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Discusses a study of the role of HLA-G molecules in graft rejection and acceptance among heart transplant patients. HLA-Gs protection of the fetus from maternal rejection by natural-killer cells; Assessment of HLA-G expression in endomyocardial biopsies; Support for the hypothesis that HLA-G may be activated during transplantation.

The article discusses the importance of implementing an effective strategy for addressing rheumatic heart disease scourge and to access life-saving cardiac surgery in developing the world. Topics discussed include requirement of treating and preventing rheumatic heart disease (RHD), the impact of the human immunodeficiency virus, and requirement of creating an international working group.

Background: After myocardial infarction (MI), mitral valve (MV) tethering stimulates adaptive leaflet growth, but counterproductive leaflet thickening and fibrosis augment mitral regurgitation (MR), doubling heart failure and mortality. MV fibrosis post-MI is associated with excessive endothelial-to-mesenchymal transition (EMT), driven by transforming growth factor (TGF)-β overexpression. In vitro, losartan-mediated TGF-β inhibition reduces EMT of MV endothelial cells.Objectives: This study tested the hypothesis that profibrotic MV changes post-MI are therapeutically accessible, specifically by losartan-mediated TGF-β inhibition.Methods: The study assessed 17 sheep, including 6 sham-operated control animals and 11 with apical MI and papillary muscle retraction short of producing MR; 6 of the 11 were treated with daily losartan, and 5 were untreated, with flexible epicardial mesh comparably limiting left ventricular (LV) remodeling. LV volumes, tethering, and MV area were quantified by using three-dimensional echocardiography at baseline and at 60 ± 6 days, and excised leaflets were analyzed by histopathology and flow cytometry.Results: Post-MI LV dilation and tethering were comparable in the losartan-treated and untreated LV constraint sheep. Telemetered sensors (n = 6) showed no significant losartan-induced changes in arterial pressure. Losartan strongly reduced leaflet thickness (0.9 ± 0.2 mm vs. 1.6 ± 0.2 mm; p < 0.05; 0.4 ± 0.1 mm sham animals), TGF-β, and downstream phosphorylated extracellular-signal-regulated kinase and EMT (27.2 ± 12.0% vs. 51.6 ± 11.7% α-smooth muscle actin-positive endothelial cells, p < 0.05; 7.2 ± 3.5% sham animals), cellular proliferation, collagen deposition, endothelial cell activation (vascular cell adhesion molecule-1 expression), neovascularization, and cells positive for cluster of differentiation (CD) 45, a hematopoietic marker associated with post-MI valve fibrosis. Leaflet area increased comparably (17%) in constrained and losartan-treated sheep.Conclusions: Profibrotic changes of tethered MV leaflets post-MI can be modulated by losartan without eliminating adaptive growth. Understanding the cellular and molecular mechanisms could provide new opportunities to reduce ischemic MR. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Dynamic cardiomyoplasty (CMP) was proposed as a treatment for refractory heart failure; more than 2000 procedures have been performed worldwide. Heart transplantation was indicated afterwards in some CMP patients with recurrent heart failure symptoms. This study reviews the multicentric French experience with CMP followed by heart transplantation. Methods: From 1985 to 2007, 212 patients (mean age 53±11 years) with refractory heart failure (LVEF=22±9%, mean NYHA 3.2) underwent CMP in France. Heart transplantation was performed in 26 patients (12.3%), mean age: 51±11 years, within 2.3±3 years after CMP. Transplantation was indicated for persistent heart failure, i.e. no immediate improvement after CMP (19%) and for recurring heart failure (81%). Results: The surgical technique of heart transplantation following cardiomyoplasty presents few particularities. Routine extracorporeal bypass was instituted between the vena cavas and the ascending aorta. As in most of these patients the CMP procedure had been performed without the need of extracorporeal circulation, hearts were free of previous cannulations for cardiopulmonary bypass. The latissimus dorsi muscle flap was divided as far as possible inside the left pleural cavity and its vascular pedicle was obturated. The proximal portion of the muscle as well as the muscular pacing electrodes were kept in place in the pleural cavity. The adhesions between the flap and the heart were not released so as to achieve an en bloc resection of the heart and the muscle flap. During removal of the recipient''s heart, care was taken not to injure the left phrenic nerve that was frequently in tight relation with the latissimus dorsi muscle. Heart transplantation was then performed in a routine manner, the donor heart being anastomosed to remnant atria and great vessels. Mean follow-up was 5.5 years (longest 13.5 years). Survival at 10 years was 40% for early heart transplantation (done within 4 months of CMP) and 57% for transplantation performed at 3±2.8 years after CMP. Conclusions: Heart transplantation after CMP is technically feasible. Hospital mortality was higher when urgent transplantation was required. Long-term survival results are similar to those for primary heart transplantation. Cardiomyoplasty, when it fails, does not preclude transplantation, and when indicated, CMP could be considered as a biological bridge to heart transplantation. [Copyright &y& Elsevier]

Aims: We compared two procedures for local myocardial treatment: transepicardial versus transendocardial catheter injection. Transepicardial injections were performed under direct surgical visualization whereas transendocardial injections were performed using electrophysiological guidance. Methods: A left ventricle (LV) myocardial infarction (MI) was surgically created in 14 sheep. At 3 months, gadolinium was injected IV followed by the injection of super paramagnetic iron oxide (SPIO) into MI. Animals were divided in two groups: transepicardial injection (Group I) versus transendocardial (Group II) using “Cell-Fix” catheter injection. This catheter was developed to identify by electrophysiology the infarcted area and to stabilize injections suctioning the device to the endocardium. Postgadolinium delayed-enhancement magnetic resonance imaging (MRI) was performed to stain the infarct size. SPIO injections were used to assess the magnitude of the treated area. The ratio between SPIO black stained treatment areas and white gadolinium stained infarcted areas was calculated using MRI. Results: The electrophysiological recordings by the catheter for the MI versus normal LV wall were: R wave amplitude 4.16 versus 12.08 mV (P = 0.003), slew rate (slope of the signal) 0.36 V/s versus 1.04 V/s (P = 0.008). The ratio of the SPIO diffusion into the MI was 41.2 ± 8.1% for surgical and 63.7 ± 8.2% for percutaneous endocardial injections (P = 0.0132). Conclusion: MRI allows evaluation of the extent of local myocardial treatments. The differences shown between epicardial and endocardial injections concerning the distribution of SPIO can be justified by the methodology of injection and by a more precise MI detection by electrophysiology. In conclusion, electrophysiological recordings to guide injections is superior to direct surgical visualization in terms of injecting into infarcted tissue. [ABSTRACT FROM AUTHOR]