Heart valve replacement, while a lifesaving procedure, is rife with problems ranging from blood clotting to tissue degeneration. The field is long overdue for innovation.
Professor Jacques Janson, a senior specialist in the Cardiothoracic Surgery Division in the Faculty of Medicine and Health Sciences, with a strong interest in heart valve repair and replacement, recently explored a new method that uses the body’s own venous tissue to recreate damaged mitral valves. In a sheep model, he took tissue from the jugular vein to fashion anterior mitral valve leaflets.
Professor Janson was partly inspired to do the research, which led to his PhD dissertation, due to frustration with the slow pace of development in this field.
He says: “There are no ‘off-the-shelf ‘ heart valves (as is the case with replacement lenses in cataract surgery, for example) and those that are available, aren’t ideal. The technology has advanced in so many surgical fields, but with heart valves it’s like we’re stuck in the 1970s. The best mechanical valve in use now has essentially been unchanged since 40 years ago.”
There are problems with both the mechanical prosthetic and bio-prosthetic valves in use. With prosthetic valves clots can form, raising stroke risk, therefore patients need to take anti-coagulants. These, in turn, increase risk for bleeding.
“You risk just exchanging one disease for another when you replace someone’s heart valve,” Professor Janson explains.
Biological materials like human pericardium and porcine valves are used in bio-prosthetic valves. These materials have to be processed and fixed with glutaraldehyde to strengthen the tissue and remove antigens. This non-living tissue deteriorates with time, requiring replacement after 10-15 years. The patient’s own pericardium can sometimes be used, but it calcifies as well and shrinks after a while unless it is also fixed and rendered non-living.
Tissue valves are usually the choice for patients over 65, because despite degeneration the valve will likely last for the rest of their lives. A mechanical valve lasts longer in younger patients, but requires the lifelong use of Warfarin. Many young patients prefer a tissue valve and to then undergo another operation after ten years. Warfarin is also contraindicated in women who wish to become pregnant: In such cases tissue valves are used with the understanding that another operation will be required later.
“Repairing a valve rather than replacing it is always first prize, because you don’t get the complications from the prostheses,” Professor Janson says.
“There is a lot of stress on a working valve and it should be able to repair itself. Ideally, you want a method that uses the patient’s own regenerative tissue. My idea was to try using a vein, as we’ve been doing for coronary bypasses. However, using a vein graft as a conduit, which is what it’s designed for, differs quite a bit from fashioning it into a valve leaflet.”
“I don’t relish using animals, but it was very useful in terms of getting the technique done. We used the sheep’s jugular vein, which is long and wide. The sheep’s heart itself is similar to a human’s, especially the mitral valves, which also made it suitable.”
To fashion the leaflet, Professor Janson used a 12cm section of vein. It was cut open lengthwise and then folded double with the inner endothelial layer on the outside, and the vein branches sutured. Gore-Tex sutures were implanted on the edge of the leaflet, acting as chords attaching to the papillary muscles to provide support for the leaflet.
“Once we’d got the sheep through the operation and did the echocardiograms, the valve looked quite good initially, but there were some technical issues.
“When we do valve repairs in humans, we insert a ring to stabilise the valve annulus to prevent enlargement. The ring basically comprises wire wrapped around a piece of Dacron, and I didn’t want to use foreign tissue in the sheep – I wanted the healing process to be natural.
“Because of this, in the sheep the valve kept growing and the leaflet shrunk in relation. The result was that over 6-10 months regression of mitral regurgitation occurred. A few of the Gore-Tex sutures tore out, again because there was so much pressure on the leaflet.
“Therefore, if we did another study we’d probably look into improving the valve’s durability by supporting the annulus, as well as supporting the leaflet with secondary chords.
“It was encouraging that the histology indicated that the vein leaflet itself was viable: The tissue survived, could take the strain of a working valve and showed the ability to heal and adapt to its new environment in the heart. So it has the potential to be used as a leaflet substitute.
“The next step would be to investigate if it would be clinically possible to replace a whole valve, but obviously we’d have to do that as a study protocol. In humans, instead of the jugular we’d use the saphenous vein in the leg (which is too small to use in sheep). We already use it for coronary bypasses and there is enough vein to create a whole leaflet from it.
“A safe way to proceed might be to try the procedure in just one or two patients and monitor them closely for a year, checking to see if the valve needs replacement. Patients with a high risk for Warfarin usage might benefit from such a procedure.
“Another possible application of this method might be to use the vein in cases where you need to replace a piece of leaflet which is missing due to infection. A vein might be a good option for the patch instead of pericardium, which would degenerate. Sometimes the leaflets retract and need to be lengthened. A vein patch might also work in these cases.
“I’ve done that in one patient where the whole anterior leaflet was infected and needed to be cut away together with the chords. I used a saphenous vein and also inserted chords. We have monitored this patient for almost 10 months now and he’s doing really well. That was the first case in which a human saphenous vein was used in valve surgery. However, that was a repair situation and not a full replacement.
“There might be applications for other valves too. The aortic valve, for example, is smaller and requires smaller leaflets, therefore you’d need less vein to replace it. The pressure the valve experiences is also less. In developed world populations the valve that tends to gets diseased is the older aortic valve, which suffers stenosis. A calcified, thickened valve often can’t be repaired and needs replacement. But with those patients you can often get away with a tissue valve, which will last them their lifespan.”
The ultimate prize, according to Professor Janson, would be a living tissue valve that can last for 20 years in a young person without needing to use Warfarin. This would be particularly useful in the South African context, where resource limitations often make repeated surgeries unfeasible.