Researchers on the Duke Heart Failure team recently found that a new left ventricular assist device (LVAD) design was associated with improved 6-month outcomes in patients with advanced heart failure. Published in the New England Journal of Medicine, two clinical trials indicated a lower incidence of pump thrombosis and pump replacement in patients who received new centrifugal-flow LVADs compared with patients who received an axial-flow LVAD, which is currently FDA approved.
Heart failure is one of the most common causes of death worldwide. In 2016, approximately 5.7 million adults in the United States developed heart failure and approximately half of these patients will die within 5 years, according to the Centers for Disease Control and Prevention. Patients with advanced heart failure that no longer responds to medication have few treatment options available.
“End-stage heart failure is something that we don’t have a cure for,” says study co-author Carmelo Milano, MD, Professor of Surgery, Division of Cardiovascular and Thoracic Surgery, and Surgical Director of the Duke LVAD program. “Heart transplantation is a very good treatment for end-stage heart failure, but there were 4,000 deaths due to chronic heart failure in North Carolina last year, and in the state approximately 100 heart transplants are performed each year. It’s still a number that’s insignificant relative to the 4,000 people who die in this state from heart failure.”
Dr. Joseph Rogers, Medical Director of the Duke LVAD program, and Dr. Carmelo Milano, Surgical Director of the Duke LVAD program, with a patient.
Left ventricular assist devices, or LVADs, are a life-saving therapy for patients with advanced heart failure. LVADs are mechanical pumps that replace a weakened left ventricle. Blood is drained from the left ventricle and pumped into the aorta and throughout the body. Duke is a leading center for ventricular assist device implantation. Duke surgeons have performed more than 1,300 LVAD implants since the program began over 30 years ago.
LVADs are most often used as a bridge to transplant. Once a donor heart becomes available, surgeons remove the device and patients receive a new heart. However, patients with end-stage heart failure who are not candidates for transplant have a low 1-year survival rate without LVAD support.
“Patients with advanced heart failure have a prognosis similar to advanced-stage cancer,” says study co-author Joseph Rogers, MD, Professor of Medicine, Division of Cardiology, Department of Medicine. “Several studies have demonstrated a 1-year survival rate of approximately 20%.”
A Longer-Term Solution
In the two studies, Dr. Milano and Dr. Rogers investigated the use of LVADs as a permanent treatment strategy to prolong survival and improve quality of life in patients with advanced heart failure, known as destination therapy.
“We have patients at this institution who have lived 8 or 9 years with LVAD support,” says Dr. Milano. “The LVADs help patients live longer and they also normalize their functional status to a point where a patient can perform most normal daily activity.”
The current axial-flow LVAD design, in which blood flows across a rotor bearing in the device, commonly leads to thrombus formation around the bearing. When pump thrombosis occurs, the LVAD must be replaced, necessitating a second operation. According to Dr. Milano, approximately 10% of patients implanted with the HeartMate II (Thoratec-Abbott, Inc., Chicago, IL) axial-flow pump develop pump thrombosis.
The Duke Heart Failure team sought to determine whether a new centrifugal-flow device design reduced the need for pump replacement due to thrombosis. Compared with the axial-flow pump, the centrifugal-flow pumps are smaller and use a magnetically levitated rotor instead of an impeller suspended by ruby bearings.
In the MOMENTUM 3 trial, 152 patients received the HeartMate III device, a new centrifugal-flow pump, and 142 patients received the HeartMate II device, an axial-flow pump. The authors found that just 1 patient in the centrifugal-flow pump group required reoperation for pump malfunction. Most importantly, pump thrombosis did not occur in any patients in the centrifugal-flow pump group but did occur in 14 patients in the axial-flow pump group.
“With the HeartMate III, there were no pump thromboses,” says Dr. Milano. “There was no need for replacement for pump thrombosis, which is a major advance in terms of adverse events. It’s very encouraging. This design almost appears to have solved this issue of pump thrombosis.”
The ENDURANCE trial assessed a different intrapericardial centrifugal-flow LVAD. In this trial, 297 patients received the centrifugal-flow HeartWare Ventricular Assist Device System (Medtronic, Inc., Minneapolis, MN) and 148 patients received the axial-flow HeartMate II. While the HVAD device had lower rates of pump thrombosis compared with the HeartMate II, the newer device was associated with a higher risk of stroke. After identifying that this risk was linked to higher blood pressure, the study sponsor repeated the trial with a protocol in place to reduce patient blood pressure. The results of the supplemental ENDURANCE trial indicate that blood pressure reduction led to a lower stroke rate for the HVAD device.
The Future of LVADs
LVADs are a promising treatment alternative for patients with end-stage heart failure when no other options are available. Future studies will continue to improve upon the design of LVADs to reduce the risk of adverse events in patients.
“I think we will see clinicians begin to make decisions about matching a pump to a patient based on patient-specific characteristics,” says Dr. Rogers. “At the end of the day, there’s still a high number of important adverse events that occur with the pumps. Some are related to the device itself or to the way they are implanted while others are related to the way physicians are managing the pumps. Over the next few years, there will be an important focus on reducing adverse events in this patient population.”
In addition to using LVADs as a bridge to transplant and a longer-term therapy, Dr. Milano and Dr. Rogers are investigating the use of LVADs as a bridge to recovery. For the small percentage of patients who recover normal function after wearing LVADs, the devices may be removed.
“If you look at the clinical trials and the registries, the recovery rate is in the 1–3% range,” says Dr. Rogers. “Many of us believe that the real future of LVAD therapy is going to be a platform to support patients with advanced heart failure while we provide another therapy that will allow their heart to heal so that their intrinsic heart function will return to normal and the LVADs can be removed. That’s our long-term vision.”
Duke is currently involved in an NIH-sponsored, multicenter trial to study the injection of stem cells into the left ventricular muscle at the time of LVAD implantation to help improve the rate of recovery.