الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions or ischemic heart disease sufficient to cause global systolic impairment.
DCM represents an important health issue, with high rates of morbidity, mortality and hospital admissions. DCM can lead to progressive heart failure and represents the most frequent indication for heart transplantation. Understanding pathophysiologic mechanisms leading to the structural and functional changes that cause the heart to fail provides the impetus for novel drug and device therapies.
At a time when pharmacological therapy for HF has made only little advances, it is appropriate to explore whether new therapies have anything else to offer to patients with heart failure.
Arguably the most important non-pharmacological intervention for chronic heart failure is enrolment of the patient in a multidisciplinary heart failure service.
Tremendous advances have occurred in implanted cardiac device therapy which include implantable cardioverter-defibrillators (ICD), cardiac resynchronization therapy (CRT), cardiac contractility modulation (CCM) and neuromodulation. Device therapy can cause the modification of the natural history of disease progression. CRT offers both prognostic and symptomatic benefit for the patients but a substantial proportion of patients remain either not eligible for CRT or simply do not respond.
New therapeutic approaches are being explored to counteract irreversible myocardial damage and subsequent alterations in remodeling in DCM. For example, the application of cells with regenerative potential is currently being explored with an increased understanding of the molecular basis of disease and supplementary therapies, such as those based on gene transfer.
During the past 20 years, great effort has been made to improve cardiac regeneration through cell-based therapies. Advanced therapeutic options are being developed to generate new myocardial tissue and blood vessels using cells, either alone (cellular cardiomyoplasty) or, more recently, with biological and/or synthetic materials and growth, proangiogenic, and differentiation factors (cardiac tissue engineering). These approaches have been demonstrated to be safe with encouraging signs of functional improvement in the pre-clinical setting.
With these advancements in stem cell biology, active translational research is now expanding in various new directions, including direct cardiac reprogramming by specific transcription factors or small molecules, augmentation of endogenous progenitor cell proliferation by short, single-stranded, noncoding RNAs (miRNAs), and local modulation of intramyocardial communication through small membrane-bound vesicles, known as exosomes, that act as intercellular communicators to shuttle proteins and miRNAs that promote the therapeutic activities of stem cells in myocardial repair.
The attraction of gene transfer is its simplicity—a one-time administration offers the possibility of safely providing benefits beyond standard pharmacological and device therapy in this devastating disease with high morbidity and mortality.
Palliative operations such as FMR proved to positively affect the symptoms and even the course of the disease.
MCS implantation has afforded patients with advanced heart failure extended survival with improved quality of life. LVADs represent a significant development in the field of advanced heart failure. Device technology continues to evolve with improved patient outcomes and there is the potential for increased utilization as destination therapy in the future as a result of the ongoing mismatch between supply and demand for donor organs. A return of pulsatile LVADs is on the horizon. Recent research has insights into the vascular responses to pulse pressure. Significant hemodynamic benefits of PF-LVADs can be seen in total cardiac output and lower pulmonary pressures and left atrial pressure providing superior unloading compared to CF- LVADs.
One of the most exciting aspects of MCS is the possibility that a device used to support cardiac function either alone or in combination with other therapy may be able to reverse maladaptive cardiac remodeling and further improve outcomes even beyond that which is possible with current therapies.
Heart transplantation offers a 10-fold survival improvement with a near-normal quality of life. Thus, it remains the standard option for patients on the transplant waiting list and the gold standard for ultimate heart failure therapies. Transplantation is sadly a therapy to die for. Unfortunately, heart transplant is not a definitive cure and patients are at risk for developing different complications during the post-transplant period.