Myocardial assistance by grafting a new bioartificial upgraded myocardium (MAGNUM clinical trial): one year follow-up.

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evaluated intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted ventricles. In 15 patients (aged 54.2 +/- 3.8 years) presenting LV postischemic myocardial scars and with indication for a single OP-CABG, autologous mononuclear bone marrow cells (BMC) were implanted during surgery in the scar. A 3D collagen type I matrix seeded with the same number of BMC was added on top of the scarred area. There was no mortality and no related adverse events (follow-up 15 +/- 4.2 months). NYHA FC improved from 2.3 +/- 0.5 to 1.4 +/- 0.3 (p = 0.005). LV end-diastolic volume evolved from 142 +/- 24 to 117 +/- 21 ml (p = 0.03), and LV filling deceleration time improved from 162 +/- 7 to 196 +/- 8 ms (p = 0.01). Scar area thickness progressed from 6 +/- 1.4 to 9 +/- 1.5 mm (p = 0.005). EF improved from 25 +/- 7% to 33 +/- 5% (p = 0.04). Simultaneous intramyocardial injection of mononuclear bone marrow cells and fixation of a BMC-seeded matrix onto the epicardium is feasible and safe. The cell-seeded collagen matrix seems to increase the thickness of the infarct scar with viable tissues and helps to normalize cardiac wall stress in injured regions, thus limiting ventricular remodeling and improving diastolic function. Patients' improvements cannot be conclusively related to the cells and matrix due to the association of CABG. Cardiac tissue engineering seems to extend the indications and benefits of stem cell therapy in cardiology, becoming a promising way for the creation of a "bioartificial myocardium." Efficacy and safety of this approach should be evaluated in a large randomized controlled trial.

Cellular cardiomyoplasty: clinical application.

Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using autologous patient serum (obtained from plasmapheresis) have been developed by our group. In this article we propose (1) a total autologous cell culture technique and procedures for cell delivery and (2) a clinical trial with appropriate endpoints structured to determine the efficacy of cellular cardiomyoplasty.

Alternatives to heart transplantation: integration of biology with surgery.

Chronic heart failure is one of the major health care issues in terms of increasing number of patients, rate of hospitalizations and costs. Heart transplantation is the best established therapy for patients with severe heart failure. However, the number of donors limits the activity to 5000 heart transplants performed annually worldwide. This limitation has generated alternative treatments. The increase of the interest in the reversibility of the heart failure and the application of new biological alternatives has generated therapeutic strategies designed to integrate biology and medical technologies in order to act to the biomechanical, the molecular and the neurohormonal mechanisms of heart failure. These treatments include cellular cardiomyoplasty, tissue engineering, surgical left ventricular restoration as well as passive and active mechanical ventricular assistance as destination therapy, bridge to recovery or bridge to transplantation. The integrated development of these approaches could offer hopeful treatments, although there is still much to be learned regarding the optimal use of these strategies.

Propagación eléctrica en los mecanismos de torsión y succión en un corazón de tres tiempos / Electrical Propagation in the Mechanisms of Twist and Suction in a Three-phase Heart

Introducción: La hipótesis de Torrent Guasp plantea que los ventrículos están conformados por una banda muscular continua que nace a nivel de la válvula pulmonar y se extiende hasta la raíz aórtica delimitando las dos cavidades ventriculares. Esta anatomía brindaría la interpretación para dos aspectos fundamentales de la dinámica ventricular izquierda: el mecanismo de torsión y el llenado diastólico rápido por efecto de succión. Objetivos: Investigar la activación eléctrica de las bandeletas endocárdica y epicárdica para comprender la torsión ventricular, el mecanismo de succión activa en la fase isovolumétrica diastólica y el significado del volumen residual. Material y métodos: La investigación se realizó mediante un mapeo electroanatómico tridimensional en cinco pacientes. Al ser la bandeleta descendente endocárdica y la ascendente epicárdica, se utilizaron dos vías de abordaje por punción. Resultados: El mapeo tridimensional endoepicárdico demuestra una activación eléctrica de la zona de la lazada apexiana concordante con la contracción sincrónica de las bandeletas descendente y ascendente. La activación simultánea y contrapuesta de la bandeleta ascendente con punto de partida de su activación radial desde la bandeleta descendente, en la zona de entrecruzamiento de ambas, es coherente con la torsión ventricular. La activación tardía de la bandeleta ascendente se compatibiliza con la persistencia de su contracción durante el período inicial de la fase isovolumétrica diastólica (base del mecanismo de succión); se produce sin necesidad de postular activaciones eléctricas posteriores al QRS. Conclusiones: Este trabajo explica el proceso de la torsión ventricular y el mecanismo de succión. Comprueba que la activación de la bandeleta ascendente completa el QRS anulando el concepto tradicional de relajación pasiva en la fase isovolumétrica diastólica.

Background: The hypothesis of Torrent Guasp considers that the ventricular myocardium consists of a continuous muscular band that begins at the level of the pulmonary valve and ends at the level of the aortic root, limiting both ventricular chambers. This anatomy would provide the interpretation for two fundamental aspects of left ventricular dynamics: the mechanism of left ventricular twist and rapid diastolic filling due to the suction effect. Objectives: The aim of this study was to investigate the electrical activation of the endocardial and epicardial bands to understand ventricular twist, the mechanism of active suction during the diastolic isovolumic phase and the significance of the residual volume. Methods: Five patients underwent three-dimensional electroanatomic mapping. As the descending band is endocardial and the ascending band is epicardial, two sites of puncture were used. Results: Three-dimensional endo-epicardial mapping demonstrates an electrical activation sequence in the area of the apex loop in agreement with the synchronic contraction of the descending and ascending band segments. The simultaneous and opposing radial activation of the ascending band segment, starting in the descending band segment, in the area in which both band segments intertwine, is consistent with the mechanism of ventricular twist. The late activation of the ascending band segment is consistent with its persistent contraction during the initial period of the isovolumic diastolic phase (the basis of the suction mechanism), and takes place without need of postulating further electrical activations after the QRS complex. Conclusions: This study explains the process of ventricular twist and the suction mechanism, and demonstrates that the activation of the ascending band segment completes the QRS, ruling out the traditional concept of passive relaxation during the diastolic isovolumic phase.