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Animal-derived heart valves are preferred to mechanical ones for valve-replacement heart surgery because they are more biocompatible and do not require a life-changing regime of anticoagulant drugs.
However, in young patients, animal-derived valves only have a lifespan of around five to ten years as the result of premature dysfunction. This means valves derived from cattle or pigs are usually only implanted into patients aged over 60.
The goal of the EU-funded TRANSLINK project was to improve the clinical outcome of animal-derived heart valve implants to make this procedure more viable for younger patients.
‘There is a limited amount of data suggesting that one of the reasons these biocompatible valves don’t last long in young individuals is immunology,’ says project coordinator Emanuele Cozzi, a transplant immunologist at Padua University Hospital in Italy. ‘The mandate of the TRANSLINK study was to find out to what extent immunological reasons underlie valve failure.’
Massive and unique dataset
The TRANSLINK partners built the world’s largest clinical and biological data bank devoted to animal-derived heart valve recipients.
‘We took a total of 388 000 measurements from 1 700 patients, at five medical centres in Europe and North America, a vast amount of data that has been collected in electronic case report forms,’ explains Cozzi. ‘We collected a huge number of blood samples – a unique collection of biological material and information on patients.’
By comparing patients with animal-derived heart valve implants with the control group, who had mechanical valve implants, the project consortium is identifying antibodies against animal-derived valves that may trigger premature valve failure. The teams have analysed the specificity of these antibodies at the molecular level and studied the mechanisms by which such antibodies may contribute to bioprosthetic heart valve failure following implantation.
The data is being analysed and the final results are yet to be announced, although markers linked to the activation of the human immune system have been found. This information may lead to the development of novel preventative and therapeutic strategies. These include a new generation of animal-derived heart valves with improved biocompatibility that are less prone to structural deterioration.
Bioengineering solutions
The results generated so far are enabling the SMEs in the TRANSLINK consortium to develop strategies for more durable animal-derived heart valves.
‘A major player in our network, Avantea, is a company that genetically engineers animals. This company can tailor the engineered pig and cattle lines to render their tissues – heart valves in this case – less immunogenic or more biocompatible,’ says Cozzi.
‘On the one hand, valves will be designed to be less immunogenic, and on the other, we also have two other partners whose mandate is to identify novel treatment strategies to mitigate the antibody response from the human immune system,’ he says.
The project results are therefore expected to open the way for strategies tailored to donors, based on whether they lack the major antigenic factors involved in premature valve deterioration. In the long term, TRANSLINK may greatly improve the outcomes of treatments for heart valve diseases in terms of longevity and well-being, and will enable the procedure to benefit younger patients, in particular.