Left ventricular assist devices (LVADs) have extended the lives of many patients with end-stage heart failure, but at a price. The devices cause significant blood trauma, with patients developing abnormal blood vessels in the gut and gastrointestinal bleeding.

Lessons learned from understanding the relationship between blood trauma and adverse events are being applied in the development of the next generation of LVADs. That knowledge also may help improve the treatment of other patient populations, including those with certain types of congenital heart defects. These developments are examined during the Douglas P. Zipes, MD, MACC, Distinguished Young Scientist Awardee Presentation given by Carlo Bartoli, MD, PhD.

"Adverse events that are choking advancement of the field and the public health impact of circulatory support devices – specifically bleeding, clotting and stroke – are directly related to blood trauma," says Bartoli, an Associate Fellow of the ACC and a pediatric cardiovascular surgeon and researcher at the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia. "LVAD devices traumatize the blood. Much like a propeller behind a boat, these devices generate a continuous flow of blood to the body with an impeller inside the device that spins very fast. Although LVADs deliver lifesaving flow to the organs, the impeller generates levels of shear stress in the blood that do not exist in mammals in nature. The result is that current-generation LVADs chew through red blood cells, which causes hemolysis, and activate platelets. They also chew through clotting factors – and in particular von Willebrand factor is destroyed."

Bartoli explains that "As you traumatize the blood, von Willebrand factor, a clotting factor that is the largest protein in the bloodstream, is degraded into small, nonfunctional fragments. These abnormal von Willebrand factor fragments circulate in high quantities in the bloodstream of patients with these devices." He adds that "We have found that these fragments cause abnormal blood vessel growth, called angiodysplasia, in the stomach, the small intestine and the colon. Angiodysplasia frequently bleeds and is responsible for the high incidence of gastrointestinal bleeding in patients with LVADs."

Researchers are beginning to develop models to predict which patients are at the highest risk for bleeding to tailor anticoagulation and antiplatelet therapies on an individual patient basis, Bartoli says. These advances are helping industry partners develop next-generation circulatory support devices designed to minimize shear stress and blood trauma and reduce adverse events.

These lessons learned may also be applied to other patient populations, such as those born with von Willebrand's disease, as well as patients with Heyde's syndrome, gastrointestinal bleeding or single-ventricle congenital heart disease who undergo multiple surgeries and develop abnormal blood vessels, he adds.

"It looks like this biology applies to multiple patient populations, which means there are similar targets regardless of the patient because the biology is conserved," Bartoli explains. "We are starting to look at different ways to block some of these targets to prevent some of these changes, which is a fancy way of saying 'therapy,' and we are beginning to understand from a mechanistic standpoint why blood vessel growth is abnormal in these patient populations."

Watch the Douglas P. Zipes, MD, MACC, Distinguished Young Scientist Awardee Presentation at Virtual.ACC.org.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Congenital Heart Disease, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Mechanical Circulatory Support

Keywords: ACC Publications, ACC Scientific Session Newspaper, ACC Scientific Session Newspaper 2020, ACC Annual Scientific Session, acc20, von Willebrand Factor, Heart-Assist Devices, Hemolysis, Blood Platelets, Public Health, Erythrocyte Count, Blood Coagulation Factors, Heart Failure, Gastrointestinal Hemorrhage, Erythrocytes, Stroke, Heart Defects, Congenital, Airway Obstruction

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