Five Years On
Regenerative Myocardial Therapy Five years ago, we predicted that regenerative myocardial therapy would continue to reveal its promise for the treatment of patients with chronic heart failure. In 2011, the most successful form of regenerative myocardial therapy continues to be stem cell treatment, using adult progenitor cells obtained from the heart itself or from extracardiac tissues such as bone marrow, fat, or skeletal muscle.4
Stem
cell therapy is being used to treat patients with acute myocardial infarction, myocardial ischemia without revascularization, ischemic cardiomyopathy, and, more recently, dilated cardiomyopathy. Various cell delivery methods are available, ranging from intracoronary infusion to intramyocardial injection (either during open heart surgery or via a catheter-based approach). After undergoing this treatment, selected patients have less angina and a greater capacity to exercise.5
Researchers are studying ways to further increase the clinical benefits of stem cell therapy. They are searching for a more potent cell type, as well as different cell sources. Most patients have been treated with cells obtained from their own tissue, but a newer approach involves the use of stem cells derived from a healthy young donor, which results in a more uniform, ‘off-the-shelf’ cell product. Although embryonic stem cells would be an even more promising source, their use is fraught with ethical problems and other complications that may not be resolved for some time. Therefore, cells with a pluripotent potential similar to that of embryonic stem cells have been artificially created. These cells, called induced pluripotent stem cells, are generated by genetically reprogramming adult somatic cells to express genes that endow cells with properties of embryonic stem cells.6 Despite the immense potential of this approach, safety concerns and regulatory issues must be addressed before these genetically modified cells can be used clinically.
Furthermore, innovative cell-labeling methods are being developed to monitor the fate of stem cells after they are delivered into the patient’s heart.7,8
Researchers hope
to use these methods to devise strategies for improving the retention of cells after delivery. Gadonanotubes are showing promise as a revolutionary non-invasive means for tracking transplanted stem cells.9
In a unique mix of technology, investigators are testing the benefits of stem cell therapy in ventricular assist device (VAD) recipients; it is hoped that combined treatment will enhance recovery of left ventricular function in bridge-to-transplant or destination-therapy patients, allowing VAD removal.
74 Cardiovascular Medicine and Surgery in 2011 and Beyond
The American Heart Hospital Journal
but the positive, clinically relevant effects of cardiovascular gene therapy have been minimal because of inefficient gene transfer. New innovations in gene delivery techniques are expected to lead to novel methods of treating cardiovascular disease.
One of the greatest current challenges is to translate cardiovascular breakthroughs at the basic science level into clinical practice. Completion of the Human Genome Project has led to the development of treatments for certain disorders involving single-gene mutations. To benefit the cardiovascular system, however, gene therapy must involve safe, efficient delivery methods. Recent cardiovascular gene therapy trials have been carried out with an excellent safety record,10
Myocardial Revascularization
In 2006, we predicted that expansion in the use of drug-eluting stents (DESs) would be a major breakthrough in cardiovascular medicine by 2011. We also predicted that the use of these stents would continue to have limited efficacy in patients with diffuse coronary disease and left main coronary artery lesions. Early randomized controlled trials had shown excellent results for DESs compared with bare metal stents in highly exclusive patient populations with lesions favorable to stenting.11,12
Therefore, by 2006, owing to favorable clinical trials and public demand for non-surgical revascularization, the use of DESs for percutaneous coronary interventions (PCIs) was expanding to include more complex ‘off-label’ coronary artery lesions. The rapid growth in PCIs and the reciprocal decline in surgical coronary artery bypass grafting (CABG) procedures led many observers to declare that PCI would soon eliminate the need for CABG.
Since 2006, several clinical trials have shown that CABG has a benefit over PCI in terms of mid- and long-term survival and freedom from complications, especially in patients with multi-vessel disease and diabetes mellitus.13–15
The Clinical
outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial16
compared medical treatment
with PCI therapy and revealed no benefit for survival or for freedom from myocardial infarction in patients undergoing PCI. In 2011, the three-year data from the randomized controlled Synergy between PCI with taxus and cardiac surgery (SYNTAX) trial showed better survival and freedom from major adverse cardiac events in patients treated with CABG versus those undergoing PCI with a DES.17
The
advantages of CABG were especially significant in patients with more complex three-vessel disease. Nevertheless, PCI continues to be the first-line therapy in most of these patients. Even though DESs have revolutionized cardiovascular medicine over the past decade and continue to benefit properly selected patients (i.e. non-diabetic patients with single- or double-vessel disease, large
Winter 2011
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