Diameter-based decision making in bicuspid aortic valve aortopathy: is it time to expand our perspective?

Bicuspid aortic valve (BAV) and the associated aortopathy (BAVA) are remarkably commonplace; the former is the most common congenital heart anomaly occurring in 1–2% of the general population and aortic dilatation to a greater or lesser degree is present in 30–60% if not more (1). Guidelines for ascending aortic intervention (AAI) to prevent acute aortic syndromes (AAS) have been established and recommend aortic replacement when aortic diameter exceeds 55 mm (Class I), at 50 mm when other factors such as family history, expansion rate are present, (Class IIa), or when the patient is low operative risk at a center with established expertise (Class IIa), or at 45 mm if concomitant aortic valve replacement is planned (Class IIa) (2). Despite these size-based guidelines, still there is controversy in the literature and, more importantly, in practice, with intervention occurring over one-third of the time in BAVA patients with diameters less than 45 mm (1).

This practice is likely driven by Pape’s observation that 40% of patients in the International Registry of Acute Aortic Dissection (IRAD) presenting with type A dissection had ascending aorta diameter less than 5.0 cm and one-third of BAV patients had aortic diameters less than 5.5 cm (3). Dare we neglect the risk of AAS to those in the “gray zone” between 4.5 and 5.5 cm? At the same time, if we operate on everyone, surely we will do some harm. Clearly, we need a more nuanced approach.

The data concerning size seem little help to us in determining who needs an operation; perhaps we should acknowledge what the data do tell us, which is that diameter alone is woefully inadequate. To be fair, the focus on valve morphology—BAV or tricuspid—is itself an effort in this direction. But even here the message is uncertain. Michelena and colleagues found the age-adjusted relative risk of aortic dissection in patients with BAVA to be eight times greater than those with tricuspid aortic valves (TAV) (4). Still, the absolute risk is low, with only two dissections (0.5%) among 416 consecutive BAVA patients followed for 16 years. In Elbadawi’s query of the NIS database yielding over 38,000 hospitalizations for AAI, the incidence of BAV was similar to the general population incidence at only 1.1%, challenging the notion that BAV is itself a risk factor for dissection (5).

What about the other established risk factors for aortic dissection? Hypertension is clearly an important predisposing factor for acute aortic dissection (3), as are other risk factors include age, smoking, chronic obstructive pulmonary disease (COPD), pregnancy/delivery, cocaine usage and fluoroquinolone use (6). And yet none of these factors are addressed in our guidelines. Evidence is accumulating for other parameters such as the presence of “root type” phenotype, in which the sinuses of Valsalva are dilated to a greater extent than the tubular portion, as an independent predictor of rapid progression (>0.9 mm/year) with a striking odds ratio of 14 (7). In the same study, functional aortic regurgitation was also predictive of rapid growth (OR 2.3). Others have focused on indexing size to body surface area (8) or height (9), arguing that one should not expect a small person’s aorta to be the same size as a larger person’s. Despite the logic, however, the data are sparse. Advanced imaging modalities such as 4D-flow MRI have shown early promise to categorize specific phenotypes of BAVA and can map patient-specific wall stress in the ascending aorta (10). Non-image-based predictors are being explored as well, such as the circulating TGF-β-1 to soluble endoglin ratio and others (11).

In the 17^th century, John Graunt transformed demography by summarizing key elements of Bills of Mortality in numerical tabular form. This permitted the application of mathematical methods of analysis to understand trends in the frequency of human disease and was the beginning of the field of epidemiology. As powerful as such an approach can be, its danger and weakness lie in the information left off the table—the individual characteristics that might serve to nuance our understanding of the disease if only we were to attend to them. Perhaps there is a lesson for us here to broaden our perspective. Guidelines are carefully constructed based on the best possible information and are intended to establish a foundation or common ground for practicing clinicians. As such they should neither be ignored nor canonized. The following century, Thomas Bayes would introduce a statistical approach that invites nuance in estimating probability as additional information accumulates. Perhaps we should accept aortic diameter as informing our “prior probability” and move on to seek new information and novel parameters, particularly for patients in the “gray zone” to inform our judgements. Accepting the limitations of our knowledge, perhaps cardiologists and surgeons should grow more comfortable in observing BAV patients with moderate-sized aortic dilation who do not have concomitant additive risk factors. Finally, let’s acknowledge that aortic diameter is the first data point but not the only data point, and as such should be the beginning of the conversation but not the end.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: The authors declare no conflicts of interest.

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References

1. Nissen AP, Truong VTT, Alhafez BA, et al. Surgical repair of bicuspid aortopathy at small diameters: Clinical and institutional factors. J Thorac Cardiovasc Surg 2020;159:2216-2226.e2. [Crossref] [PubMed]
2. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010;121:e266-369. Erratum in: Circulation 2010;122:e410. [PubMed]
3. Evangelista A, Isselbacher EM, Bossone E, et al. Insights From the International Registry of Acute Aortic Dissection: A 20-Year Experience of Collaborative Clinical Research. Circulation 2018;137:1846-60. [Crossref] [PubMed]
4. Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves. JAMA 2011;306:1104-12. [Crossref] [PubMed]
5. Elbadawi A, Mahmoud AA, Mahmoud K, et al. Temporal Trends and Outcomes of Elective Thoracic Aortic Repair and Acute Aortic Syndromes in Bicuspid Aortic Valves: Insights from a National Database. Cardiol Ther 2021;10:531-45. [Crossref] [PubMed]
6. Lee CC, Lee MG, Hsieh R, et al. Oral Fluoroquinolone and the Risk of Aortic Dissection. J Am Coll Cardiol 2018;72:1369-78. [Crossref] [PubMed]
7. Della Corte A, Bancone C, Buonocore M, et al. Pattern of ascending aortic dimensions predicts the growth rate of the aorta in patients with bicuspid aortic valve. JACC Cardiovasc Imaging 2013;6:1301-10. [Crossref] [PubMed]
8. Davies RR, Gallo A, Coady MA, et al. Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms. Ann Thorac Surg 2006;81:169-77. [Crossref] [PubMed]
9. Zafar MA, Li Y, Rizzo JA, et al. Height alone, rather than body surface area, suffices for risk estimation in ascending aortic aneurysm. J Thorac Cardiovasc Surg 2018;155:1938-50. [Crossref] [PubMed]
10. Rodríguez-Palomares JF, Dux-Santoy L, Guala A, et al. Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease. J Cardiovasc Magn Reson 2018;20:28. [Crossref] [PubMed]
11. Forte A, Bancone C, Cobellis G, et al. A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming Growth Factor β-1 to Soluble Endoglin Ratio. Circ Res 2017;120:1800-11. [Crossref] [PubMed]