Machines vs transplants

The ageing population and growing risk factors have made a significant impact on driving up the number of registered heart failure cases. Existing pharmacological strategies are improving the survival rates of acute and early-stage heart failure patients, ironically providing a growing body of patients with progression of the disease to heart failure. With no new drug therapies addressing advanced heart failure and existing pharmacological strategies failing to compensate for a weakening heart, alternative solutions have to be found. In view of long waiting lists for heart transplantation and the growing lack of donor hearts, significant numbers of patients die while waiting for a heart transplant. But cardiac resynchronization therapy, mechanical circulatory support devices and other alternative technologies have demonstrated promising results, and the continuing rapid technological developments in this area suggest we may only be a decade away from eliminating the reliance on heart transplantation, according to a new report* by independent market analyst Datamonitor.

Growing heart failure population

The number of sufferers of heart failure is expected to climb to epidemic proportions. Worldwide, heart failure (HF) affects nearly 23 million people. In the United States, HF affects approximately 4.7m persons with approximately 550,000 incidences of HF diagnosed annually. Estimates of the prevalence of symptomatic HF in the general European population are similar to those in the United States and range from 0.4 to 2% of the total population. Existing gold-standard pharmacological strategies are able to provide superior compensation of acute and early-stage heart failure patients, increasing their survival rates without ensuring a full recovery. This results in an increasing long-term shift of such patients into the advanced heart failure group.

With no new drug therapies addressing advanced heart failure and existing pharmacological strategies failing to compensate for a weakening heart, alternative, non-pharmacological solutions have to be found, says Datamonitor senior cardiovascular analyst Dr. Sergey Ishin. “Cardiac transplantation continues to be the gold standard for the treatment of end-stage heart failure. However, the number of potential transplants far exceeds the number of donors.

“In the US, proximally 2,500 heart transplants are carried out each year and research has suggested that up to 100,000 patients have advanced heart disease that would benefit from transplantation. This leads to 30% of patients on the waiting list dying annually,” he says.

Cardiac resynchronization therapy (CRT), through multiple randomized clinical trials has demonstrated promising results in terms of both safety and efficacy, improving left ventricular efficiency and, subsequently, improving functional class. “However, one of the greatest limitations of this technology is the fact that existing CRT devices, similarly to pharmacological treatment, can only temporarily improve symptoms and to some degree delay the progression of myocardial deterioration. Unfortunately, neither can prevent, stop nor reverse it.

“This unfortunate situation eventually brings advanced heart failure patients back to the heart transplant waiting lists,” Dr. Ishin says.

Improving patient's survival with alternative solutions

Although the advancements in surgical techniques and immunosuppressant therapy make it possible to perform successful heart transplantations even in the most critically ill patients, the rapidly growing end-stage heart failure population creates a tremendous gap in the number of patients waiting for new hearts and the number of organs that actually become available, Dr. Ishin says. “In view of this situation, in addition to avoiding the immunosuppression and rejection complications of transplantation, mechanical circulatory support devices work as the only promising option which can help resolve the issue of organ availability and save more patients.”

The idea of finding a mechanical alternative to donor transplants is not new. Mechanical circulatory support devices and total artificial hearts have been under development since the 1950s, but only recently, with advancements in technology, have they started demonstrating some serious potential in completely eliminating the need for heart transplantation. With many different design concepts tested throughout the decades the new face of mechanical circulatory support technology started to emerge. Bulky, immobile systems have gradually been replaced with more portable and even fully implantable solutions providing full patient mobility.

Even though scientists initially desired to create a complete artificial heart the lack of technological solutions at the time prevented rapid development in this area. Further research subsequently showed that it is more feasible to create a device that supports only the left ventricle. Presently, ventricular assist devices are the most well researched and technologically diverse area, Dr. Ishin says. “The biggest advantage of ventricular assist devices over a complete artificial heart is the ability to instantly provide sufficient cardiac output to the patient, possibly for a very long period of time, and at the same time avoid any irreversible surgical modifications and keep an albeit weak, yet still functioning patient's heart working while potentially improving its functionality.

“Originally most of these devices were designed just to provide the necessary support while a patient is waiting for the donor heart. This is so called bridge-to-transplantation approach.

“Technological progress, however, made it possible to implant these devices for a significantly longer period of time, creating an opportunity for the so-called ‘destination therapy' approach, when the device can be left implanted permanently, eliminating the need for heart transplant,” he says.

Miniaturization of the components is one of the most important keys in the developmental process. New, totally implantable solutions such as Jarvik 2000 and BerlinHeart Incor may not only eliminate the need for the heart transplantation but also allow full patient mobility, making it possible for the patients to return to their normal life.

Yet far away from complete replacement of heart transplantation

In spite of rapid technological developments and successful clinical trials, there are still a considerable number of issues associated with this technology Dr. Ishin says. “Among them are material biocompatibility and coagulation control, mechanical reliability of internal components, smaller device size allowing implantation into smaller patients and children, power sources, size of the batteries and device energy consumption, which would allow for fully implantable solutions with better infection control and patient mobility.

“Even the most advanced devices allow fully independent device operation for no longer than 20 minutes before it has to be connected back to its external batteries, which can be rather bulky and heavy,” he says.

In 2007, the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) reported device malfunction in 9% of all reported implantation cases. Factors that affect the probability of device malfunction are directly related the number of individual components and moving parts in the system. Hence, simplification of design and reduction in the number of components and moving parts should improve long-lasting performance and durability of devices.

In addition to device malfunction, device-related infections are one of the most frequent complications of ventricular assist device placement. Infections are reported to occur in no less than 13% of cases, Dr. Ishin says. “Although device-related infections can involve any aspect of the device: the surgical site, the driveline, the device pocket, or the pump itself, and more than half of all device-related infections include multiple sites, the existence of external components such as drivelines and batteries leads to a significant increase in the chance of an infection, leading back to the problem of external power supply and longer lasting batteries.

“Although at present we can not completely eliminate the need for heart transplantation, rapid technological developments indicate that we are not that far away from sorting mechanical issues, coagulation control and device-related infections with serious breakthroughs expected within next five to 10 years,” he says.

* Stakeholder Opinions: Heart Failure; When drugs do not work: Treatment of advanced heart failure with medical device therapies

Datamonitor's report Stakeholder Opinions: Heart Failure; When drugs do not work: Treatment of advanced heart failure with medical device therapies, provides in-depth analysis of the current status and future potential of treatment opportunities in advanced stages of heart failure. It includes an overview of existing and emerging technologies including cardiac resynchronization therapy and mechanical circulatory support devices.