2024-2025 SCAD Study Update

Dear SCADaddles:

Apologies for being late with this report.

Firstly, sincere thanks 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 continued generous support – this has been absolutely critical to our studies as it allows us to continue to get DNA sequence information (-$1800.00 per person) for which it is almost impossible to get regular grant funding. This has allowed us to continue to be very productive and to get valuable new data on the genetic changes causing a predisposition to SCAD, as well as to gain insights into various clinical aspects of SCAD and its association in many cases with fibromuscular dysplasia, as is evident from the many papers we have published in 2024-2025 (see below).

These studies have shown that except for those rare cases associated with a so-called connective tissue disorder (CTD), where a well-defined gene mutation (eg fibrillin in Marfan’s syndrome) in a single gene causes the problem, in SCAD no one gene change has a big effect, but rather the genetic predisposition is due to small effects from many different genes. Indeed, together with international colleagues, we have already identified 16 different genes involved, and there is no doubt many more are still to be found. This, of course, makes it more difficult for us to advise SCAD sufferers about inheritance by their children, but the good news is that it also makes it much less likely that the children of people who have had a SCAD will inherit the predisposition, since they would need to inherit many of the numerous gene variants required for predisposition to SCAD.

Again, apart from those few cases of SCAD associated with a CTD, where a single gene change has a big effect, neither our studies nor those of others have identified a single gene that has a big effect in determining a predisposition to SCAD. What we have been able to show recently is that a potentially SCAD predisposing gene variant (what we call a pathogenic variant) is reported more frequently in the gene for collagen 3A1, a crucial component of multiple tissues, including blood vessel walls, than in any other gene, albeit that this variant is still found very rarely in a large population of people who have suffered a SCAD; being found more commonly in men and those who are younger (less than 40 years).

Interestingly, we have also shown an association between SCAD in women and dissection of the aorta in a male relative, suggesting that similar genes may be predisposing to both conditions, albeit that they manifest in a sexspecific manner. Based on this work, we have also been able to contribute to the education of clinicians looking after SCAD sufferers (which is sorely needed!) by providing them with guidelines on the complexities of SCAD genetics, when to order genetic testing, and how to interpret such tests.

Working with Prof Alun Jackson and Dr Barbara Murphy at the Australian Heart Health Centre in Melbourne, we have also made great in-roads into the significant psychosocial problems associated with SCAD and how to address them.

These studies have shown that anxiety and depression are very common after-effects of having had a SCAD, as is fear of a recurrence and so-called ‘brain fog’, where people who experience this feel that for much of the time their thinking is clouded and not sharp. Fortunately, at least in early pilot studies, we have also shown that focus groups, where SCAD sufferers come together and discuss their concerns and other after-effects with other SCAD sufferers, really seems to help.

So hopefully, this provides a bit of a snap shot of the work that you have so kindly contributed to.

Finally, let me acknowledge our core team of researcher including, in particular, Eleni Ciannoulatou, Ingrid Tarr and their colleagues, who provide the genetic analyses and insights into our gene work; Stephanie Hesselson, who does an extraordinary job managing all our SCAD sufferers, consenting patients for our studies, and getting DNA samples; Monique Bax and Keerat Junday, who are working hard making cell models of SCAD and testing them for changes that may underlie the predisposition to SCAD; Lucy McGrath-Cadell who works on the clinical
genetics of SCAD; Xenia Kaidonis and Michael Tsang, who are working on the development and characterisation of a rodent model of SCAD; Siiri lismaa who curates all of our DNA samples and makes sure they are handled properly when they are sequenced, as well as being actively involved (together with Stephanie) with Barbara Murphy and Alun Jackson in our SCAD psychosocial studies, and last but certainly not least, my colleague, Prof Jason Kovacic, Director, VCCRI, who provides enormously valuable input into all of our studies, as well as leading our international collaboration with iSCAD. Indeed, because of Jason, the VCCRI is the only non-US institute that has thus far been asked to join iSCAD, a very large study that collects clinical data from many, many medical centres throughout the US to look carefully at the clinical manifestations, management and outcomes of SCAD.

To end on a positive note, I have now restricted my clinical practice to seeing exclusively only SCAD sufferers, both at St Vincent’s Hospital and once a month I do a SCAD clinic at the John Hunter Hospital (JHH) in Newcastle, to make it more convenient for patients from the Central and North Coasts (the JHH serves patients from a huge catchment area) to be seen. And it’s heartening to see that despite their episode of SCAD, the great majority of patients retain normal or almost normal heart function after their SCAD – presumably because unlike
the hearts of patients who develop a traditional atherosclerotic heart attack, the hearts of SCAD sufferers were completely normal before the SCAD. In addition, apart from the SCAD-affected coronary artery branch, which generally heals within about one month, all their unaffected coronary vessels are “whistle clean” without any evidence of disease or plaque – a hallmark of SCAD.

 

SCAD Papers 2024-2025:
Tarr I, Hesselson S, Troup M, Young P, Thompson J-L, McGrath-Cadell L, lismaa SE, Kovacic J,
Graham RM, Giannoulatou E. Polygenic risk in families with spontaneous coronary artery dissection. JAMA Cardio/2024\ 9:254-261.

McGrath-Cadell L, Hesselson S, Thompson J-L, lismaa SE, Tarr I, Muller DWM, Kovacic J, Graham RM, Giannoulatou E. COL3A1 variants in spontaneous coronary artery dissection. JACCAdvances2024,3{7)AQ)09%6. doi: 10.1016/j.jacadv.2024.100986.

McGrath-Cadell L, Hesselson S, Muller DWM, Kovacic JC, Giannoulatou E, Graham RM.
Understanding the complex genetics of spontaneous coronary artery dissection: a guide for clinicians. Circulation: Genomic and Precision Medicine 2024;17(6):e004800.

Gharleghi R, Zhang M, Adikari D, McGrath-Cadell L, Graham RM, Wentzel J, Webster M, Ellis C, Doi S-Y, Beier S. Sex-specific variances in anatomy and blood flow of the left main coronary bifurcation: implications for coronary artery disease risk. IEEE Trans BiomedEng
2025; DOI 10.1109/TBME.2025.3536161.

McGrath-Cadell L, Hesselson S, Tarr I, Rath E, Troup M, Gao Y, Junday K, Bax M, lismaa SE, Collins N, Muller DWM, Kovacic JC, Giannoulatou E, Graham RM. Spontaneous coronary artery dissection and a family history of aortic dissection: a genetic association study.
JAmer HeartAssoc2025 Apr 15;14(8):e037921.

McGrath-Cadell L, HeerM, Mahajan N, Graham RM. Screening for fibromuscular dysplasia after spontaneous coronary artery dissection unmasks a massive right renal artery aneurysm requiring ex vivo surgical resection and auto-transplantation. BMJ Case Reports,18:e263132.

BaxM, Junday K, Hurley E, Muller D, Hesselson S, McGrath-Cadell L, Kaidonis X, Tarr I, Giannoulatou E, lismaa SE, Graham RM. Generation of an induced pluripotent stem cell line from an unaffected female whose two sisters suffered spontaneous coronary artery dissections (SCAD) (VCCRIi024-A). Stem Cell Research 2025 (submitted).

Murphy BM, LeCrande MR, Rogerson MC, Hesselson 5, lismaa SE, Graham RM, Jackson AC.
Prevalence and correlates of anxiety and depression symptoms after spontaneous coronary artery dissection: a cross sectional study. Europ J Cardiovasc Nursing202A\ May 6:zvae071.

Rogerson MC, Jackson AC, Le Grande MR, Hesselson S, lismaa SE, Graham RM, Murphy BM.
Posttraumatic growth after spontaneous coronary artery dissection: A mixed-methods study. Heart Mind2024;8, pp. 325 – 339.

Clarke S; Murphy B; Le Grande M; Rogerson M; Hesselson S; lismaa S; Graham RM; Hester R; Jackson A. Fear of recurrence and its association with mental health outcomes after spontaneous coronary artery dissection (SCAD). 2024 Europ HeartJ, 45.

Dang Q; Murphy B; Graham RM; Puri A; Ford S; Marschner S; Chong JJH; Zaman S. Patients’ perspective of quality-of-care and its correlation to quality-of-life following spontaneous coronary artery dissection, Europ J Cardiovasc Nurs, 2024;23, pp. 400 – 407.

Weddell J, Rogerson MC, Gallagher R, Hesselson S, lismaa SE, Graham RM, Jackson AC, Redfern J, Buckley T, Murphy BM. Cognitive and physical fatigue: the experience and consequences of ‘brain fog’ after spontaneous coronary artery dissection, a qualitative study. Europ J Cardiovasc Nursing 2024 Jun 25:zvae097. doi:10.1093/eurjcn/zvae097.

Murphy BM, Rogerson MC, lismaa SE, Hesselson S, LeGrande MR, Graham RM, Jackson. Attitudes to and attendance at cardiac rehabilitation after spontaneous coronary artery dissection. J Cardiac Rehab Prevent 2025;00:1-11.

Rogerson MC, Higgins RO, Grande MR, Hesselson S, lismaa SE, Brown J, Wynd A, Baird D, Zaman S, Ford S, Musgrave-Edwards T, Graham RM, Jackson AC, Murphy BM. Supporting emotional recovery after spontaneous coronary artery dissection: development and pilot
-testing an online facilitated support group program. Europ J Prevent Cardiol(submitted).