Cardiology 07/2012; 60(1):28-35. · 14.09 Impact Factor
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    ABSTRACT: Patients with severe symptomatic aortic stenosis have a poor prognosis with medical management alone, and balloon aortic valvuloplasty has failed to provide durable clinical benefit. Open surgical replacement of the aortic valve can improve symptoms and survival. Recently, transcatheter aortic valve implantation (TAVI) has been demonstrated to improve survival, quality of life, and functional status in nonoperable patients and to be a viable option for patients in whom the risk of open surgical morbidity or mortality is high. This Canadian Cardiovascular Society position statement represents the consensus of a representative group of cardiologists and cardiac surgeons as to the current, but evolving, role of this less-invasive new therapy. Specific recommendations are provided for selection of patients for TAVI vs surgical aortic valve replacement for native valves and for bioprostheses, approaches to patient evaluation for TAVI, appropriate constitution of multidisciplinary teams involved in performing TAVI, essential facilities that are needed to perform TAVI safely and effectively, and training/qualifications for TAVI operators. Cost considerations, complication rates, and the quality of the available evidence are also discussed. It is hoped that this consensus document will prove to be a useful resource for health professionals, institutions, departments, and decision-making bodies dealing with this important and rapidly evolving therapy.
    The Canadian journal of cardiology 06/2012; 28(5):520-8. · 3.12 Impact Factor

Publication Stats

3k Citations
1,042.50 Total Impact Points

Institutions

  • 1984–2014
    • University of Toronto
      • • Division of Cardiac Surgery
      • • Institute for Clinical Evaluative Sciences
      • • Department of Surgery
      • • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 1993–2012
    • Sunnybrook Health Sciences Centre
      • Division of Cardiology
      Toronto, Ontario, Canada
  • 2004–2008
    • Institute for Clinical Evaluative Sciences
      Toronto, Ontario, Canada
  • 2006
    • Women's College Hospital
      Toronto, Ontario, Canada
  • 2001–2004
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 2003
    • The Toronto Centre for Phenogenomics
      Toronto, Ontario, Canada
  • 2000
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
  • 1996
    • University of British Columbia - Vancouver
      • Department of Surgery
      Vancouver, British Columbia, Canada
  • 1990
    • Toronto Western Hospital
      Toronto, Ontario, Canada