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pharmafile | June 30, 2008 | News story | Sales and Marketing |Â Â Â
Can technology diminish reliance on heart transplants?
Growing risk factors in an ageing population have driven the rising prevalence of heart failure. With no new drug therapies, and existing pharmacological strategies failing to compensate for a weakening heart, other solutions must be found. Alternative technologies in particular have demonstrated promising results, suggesting we may soon eliminate the reliance on transplantation.
The number of sufferers of heart failure is expected to climb to epidemic proportions. Worldwide, heart failure affects nearly 23 million people. In the US, the condition affects 4.7 million people with approximately 550,000 incidences diagnosed annually. Estimates of the prevalence of symptomatic heart failure in the general European population are similar to those in the US, 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. Consequently, there is an increasing long-term shift of such patients into the advanced heart failure group.
With no new drug therapies addressing advanced heart failure, alternative, non-pharmacological solutions have to be found.
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, approximately 2,500 heart transplants are carried out each year, but research has suggested that up to 100,000 patients have advanced heart disease that would benefit from transplantation. This means that 30% of patients on the waiting lists are dying annually.
Through multiple randomized clinical trials, cardiac resynchronization therapy (CRT) 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 or reverse it. This situation eventually brings advanced heart failure patients back to the heart transplant waiting lists.
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. With this in mind, it would seem that mechanical circulatory support devices are the only feasible option to resolve the issue of organ availability. They also provide the additional benefits of avoiding the immunosuppression and rejection complications of transplantation.
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, thanks to significant advancements in technology, have they begun to demonstrate serious potential for the complete elimination of the need for heart transplantation. As many different design concepts have been tested throughout the decades, the new face of mechanical circulatory support technology has 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.
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, while at the same time avoiding any irreversible surgical modifications and keeping an albeit weak, yet still functioning patient's heart working while potentially improving its functionality.
Originally, doctors designed these devices to just provide the necessary support while a patient waited for the donor heart: a 'bridge-to-transplantation' approach. Technological progress, however, has 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, ultimately eliminating the need for heart transplant.
Miniaturization of the components is one of the most important landmarks 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.
In spite of rapid technological developments and successful clinical trials there are still a considerable number of issues associated with this technology. Among them are material biocompatibility and coagulation control; the mechanical reliability of internal components; device sizing; power sources; size of the batteries and device energy consumption.
The latter issue is particularly significant: 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.
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 a reduction in the number of components and moving parts should improve the 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. 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 far away from finding solutions for the mechanical issues, coagulation control and device-related infections inherent in mechanical circulatory support devices. Major breakthroughs are expected within the next five to 10 years.
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