Ali Fethi Toprak
Cardiovascular disease is a progressive, debilitating, and deadly disease affecting over 23 million people worldwide.1 The physiopathology of heart disease is the minimal regeneration capacity of the heart that could eventually lead to heart failure. The only definitive treatment for heart failure remains heart transplantation, which is limited by donor availability. This urges alternative approaches to meet the necessary functionality of the heart by developing assist devices or artificial hearts.
The heart is basically a pump that provides the force needed to circulate blood and its contents to the body. It consists of four chambers: left ventricle, left atrium, right ventricle, and right atrium. The right ventricle and atrium collect the blood from the whole body and pump it to the lungs for removal of carbon dioxide and replenishment of oxygen. On the other hand, the left ventricle and atrium are responsible for collecting the blood from the lungs and pumping it to the body through the aorta (main artery). Non-stop blood circulation requires life-long and unfailing heart muscle power. Common symptoms of heart failure include waking up at the middle of night with shortness of breath and decreased ability to walk a few steps upstairs. Heart failure could arise due to any condition that decreases efficiency of the myocardium (heart muscle - Figure 1) through myocardial infarctions (death of muscles due to lack of oxygen, also known as heart attack) or overloading, such as hypertension, that requires increased contraction force. Loss of function in the ventricles (lower chamber of the heart) may require the use of ventricular assist devices (VAD).
Ventricular assist devices
A VAD is a mechanical pump that is implanted into the chest of patients to support the heart function through bridging the blood flow from the lower chamber to the aorta (Figure 2).2,3 A VAD is usually useful during or after cardiac surgeries until recovery of the heart or while waiting for a heart transplant. VADs could also be used long term if the patient is not eligible for a heart transplant due to other complications. A VAD has several components, including a tube carrying blood out of the heart into a pump, a pump with another tube carrying blood to the aorta, and a power supply connecting to a control unit that monitors the VAD`s functionality.
There are different designs of VADs such as HeartMate, HeartWare, DuraHeart, and so on. Some VADs pump like the heart does, using a pumping action, and others use continuous blood flow. Intriguingly, VADs with continuous flow lead to a loss of normal pulse, but this has been found to decrease complications and increase survival. Two types of VADs include left ventricular assist device (LVAD) or right VAD (RVAD). LVADs are the most commonly used ones due to higher incidence of left ventricular function loss. If both LVAD and RVADs are used together, they are called a biventricular assist device (BVAC). VADs nowadays could be used not only for people with end stage heart failure, but also earlier stages of heart failure, including children. A VAD takes ninety percent of the pumping function of the heart. When using a VAD, your heart will still beat and have a rhythm. If none of these works for a patient, this requires the use of a mechanical or artificial heart, also known as total artificial heart (TAH).
Total artificial hearts
An artificial heart is a mechanical device that substitutes for the failing heart.4,5,6 They are commonly used during heart transplantations to bridge the blood flow temporarily or to replace the heart permanently during a shortage of transplantable hearts. Early studies with artificial heart trials go back to the 1940s. Since then, various groups worldwide have invested in development of artificial heart prototypes and performed animal and human trials. Total artificial heart prototypes include, but are not limited to, SynCardia, ABIOMed (AbioCor), and Carpentier (CARMAT).6
SynCardia is developed from the Jarvik-7. It was first implanted in 1982. Dr. Robert Jarvik originally designed the Jarvik-7 (Figure 3). Barney Clark underwent the first artificial heart implantation at the University of Utah and survived for 112 days. This was followed by other implants. The longest survival with the Jarvik-7 is 620 days. However, the device is more commonly used on patients as a bridge during heart transplants. It has two pumps that resemble the two ventricles of the heart and is pneumatically (air) powered. The pump of SynCardia is covered with polyurethane. A pneumatic driver used in the US is a non-portable console, and requires patients to stay in the hospital. However, a portable version has been developed in Europe that could be carried a backpack while a patient waits for a donor heart.
The ABIOMed (AbioCor) is a completely self-contained, total artificial heart, which avoids the need for an external console or having wires or tubes piercing the skin to power the device. It uses a wireless energy transfer system, also known as a transcutaneous energy transmission system. This decreases the risk of developing infections due to implants.
CARMAT, on the other hand, is designed by Alain F. Carpentier.7 It is a fully implantable artificial heart with embedded biomaterials that make the device more biocompatible. In addition, the CARMAT includes valves made from cow heart tissue and has internal pressure sensors. This allows a person to adjust the flow rate in response to increased demand, such as during exercise. This feature distinguishes the CARMAT from other artificial hearts that provides a constant flow rate.
Biological artificial hearts
Synthetic replacement of organs is one of the long-sought dreams of modern medicine. To this end, there are efforts to develop biological artificial hearts in the laboratory. One recent study took the approach of producing a decellurized (empty from cells) scaffold of a mouse heart and recellurized it with human cardiac cells, and showed that lab-grown human heart tissue can beat on its own (about 40-50 beats per minute) in as short as a few weeks (Figure 4).8 They took the advantage of induced pluripotent cell (iPS cells) technology to produce multi-potential cardiovascular progenitor (MCP) cells, which could give rise to all three types of cardiac cells found in the heart. This area of research is still in its infancy but in the future, at least, it may provide tools to generate patches of heart tissue to replace damaged parts of the hearts. Given the success of a mouse heart cellurized with human cardiac cells, it's possible that scientists will also try to decellurize the heart of a monkey or another animal and then cellurize it with human cardiac cells to produce a beating human heart in the laboratory as an alternative source to a full heart transplant.
Another approach to a biological artificial heart is to genetically modify animals in a way that their hearts will be compatible with a human body. Genetic engineering is a rapidly evolving field that one day could provide such tools for scientist to grow necessary organs in monkeys, dogs, or maybe even horses. Genetic modification may overcome tissue rejection issues when they are transplanted into a human body. For instance, one study tested the possibility of a heart transplant from genetically modified pigs into monkeys and showed the applicability of heart transplants between different species.9,10
Until the development of biological artificial hearts, ventricular assist devices and mechanical artificial hearts seem to the best options. However, artificial heart implants have had various complications, including infections, pneumonia, high fevers, and multiple organ failures with variable survival rates based on the type of device and materials used. Another issue is the necessity of artificial heart to meet requirements of the body in terms of heart flow rate. For instance, the required flow rate of someone walking or exercising is different than someone at rest. In addition, the possibility of mechanical or computerized systems to fail may be a source of distress in patients implanted with artificial hearts or assist devices. This reminds us of that as long as we take care of our heart's health, we won't have worry whether its battery could fail - and what a mercy that is.
It is stunning that even with so much need and effort we are still not able to develop something that completely replaces all the functions of a heart. This clearly points that the heart is a marvelous gift granted to us. We are counting on every beat of the heart for our survival, and we should give thanks, with every beat, for what an incredible gift we've been given.
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8. Lu, Tung-Ying, Bo Lin, Jong Kim, Mara Sullivan, Kimimasa Tobita, Guy Salama, and Lei Yang. "Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells." Nature communications 4 (2013).
9. Heart of genetically modified pig 'successfully transplanted into monkey', South Korea scientists claim. Retrieved from http://www.dailymail.co.uk/news/article-2164964/South-Korea-scientists-successfully-transplant-heart-genetically-modified-pig-monkey.html on 12/1/14
10. Pig to human transplants. Retrieved from http://www.theguardian.com/world/2002/jan/03/qanda.simonjeffery on 12/1/14