Search

Background The electro-hydraulically actuated Carmat total artificial heart (C-TAH) is designed to replace the heart in patients with end-stage heart failure, either as bridge to transplant or destination therapy. It provides pulsatile flow and contains bio-prosthetic blood contacting materials. A clinical feasibility study was conducted to evaluate the C-TAH safety and performance. Methods Hospitalized patients, at imminent risk of death from irreversible biventricular failure despite optimal medical management, and not eligible for transplant or eligible but on extracorporeal life support, were enrolled. The primary endpoint was 30-days survival. Results Four patients were implanted with the C-TAH, three as destination therapy (ages 76, 68, 74) and one as bridge to transplant (age 58). They had implant times of 74, 270, 254 and 20 days respectively. All patients were free from hemolysis, clinical neurologic events, clinical evidence of thrombus and device-related infections. Hemodynamic and physical recovery allowed two patients to be discharged home for a cumulative duration of 7 months. The anticoagulation management strategy comprised initial unfractionated heparin, from postoperative day 2, followed by low molecular weight heparin and aspirin. An increased D-dimer level was observed in all patients during months 1 to 4. Temporary suspension of heparin anticoagulation resulted in thrombocytopenia and increased fibrin monomer, reversed by resuming anticoagulation with heparin. Causes of death were device-related (2 cases), respiratory failure and multi-organ failure. Conclusions Preliminary clinical results with the C-TAH demonstrated good safety and performance profiles in patients suffering from biventricular failure, which need to be confirmed in a pivotal study. [ABSTRACT FROM AUTHOR]

OBJECTIVES Ventricular constraint devices made of polyester and nitinol have been used to treat heart failure patients. Long-term follow-up has not demonstrated significant benefits, probably due to the lack of effects on myocardial tissue and to the risk of diastolic dysfunction. The goal of this experimental study is to improve ventricular constraint therapy by associating stem cell intrainfarct implantation and a cell-seeded collagen scaffold as an interface between the constraint device and the epicardium. METHODS In a sheep ischaemic model, three study groups were created: Group 1: coronary occlusion without treatment (control group). Group 2: postinfarct ventricular constraint using a polyester device (Acorn CorCap). Group 3: postinfarct treatment with stem cells associated with collagen matrix and the polyester device. Autologous adipose mesenchymal stem cells cultured in hypoxic conditions were injected into the infarct and seeded into the collagen matrix. RESULTS At 3 months, echocardiography showed the limitation of left ventricular end-diastolic volume in animals both treated with constraint devices alone and associated with stem cells/collagen. In Group 3 (stem cell + collagen treatment), significant improvements were found in ejection fraction (EF) and diastolic function evaluated by Doppler-derived mitral deceleration time. In this group, histology showed a reduction of infarct size, with focuses of angiogenesis and minimal fibrosis interface between CorCap and the epicardium due to the interposition of the collagen matrix. CONCLUSIONS Myocardial infarction treated with stem cells associated with a collagen matrix and ventricular constraint device improves systolic and diastolic function, reducing adverse remodelling and fibrosis. The application of bioactive molecules and the recent development of nanobiotechnologies should open the door for the creation of a new semi-degradable ventricular support bioprosthesis, capable of controlled stability or degradation in response to physiological conditions of the left or right heart. [ABSTRACT FROM PUBLISHER]

Electrostimulation (ES) can be defined as a safe physical method to induce stem cell differentiation. The aim of this study is to evaluate the effectiveness of ES on bone marrow mesenchymal stem cells (BMSCs) seeded in collagen scaffolds in terms of proliferation and differentiation into cardiomyocytes. BMSCs were isolated from Wistar rats and seeded into 3D collagen type 1 templates measuring 25 x 25 x 6 mm. Bipolar in vitro ES was performed during 21 days. Electrical impedance and cell proliferation were measured. Expression of cardiac markers was assessed by immunocyto- chemistry. Viscoelasticity of collagen matrix was evaluated. Electrical impedance assessments showed a low resistance of 234±41 Ohms which indicates good electrical conductivity of collagen matrix. Cell proliferation at 570 nm as significantly increased in ES groups after seven day (ES 0.129±0.03 vs non-stimulated control matrix 0.06±0.01, P=0.002) and after 21 days, (ES 0.22±0.04 vs control 0.13±0.01, P=0.01). Immunocytoche mistry of BMSCs after 21 days ES showed positive stain- ing of cardiac markers, troponin I, connexin 43, sarcomeric alpha-actinin, slow myosin, fast myosin and desmin. Staining for BMSCs marker CD29 after 21 days was negative. Electrostimulation of cell-seeded collagen matrix changed stem cell morphology and biochemical characteristics, increasing the expression of cardiac markers. Thus, MSC-derived differentiated cells by electrostimulation grafted in biological scaffolds might result in a convenient tissue engineering source for myocardial diseases. [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]

Objectives: Large animal experimental models of chronic heart failure (HF) permit repeated invasive assessment of cardiovascular function, and evaluation of new medical or surgical therapies. The existing models however fail to achieve stable and long-term HF. The aim of this study was to create a simple and stable chronic model of HF in goat, using both arteriovenous fistula and weekly intravenous doxorubicin injections.Methods: After a preliminary experiment on four goats receiving weekly 1 to 2 mg/kg of doxorubicin, six adult female goats, having had an arteriovenous fistula without signs or symptoms of heart failure, received weekly two different dosages of doxorubicin for 13 weeks: group A (n = 3) received 0.5 mg/kg and group B (n = 3) received 1 mg/kg. After a three-month period without medication, both groups received again 1 mg/kg for four weeks. Cardiac function was assessed by repeated electrocardiographic and echocardiographic examinations.Results: Four goats died during the medication period (one in group A, three in group B). During the period without medication a stable ventricular hypocontractility with left ventricular dilation was observed. Left ventricular dysfunction was more pronounced in group B, and was associated with clinical symptoms of HF.Conclusions: Arteriovenous fistula alone did not produce HF. Its association with doxorubicin injections provides a simple and stable chronic model of HF. This association allows reduction of the required doxorubicin dose and toxicity in animals and in the environment. Depending of the dose of doxorubicin, it is possible to obtain a model of heart dilatation and ventricular hypokinesia with or without clinical symptoms of HF, with a different mortality. [ABSTRACT FROM AUTHOR]