2023 SCAD Update

So far this year we are off to a great start! Thank you to everyone involved in the study who took time this year to help us by giving us medical history information and biological samples, and to the SCADaddles for their generous support.

You may have seen the story in the Sydney Morning Herald, The Age, and on Channel 7 news about our recently paper published in the leading journal, Nature Genetics. In this paper, we along with several groups around the world, investigated if common genetic changes influenced an individual’s risk of developing SCAD. Based on this work, it appears that it is not just one gene that will determine your risk for developing SCAD. Common changes in 16 genes were found more frequently in people who have had a SCAD compared to those who haven’t. Genes are instructions for proteins. Proteins make up all the tissues in your body including the walls of blood vessels. Some changes in DNA mean that the proteins made will not be the correct shape or may not function properly, which may weaken the walls of blood vessels making them more likely to tear. In this work most of the DNA changes occurred in genes that provide the instructions for proteins that are part of blood vessel walls or those that maintain it. This result is consistent with previous work by our group and others that had shown that rare changes in similar genes have been found in people who have had a SCAD. However, there were some new findings. Other changes were found in genes are associated with blood clotting and blood pressure regulation. Our sincere thanks to everyone who so kindly contributed DNA for this paper.

In these media stories, we also announced that the Victor Chang Cardiac research Institute is the first outside the USA to be invited to join the international SCAD registry (iSCAD) that already has data from some 1300 SCAD sufferers. My colleague, Prof Jason Kovacic, is leading this effort. The iSCAD registry collects detailed clinical information and participant surveys after a SCAD event and recurrences. Jason and I have begun to enrol SCAD sufferers into this large effort to investigate the natural history and its consequences of SCAD.

We are continuing our successful collaboration with Dr Barbara Murphy and Prof Alun Jackson at the Australian Centre for Heart Health in Melbourne to address the psychosocial effects of having had a SCAD and their need for specific support programs to help with their rehabilitation. As you know, most cardiac rehabilitation programs are targeted to survivors of traditional heart attacks and do not
address the emotional support needs of SCAD patients. So far, Dr Murphy has conducted 7 focus groups to understand how having a SCAD affected the participants and we have published a paper based on this work. She has also developed the anonymous survey sent to SCAD survivors this year. A huge thanks to everyone who took the time to complete this survey! Currently, we are running support group trials with some study participants who have recently had a SCAD. Thank you to everyone who has participated in these groups! The ultimate goal is to develop support programs that will serve as a model for rehabilitation after a SCAD heart attack, for people worldwide.

We have several other research projects in progress:
We are investigating if SCAD and aortic dissections have any common genetic causes. We have finished DNA sequencing of people who have had a SCAD and also have a family history of aortic dissection, and their relatives from 16 families. A/Prof Eleni Giannoulatou and her laboratory along with Dr Lucy McGrath-Cadell, a cardiologist doing a PhD with us, and Dr Stephanie Hesselson, our study coordinator, are leading the effort to analyse this data. Thank you very much to all these patients and their unaffected family members for their participation.

We are also comparing the genetics of SCAD sufferers in families where more than one person has had a SCAD to their relatives who have not had a SCAD. Often when a condition runs in a family it can be easier to determine the genetic cause than in individuals with no known family history of the condition. We have genetic data from 22 families and are in the process of analysing this data.
Through the analysis that has been done so far, we believe we may have found DNA changes in at least 2 of these families that contributed majorly to their risk of SCAD. We are going to investigate if these changes do affect an individual’s risk of developing SCAD. Although this is a long slow process, we have made cell lines from the SCAD patients and their unaffected sisters in these 2 families. This, is in addition to cell lines from five SCAD subjects that were made in 2019- so good progress, thanks to my very able colleagues, Dr Monique Bax, Keerat Junday, and Dr Siiri lismaa. Thank you very much to the families who have donated blood for this work.

We would like to determine the genotypes for everyone in the study for the common DNA changes I discussed at the beginning of this letter and compare people who have had more than one SCAD with individuals who have only had one SCAD. This will help us understand if genetic factors contribute to the recurrence risk of SCAD. From our findings to date, the good news is that it is uncommon for SCAD to occur in families. So, while the genetics of SCAD is complex, it is likely that children of SCAD sufferers are less likely to inherit a genetic  predisposition to developing a SCAD than the children of those suffering a more traditional genetic disorder.
To date there have been no randomised, controlled clinical trials to guide SCAD management, as it is difficult for any single centre to enrol sufficient SCAD sufferers to definitely answer what treatment is best. To that end an international consortium involving some 190 centres in 10 countries has been established to undertake such a trial and I have been asked by the National Heart Foundation to lead Australia’s contribution (about 220 SCAD patients) to the study. However, each country has to find its own funding from government grants, which we are all currently trying to secure – the total cost of the study, which will involve over 3000 patients, will be more than $16 million.

So again, most sincere thanks to everyone in the SCAD community for your support. Look forward to continuing to work with you and to making more progress during the rest of the year.

Best wishes for 2023,

Robert M Graham, AO, MD, FAA, FAHMS
Head, Molecular Cardiology Laboratory, Victor Chang Cardiac Research Institute (VCCRI);
Des Renford Professor of Medicine, UNSW;
Vice President and Secretary, Biological Sciences, Australian Academy of Science
9 June,2023