Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct 13:9:1009947.
doi: 10.3389/fcvm.2022.1009947. eCollection 2022.

Long-term outcomes in heritable thoracic aortic disease

Elizabeth N Robertson  1   2 , Paul G Bannon  1   3   4 , Richmond W Jeremy  1   2   3
Affiliations

Long-term outcomes in heritable thoracic aortic disease

Elizabeth N Robertson et al. Front Cardiovasc Med. .

Abstract

Heritable aortic aneurysm is an increasingly recognized cause of morbidity and mortality. Whilst Marfan syndrome (MFS) is well-known, the clinical presentation and prognosis of more newly described genetic syndromes is less familiar to clinicians. There is a particular lack of knowledge regarding clinical outcomes for non-syndromal heritable aortic disease. This study investigated the presentation, clinical course and survival of patients with syndromal [Loeys-Dietz, aneurysm-osteoarthritis, and aneurysm-cerebral arteriopathy (ACTA2) syndrome] and non-syndromal heritable aortic disease in comparison to MFS. The study group includes 536 individuals (283 Marfan, 176 non-syndromal heritable aortopathy, 36 aneurysm-osteoarthritis, 32 Loeys-Dietz, and 9 ACTA2 aneurysm) enrolled in a longitudinal clinical follow-up between 1990 and 2022. Age at diagnosis differed between groups: Marfan = 22.0 ± 16.6; Loeys-Dietz = 29.6 ± 21.5; aneurysm-osteoarthritis = 36.4 ± 18.8; ACTA2 aneurysm = 43.4 ± 18.6; non-syndromal heritable aortopathy = 47.2 ± 16.6 years (p < 0.001). Aortic dissection was the presenting event in 8% individuals with Marfan compared to 27% with non-syndromal heritable aortopathy and 34% with Loeys-Dietz syndrome (p < 0.01). Mean follow-up duration for the group was 16.4 years (range 0.2-30 years) and 74 individuals died during follow-up (Marfan = 52, Loeys-Dietz = 6, aneurysm-osteoarthritis = 4, ACTA2 aneurysm = 1, heritable non-syndromal aortopathy = 11). At 10 years follow-up, actuarial mean survivals were: aneurysm-osteoarthritis = 77.5 ± 10.4%; Loeys-Dietz = 90.0 ± 6.8%; Marfan = 94.6 ± 1.4%; heritable non-syndromal aortopathy = 95.9 ± 2.1% (NS). There were 60 aortic dissections (24 Type A, 36 Type B) during follow-up. At 10 years, survival free of dissection was comparable between groups: aneurysm-osteoarthritis = 90.7 ± 6.4%; Loeys-Dietz = 94.4 ± 5.4%; Marfan = 96.1 ± 1.2%; heritable non-syndromal aortopathy = 93.9 ± 2.3%, with similar findings at 20 years. Prophylactic aortic surgery was a first event during follow-up for 196 individuals (ACTA2 aneurysm = 3; aneurysm-osteoarthritis = 10; Loeys-Dietz = 19; Marfan = 119; heritable non-syndromal aortopathy = 45). A second surgical intervention was required in 45 individuals and a third intervention in 21 individuals. At 10 years follow-up, survival free of surgery differed between groups: aneurysm-osteoarthritis = 68.5 ± 10.1%; Loeys-Dietz = 40.8 ± 11.2%; Marfan = 75.5 ± 2.7%; heritable non-syndromal aortopathy = 63.8 ± 4.7% (p < 0.001). At 20 years follow-up mean survival free of surgery was: aneurysm-osteoarthritis = 26.6 ± 14.7%; Loeys-Dietz = 9.1 ± 8.2%; Marfan = 57.2 ± 3.4%; heritable non-syndromal aortopathy = 41.6 ± 8.2% (p < 0.001). Diagnosis of newer syndromic and non-syndromal heritable aortopathies is delayed compared to MFS, with associated complications of presentation with aortic dissection. Survival of individuals enrolled in follow-up surveillance is comparable between different genetic aortopathies, however aortic dissections still occur and need for surgical intervention is high.

Keywords: Loeys-Dietz; Marfan; aneurysm; dissection; genetic; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Cumulative presentation rate, according to age, for different heritable aortopathies. (B) Cumulative presentation rate with MACE, according to age, for different heritable aortopathies. Abbreviations as per text.
FIGURE 2
FIGURE 2
(A) Cumulative presentation rate, according to sex. (B) Cumulative presentation rate with MACE, according to sex. Abbreviations as per text.
FIGURE 3
FIGURE 3
(A) Comparative event-free survival (all-cause mortality), according to age at death or last follow-up. (B) Comparative event-free survival (all cause-mortality), according to length of follow-up. Abbreviations as per text. Numbers at risk shown at bottom of plots.
FIGURE 4
FIGURE 4
(A) Comparative survival free of death or major adverse cardiovascular event, according to age at event or last follow-up. (B) Cumulative event rate, for death or MACE, according to length of follow-up. Abbreviations as per text. Numbers at risk shown at bottom of plots.
FIGURE 5
FIGURE 5
(A) Comparative survival free of dissection, according to age at dissection or last follow-up. (B) Cumulative event rate for any dissection, according to length of follow-up. Abbreviations as per text. Numbers at risk shown at bottom of plots.
FIGURE 6
FIGURE 6
(A) Comparative survival free of any surgery, according to age at surgery or last follow-up. (B) Cumulative event rate for any surgery, according to length of follow-up. Abbreviations as per text. Numbers at risk shown at bottom of plots.
FIGURE 7
FIGURE 7
(A) Comparative survival free of aortic surgery, according to age at surgery or last follow-up. (B) Cumulative event rate for aortic surgery, according to length of follow-up. Abbreviations as per text. Numbers at risk shown at bottom of plots.
See this image and copyright information in PMC

References

    1. Melvinsdottir IH, Lund SH, Agnarsson BA, Sigvaldason K, Gudbjartsson T, Geirsson A. The incidence and mortality of acute thoracic aortic dissection: results from a whole nation study. Eur J Cardiothorac Surg. (2016) 50:1111–7. 10.1093/ejcts/ezw235 - DOI - PubMed
    1. Bossone E, Eagle KA. Epidemiology and management of aortic disease: aortic aneurysms and acute aortic syndromes. Nat Rev Cardiol. (2020) 18:331–48. 10.1038/s41569-020-00472-6 - DOI - PubMed
    1. Robertson EN, van der Linde D, Sherrah AG, Vallely MP, Wilson M, Bannon PG, et al. Familial non-syndromal thoracic aortic aneurysms and dissections – incidence and family screening outcomes. Int J Cardiol. (2016) 220:43–51. 10.1016/j.ijcard.2016.06.086 - DOI - PubMed
    1. Renard M, Francis C, Ghosh R, Scott AF, Witmer PD, Adès LC, et al. Clinical validity of genes for heritable thoracic aortic aneurysm and dissection. J Am Coll Cardiol. (2018) 72:605–15. 10.1016/j.jacc.2018.04.089 - DOI - PMC - PubMed
    1. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathhology. Genet Med. (2015) 17:405–24. 10.1038/gim.2015.30 - DOI - PMC - PubMed