Ascending aortopathy with bicuspid aortic valve: More, but not enough, evidence for the hemodynamic theory

Central MessageEvidence is increasing for the hemodynamic role of aortic dilation in patients with a bicuspid aortic valve. It is time to move to the next level of investigation of this morbid disorder.See Article page 8. Evidence is increasing for the hemodynamic role of aortic dilation in patients with a bicuspid aortic valve. It is time to move to the next level of investigation of this morbid disorder. See Article page 8. Bicuspid aortic valve (BAV) is the most common congenital cardiac defect and it is frequently associated with progressive dilation of the ascending aorta. Two theories exist to explain the association between BAV and ascending aortopathy—the genetic theory and the hemodynamic theory.1Andreassi M.G. Della Corte A. Genetics of bicuspid aortic valve aortopathy.Curr Opin Cardiol. 2016; 31: 585-592Crossref PubMed Scopus (39) Google Scholar Even without stenosis or regurgitation, blood passing through a BAV is abnormally directed toward the greater curvature of the ascending aorta, often with slight flow acceleration. Studies using either 4-dimensional cardiac magnetic resonance imaging (CMR), or conventional magnetic resonance angiography (MRA) with computational fluid dynamics (CFD) have shown that flow asymmetry and helicity are increased in BAV, and that aortic wall shear stress (WSS) is greatly increased in the greater curvature of the aorta, compared with normal patients.2Meierhofer C. Schneider E.P. Lyko C. Hutter A. Martinoff S. Markl M. et al.Wall shear stress and flow patterns in the ascending aorta in patients with bicuspid aortic valves differ significantly from tricuspid aortic valves: a prospective study.Eur Heart J Cardiovasc Imaging. 2013; 14: 797-804Crossref PubMed Scopus (109) Google Scholar, 3Mahadevia R. Barker A.J. Schnell S. Entezari P. Kansal P. Fedak P.W. et al.Bicuspid aortic cusp fusion morphology alters aortic three-dimensional outflow patterns, wall shear stress, and expression of aortopathy.Circulation. 2014; 29: 673-682Crossref Scopus (299) Google Scholar Studies have demonstrated that these fluid dynamic stresses can promote local medial degeneration via matrix metalloproteinase-dependent pathways.4Atkins S.K. Cao K. Rajamannan N.M. Sucosky P. Bicuspid aortic valve hemodynamics induces abnormal medial remodeling in the convexity of porcine ascending aortas.Biomech Model Mechanobiol. 2014; 13: 1209-1225Crossref PubMed Scopus (53) Google Scholar, 5Atkins S.K. Sucosky P. Etiology of bicuspid aortic valve disease: focus on hemodynamics.World J Cardiol. 2014; 6: 1227-1233Crossref PubMed Scopus (18) Google Scholar Youssefi and colleagues6Youssefi P. Gomez A. He T. Anderson L. Bunce N. Sharma R. et al.Patient-specific computational fluid dynamics—assessment of aortic hemodynamics in a spectrum of aortic valve pathologies.J Thorac Cardiovasc Surg. 2017; 153: 8-20.e3Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar add to the body of clinical evidence that aortic hemodynamic parameters are abnormal in BAV. They performed MRA with CFD studies on 5 groups of patients (N = 45) with different valve pathologies. Patients with BAV with right-noncoronary leaflet fusion and aortic stenosis had the largest ascending aortas, greatest flow asymmetry, greatest mean WSS, and lowest oscillatory shear stress. Although the calculated values were generally in line with prior studies, the patient groups were not matched for age, body surface area, gender, or ventricular function; cardiac output was not adjusted for; and WSS was not indexed to aortic diameter. These omissions make comparison of the groups somewhat difficult to interpret. Inclusion of BAV groups without aortic stenosis and aortic regurgitation could have added significant insight to the analysis. In a comparable work but using 4-dimensional CMR, Bissel and colleagues7Bissel M.M. Hess A.T. Biasiolli L. Glaze S.J. Loudon M. Pitcher A. et al.Aortic dilation in bicuspid aortic valve disease: flow pattern is a major contributor and differs with valve fusion type.Circ Cardiovasc Imaging. 2013; 6: 499-507Crossref PubMed Scopus (287) Google Scholar studied 142 subjects (95 with BAV and 47 normal controls) using groups with comparable distributions in age, peak velocity, regurgitant fraction, and left ventricular function. All hemodynamic variables in BAV with right-handed helical flow were abnormal compared with normal controls. Most variables were more abnormal in the right-noncoronary leaflet fusion group compared with the right-left fusion group. The presence of valve stenosis significantly accentuated most of the hemodynamic abnormalities. The hemodynamic theory is supported by the fact that aortic valve replacement (AVR) seems to slow the progression of aortic dilation. In 93 patients undergoing AVR, Regeer and colleagues8Regeer M.V. Versteegh M.I.M. Klautz R.J.M. Schalij M.J. Bax J.J. Marsan N.A. et al.Effect of aortic valve replacement on aortic root dilatation rate in patients with bicuspid and tricuspid aortic valves.Ann Thorac Surg. July 22, 2016; (Epub ahead of print)Google Scholar found that the preoperative rate of dilation was 0.42 mm/year (BAV) and 0.15 mm/year (trileaflet) (P = .02). Postoperatively, these values were 0.28 mm/year (regression coefficient [growth rate] with 95% confidence interval, 0.15-0.42 mm/year) and 0.35 mm/year (regression coefficient [growth rate] with 95% confidence interval, 0.24-0.46 mm/year), respectively (P = .5). Kinoshita and colleagues9Kinoshita T. Naito S. Suzuki T. Asai T. Valve phenotype and risk factors of aortic dilatation after aortic valve replacement in Japanese patients with bicuspid aortic valve.Circ J. 2016; 80: 1356-1361Crossref PubMed Scopus (13) Google Scholar studied 47 BAV patients undergoing AVR and found that the only variable associated with rapid postoperative dilation was greater-than-moderate preoperative regurgitation. We still have inadequate evidence to show which theory dominates, and the heterogeneity of this disorder suggests that both mechanistic pathways can coexist. This compels us to move to the next levels of investigation. CFD should incorporate formal fluid–structure interaction modeling. Four-dimensional CMR, augmented perhaps with intravascular ultrasound, must look with greater precision at aortic wall structure and mechanics. To distinguish between the competing theories, longitudinal studies using multivariable risk–hazard models are needed that account for standardized and state-of-the-art (eg, 4-dimensional CMR or MRA with CFD) hemodynamic as well as genetic (including familial) variables. Millions of people in the US population have BAV, but based on a search of ClinicalTrials.gov, only 1 registry-based clinical trial is in progress—and that study has a targeted enrollment of 500.10Bicuspid aortic valve registry (BAV). Available at: https://clinicaltrials.gov/ct2/show/NCT01756222. Accessed Oct 28, 2016.Google Scholar A multi-institutional registry that targets a substantially larger enrollment with intention to follow for life may be necessary to power the proposed risk-hazard models. The International BAV Consortium is working on this and other means to address the current knowledge gaps (Figure 1).11Della Corte A. Body S.C. Booher A. Schaefers H.J. Milewski R.K. Michelena H.I. et al.Surgical treatment of bicuspid aortic valve disease: knowledge gaps and research perspectives.J Thorac Cardiovasc Surg. 2014; 147: 1749-1757Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar With this leap in progress we may effectively determine optimal therapeutic algorithms for BAV in a patient-specific manner. Patient-specific computational fluid dynamics—assessment of aortic hemodynamics in a spectrum of aortic valve pathologiesThe Journal of Thoracic and Cardiovascular SurgeryVol. 153Issue 1PreviewThe complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are met. Patient-specific computational fluid dynamics (CFD) were used to assess the effect of different aortic valve morphologies on velocity profiles, flow patterns, helicity, wall shear stress (WSS), and oscillatory shear index (OSI) in the thoracic aorta. Full-Text PDF Open Archive