Frank Giordano, MD, assistant professor of cardiovascular medicine and director of the molecular cardiology program at Yale University School of Medicine, suggested that the future of interventional cardiology will be a synergism of biology and devices. In a counterpoint presentation, Daniel, Burkhoff, MD, associate professor of medicine at Columbia University in New York City said that device-based therapies provide the most realistic methods for the foreseeable future in the field.
These point-counterpoint lectures were presented in a series, “Cell Therapy: The Great Debates,” at the Transcatheter Cardiovascular Therapeutics conference held in Washington, D.C., Oct. 20-25.
Giordano said that “every standalone mechanical approach to coronary artery disease (CAD) has been limited by either graft failure (CABG), or unacceptable restenosis rates,” with such methods as balloon angioplasty (POBA) and arthrectomy.
According to Giordano, “the best success to date in overcoming these issues has been with the combination of bio and pharmaceutical agents and devices,” such as drug-eluting stents (DES). Giordano purported that “current hopeful approaches to overcome the limitations of DES are based in biological developments,” such as biodegradable coatings and biodegradable stents.
As an example, Giordano emphasized myocardial infarction (MI) as a clinical entity for which bio treatment was supplanted by a mechanical treatment. He mentioned thrombolysis and percutaneous coronary intervention (PCI) as different effective treatments for MI.
Giordano said that “devices have not been a panacea for heart failure” either.
He stressed that “it’s not just the DNA sequence that defines bio. The central dogma of DNA to RNA to protein is only part of the story.” For DNA binding proteins, zinc protoporphyrins (ZnPs) are currently the most abundant.
To conclude, Giordano noted that environmental influences have a tremendous effect on gene expression and epigenetics. To exemplify, he described an experiment performed by he and his colleagues at Yale, in which they feed fatty foods to healthy pregnant mice. As a result, the offspring had an unhealthy pre-disposition to being overweight. Giordano used this research to explain that environmental influences can never be separated biological fate.
For the counter-point lecture, Burkhoff restricted most of his comments to chronic heart failure (CHF). He conceded that for the use of cells in myogenesis or angiogenesis, “this form of therapy would provide benefits in more chronic phases.”
Burkhoff said that in order for biology therapy to be effective in CHF, left ventricular dysfunction (LVD) and angiogenesis, the correct cell type must be identified and isolated. For the therapy to be successful, the cardiologist would have to expand the cell and then it must be deployed and maintained, which is difficult, according to Burkhoff. In addition, cell therapy also would deal with the complications of engraftment, vascular supply, gap junctions, mechanical contradictions and would have to overcome abnormal myocardial stress.
Burkhoff said it is a “daunting task and most of the steps await scientific validation.”
There is a lack of solid, reproducible evidence from preclinical studies in modification, and “we don’t know what is happening with this therapy at this point,” Burkhoff said. He also said that there are no specific results on stem-cell transplantation.
Contrarily, Burkhoff said that device-based therapeutics for CHD improves hemodynamics and exercise tolerance in the survival and treatment of patients with heart failure. He highlighted such device-based therapies as cardiac resynchronization therapy (CRT) and left ventricular assistance device (LVAD).
According to Burkhoff, HF is a constellation of mechanical and electrical problems, and those methods should be used to treat it. He reiterated that cell therapies are in their infancy, and it would even be “a premature jump to clinical trials of stem cell therapies.” “Understanding the mechanisms of devices is much easier than understanding biological methods.” He added, “Is CRT a perfect method—absolutely not. But, we have a much better understanding of them and they follow a logical pattern of development.”
Burkhoff did concede that devices can not be studied with such a large body of patients, such as pharmaceuticals and biologics.