In Good Company

A tradition of innovation: Mark Anstadt builds on a family legacy while breaking new ground

Vital Signs » Spring 2010
Photo of Mark Anstadt, M.D. (’86), receiving the 2009 Outstanding Alumni Award from Wright State University President David R. Hopkins, P.E.D.

With significant new advances announced every year, the pace of change in medicine often seems lightning-fast. In reality, many years of diligent work may be necessary to develop, test, refine, and roll out new treatments or technology. In fact, sometimes the quest to bring the benefits of a medical innovation to patients can become a family legacy spanning generations.

Such is the case for Mark Anstadt, M.D., (’86) FACS, who has worked for more than 30 years to perfect a life-saving device his father, George L. Anstadt, invented in the early 1960s.

“The device I’ve been spending time with since I was actually in high school, or even earlier,” Anstadt said, “is something my father termed Direct Mechanical Ventricular Actuation, or DMVA.”

In essence, the device is a form-fitting cup that surrounds the heart and physically compresses and expands it when the heart is failing. While versatile enough to be useful in a variety of scenarios, it is ideal for quick application when a patient experiences sudden cardiac arrest or significant heart failure. The device then maintains heart function and blood flow, allowing physicians to undertake further interventions while the patient stabilizes.

Anstadt has researched the device to improve and better understand its functionality over the years. In parallel, he has built a highly successful career as a cardiothoracic surgeon. He is currently an associate professor of surgery and an adjunct associate professor of pharmacology and toxicology with the medical school, and he serves as medical director of cardiothoracic surgery, chair of the department of surgery, and chair of the section of cardiothoracic surgery with Miami Valley Hospital in Dayton. In addition, he recently became section chief of cardiovascular and thoracic surgery at Upper Valley Medical Center in Troy, Ohio.

Anstadt is a member of many professional organizations, including the American Heart Association, the Society of Thoracic Surgeons, and the American Society for Artificial Internal Organs, and is a Fellow of the American College of Surgeons. Additionally, Wright State University honored him in 2009 with its Outstanding Alumni Award, given annually to a single graduate of the medical school for distinguished achievement,strong character and integrity, and a widespread positive impact on the world.

Pumping the blood without touching it
“Most heart pumps we use today,” Anstadt said, “are devices that require cannulas be placed into the heart or great vessels. The devices remove blood from either the heart or great vessels and pump the blood back into the circulatory system, circumventing the heart.”

Unfortunately, he added, “All these devices, including the total artificial heart, have significant issues with bleeding and clot formation. The entire blood-contacting issue has just not been solved. That’s where the major morbidities and mortalities with these devices come from.”

The problem is exacerbated by the need to use blood thinners when the devices are implanted to lower the risk of clotting. Without the blood thinners, a patient can have a stroke. These same drugs, however, can greatly increase the chances of significant blood loss.

“You’re between a rock and a hard place,” Anstadt said. “The problems with bleeding, you can’t overemphasize. It’s just a nightmare.”

In contrast, DMVA, is much less invasive.

“It’s got a vacuum line that generates negative pressure, so you just put it over the heart, and it literally aspirates itself onto the heart,” Anstadt said. “It gets on the heart and sort of girdles it. It’s atraumatic. You don’t have to sew or cause any bleeding.”

In fact, DMVA has no contact with blood at all, which is the most significant advantage, according to Anstadt.

“This truly is a heart pump,” he said, “as opposed to a blood pump.”

Some other heart-girdling devices that are in use or under development merely prevent the heart from becoming distended to avoid serious heart failure, while still others apply external pressure to help pump the blood. Both categories of devices have serious limitations, though. Simply girdling the heart doesn’t compress the muscle to support blood flow, while actively compressing it can force the heart to work harder to re-expand and refill with blood.

“DMVA actually assists the heart both during contraction and relaxation,” Anstadt said, because the slight negative pressure that allows the device to fit snugly around the heart facilitates its ability to fully expand the heart during refilling.

Anstadt’s most recent research, conducted at Wright State with transesophageal echocardiographic imaging, evaluated muscle contraction and showed that DMVA enhanced both the systolic and diastolic phases of the cardiac cycle. Additionally, Anstadt was enthused to learn that beyond applying uniform pressure, the device seems to facilitate normal synchrony of complex, multidirectional contractions within the various layers of the heart. Exactly why this should be the case is still unknown, but Anstadt believes the optimal forces delivered by the device may mimic and reinforce the heart’s natural twisting motion and rhythm.

Quick, simple, and good for the cells
In addition to studying the mechanical properties of the device, Anstadt is investigating its impact on heart health and healing on a cellular level.

“We’re looking at the metabolic, molecular markers of heart failure,” he said, “a whole slew of so-called maladaptive cell signals.”

These cell signals can help the heart deal with stressful conditions, but in patients with repeated or chronic cardiac trouble, the signals can malfunction. In particular, heart failure tends to increase apoptosis (pre-programmed cell death), which normally allows for the ongoing, beneficial replacement of old cells by new ones. Too much apoptosis results in healthy, necessary cells being damaged (often leading to heart failure), while too little can cause uncontrolled, harmful cell growth, as in cancer.

“We’re not only helping the heart contract,” Anstadt said, “but it looks like at a cellular level, this might also be beneficial.”

The single greatest benefit of DMVA, however, may be its simplicity.

“All those other things are kind of like icing on the cake,” Anstadt said, “because the reality of this device is that it’s really needed when you have a patient dying in front of you, and you don’t have any time. Even though we have all of this sophisticated technology, it takes, literally, in the best circumstances, probably 15 to 20 minutes to get most devices in. DMVA takes about three minutes. You can get it in quickly, and you can save the brain, because if the brain dies, the patient is dead.”

From materials to mitochondria
While the concept of DMVA has not evolved radically since George Anstadt developed early prototypes decades ago, it has taken years to refine and study the device to better understand its functionality and clinical potential. The reasons for the prolonged time frame have been many, including setbacks with early prototypes, the contrast between the conceptual simplicity and more nuanced application, and the challenges of user-friendly drive control.

Anstadt devoted some time to these issues while pursuing a B.S. in animal biosciences at Pennsylvania State University, as a medical student at Wright State, and during his first two years as a general surgery resident at the Ohio State University. His focused heart research began once he became a cardiothoracic surgery research fellow at Duke University, where he stayed for 10 years, completed his general surgery and cardiothoracic residencies and a clinical fellowship, and served as a teaching scholar in cardiothoracic surgery. Based on his ongoing work with DMVA and on other research over the years, Anstadt has published more than 50 scientific papers and written seven book chapters.

“When I was at Duke, one of the first things I studied was materials,” Anstadt said.

Early prototypes were made of polyurethane, which is strong and durable, but Anstadt found it traumatized the mitochondria in heart muscle cells, rendering them unable to convert oxygen into energy. As a result, after four hours on the pump, hearts he studied were mechanically functional (i.e., the artificially driven blood flow was strong), but the tissue was dead. Current DMVA devices are made of silicone rubber and do not cause this problem, but Anstadt still hopes to work with colleagues at Wright State to explore the impact of polyurethane models on mitochondria.

“I think it would be nice to delineate the mechanism of injury scientifically and explain why you shouldn’t go down that path,” he said, “because other companies with other technology are going back to polyurethane.”

A long, winding path to the patient’s bedside
After several difficult and unsuccessful startup ventures to bring DMVA to market, Anstadt is now taking a more personal role. In addition to pursuing federal research and development grants, he is exploring options for venture capital.

“I’m involved in industry to try to raise funds and develop this device for use in the clinical setting,” he said. “To get it into the market, I think it’s pretty much where it needs to be in terms of concept and design.”

What is lacking, he believes, is a more automated and user-friendly system to operate the device once it is in place, making minor adjustments to maintain the proper fit, pressure, compression strength and rhythm, and other parameters.

“Right now, the operation of this device is a big box with a lot of dials,” Anstadt said. “I can adjust it, and so could anyone with training, but that training takes a lot of time. It’s not intuitive.”

Anstadt also believes it is important to focus on enhancing the device itself rather than building a marketing plan around it.

“Historically,” he said, “a lot of money’s been wasted around advertising it as an answer—which it isn’t—but not putting the money into technology. I’m interested in raising money to put into technology.”

Anstadt feels the obstacles to widespread clinical use of DMVA are significant but surmountable. He is determined to overcome them not only to realize a shared aspiration that he and his father have pursued for nearly half a century, but also to bring life-saving benefits to patients everywhere.

“The real goal, in my view, is to save lives and do something for society,” he said. “That’s the reason I think this is worthwhile.” VS

Photo: Mark Anstadt, M.D. (’86), receiving the 2009 Outstanding Alumni Award from Wright State University President David R. Hopkins, P.E.D. (right)

Last edited on 09/22/2015.