Data from Marshall Pearce - Curated by EPG Health - Last updated 19 September 2017
Advanced heart failure is a substantial and growing problem – both in population terms, where it represents 5–10% of the population with heart failure, and for the individual, where prognosis is extremely poor. Not only is it a large-scale problem, but heart failure as a clinical entity has a 5-year survival rate of less than 50%.
Heart failure is medically managed in its early stages, but definitive management for more advanced disease is heart transplantation. Organ availability is a limiting step, with only around 80% of people in the UK on the waiting list likely to receive a heart transplant, while the UNOS data for the USA suggest nearly 4,000 people are awaiting heart transplant, with only 3,191 performed in the last year. Unfortunately, given the poor prognosis, many patients amenable for transplant will die on the waiting list.
Heart transplantation itself carries risks, and the balance between immunosuppression and rejection is a considerable one. Following any solid organ transplantation, there are much higher rates of infection and cancer, while cardiovascular disease and rejection are major sources of mortality. While heart transplantation is a key end-stage treatment, an alternative may provide a much less drastic option.
With that in mind, mechanical pump devices have a significant history, and range from a completely mechanical replacement heart – which remains an experimental option – to ventricular assist devices.
Historically, left ventricular assist devices (LVAD) were first approved exclusively as a ‘bridge’ to transplant by the FDA in 1994. Following the REMATCH trial in 2001, LVADs were approved as a destination therapy – demonstrating a significant improvement in quality of life, functional status and depressive symptoms compared to optimal medical management.
For several years there has been the suggestion that cardiac tissue has reasonable capacity for regeneration – with improvements in cardiac biochemistry, anatomy and physiology noted following prolonged mechanical circulatory support. LVADs have demonstrated improvement in cardiac function, both at rest and during gentle exercise.
If the utility of LVADs have been slowly growing over time as the devices become better and better, a study by Jakovljevic et al (2017) has flagged up LVADs as potentially being a key therapeutic option for the future. Their study reviewed the cardiac and respiratory performance status of four groups of patients: heart transplant candidates, LVAD implanted patients, patients who had had their LVAD removed (after a mean period of 396 days; range 22–638 days), and healthy controls. They noted that the group of patients who had their LVAD explanted had significantly better cardiac and functional capacities than those awaiting transplant and those who still had an LVAD in situ. Most impressively, some of those with their LVAD explanted had peak exercise performance within the range of the healthy controls.
This is fascinating from a physiological perspective, as it demonstrates that in some circumstances, significant myocardial recovery is possible. From a practical perspective, it suggests that LVAD implantation can be a significant step towards treatment of some causes of heart failure. If pharmacological therapies can be developed that further aid myocardial recovery, there may be the possibility for avoidance of transplantation in some cases.
Technical challenges and future considerations
There are several technical challenges that relate to the implants. Some of these have been addressed to a varying extent, while others are yet to be resolved. Certainly LVADs are not without potential for complication – they require anticoagulation, and thrombosis and haemorrhage are the most common adverse events, while infection remains a risk.
There has been debate over this issue since the concept initially arose. The larger arteries have an elastic component to their walls, responding to pulsatile flow and maintaining a constant pressure gradient. A 2009 study demonstrated superior bridge-to-treatment survival with the continuous flow device Heartmate II over the pulsatile flow XVE. This led to a shift away from pulsatile flow devices – but it is unclear whether this is an intrinsic effect of the flow mechanism – or more to do with the device itself.
Continuous flow devices unload pressure from the left ventricle, but may theoretically lead to right ventricular dysfunction due to a shift in the interventricular septum – as this decreases the efficiency of the right ventricle. The rate of right heart failure has not been shown to vary with pulsatile or continuous flow devices – the theory is that pulsatile flow allows more physiologic unloading of the ventricle, but this has yet to be investigated thoroughly. In cases of aortic valve dysfunction, the higher pressures generated by pulsatile flow may improve aortic valve opening.
The size of the devices is decreasing. In some respects, this is linked to pulsatile flow, older generation devices were considerably larger and had multiple moving parts to the extent that patient size was a factor that needed to be accounted for when considering LVAD implantation.
The surgical implantation of these devices is also dependent on their size. Older generation devices such as the HeartWave I and II (Thoratec) required implantation in the abdomen as there was insufficient space within the thorax. The reduction in size of devices since then has meant that the formation of an abdominal “pocket” is no longer necessary. For some of the newer devices, surgical techniques are being explored which allow for the avoidance of sternotomy entirely.
The fact that these mechanical devices have a finite lifespan remains an issue. By definition, patients with end-stage heart failure carry a level of anaesthetic and surgical risk – so performing major surgery, and particularly repeated surgery can be problematic. This is another area where the advance of the technology has been beneficial. Pump thrombosis and malfunction are significant reasons for morbidity, and it is a technical challenge to limit the development of these issues.
One of the existing technologies which continues to be iterated upon is a magnetically levitated rotor; the approved HVAD system (Heartware) utilises this technology. The MOMENTUM 3 study also examined a pump (Heartmate 3) using a completely magnetically levitated mechanism. It used centrifugal rather than axial flow, and demonstrated improved outcomes relative to axial flow devices . Although long-term data are not available, the theory is that it will wear a lot more slowly as there are no parts in direct contact. Further advances may continue to improve reliability and decrease rates of pump failure, making replacement less likely to be required.
How to provide power to the device remains one of the hurdles that is being explored. At present, all devices have a ‘driveline’ that requires an external power source. This remains a vector for potential infection and colonisation. A possible alternative that can address this issue is Transcutaneous Energy Transfer (TET [Millar OEM]). This is an induction system that has been used in lower-energy devices, such as pacemakers and implantable defibrillators.
Due to the induction charging however, there have been reports of interference from home electronics. In high risk devices such as LVADs, this needs to be examined further, and there is optimism that it will be integrated within the next few years – with a potential device already in early development.
Devices in development
- As alluded to above, the MOMENTUM 3 study is ongoing, and exploring the Heartmate 3 device (Thoratec). It has various innovations, including a magnetically levitated rotor, and several strategies which attempt to combat the issue of pump thrombosis. The study is ongoing.
- The first attempt to address the issue of requiring transcutaneous lines is in development – the company behind the HeartAssist 5 device (ReliantHeart) have announced that they are examining a transcutaneous power option.
- The FDA has granted a conditional approval for a study of a miniaturised version of the Jarvik 2000 LVAD system (Jarvik Heart) – primarily aimed at children and infants.
Alongside a pharmacological strategy to aid myocardial recovery, LVADs may prove to have a significant role to play in the ever-growing problem of heart failure. There are technological hurdles to overcome, yet the limited supply of organs for transplantation means that if LVAD therapy can be a viable therapeutic aid to myocardial recovery, it may relieve some of the pressure from the organ donor supply. Although LVADs are not new onto the scene, the advance of technology – smaller, more efficient devices with better reliability and potentially transcutaneous power transfer – means we may be on the cusp of seeing many more deployed to tackle heart failure.
References for further reading
Canseco DC, Kimura W, Garg S, Mukherjee S, Bhattacharya S, Abdisalaam S, et al. Human ventricular unloading induces cardiomyocyte proliferation. J Am Coll Cardiol. 2015 Mar 10;65(9):892-900.
Jakovljevic DG, Yacoub MH, Schueler S, MacGowan GA, Velicki L, Seferovic PM, et al. Left Ventricular Assist Device as a Bridge to Recovery for Patients With Advanced Heart Failure. J Am Coll Cardiol. 2017 Apr 18;69(15):1924-1933.
Kilic A. The future of left ventricular assist devices. J Thorac Dis. 2015 Dec;7(12):2188-93.
Reineke DC, Mohacsi PJ. New role of ventricular assist devices as bridge to transplantation: European perspective. Curr Opin Organ Transplant. 2017 Jun;22(3):225-230.
Roberts SM, Hovord DG, Kodavatiganti R, Sathishkumar S. Ventricular assist devices and non-cardiac surgery. BMC Anesthesiol. 2015 Dec 19;15:185.
Schumer EM, Black MC, Monreal G, Slaughter MS. Left ventricular assist devices: current controversies and future directions. Eur Heart J. 2016 Dec 7;37(46):3434-3439.
Selzman CH, Madden JL, Healy AH, McKellar SH, Koliopoulou A, Stehlik J, et al. Bridge to removal: a paradigm shift for left ventricular assist device therapy. Ann Thorac Surg. 2015 Jan;99(1):360-7.