Medtronic recently announced the early success of the HVAD LATERAL trial. The trial is investigating the potential to implant Medtronic’s HVAD device via a less invasive lateral thoracotomy, instead of the more conventional median sternotomy. The HVAD is a ventricular assist device, consisting of a mechanical pump attached to the heart, that assists in pumping blood around the body in patients with heart failure. In the United States, the device is implanted using a median sternotomy, where the sternum is parted and the chest opened. This latest trial investigates placing the device through a lateral thoracotomy, in which a small incision between the ribs is used to access the heart. The idea is that a thoracotomy is much less invasive than a median sternotomy, and the recovery time should be less. The device is already approved in Europe for surgical placement through a thoracotomy.
Medgadget asked David Steinhaus, M.D., vice president and general manager of the Heart Failure business at Medtronic, some questions about the technology and the ongoing trial.
Conn Hastings, Medgadget: Please give us a brief overview of the HVAD and the type of patient who is eligible for treatment with an HVAD.
David Steinhaus: The HeartWare centrifugal-flow, ventricular assist device (HVAD) is a mechanical pump that attaches directly to the heart and circulates oxygen-rich blood throughout the body in patients with advanced heart failure. The HVAD System consists of a pump, an external controller, a connecting cable and power sources that run the pump and controller. The HVAD has been proven to extend life, augment cardiac function and improve quality of life for end-stage heart failure patients, and the HVAD system is approved as a bridge to transplant in the U.S.
Medgadget: Can you explain the advantages of thoracotomy as opposed to median sternotomy in terms of patient morbidity and recovery time?
David Steinhaus: A thoracotomy is a small, lateral surgical incision between the patient’s ribs on the left side of the chest, whereas the more commonly used median sternotomy is a surgical procedure in which a vertical incision is made down the middle of the chest, then the sternum is divided. The thoracotomy technique is less invasive and preserves the chest for a possible subsequent sternotomy, such as that occurring at the time of heart transplantation. Additionally, the thoracotomy technique may provide patient benefits such as less tissue trauma and shorter hospital stays.
Medgadget: Is a thoracotomy more challenging for the surgeon, in terms of limited space to operate? Is the HVAD well-suited to delivery via thoracotomy?
David Steinhaus: In Europe, the HVAD System is the only full-support, centrifugal LVAD approved for implantation via the thoracotomy procedure, in addition to a median sternotomy procedure. The thoracotomy option is possible because of its smaller size relative to other LVADs on the market. But in the U.S., this implant technique is not approved by the FDA for any LVADs.
Medgadget: The trial has successfully met its primary endpoint. Can you summarize these early results and explain their significance?
David Steinhaus: The LATERAL trial sought to evaluate the thoracotomy implant technique of the HeartWare HVAD System in patients with advanced heart failure who are eligible for heart transplant. It is a multicenter, prospective, controlled clinical trial of 145 patients with end-stage heart failure who have not responded to medical management.
LATERAL successfully met its primary endpoint, with 87.6 percent of patients alive on the original device, free from disabling stroke, or having been explanted due to recovery at six months. This is compared to the performance goal of 77.5 percent, so you can see the study succeeded, and even surpassed its target (p-value=0.002). Overall survival among patients receiving an HVAD via the thoracotomy procedure was 91.8 percent at six months.
LATERAL validates that HVAD implantation via a thoracotomy is a viable alternative to median sternotomy. FDA approval of this investigational approach could ultimately result in more flexibility in implant planning and changes to patient management and recovery.
Medgadget: If it can be shown that delivery of HVAD through a thoracotomy produces similar or better therapeutic outcomes than delivery with median sternotomy, do you envisage this being the sole delivery method for the device globally?
David Steinhaus: There is a growing trend toward the use of less-invasive approaches in all fields of cardiac surgery. The positive results of the LATERAL trial show that the less-invasive thoracotomy procedure for implanting the HVAD System is feasible.
A sternotomy leads to adhesions and scar tissue, which are much more difficult to work through in a subsequent sternotomy, particularly at the time of a heart transplant. Of course, physician preference for implant technique certainly comes into play, but what we are seeing in Europe – where the thoracotomy approach for the HVAD is already approved – is the smaller size of the HVAD System makes it suitable for either implant approach. The thoracotomy option is not seen by physicians as feasible with the larger LVAD pumps.
Medgadget: The ENDURANCE trial is examining the potential of the HVAD system as a long-term therapy for heart failure patients, as opposed to a stop-gap treatment until heart transplant can occur. Recently, a subset of data showing that sicker patients in the trial did not have worse outcomes than less sick patients has been presented at the International Society for Heart and Lung Transplantation Scientific Meeting in San Diego. Can you comment on the significance of these results?
David Steinhaus: This was an interesting finding from the original ENDURANCE trial – that sicker patients didn’t necessarily have worse outcomes, which is contrary to some of the other published literature.
But a bigger splash at the ISHLT was from the ENDURANCE Supplemental trial, which was one of the other late breakers. You may remember that the original ENDURANCE trial demonstrated the safety and efficacy of the HVAD System for destination – or long-term – therapy; those results were presented at this meeting two years ago. But we saw a higher stroke rate than anticipated, so this second trial included intentional blood pressure management of HVAD patients in an effort to bring down the stroke rate – which it did. In fact, one of the prespecified secondary endpoints showed that the HVAD was superior to the control device in terms of being alive on the originally implanted device and free of disabling stroke – which is the endpoint of most LVAD therapy clinical trials. As you may imagine, these results were very well received by the physician community.