ESC Rene Laennec Lecture in Clinical Cardiology
Personalised approaches to managing heritable thoracic aortic disease
31 Aug 2024
The presenter of this year’s ESC Rene Laennec Lecture in Clinical Cardiology is Professor Julie De Backer (Ghent University Hospital - Ghent, Belgium), whose translational research on in-depth profiling has accelerated understanding of genotype/phenotype relationships for several heritable cardiovascular diseases and underpinned the quest for novel treatment targets.
What are the key themes of your lecture?
Clinical knowledge about heritable thoracic aortic diseases (HTAD) has increased dramatically over the last two decades. Initially, the only clinical entity for which we had diagnostic criteria was Marfan syndrome. Now, there are multiple other diseases that have been identified and for which more genes have been described. Study of specific gene variants has informed our knowledge about the pathophysiology of these diseases, how they occur and the mechanisms involved in how they develop. We have evolved to an era where genetics can be used for diagnosis, for directing management and for guiding the search for molecular targets that will help us to personalise treatment. From a clinical cardiology perspective, it is also important to mention that there is increasing evidence that the pathology in HTAD is not limited to the aorta but that mitral valve pathology, including mitral annular disjunction, arrhythmia and heart failure also plays an important role. What is more, research into rare HTAD has a far wider application in helping us to better understand, and manage, more common cardiovascular conditions, namely aneurysms and dissections as well as heart failure that occur in people with acquired cardiovascular diseases.
I will emphasise that personalisation should occur at two levels: tailored medicine and the human connection. In these times of increasingly innovative technology, which we should and do embrace, we must remember that there is a human being at the centre who needs care and reassurance.
What are the most important knowledge gaps and challenges?
There are many knowledge gaps in HTAD, but defining better risk stratification would help us to improve care. Yes, there are guidelines to help with this, but it is increasingly apparent that stratification is complex and requires a multifactorial approach. It is as much about pinpointing those patients at low risk – and avoiding potentially unnecessary treatment – as it is about identifying those at high risk. We also need more effective treatments and better ways to manage patients beyond administering generic anti-hypertensives.
Despite its benefits, there are challenges associated with the genetic testing, which is rapidly becoming integrated into clinical practice. Strategies should be put in place to determine, for example, how results will be communicated to patients, who is responsible for screening families and how issues surrounding the identification of a genetic disorder unrelated to the disease for which the person was tested will be managed.
What are the most promising avenues of research?
In terms of understanding disease processes, interesting evidence is being revealed about the potentially important role of inflammation in the pathophysiology of aortic diseases, which could open the door to the use of immunotherapies. Samples from patients with end-stage aortic disease show infiltration of inflammatory cells, although whether these are due to advanced disease or are involved in early pathogenesis remains to be clarified.
There is also a need to better understand the genetics of HTAD. For example, information is required regarding which genetic variants are causally linked to disease and which are not, and novel in vitro testing models are being developed. In addition, research is at the early stages of trying to pinpoint the role of polygenic mechanisms. Finally, the study of rare diseases would make little progress without international collaboration, so it is crucial that we redouble efforts to learn from registries and foster network connections in the search for personalised ways to manage HTAD.
- Don't miss! ESC Rene Laennec Lecture in Clinical Cardiology: 09:15-10:00, Helsinki
