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Editorial |
Department of Cardiovascular Surgery, Pompidou Hospital, 20 rue Leblanc, 75015 Paris, France
Received 18 September 2008;
* Corresponding author. Fax: +33 140728608. (Email: j.chachques{at}brs.aphp.fr).
Key Words: Congestive heart failure • Cardiac assist • Cardiomyoplasty • Latissimus dorsi muscle • Stem cell therapy • Tissue engineering
‘The best way to predict the future is to create it...’
Congestive heart failure (CHF) is the leading cause of hospitalization and death in the developed world. Heart transplantation (HT) is still the most effective therapy for end-stage heart disease, but because of the shortage of donors, there is an increasing interest in more favorable alternatives. This circumstance and the escalating prevalence of end-stage CHF lead to a progressive lengthening of average waiting time, with more patients deteriorating to urgent status, and HT increasingly reserved only for patients in an advanced state of CHF. Even if the availability of donor hearts increases, it is unlikely that donor availability will keep pace with the escalating prevalence of end-stage heart failure. The biomedical improvements and the progress of surgical and intensive care strategies have led to interest in different surgical options for the treatment of patients with end-stage heart disease. Great progress has been made in the development of new surgical approaches, either as a bridge to HT or as recovery and destination therapy.
Latissimus dorsi dynamic cardiomyoplasty (CMP) is an alternative surgical approach for severe CHF in which skeletal muscle works in concert with myocardium to improve hemodynamics via a cardiomyostimulator device, which has a critical role in optimal functioning of the wrapped muscle affecting the clinical status. CMP provides an autologous source of circulatory assistance; presents a low intra-, mid- and long-term mortality and has reduced costs [1–7].
Since 1980, our group has performed experimental studies to achieve a safe and reproducible CMP surgical technique, developing specific electrodes and pacing devices and a postoperative electrostimulation protocol [1]. Following the first clinical CMP case reported by our group in 1985, progress has been carried out in identifying the selection criteria of patient's benefiting from this procedure, in improving the surgical technique and the cardiomyostimulator device [2,3]. Active systolic dynamic assistance has been shown in heart failure models, as well as in many patients, to decrease myocardial stress and improve myocardial energetics [4]. Progress in cardiac and latissimus dorsi synchronization has contributed to obtain a more homogeneous and synchronous biventricular contraction, allowing CMP to act like a sort of biomechanical resynchronization therapy. Functional parameters as LV ejection fraction, stroke volume and stroke work index significantly improved in a phase II multicenter FDA study. This study also revealed consistent improvements in quality of life and NYHA functional class of patients’ benefiting from this procedure [5].
Concerning the mechanisms of action, a reduction in mechanical stress seems to contribute to a reduced level of myocardial apoptosis after CMP. Subsequent recurrence of LV dilatation due to the detrimental evolution of the underlying myocardial disease observed in some cases could, in turn, instigate a return to pathologic levels of wall stress, and to the vicious cycle of apoptotic cell loss and further progressive LV enlargement. Long-term results of dynamic cardiomyoplasty are limited by the patient's preoperative condition and by a high incidence of sudden cardiac death [6,7]. These results could be improved using modified skeletal muscle stimulation protocols and cardioverter-defibrillator implantation.
In this EJCTS issue the article of Salmons [8] shows the scientific advances achieved in the past years regarding the potential of skeletal muscles that should allow exploitation in a more physiological basis the concept of ‘cardiac bioassist’. Present knowledge of the vascular anatomy of the latissimus dorsi muscle (LDM) and the adaptive response of muscle to electrical stimulation would be related with viable and powerful skeletal muscle grafts. Cardiomyoplasty performed with emerging electrostimulation protocols could well provide a reduction of systolic wall stress and provide beat-to-beat assistance in the short-term, together with reverse remodelling and extramyocardial revascularization in the long-term.
In the last years clinical applications of CMP have been expanded to other areas:
Our series strongly suggest that CMP offers a relative secure mid- to long-term bridge to HT allowing critically ill patients to significantly improve their quality of life while waiting for a heart donor and it represents an alternative definitive surgical treatment for LV and RV severe cardiomyopathies [7].
In the field of ‘translational medicine’, the knowledge acquired with dynamic cardiomyoplasty has been applied for regenerative cardiology [14]. Stem cell therapy (cellular cardiomyoplasty) for myocardial regeneration in ischemic and non-ischemic cardiomyopathies is a rapidly burgeoning field. Numerous studies are evaluating the benefits of stem cell delivery to injured myocardium, and more recent reports have also described bioartificial matrices that may provide mechanical support and enhance myocardial regeneration. It is important to remark that current indications for cell-based regenerative therapy are small ischemic scars and not large ischemic lesions responsible for end-stage ventricular failure. The association of electrostimulation with cellular CMP could be a way to transform passive cell therapy into ‘dynamic cellular support’ [15]. Thus, the principles of electrophysiological conditioning of skeletal muscle fibers developed for dynamic CMP are now applied in cellular CMP. The hypothesis is that electrostimulation of both ventricles following skeletal myoblast implantation should induce the contraction of the transplanted cells and a higher expression of slow myosin, better adapted for chronic ventricular assistance. The use of electrostimulation seems to drive stem cells towards differentiating into cardiac-type myogenic cells. This type of differentiation should include the induction of gap junction formation, improving stem cells engraftment and reducing the risk of arrhythmogenic events. Furthermore, in vitro electrostimulation of cell cultures was able to induce both morphological and biochemical changes in mesenchymal stem cells realizing a shift toward a striated muscle cell phenotype expressing cardiac specific markers [16].
Cardiac tissue engineering emerges as a new therapeutic tool and extends even more the amazing possibilities of cardiac bioassist procedures, becoming a promising way for the creation of a bioartificial myocardium. In a recent published study (MAGNUM clinical trial) it was demonstrated that cellular CMP associated with a cell seeded collagen matrix increases the thickness of the infarct scar with viable tissues and helps to normalize cardiac wall stress in injured regions, thus limiting ventricular remodelling and improving diastolic function [17].
Future developments include bioengineered platforms where stem cells are preconditioned to resist their implantation into a highly stressed myocardial tissue. Basically this approach consists of the development of bioactive membranes made of two integrated materials: (a) one nanofiber matrix made out of self-assembling peptides with molecule-release capacity (for growth factors such as VEGF and FGF), and (b) contained in a microscale elastomeric scaffold that provides the mechanical framework (elastic, loading) that will match the cardiac tissue mechanics. Both are essential to promote local angiogenesis in a necrotic affected tissue as well as its regeneration [18].
It seems that the main mechanisms by which cell transplantation and tissue engineering can bring functional benefits is that this implanted material should provide a supporting ‘band-aid’ scaffolding effect, which can limit the spread of the infarcted area, preventing excessive remodelling and dilatation of the ventricle. Closing the loop, the mechanisms mentioned above were one of the main effects demonstrated by the application of ‘latissimus dorsi dynamic cardiomyoplasty’....
The exposed relevant research studies and clinical data allow us to revive a permissible debate: is CMP still a viable option in patients with end-stage CHF?
References
This article has been cited by other articles:
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  A. Shafy, T. Lavergne, C. Latremouille, M. Cortes-Morichetti, A. Carpentier, and J. C. Chachques Association of electrostimulation with cell transplantation in ischemic heart disease J. Thorac. Cardiovasc. Surg., October 1, 2009; 138(4): 994 - 1001. [Abstract] [Full Text] [PDF]
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 F. B. Sozzi, L. Iacuzio, F. Civaia, and V. Dor Reply to Elsayed and Poullis Eur. J. Cardiothorac. Surg., January 1, 2009; 35(1): 199 - 199. [Full Text] [PDF]
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