Next-Generation Cardiology Care

Genetics research is at the cutting edge of cardiovascular care with arrhythmia syndrome screening advancements and opportunities for personalized medicine.

This article first appeared in the July/August 2016 issue of HealthLeaders magazine.

Cardiovascular care is often on the cutting edge of medicine, but hospitals are now making progress toward the next generation of cardiology with genetic testing and treatment that enable care to be far more targeted than past service lines. Contrasting the usual focus on identifying those at risk for cardiovascular issues, one of the main goals now is to identify those who are not at risk and to keep them healthy and out of the healthcare system.

The drive for more targeted care stems in part from years of criticism for the overuse of stents and other unnecessary treatment in cardiovascular care, but advances in genetics research are leading to what could be dramatic steps forward. Much of the leading edge in cardiovascular care involves the study of patients with genetic arrhythmia syndromes, in which otherwise healthy young people die suddenly or develop life-threatening heart rhythms.

At the forefront of that effort is Melvin Scheinman, MD, chief of the Comprehensive Genetic Arrhythmia Program at the University of California, San Francisco, which is devoted to discovering new genes related to heart rhythm disorders. Scheinman was one of the pioneers of cardiac electrophysiology, and he says genetics advancements could bring similarly dramatic changes in cardiovascular care.

Not all arrhythmias are genetic in nature, but many pose a serious health risk, with the Centers for Disease Control and Prevention reporting more than 600,000 sudden cardiac deaths per year. Most sudden cardiac deaths are caused by arrhythmias, as cited by Cleveland Clinic. Genetic arrhythmia syndromes include arrhythmogenic right ventricular dysplasia, Brugada syndrome, catecholamine-induced polymorphic ventricular tachycardia, long QT syndrome, and short QT syndrome.

Alterations in genes that make proteins important in regulating the heart rhythm may predispose a person to developing dangerous heart rhythms. Research on hundreds of families affected with LQTS in the 1990s (based on the study SCN5A Mutations Associated With an Inherited Cardiac Arrhythmia, Long QT Syndrome by Wang, Q., et al.) led to the discovery of several genes that are crucial to normal heart rhythms.

"We are studying patients with arrhythmia syndromes to check them and their family members for genetic abnormalities and, depending on the diagnosis, we can determine a genetic mutation up to 80% of the time," Scheinman says. "The importance of this is that if we can find a pathogenic genetic mutation, other first-degree family members have a 50% chance of having the same mutation. We can pinpoint those at risk of dying from serious heart rhythm disorders."

Success key No. 1: Rule out family members
On the other hand, family members without the mutation can stop worrying and know that they are not at risk after they have undergone genetic testing. This knowledge can significantly change the way cardiovascular care is delivered, Scheinman says, because it can eliminate the cautionary testing and treatment that might have been delivered to family members just in case they were at risk of an arrhythmia syndrome.

Genetic testing will lead to the ultimate form of personalized medicine, Scheinman says.

"If you examine the genetic background of a patient, you may be able to identify sensitivity to specific drugs, propensity for developing some very serious heart disorders, and at the same time rule out those same things for other people," Scheinman says. "That is really what personalized medicine is all about—delivering the right care to the patient because you truly understand the patient and don't have to treat him or her as just a member of a group with certain statistical risks."

Scheinman says genetic arrhythmia programs across the country have reduced what used to be the wasteful response to a sudden death or an aborted sudden death in the family. Before genetic testing, such a death typically triggered a cascade of preventive healthcare, testing, and monitoring for all family members. Without genetic testing, cardiologists were forced to take a defensive posture and order the same care for everyone, knowing that it probably was unnecessary for many of them. In many cases, genetic testing can identify new opportunities for medical resources. 

Genetic testing can be used with standard cardiac testing such as electrocardiograms and treadmill tests to determine whether a person has an arrhythmia condition. It can be useful when there is uncertainty about the exact diagnosis, Scheinman says. A patient who does not quite meet the diagnostic criteria for LQTS based on the family history and cardiac tests, for example, could be tested for the five to 13 genes that are known to cause LQTS. Finding the gene alteration known to cause LQTS would make the diagnosis more certain. Not finding it would make it less likely that the patient has LQTS, but not impossible.

Success key No. 2: Use genetics to improve screening
Genetics research is slowly starting to affect many aspects of cardiovascular care, says Thomas P. Cappola, MD, ScM, chief of the division of cardiovascular medicine at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

"I believe we are right on the cusp of genetic testing for cardiac conditions being very mainstream and low cost. We already have some genetic tests in the cardiac space that have an out-of-pocket, self-pay rate of less than $500."

Cappola's application of genomic methodologies to identify the molecular and genetic basis of heart failure was recognized in 2009 with a Presidential Early Career Award for Scientists and Engineers, which he received from President Barack Obama. Cappola says cardiovascular care is a field in which physicians are constantly seeking improved treatment options, including drugs and devices in the short term. Long-term efforts are underway to explore cell-based therapies and gene therapies. "There is tremendous demand for those clinical services, so our research is always pushing boundaries to see what we can offer that is new for our patients," he says.

Scheinman says, "The effect from genetic arrhythmia testing has been tremendous, particularly because it is so tragic when young people drop dead suddenly. The main thrust now is to find the genes responsible for coronary artery disease, atrial fibrillation, and other cardiovascular conditions. This is the next big thing."

Quantifying the effect of arrhythmia testing relies on modeling derived from the prevalence of these conditions, so it is difficult to say how many lives have been saved, says Julianne Wojciak, MS, licensed genetic counselor who works closely with Cappola at the Perelman School of Medicine.

The most certain benefit is the ability in many cases to screen family members and identify the 50% who are not at risk, reassuring them and avoiding the unnecessary expense of further testing and precautionary care, she says. A challenge with genetic testing for arrhythmias is interpreting the genetic variations in a patient accurately, distinguishing between the variations that are disease-causing mutations and others that are without medical consequences, Wojciak says.

"It's an order of magnitude of increased complexity when it comes to the more common cardiovascular abnormalities, such as aortic valve stenosis or atrial septal defect," Scheinman says. "The genetic origins of cardiac arrhythmia were relatively straightforward when compared to what we're seeing with these other conditions, and as a result the practical application has been slower. But I'm optimistic that we'll get there just as we did with arrhythmia."

Success key No. 3: Overcome the financial challenge
Cappola says that the influence of genetics in cardiovascular care is slowed by the fact that genetic testing and acting properly on the results requires considerable expertise. It is not something that a hospital can simply add to its cardiovascular line of care and expect results, he says.

"It's not the kind of thing that is easily deployed. What genetic testing can do and what you can do with the information, that's a constantly moving target," Cappola says. "We know some inherited gene variances that are convincingly disease-causing, and we know many more that might be associated with disease but not in a very convincing way. That bar between what's convincing and what is murky is moving, so what is not actionable now might be actionable in the future."

Genetic testing also has been expensive, which posed a challenge for insurance reimbursement, Cappola says. Wojciak says that situation is improving, however. Genetic testing used to cost between $3,000 and $10,000 per patient, but new technology is making it possible to test large amounts of DNA at a low cost, she says.

"Nailing down the cost of testing is a moving-target situation because you have some older laboratories that are still charging high prices and newer laboratories using the new technology to push tests through in a very affordable way," she says. "I believe we are right on the cusp of genetic testing for cardiac conditions being very mainstream and low cost. We already have some genetic tests in the cardiac space that have an out-of-pocket, self-pay rate of less than $500."

Reimbursement is uncertain at the moment, Wojciak says. Most insurance companies do not yet have uniform guidelines for genetic testing for arrhythmias, but there is movement forward in that area, she says.

Success key No. 4: Pursue additional cardiovascular advances
Cappola says that the next generation of cardiovascular care will be influenced by such nonclinical factors as the increased use of mobile devices and apps, which he says will change the way clinicians interact with patients and monitor their cardiac health. Drug advancements also will play a role, he says. 

An example is the CardioMEMS device, an implantable pressure monitor that enables doctors to follow pressures inside the heart remotely. The technology behind CardioMEMS was invented by Professor Mark G. Allen in the University of Pennsylvania's School of Engineering and scientific director of the school's Singh Center for Nanotechnology. Cappola says he expects similar advancements as engineers and physician-scientists continue working together. 

"The future in cardiovascular care is very promising. We've never been able to do more, and there is more on the horizon," he says. "Devices and drugs will continue to improve what we can do for our patients. The decline in mortality of heart disease over the past two decades really speaks to the success in cardiology we've had so far—with genetics as a part of it, and I expect more in the future."