Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions

Kathryn W Holmes; Sheila Markwardt; Kim A Eagle; Richard B Devereux; Jonathan W Weinsaft; Federico M Asch; Scott A LeMaire; Cheryl L Maslen; Howard K Song; Dianna M Milewicz; Siddharth K Prakash; Dongchuan Guo; Shaine A Morris; Reed E Pyeritz; Rita C Milewski; William J Ravekes; H C Dietz; Ralph V Shohet; Michael Silberbach; Mary J Roman; GenTAC Investigators

doi:10.1016/j.jacc.2022.03.367

Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions

J Am Coll Cardiol. 2022 May 31;79(21):2069-2081. doi: 10.1016/j.jacc.2022.03.367.

Authors

Kathryn W Holmes¹, Sheila Markwardt², Kim A Eagle³, Richard B Devereux⁴, Jonathan W Weinsaft⁴, Federico M Asch⁵, Scott A LeMaire⁶, Cheryl L Maslen⁷, Howard K Song⁷, Dianna M Milewicz⁸, Siddharth K Prakash⁸, Dongchuan Guo⁸, Shaine A Morris⁹, Reed E Pyeritz¹⁰, Rita C Milewski¹¹, William J Ravekes¹², H C Dietz¹², Ralph V Shohet¹³, Michael Silberbach¹⁴, Mary J Roman⁴; GenTAC Investigators

Affiliations

¹ Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA. Electronic address: holmesk@ohsu.edu.
² School of Public Health, Oregon Health and Science University, Portland, Oregon, USA.
³ Division of Cardiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
⁴ Division of Cardiology, Weill Cornell Medicine, New York, New York, USA.
⁵ MedStar Cardiovascular Research Network, Washington, DC, USA.
⁶ Division of Cardiothoracic Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas, USA.
⁷ Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA.
⁸ Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA.
⁹ Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
¹⁰ Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹¹ Division of Cardiothoracic Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
¹² Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹³ Department of Medicine, John A. Burns School of Medicine, Honolulu, Hawaii, USA.
¹⁴ Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.

Abstract

Background: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

Objectives: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

Methods: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome (LDS) (n = 121) were analyzed.

Results: The 25% probability of elective proximal aortic aneurysm surgery was 30 years for LDS (95% CI: 18-37 years), followed by MFS (34 years; 95% CI: 32-36 years), nsHTAD (52 years; 95% CI: 48-56 years), and BAV (55 years; 95% CI: 53-58 years). Any dissection surgery 25% probability was highest in LDS (38 years; 95% CI: 33-53 years) followed by MFS (51 years; 95% CI: 46-57 years) and nsHTAD (54 years; 95% CI: 51-61 years). BAV experienced the largest relative frequency of elective surgery to any dissection surgery (254/33 = 7.7), compared with MFS (273/112 = 2.4), LDS (35/16 = 2.2), or nsHTAD (82/76 = 1.1). With MFS as the reference population, risk of any dissection surgery or cardiovascular mortality was lowest in BAV patients (HR: 0.13; 95% CI: 0.08-0.18; HR: 0.13; 95%: CI: 0.06-0.27, respectively). The greatest risk of mortality was seen in patients with vEDS.

Conclusions: Marfan and LDS cohorts demonstrate age and event profiles congruent with the current understanding of syndromic aortopathies. BAV events weigh toward elective replacement with relatively few dissection surgeries. Nonsyndromic HTAD patients experience near equal probability of dissection vs prophylactic surgery, possibly because of failure of early diagnosis.

Keywords: Loeys-Dietz; Marfan; Turner; aortic aneurysm; aortic dissection; bicuspid aortic valve; nonsyndromic heritable aortic disease; vascular Ehlers-Danlos.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Aortic Dissection* / epidemiology
Aortic Dissection* / genetics
Aortic Dissection* / surgery
Bicuspid Aortic Valve Disease*
Ehlers-Danlos Syndrome* / complications
Humans
Loeys-Dietz Syndrome* / complications
Loeys-Dietz Syndrome* / epidemiology
Loeys-Dietz Syndrome* / genetics
Marfan Syndrome* / complications
Marfan Syndrome* / genetics
Marfan Syndrome* / surgery
Prospective Studies
Registries
Retrospective Studies

Abstract

Publication types

MeSH terms

Grants and funding