Current Treatment Options

Many symptoms associated with heart failure can be treated, but often the underlying functional impairment of the heart cannot.

Heart transplantation is the only current curative therapy and ultimately provides the best recovery of cardiac function. However the therapy is significantly limited by the availability of donor hearts. There are currently fewer than 4,000 donor hearts available worldwide each year and this number is falling. Also, many patients with heart failure are ineligible for heart transplantation because of factors such as co-morbidity or age.

Drug treatment and pacing devices that are designed to stimulate the heart do not halt the progression of the disease. Other approaches such as devices that allow physicians to reduce the size of the heart and cell based therapy are either in the early stages of development or are otherwise not achieving outcomes that lead physicians to see them as viable solutions.

Ventricular Assist Devices are gaining increasing clinical recognition as a viable long term treatment option. In 2001, the REMATCH clinical trial for "Randomized Evaluation of Mechanical Assistance Device for the Treatment of Congestive Heart Failure" was published in the New England Journal of Medicine. The trial concluded that "The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation".

Notably, the REMATCH trial was based on relatively old "volume displacement" pump technology. With the more recent introduction of smaller, more reliable "continuous flow" devices, patient outcomes have improved significantly. The use of LVADs has become largely mainstream for "bridging" transplant patients until a donor heart becomes available. As long term clinical outcomes continue to improve, LVADs are gaining increasing acceptance as potentially presenting a viable long term alternative to transplantation for patients suffering advanced heart failure.

A more complete summary of the current treatment options for heart failure is as follows:

• Drugs. Pharmacologic management of CHF focuses primarily on increasing the force of heart contractions. A drug regimen of beta-blockers, diuretics, digitalis and angiotensin-converting enzymes (ACE inhibitors) aim to improve the effectiveness of the heart's contractions and slow CHF progression. Some investigations have suggested that the increase in survival is limited and that drug treatments merely delay the advance of CHF. Although drug therapy for heart failure can improve the quality of life and also modestly prolong survival, the currently available approaches do not halt the progression of this disease.
  
• BiVentricular Pacing ("BVP"). BVP devices are designed to stimulate both sides of the heart electrically such that the contractions of the left and right ventricles are re-synchronized. The MIRACLE (Multicenter InSync Randomized Clinical Evaluation) trial demonstrated that, of the eligible CHF patients,almost one third showed no improvement or became worse after treatment. In those patients who responded, the heart's pumping ability improved only minimally by approximately 5%. Like drugs, pacing has not been shown to halt or reverse disease progression.
  
• Coronary Artery Bypass Graft Surgery. This is a surgical procedure to route blood flow around a blockage or narrowing of an artery located on the heart. This procedure is considered in heart failure patients primarily when there is evidence of "hibernating" heart muscle that will exhibit improved function with restoration of normal blood flow. Improvements have resulted following bypass in such cases, however the inability to accurately identify suitable patients limits the applicability of the procedure.
  
• Heart Restraint Devices. These are devices placed either inside or outside of the dilated heart which are intended to reduce the size of the enlarged heart, lower wall stress and improve cardiac function. The use of a device inside the heart involves surgeons removing sections of the heart thereby allowing the reduced heart to pump more effectively. In the alternative, outside-the-heart approaches involve a sock-like device that is designed to reduce the heart's size by physically pushing inwards on it. The first such device from Acorn, failed to meet its clinical study endpoint and the US Food and Drug Administration denied approval for this device.
  
• Cell-Based Therapies. Currently at an early research stage, cell based therapies may ultimately provide a cure for the underlying myocardial dysfunction in CHF. We believe that viable cell based CHF therapies are at least a decade away.
  
• Intra-aortic Balloon Pumps ("IABP"). IABPs have been in clinical use since the late 1960s and are inserted by a cardiologist or surgeon to reduce acute heart failure symptoms or improve cardiac output. A balloon-tipped catheter is placed in the aorta, where the balloon inflates and deflates in counter pulsation to the heart's natural contractions. Clinically, these pumps are used for temporary support in patients with acute reversible heart failure and are not perceived as a curative therapy for advanced heart failure.
  
• Extra-aortic Balloon Pumps ("EABP"). These devices are applied to the external surface of the ascending aorta, with advantages of ease of surgical implantation and no contact with circulating blood. Several of these devices are in clinical trials. We believe these devices may not provide sufficient flow augmentation for patients in end-stage heart failure.
  
• Total Artificial Heart ("TAH"). Similar to cardiac transplantation, a TAH is implanted to replace the patient's native heart. TAHs are large, mechanically complex devices. We believe they will be used in only a very minor subset of end-stage CHF patients.
  
• Heart Transplantation. Heart transplantation has become an effective and accepted surgical procedure that can result in end-stage heart failure patients resuming relatively normal lives for a period usually expected to be up to ten years. Transplants are the only curative treatment for CHF but this procedure is limited due to the relatively small and declining number of available donor hearts. In consequence, global transplant numbers are falling.
  
• Ventricular Assist Devices ("VAD"). VADs are designed to take over some or all of the pumping function of the heart. VADs are implanted either as a bridge-to-transplantation or, currently in lesser numbers, as an alternative to transplantation (so called "destination therapy"). Recent studies have also indicated that VADs may be used for "bridge to recovery". A study published in the November 2006 issue of the New England Journal of Medicine study showed that for a subset of patients, the use of a VAD in conjunction with a particular drug regimen allowed the heart to recover to such an extent that the device was subsequently removed. The study was conducted at Harefield Hospital, one of HeartWare's investigational sites, and was co-authored by Dr Asghar Khaghani, a member of HeartWare's Medical Advisory Board. Confirmatory studies relating to this potential "bridge to recovery" indication are currently underway.