MEDTRONIC HEARTWARE HVAD SYSTEM

A ventricular assist device (VAD) is a mechanical pump. When one of the heart’s natural pumps (a ventricle) does not perform well, a VAD is used to increase the amount of blood that flows through the body. Having a VAD implant allows most people with advanced heart failure to return to a fuller life. A VAD consists of:

• A pump that is attached to a ventricle inside the body
• An external controller, which is a small computer that monitors the pump
• A driveline cable, which connects the pump to the controller
• Power sources that run the pump and controller

LVAD therapy has been demonstrated to extend life, augment heart function, and improve quality of life in patients with advanced heart failure for whom the device is indicated.³

The Medtronic HVAD System features the world’s smallest, commercially available, centrifugal flow pump. Weighing 160 grams, the HVAD System’s continuous flow pump is 30 percent thinner and has 38 percent less volume than other centrifugal-flow devices.^4,5

• The HVAD Pump fits in the area around the heart known as the pericardial space. It is connected directly to the heart at the bottom of the left ventricle. There it draws oxygen-rich blood through the pump and pushes it into the aorta where it flows to the rest of the body.
• The system can pump enough blood every minute to decrease heart failure symptoms.⁶ A physician programs the system to deliver the proper amount of flow for the body’s needs.
• Worldwide, more than 17,000 patients have received the HVAD System since it was first approved in Europe in 2009.
  
  

The HVAD System was evaluated in the destination therapy patient population of the ENDURANCE and ENDURANCE Supplemental trials. Data from these trials support the safety and effectiveness of the HVAD System for destination therapy in patients with advanced heart failure for whom subsequent transplantation is not planned.

In the multicenter ENDURANCE trial, 445 patients with end-stage heart failure who were ineligible for cardiac transplantation were randomized in a two-to-one ratio to receive the HVAD System or an alternative LVAD approved by the FDA for destination therapy. The trial met its primary endpoint, demonstrating non-inferiority of the HVAD System to the control device.⁷ Results were published in The New England Journal of Medicine in 2017.

The ENDURANCE Supplemental trial was a follow-up trial to the ENDURANCE trial. This prospective, randomized, controlled, multicenter trial evaluated the impact of enhanced blood pressure management on patient outcomes in destination therapy patients receiving the HVAD System. A total of 465 patients were randomized in a two-to-one ratio to receive the HVAD System or a control device, i.e., an alternative LVAD approved by the FDA for destination therapy. While the study did not meet its primary endpoint, it did demonstrate that careful attention to blood pressure management may reduce the risk of stroke in patients with an HVAD System.⁸

Similarly, FDA approval for HVAD implantation via thoracotomy was based on data from the prospective LATERAL clinical trial, which enrolled 144 patients with end-stage heart failure who were eligible for heart transplant. The primary endpoint of the trial demonstrated non-inferiority of the HVAD implanted in patients via thoracotomy, where survival at six months free from disabling stroke or device explant or exchange due to malfunction was achieved in 88.1 percent of patients. The key secondary endpoint revealed a significant reduction in total length of hospital stay, from an average of 26.1 days down to 18 days. Overall survival among patients receiving an HVAD via the thoracotomy procedure was 88.8 percent at one year.⁹

VADs are an emerging technology designed to treat patients with end-stage heart failure, and longer-term performance measures are underway. Early performance is available via clinical trial results (see below).

ENDURANCE TRIAL:

• 445 patients with end-stage heart failure who were ineligible for heart transplants.
• Randomized in a two-to-one ratio to receive the HVAD System or an alternative LVAD approved by the FDA for destination therapy.
• The trial met its primary endpoint, demonstrating non-inferiority of the HVAD System to the control device.⁷
• Results were published in The New England Journal of Medicine in 2017.

The overall stroke rate of the HVAD System in the ENDURANCE clinical trial was 29.7 percent at two years, compared to 12.1 percent with the control device. Most strokes experienced by HVAD patients occurred in the first six months, with a steady decrease in the stroke rate during the remaining two years on support.

The medical community has learned a great deal about management of patients with a centrifugal flow LVAD through participation in ENDURANCE and other clinical trials. The ENDURANCE trial demonstrated the importance of anticoagulation and antiplatelet therapy, as well as a potential relationship between elevated blood pressure and occurrence of stroke in patients who received the study device. Medtronic evaluated this correlation in the ENDURANCE Supplemental Destination Therapy clinical trial, the results of which were presented as a late-breaking clinical trial at the International Society for Heart and Lung Transplantation (ISHLT) annual meeting in April 2017.

ENDURANCE SUPPLEMENTAL TRIAL:

• A follow-up trial to the ENDURANCE trial.
• Prospective, randomized, controlled, multicenter trial that evaluated the impact of enhanced blood pressure management on patient outcomes in destination therapy patients with the HVAD System. 465 patients were randomized in a two-to-one ratio to receive the HVAD System or a control device, i.e., an alternative LVAD approved by the FDA for destination therapy.
• The primary endpoint established a conservatively narrow non-inferiority margin of 6 percent. The trial showed that 14.7 percent of patients who received the HVAD System experienced a neurologic event within 12 months of implantation, compared to 12.1 percent of patients in the control arm (p=.014). Although the observed difference in stroke and transient ischemic attack (TIA) rates between patients receiving the HVAD System and the control device was small, the study did not meet the primary endpoint.
• The trial did demonstrate that careful attention to blood pressure management may reduce the risk of stroke in patients with an HVAD System.⁸

LATERAL TRIAL:

• Prospective trial with 144, end-stage heart failure patients who were eligible for heart transplants.
• Primary endpoint demonstrated non-inferiority of the HVAD implanted in patients via thoracotomy, where survival at six months free from disabling stroke or device explant or exchange due to malfunction was achieved in 88.1 percent of patients.
• Secondary endpoint revealed a significant reduction in total length of hospital stay, from an average of 26.1 days down to 18 days.
• Overall survival of thoracotomy HVAD patients was 88.8 percent at one year.⁹