Repairing broken hearts
In 1967, Professor Christiaan Barnard undertook the world’s first heart transplant at Groote Schuur Hospital of UCT. This success paved the way for heart transplants to become a relatively common and successful surgical procedure for many patients throughout the world.
Heart transplants depend on donor organs, but their availability has steadily declined over the years. At the same time, the number of patients with cardiovascular diseases such as coronary artery disease, heart attack (myocardial infarction) and heart failure is increasing, and alternative therapies are needed.
Since the first heart transplant there have been enormous advances in promoting cardiovascular health. Some of these are preventative – no smoking, more exercise – but there has also been much progress in “fixing” diseased hearts. This can take a number of forms – endovascular stents, coronary artery bypass surgery and the introduction of pacemakers. These advances are dependent on bringing a number of approaches together – engineering, biomaterials, cell and regenerative therapies and computer modelling – and addressing some of the challenges that are associated with trying to treat diseased hearts.
Treatment of coronary artery and heart diseases has a number of aspects. This includes ballooning (ie angioplasty) and inserting stents in coronary blood vessels to widen atherosclerotic narrowing that limits the blood flow and causes ischemic heart disease.
One can also implant vascular grafts to bypass narrowed or blocked coronary arteries, or place a mesh around the heart to improve the pump function and prevent the dilation of the heart after a heart attack that can lead to heart failure.
Angioplasty and stenting of coronary arteries provide improvement of the symptoms of coronary artery disease; however, a repeated narrowing (restenosis) of the arteries over time has been observed in many patients. This may require repeated interventions and coronary artery bypass surgery during which the patient receives bypass blood vessels to circumvent blocked or overly narrowed arteries.
First choice for replacement blood vessels – 571 000 were required in the US in 1999 alone – are the patients’ own internal mammary artery (located in the chest), brachial artery from the arm, and saphenous veins from the leg.
If the patient’s arteries and veins are not available (eg due to disease or use in previous bypass procedures), synthetic blood vessels are needed. These synthetic blood vessels have, however, a limited lifetime due to imperfect integration in the patient’s body, for example, when used for coronary artery bypass surgery. More than half of all synthetic blood vessels fail (by narrowing or blockage) within three years after surgery and 70 percent of the synthetic grafts fail after six years – requiring that patients undergo repeated surgeries.
Advances in science have encouraged the development of alternatives to synthetic blood vessels. Tissue-engineered prostheses can now be created that stimulate the incorporation of the patient’s own cells and tissue. Tissue regenerative approaches aim one step further at creating a new blood vessel entirely made from the patient’s own tissue.
In work with Associate Professor Deon Bezuidenhout at the UCT Chris Barnard Division of Cardiothoracic Surgery, fibrous polymeric structures have been developed to function as initial scaffolds for regenerated blood vessels. These scaffolds are meant to degrade safely in the patient’s body as tissue develops, eventually removing all synthetic material.
Important aspects for the development of such scaffolds are to optimise the initial mechanics and structural properties while minimising the amount of synthetic material to be implanted and to tailor the rate of degradation to that of the tissue development so that the maturing blood vessel does not fail, eg rupture due to the blood pressure. Such tissue-regenerated blood vessels mean a better integration in the patient’s body, and consequently promise to last far longer than synthetic blood vessels – sparing patients recurring open heart surgeries.
Heart attacks (when cardiac tissue dies from a lack of oxygen due to the sudden blockage of one of the coronary arteries at the heart) remain a major treatment challenge. A recent study by Finegold et al shows ischemic heart disease, including heart attacks, to be the leading cause of death worldwide with 7 249 000 deaths in 2008.
Low and middle-income countries account for more than 80 percent of these deaths. According to the South African Heart and Stroke Foundation 33 people a day die because of a heart attack in this country alone. Since there is nothing that can restore infarcted dead heart tissue to life at present, the heart eventually fails to effectively pump blood through the body (heart failure). The only treatment for heart failure is to replace the entire heart (heart transplant).
Pre-emptive measures include placing a synthetic mesh around the heart, but this does not restore full functionality of the heart and is an invasive procedure.
We now know that invasive surgery has side effects that can be injurious to the overall health of the patient. Medical science is increasingly exploring how to reduce invasive procedures. Less invasive procedures and interventions that lead to the protection of the heart and regeneration of infarcted cardiac tissue are of much interest.
Stem cell therapies have shown some, although limited, benefits in treating heart attacks. Cells are injected with a carrier material into the injured region of the heart. It is not clear whether the positive outcomes observed are a result of the cellular activity and tissue regeneration, the mechanical effects of injected carrier material (ie supporting the injured cardiac tissue), or both.
Recent collaborative research with Dr Neil Davies has combined bioengineering and computational modelling to investigate this question. Pre-clinical experiments involving the injection of a biomaterial in infarcted hearts only indicated that the therapy without cells shows some improvement in cardiac function and reduction of the adverse changes the heart undergoes after infarction.
This includes prevention of thinning of the ventricular wall in the infarcted region and the dilation of the left ventricle over time that often leads to volume overload and heart failure.
To further advance this type of treatment and accelerate the translation into clinical application, computational modelling can be helpful to obtain additional information that is not accessible with experimental methods.
The use of MRI (magnetic resonance imaging) allows the anatomical analysis of the heart. With the aid of computer models developed from MR images, the filling and contraction of the heart can be simulated and its deformation and pump function analysed.
With this, computational modelling makes possible a theoretical examination of the impact of biomaterials on the functioning of the heart and optimisation of the biomaterial therapy.
Tissue regenerative blood vessels will save many patients from undergoing repeated open heart surgery once the technology is transferred into the hospital. Computational modelling of heart attack therapies allows doctors to assess how successful the use of biomaterials will be for a particular patient even before invasive surgery has been performed.
This is a huge advance, giving clinicians support in treatment decisions, reducing risks to the patient and reducing costs associated with procedures whose outcomes are not known with a great deal of certainty.
To reach this goal, further expansion of inter and transdisciplinary research and innovation is required at national and international level.
To understand better how to deal with chronic diseases, a British High Commission-funded workshop on cell mechanics and mechanobiology was recently held in Cape Town. It brought together international experts from academia and industry from South Africa, the UK, Germany and Spain to discuss how cells migrate and interact with their physical environment and what role this plays in development and treatment of diseases.
The future of heart health lies in developing a new generation of treatments that treat disease with as little invasion as possible.
This is a long way from the Chris Barnard heart transplant where somebody had to lose a life in order for another person to have a chance of a better life. New approaches, technologies and materials are bringing this future ever closer.
l Franz is Associate Professor in the Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, UCT and a fellow of the Programme for the Enhancement of Research Capacity in the research office at UCT.