One-time screening for abdominal aortic aneurysm in Ontario, Canada: a model-based cost-utility analysis.

BACKGROUND: Screening programs for abdominal aortic aneurysm (AAA) are not available in Canada. We sought to determine the effectiveness and costutility of AAA screening in Ontario. METHODS: We compared one-time ultrasonography-based AAA screening for people aged 65 years to no screening using a fully probabilistic Markov model with a lifetime horizon. We estimated life-years, quality-adjusted life-years (QALYs), AAA-related deaths, number needed to screen to prevent 1 AAA-related death and costs (in Canadian dollars) from the perspective of the Ontario Ministry of Health. We retrieved model inputs from literature, Statistics Canada, and the Ontario Case Costing Initiative. RESULTS: Screening reduced AAA-related deaths by 84.9% among males and 81.0% among females. Compared with no screening, screening resulted in 0.04 (18.96 v. 18.92) additional life-years and 0.04 (14.95 v. 14.91) additional QALYs at an incremental cost of $80 per person among males. Among females, screening resulted in 0.02 (21.25 v. 21.23) additional life-years and 0.01 (16.20 v. 16.19) additional QALYs at an incremental cost of $11 per person. At a willingness-to-pay of $50 000 per year, screening was cost-effective in 84% (males) and 90% (females) of model iterations. Screening was increasingly cost-effective with higher AAA prevalence. INTERPRETATION: Screening for AAA among people aged 65 years in Ontario was associated with fewer AAA-related deaths and favourable cost-effectiveness. To maximize QALY gains per dollar spent and AAA-related deaths prevented, AAA screening programs should be designed to ensure that populations with high prevalence of AAA participate.

Feasibility of patchless proximal profundoplasty and common femoral endarterectomy.

BACKGROUND: Typical repair of common femoral artery (CFA) occlusive disease involves surgical endarterectomy followed by patch closure; however, prosthetic materials may become infected. In addition, in our institution, we have experienced an increased incidence of severe patch-related restenosis. We describe a technique for CFA endarterectomy and patchless proximal profundoplasty, and evaluate its feasibility. METHODS: We performed a single-centre retrospective cohort study of patients who, between July 1, 2020, and June 30, 2021, underwent a procedure that consisted of transection of the superficial femoral artery (SFA) off the femoral bifurcation in a bevelled manner, eversion endarterectomy of the SFA, remote-type endarterectomy of the CFA, direct visualization of the end point in the profunda femoris artery (PFA) with a longitudinal arteriotomy extension if needed and reimplantation of the SFA "hood" as a patch. We collected clinical information and outcomes from the patients' charts. RESULTS: Ten patients who underwent a patchless profundoplasty procedure during the study period were identified. Indications for repair included tissue loss (3 patients), rest pain (2 patients), claudication (3 patients) and establishing access for other procedures (2 patients). Profunda femoris artery arteriotomy extensions were used in 5 cases. Six cases included simultaneous iliac or infrainguinal revascularization. All cases were technically successful. There was 1 intraoperative complication of remote tibial balloon angioplasty tear. The mean follow-up time was 199 (range 29-381) days. There were no surgical site infections. All patients were asymptomatic, with patent CFAs, at last follow-up. There was 1 case of surgical site restenosis and 1 reintervention for remote stenosis. The average increase in ankle and toe brachial indices was 44% and 75%, respectively. One patient was readmitted for gastrointestinal bleeding. One patient died from an acute myocardial infarction, on postoperative day 34. CONCLUSION: The patchless profundoplasty technique is feasible and results in autologous anatomic repair of CFA disease without the need for vein, and allows direct visualization and tacking sutures of the proximal PFA. This technique may replace the ubiquitous vascular procedure of patch arterioplasty of the CFA, depending on the anatomic configuration.

Inflammatory bowel disease and pregnancy: evidence, uncertainty and patient decision-making.

Inflammatory bowel disease (IBD) often affects women during their child-bearing years. Management of a pregnant IBD patient, or a patient contemplating pregnancy, poses unique challenges and can be quite daunting. Knowledge of the basic interplay among disease, normal host physiology and pregnancy is vital to managing these patients. One of the most important advances in the management of IBD over the past decade has been the finding that normal pregnancy outcomes can be achieved when a woman enters the pregnancy in remission. New insights into the safety of a wider spectrum of drugs in these patients has allowed for increased success in IBD management. The evidence supporting medical interventions including biological therapy such as antibodies to tumour necrosis factor agents is reviewed. Once the treating physician understands this complex relationship, management of the pregnant IBD patient can often become a rewarding experience.

Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac function.

OBJECTIVE: Recent evidence suggests that the effects of mesenchymal progenitor cell transplantation into the infarcted myocardium might be mediated by local paracrine angiogenesis. We compared the effects of mesenchymal progenitor cell transplantation versus those of a primarily angiogenic cell, the endothelial progenitor cell, in a rat model of myocardial infarction. METHODS: Twenty-one days after left anterior descending artery ligation, rats were injected in their infarcted anterior myocardium with 1 x 10(6) mesenchymal progenitor cells, 1 x 10(6) endothelial progenitor cells, 5 x 10(5) mesenchymal progenitor cells plus 5 x 10(5) endothelial progenitor cells, or phosphate-buffered saline (n = 6-8 per group). Echocardiography was performed before injection and 4 weeks later, after which rats were killed and immunohistochemical analyses performed. RESULTS: Connexin43 density was greater in cell-treated groups compared with that seen in the phosphate-buffered saline group (by 91.6% +/- 15.2%, P < .001), with no observed difference between cell-treated groups (P > or = .3). Endothelial progenitor cell treatment increased arteriolar density within the infarct border zone (by 297%, 205%, and 101% vs phosphate-buffered saline, mesenchymal progenitor cell, and mesenchymal progenitor cell/endothelial progenitor cell treatment, respectively; P < .01). Postoperative left ventricular ejection fraction (endothelial progenitor cell: 68.3% +/- 9.8% vs mesenchymal progenitor cell/endothelial progenitor cell: 55.0% +/- 11.1%, mesenchymal progenitor cell: 53.0% +/- 6.0%, and phosphate-buffered saline: 49.6% +/- 9.5%) and fractional shortening (endothelial progenitor cell: 32.4% +/- 5.1% vs mesenchymal progenitor cell: 22.5% +/- 5.4% and phosphate-buffered saline: 21.3% +/- 5.3%) were greater in endothelial progenitor cell-treated rats versus those receiving other treatments (all P < .05). Only endothelial progenitor cells prevented further contractile deterioration compared with baseline values (P = .8), whereas other groups had continued loss of function after treatment. CONCLUSION: Compared with the use of mesenchymal progenitor cells, cell transplantation with endothelial progenitor cells after myocardial infarction resulted in better neovascularization and contractility. This suggests that angiogenesis is an important mechanism in attenuating the progression of left ventricular dysfunction after myocardial infarction.

Tissue-engineered injectable collagen-based matrices for improved cell delivery and vascularization of ischemic tissue using CD133+ progenitors expanded from the peripheral blood.

BACKGROUND: The use of stem and/or progenitor cells to achieve potent vasculogenesis in humans has been hindered by low cell numbers, implant capacity, and survival. This study investigated the expansion of CD133+ cells and the use of an injectable collagen-based tissue engineered matrix to support cell delivery and implantation within target ischemic tissue. METHODS AND RESULTS: Adult human CD133+ progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133- cell fractions, and delivered within an injectable collagen-based matrix into the ischemic hindlimb of athymic rats. Controls received injections of phosphate-buffered saline, matrix, or CD133+ cells alone. Immunohistochemistry of hindlimb muscle 2 weeks after treatment revealed that the number of CD133+ cells retained within the target site was >2-fold greater when delivered by matrix than when delivered alone (P<0.01). The transplanted CD133+ cells incorporated into vascular structures, and the matrix itself also was vascularized. Rats that received matrix and CD133+ cells demonstrated greater intramuscular arteriole and capillary density than other treatment groups (P<0.05 and P<0.01, respectively). CONCLUSIONS: Compared with other experimental approaches, treatment of ischemic muscle tissue with generated CD133+ progenitor cells delivered in an injectable collagen-based matrix significantly improved the restoration of a vascular network. This work demonstrates a novel approach for the expansion and delivery of blood CD133+ cells with resultant improvement of their implantation and vasculogenic capacity.

Natural history and predictors of outcome in patients with concomitant functional mitral regurgitation at the time of aortic valve replacement.

BACKGROUND: Concomitant functional mitral regurgitation (FMR) in patients undergoing aortic valve replacement (AVR) is frequently not corrected because it may improve after AVR; however, data supporting this assumption are sparse. We ascertained the impact of clinical and echocardiographic parameters on the outcome of patients with or without concomitant FMR at the time of AVR. METHODS AND RESULTS: Clinical and echocardiographic follow-up was performed on 848 patients who underwent AVR after 1990. Risk factors for mortality and a composite outcome of heart failure (CHF) symptoms, CHF death, or subsequent mitral repair or replacement, were examined with bootstrapped Cox proportional hazard models. Follow-up was 4591 patient-years (mean 5.4+/-3.4 years; maximum 14.2 years). FMR > or = 2+ had no independent adverse effect on survival in patients with aortic stenosis (AS) or insufficiency (AI). However, AS patients with FMR > or = 2+ and 1 additional risk factor (left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation) were at increased risk for the composite outcome (hazard ratio [HR]: 2.7; P=0.004). AI patients with FMR > or = 2+ and a left ventricular end-systolic diameter <45 mm were also at risk (HR: 4.0; P=0.02). Clinical risk factors in the AS and AI subgroups were associated with an increased likelihood of mitral regurgitation > or = 2+ at 18 months postoperatively. CONCLUSIONS: AS patients with FMR > or = 2+ and a left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation have a significantly higher risk of CHF and persistent mitral regurgitation after AVR than other AS patients. AI patients with FMR > or = 2+ and a left ventricular end-systolic diameter <45 mm preoperatively are also at increased risk. Others fare well after AVR.

Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch.

BACKGROUND: The long-term outcomes of patients with low-gradient aortic stenosis (LGAS) after aortic valve replacement (AVR) are poorly defined. The purpose of this study was to define the long-term outcomes of LGAS patients after AVR and to evaluate the potential impact of prosthesis-patient mismatch (PPM) in these patients. METHODS AND RESULTS: A cohort of 664 patients undergoing AVR for aortic stenosis after 1990 were followed-up prospectively with annual clinical assessment and echocardiography (total follow-up 3447 patient-years; mean follow-up 5.2+/-3.3 years). LGAS was defined as an aortic valve area <1.2 cm2, a mean transvalvular pressure gradient <40 mm Hg, and a left ventricular (LV) ejection fraction <50%, and was present in 79 patients. Rates and correlates of survival, freedom from congestive heart failure (CHF), and LV mass regression after AVR were determined using multivariate regression methods. Ten-year survival and freedom from CHF after AVR were 72.7+/-7.5% and 68.2+/-9.5%, respectively, for patients with LGAS, compared with 89.6+/-1.8% and 84.1+/-4.2% for patients without LGAS (hazard ratio [HR] for death and postoperative CHF, 3.1+/-1.1 and 2.7+/-0.9, respectively; P<0.01). In LGAS patients, PPM, defined as an indexed effective orifice area < or = 0.85 cm2/m2, was independently associated with increased rates of CHF (HR, 3.6+/-2.2; P=0.039), impaired LV mass regression (P=0.037), and a trend toward increased late mortality (HR, 3.0+/-1.9; P=0.084). CONCLUSIONS: Patients with LGAS have worse long-term outcomes after AVR compared with patients without LGAS. PPM adversely affects the long-term outcomes of LGAS patients and should be avoided in this population.

Generation of CD133+ cells from CD133- peripheral blood mononuclear cells and their properties.

OBJECTIVE: CD133 may be the most specific marker of endothelial progenitor cells (EPCs), which are thought to be largely confined to the bone marrow milieu. This study reports on the phenotypic characterization and functional analysis of human CD133+ cells and their generation from cells in the peripheral circulation. METHODS: Adult human CD133+ and CD133- cells were isolated from peripheral blood mononuclear cells, and the generation of CD133+ cells in culture was attempted using different culture combinations. The phenotypic, migratory, adhesive, and angiogenic properties of the native and generated populations were investigated. RESULTS: In adherent and in suspension culture systems, CD133+ cells also expressing CD34 and VEGFR-2 were successfully derived from a previously CD133- population. The migratory potential of CD133+ cells was enhanced by the presence of the CD133- cells. Also, the CD133+ cells derived from the CD133- cells demonstrated improved adhesion to extracellular matrix and endothelial monolayer substrates, and their contribution to in vitro angiogenesis was enhanced compared to freshly isolated CD133+ cells. CONCLUSIONS: These results demonstrate a source of blood CD133+ cells other than direct mobilization from the bone marrow. Cellular interaction was observed between fractions, with CD133+ cells showing better in vitro function in the presence of CD133- cells. These findings provide a novel source for CD133+ cells and a rationale for the investigation of angiogenic cell recruitment or delivery strategies involving more than one cell type at ischemic sites.

Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells.

OBJECTIVE: Off-pump coronary artery bypass grafting may result in fewer myocardial and vascular complications than on-pump. Although differences in aortic manipulations likely play a role, the systemic responses of endothelial progenitor cells to both types of operations have not been examined. We sought to examine endothelial progenitor cell characteristics after off-pump versus on-pump coronary artery bypass grafting. METHODS: Twenty patients undergoing off-pump or on-pump coronary artery bypass grafting were prospectively enrolled and had endothelial progenitor cells isolated and cultured from their peripheral blood before and 24 hours after surgery. Endothelial progenitor cells were identified by fluorescent dual lectin/low-density lipoprotein binding. Their number, phenotype characteristics, proliferation, migratory function, and viability were determined in a blinded fashion. RESULTS: Patient characteristics and numbers of grafts were equivalent. Endothelial progenitor cells had similar phenotypes between groups before and after surgery. Off-pump and on-pump coronary artery bypass grafting resulted in similar increases in endothelial progenitor cell numbers and showed equivalent proliferation activity. However, endothelial progenitor cell migratory function was higher in off-pump patients (25.3 +/- 5.0 vs 5.0 +/- 1.0 cells per high-powered field for off-pump vs on-pump coronary artery bypass grafting, respectively; P = .04). Postoperative endothelial progenitor cell viability adjusted for preoperative baseline was also higher after off-pump than on-pump coronary artery bypass grafting by 72.4% +/- 14.6% (P = .01). Endothelial progenitor cells of on-pump patients were less viable after surgery than before surgery, whereas the reverse was observed in off-pump patients. CONCLUSIONS: Both on-pump and off-pump coronary artery bypass grafting elicit mobilization of endothelial progenitor cells into the peripheral blood. On-pump coronary artery bypass grafting, however, impairs the migratory function and viability of these vascular repair cells, which are conversely preserved after off-pump surgery. Further work is necessary to determine whether the function and viability of endothelial progenitor cells correlate with vascular outcomes and whether their therapeutic modulation may one day benefit coronary artery bypass grafting patients.

Nitric oxide and the angiogenic response: can we improve the results of therapeutic angiogenesis?

Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dysfunction may play a role in this bench-to-bedside discrepancy has led to further research on the role of endothelial-derived mediators in the angiogenic cascade. One of these mediators is nitric oxide (NO), which plays an integral role in the development and maintenance of a microvascular network and whose local availability is altered in endothelial dysfunction. This article outlines the role of NO in the angiogenic response and discusses possible therapeutic options to optimise endothelial dysfunction and NO availability in patients undergoing angiogenic therapy.