Given the ever-increasing advances in genetics, robotics and biotechnology, it’s not surprising that discussions about how and when to leverage these technologies are taking place in the halls of Congress, at scientific meetings around the globe, and even around the kitchen table.
Proponents of these advances see potential cost-saving and patient safety benefits, particularly when it comes to targeting treatments to individuals. At the same time, others have expressed concern about the high costs of these technologies outweighing the currently known benefits to patients. The July/August 2012 issue of Cardiology takes a closer look at each of these three areas of cardiovascular innovation in terms of where they are today and challenges and opportunities for the future.
Biomarkers: A Personalized Approach to Medicine
Hippocrates once said, "It is more important to know what sort of person has a disease than to know
what sort of disease a person has." Today, with the sequencing of the human genome and further research underway, opportunities to tailor medical treatments to individuals are increasingly more prevalent.
In particular, cardiac biomarkers are proving important tools for better identifying individuals at high-risk for cardiovascular disease, diagnosing disease conditions promptly and accurately, and effectively treating and monitoring patients with cardiovascular disease.
"More and more of the patients we see have numerous co-morbidities. Biomarkers allow us to help differentiate one disease from the other, and thus can be very valuable for the health care practitioner," notes Alan S. Maisel, MD, FACC, associate editor of the Journal of the American College of Cardiology
, in an interview with CardioSource WorldNews
"A simplistic way to think of biomarkers is as indicators of disease trait (risk factor or risk marker), disease state (pre-clinical or clinical), or disease rate (progression)," said Vasan Ramachandran, MD, FACC, in a 2006 article published in Circulation. According to the article, in a patient presented to the emergency department with acute severe chest pain, a biomarker may help to differentiate patients with an acute myocardial infarction (MI) from those with unstable angina, acute pulmonary embolism, or an aortic dissection in time to facilitate targeted management. Similarly, in a patient with acute MI, a biomarker may help to assess the likelihood of a therapeutic response; the extent of myocardial damage; the severity of underlying coronary disease; the degree of left ventricular dysfunction; the risk of future recurrences; and progression to heart failure.
Genetic biomarkers are another way biomarkers can help with identifying susceptibility to certain cardiovascular diseases. For example, hypertrophic cardiomyopathy (HCM), a heart disorder affecting about 620,000 Americans, is caused by genetic mutations that alter the construction of heart muscle. The "2011 ACCF/AHA Guideline for the Diagnosis and Treatment of HCM" recommends genetic testing in patients with an atypical clinical presentation of HCM or when another genetic condition is suspected to be the cause. In addition, it recommends screening (clinical, with or without genetic testing) in first-degree relatives of patients with HCM.
Despite the benefits, there are also several hurdles to biomarker use in routine patient care. First, new biomarkers must meet several requirements, including cost-effectiveness and demonstrated ability to improve patient outcomes. However, limited interoperability between electronic health record (EHR) systems, coupled with limited—albeit increasing—EHR adoption, has made it difficult to track and monitor outcomes to prove these requirements. Coverage of genetic tests by payers is another key hurdle due to limited research and data. In a recent case in Indiana, Wellpoint Inc. had refused genetic testing of three children whose father has HCM, claiming it was "experimental." While the company recently agreed to make an exception for these children, its reason for the initial denials are not uncommon among payers. Proper interpretation of these tests is also an issue. Some findings on genetic testing have imperfect sensitivity and specificity in predicting a disease state and the expression of that disease.
Moving forward, there is strong potential that diagnostic markers will find use in point-of-care testing in emergency departments and by the bedside. Biomarkers that facilitate appropriate drug use may also benefit efforts to ensure the most appropriate and effective cardiovascular treatments. Of course, continued research will be key.
Robotics: A Brave New World
Although robotic procedures in cardiac revascularization and valve surgery have been slow to catch on for various reasons, including longer procedure time, demanding training, and high learning curve, they are definitely making inroads in the cardiac arena. Although the jury may still be out on the ultimate fate of robotics, more and more procedures are testing their use, including minimally invasive direct coronary artery bypass (MIDCAB), totally endoscopic coronary artery bypass (TECAB), and percutaneous coronary intervention (PCI).
One of the appeals of incorporating robotics into cardiac surgery is the ability to minimize patient harm while maximizing benefits. For example, MIDCAB avoids having to perform a median sternotomy to access the heart, leaving patients without a six-inch scar. TECAB, which started in single bypass procedures about 10 years ago and has evolved to include double bypass and multivessel disease, is also much less invasive. In particular, TECAB can be particularly advantageous in morbidly obese patients as some surgeons hesitate to use two internal mammary arties during sternotomy because of wound healing problems. In addition, the reduction in surgical trauma also allows earlier return to normal activities. Another area in which robotics is gaining a foothold is with hybrid suites. These suites combine the technology and equipment of operating rooms and cath labs into one all-inclusive suite enabling patients to undergo procedures that combine traditional, keyhole or robotically-assisted surgeries with coronary stenting.
These hybrid procedures seem especially beneficial in patients with multivessel disease. A study presented in May at The Society for Cardiovascular Angiography and Interventions 2012 Scientific Session in Las Vegas, found that patients undergoing a hybrid revascularization procedure using robotic assistance for LIMA harvesting and minithoracotomy for distal anastomosis were 16 percent less likely to die or experience major complications when compared with outcomes expected in patients who had undergone conventional sternotomy. By one month post-procedure, patients were back to pre-surgical activity levels. Hybrid procedures could have another arm added to their armamentarium in future years with the advent of robotically assisted PCI procedures. Although not commercially available, clinical trials are testing the use of robotics in the cath lab. Unlike robotics in coronary artery bypass procedures, the robotics being tested in PCI change little about the procedure, but instead allow physicians to more efficiently deliver guide wires and devices down the coronary artery, according to George Vetrovec, MD, FACC, professor of medicine and director of the adult cardiac catheterization laboratory at Virginia Commonwealth University. The final answer of whether robotics will continue to have a role in cardiac revascularization procedures may come with time as more trials are conducted to analyze outcomes of the procedures alone and compared to traditional procedures. Knowledge about what gives the best results for patients will ultimately guide practice.
Stem Cell Therapy: A Cure vs. Treatment
Millions of patients suffer from heart failure. If medications, surgery, or stents fail to control the disease, physicians often have few treatment options to offer. Now, advances in stem cell therapy offer opportunities to cure, not just treat, patients with cardiovascular disease.
The first application of stem cell transplantation occurred in 2000 and involved heart failure therapy. Since then, Phase I and Phase II trials have indicated that it is both feasible and safe for physicians to isolate stem cells and transplant them. One of the largest stem cell therapy studies to date was presented at ACC.12 in Chicago. The study found that using a patient's own bone marrow cells may help repair damaged areas of the heart. Researchers found that left ventricular ejection fraction increased by a small but significant amount (2.7 percent) in patients who received stem cell therapy. The study also revealed that the improvement in ejection fraction correlated with the number of CD34+ and CD133+ cells in the bone marrow.
"This is the kind of information we need in order to move forward with the clinical use of stem cell therapy," said Emerson Perin, MD, PhD, FACC, director of clinical research for cardiovascular medicine at the Texas Heart Institute and the study's lead investigator.
Researchers are now looking at the best method for stem cell delivery. Among the methods being tested: direct epicardial injection, intravenous infusion and endocardial delivery. However, no single method has emerged as a standard. Speaking at the Heart of Innovation featured learning destination at ACC.12 in Chicago, Nabil Dib, MD, MSc, FACC, director of cardiovascular research at Mercy Gilbert and Chandler Regional Medical Centers in Gilbert, AZ, said catheter-based technology may prove to be the best method of delivery because it avoids the risks associated with anesthesia and shortens hospital time. However, the jury is still out.
"Ultimately the goal of stem cell transplantation is to rebuild blood vessels and increase the blood supply to the heart. The increased blood flow, combined with today's standard-of-care therapies, could make a big difference in treating cardiovascular disease," Dib said. "In the heart failure population, you transplant the stem cells to delay or reverse heart failure. Hopefully that will decrease hospitalization and sudden cardiac death. This approach may also help affect heart transplantation."