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 5.4Ϯ3.4 years; maximum 14.2 years). FMR Ն2ϩ had no independent adverse effect on survival in patients with aortic stenosis (AS) or insufficiency (AI

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 ϩ 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 CD133ϩ progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133 Ϫ 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

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 5.2Ϯ3.3 years).LGAS was defined as an aortic valve area Ͻ1.2 cm 2 , a mean transvalvular pressure gradient Ͻ40 mm Hg, and a left ventricular (LV) ejection fraction Ͻ50%, 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 72.7Ϯ7.5% and 68.2Ϯ9.5%, respectively, for patients with LGAS, compared with 89.6Ϯ1.8% and 84.1Ϯ4.2% for patients without LGAS (hazard ratio [HR] for death and postoperative CHF, 3.1Ϯ1.1 and 2.7Ϯ0.9, respectively; PϽ0.01). In LGAS patients, PPM, defined as an indexed effective orifice area Յ0.85 cm 2 /m 2 , was independently associated with increased rates of CHF (HR, 3.6Ϯ2.2; Pϭ0.039), impaired LV mass regression (Pϭ0.037), and a trend toward increased late mortality (HR, 3.0Ϯ1.9; Pϭ0.084). Conclusions-Patients withLGAS 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.

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.

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.

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.

We thank Bleiziffer and colleagues for their interest and insightful comments regarding our article 1 describing long-term outcomes after valve replacement for patients with low-gradient aortic stenosis. In our analyses, prosthesis-patient mismatch (PPM) was characterized as an indexed effective orifice area (EOA) of Յ0.85 cm 2 /m 2 because this definition constitutes the most generally accepted criterion for PPM. 2 As Bleiziffer et al note in their letter, the use of geometric internal orifice area as a measure of prosthesis size is limited and does not effectively predict hemodynamic or clinical outcomes. We did not use geometric orifice area in our analyses because geometric orifice area does not account for many valve characteristics that contribute to the EOA, such as prosthesis height, profile, opening angle, and leaflet inertia.We agree with Bleiziffer and colleagues that the EOA derived by Doppler echo continuity equation from individual patients after implantation of the prosthesis may have better quantified the degree of PPM in our study of low-gradient aortic stenosis patients. This methodology has several important limitations, however, related to the difficulties caused by prosthetic valve reverberations in accurately measuring left ventricular outflow diameter after surgery. Moreover, the presence of large localized transprosthetic gradients or nonuniform transprosthetic spatial velocity profiles frequently result in large discrepancies between Doppler echo and actual EOA measurements. 3,4 Therefore, we used fixed values of in vivo EOAs (also known as projected EOAs) for each prosthesis type and size from literature sources of patients with normally functioning prostheses. 2 Projected EOA values can be attributed to patients who have not yet been echocardiographically examined with their new valve prosthesis, and projected EOA values may also be applied in advance of surgery.EOAs derived from individual patients are obviously not available at the time of surgical decision making. The EOA can only be determined after the prosthesis has been inserted, the patient has been weaned from cardiopulmonary bypass, and the preload, afterload, and contractility have normalized. Therefore, the EOA of an individual patient (determined after surgery) has little or no role in predicting whether PPM will be avoided with a given prosthesis type and size. From a practical perspective, projected EOAs have greater interpretability and predictability for surgeons performing aortic valve replacement because projected EOAs can be used to decide whether another prosthesis type or size should be selected or whether aortic root enlargement should be performed before implantation of the prosthetic valve. This provided the rationale for our analyses. DisclosuresNone.

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.