Matters of the heart

Once upon a time, the practice of medicine took the individuality of the patient into account only if the patient did not respond appropriately to treatment.

A medication, for example, could be increased or, if side effects were too onerous, the dosage could be decreased or another medication substituted.

But a sea change came to medicine with information made available through genomics. More than a decade ago, the journals Science and Nature detailed early results of mapping the entire human genome. It was an important signpost of progress at the time, and a detailed understanding of the inner workings of human cells and tissues has only accelerated in the years since. Consider the discovery of the tumor-suppressing BRCA1 and BRCA2 genes and the related genetic tests that can predict a woman’s susceptibility to developing breast cancer later in life.

Now Francis G. Spinale, a professor of cell biology and anatomy and adjunct professor of surgery at the School of Medicine and a staff physician in cardiology at the Dorn VA Hospital, is helping lead the way in a still-underdeveloped area of personalized medicine — cardiovascular disease — and he is going even further downstream than the genetic code of an individual. That is because genes, while an important part of understanding a patient’s susceptibility to disease or response to treatment, are, in a sense, frozen in time.

For example, identical twins are born with the same genetic makeup, but they might lead very different lives. Their diets, environmental exposure, exercise habits and injuries can change the underlying functioning of the biomachinery that runs their bodies. Rather than studying the unchanging genetic makeup of the individual, Spinale focuses instead on the actual products of genes — proteins and enzymes — that can be measured in the blood. These blood measurements, called biomarkers, can reflect normal and abnormal functions of the body and provide unique insight into these functions on an individual basis.

If the genetic code is the blueprint for constructing the parts that allow the human body to function, biomarkers are the actual components as they go about the business of making the body run. An example of Spinale’s biomarker research is that of heart failure. Specifically, he has shown that one common thread in heart failure is a change in the extracellular matrix. By examining changes in a family of enzymes that regulate the structure of the extracellular matrix, he has uncovered valuable diagnostic information.

Another important example is how to use biomarkers to identify at a personalized level how a patient might respond to a heart failure therapy. “Cardiac resynchronization therapy, or CRT, is a very effective treatment for heart failure, at least for a subset of patients,” says Spinale. “But it is expensive, at $50,000 to $125,000, and 50 percent of patients do no better or worse with CRT.”

Spinale was part of a team that discovered that a specific set of biomarkers can predict how a patient will respond to CRT, which was a featured presentation at the International Heart Rhythm Society in May and is under review in the Journal of the American Medical Association. The team enrolled 800 patients in a medical trial that examined blood samples before CRT and measured the success of the intervention. “It was the largest clinical trial of its kind, and we surveyed 170 biomarkers,” Spinale says. “What we found was a unique signature that could predict patients with a high risk of poor response to CRT.”

One of the leading causes of death and disability in South Carolina is cardiovascular disease and heart failure leads the way. Spinale is developing blood tests to not only identify patients early on who are at risk for heart failure but also to develop a blood test to keep these patients out of the hospital. One of the leading health care costs is early heart failure readmission. In fact, this is a key health care indicator in the new health care affordability act.

“If you have high blood pressure, you have a 50 percent risk for developing the signs and symptoms of heart failure — and that is even if the hypertension is controlled,” Spinale says. “We need to develop a blood test to find those with the greatest risk and work with them because once you present with heart failure secondary to hypertension, there is no treatment.”

Spinale is helping to organize a large-scale study in South Carolina, the first of its kind in the state, to identify and predict patients who are at the greatest risk for heart failure readmission. Working with biomarker panels developed from his earlier studies, Spinale is partnering with Palmetto Health to establish outreach programs and clinics throughout the state to do the blood tests and follow-up clinical work.

Success could have a dramatic impact on the longevity of many South Carolinians. “Heart failure affects more people than all cancers combined,” Spinale says.

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