Comparison Between Bicuspid and Tricuspid Aortic Regurgitation

Background Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.

B icuspid aortic valve (BAV) is the most frequently seen congenital heart defect 1 and represents an increasing etiology of hemodynamically significant aortic regurgitation (AR), which is the third most common valvular heart disease. 2 Compared with patients with tricuspid aortic valve (TAV), patients with BAV-AR are distinctly different: they are more than a decade younger, 2 have more mixed mechanisms of AR (including cusp prolapse and root dilatation), have larger aortic annulus, and exhibit better survival. 3 Despite these inherent differences, publications comparing BAV vs TAV in hemodynamically significant AR are scarce, 3 and Asian data are especially lacking. 4 Interethnic differences in BAV have been reported, 5 suggesting that findings from Western populations may not hold true completely in those of Asian ancestry.
The Asian population is growing and accounts for 60% of the global population. However, data that serve as the backbone of practice guidelines, which most Asian clinicians abide by, frequently come from Western populations. Understanding contemporary profiles of valvular heart disease in Asia helps to reduce global disease burden and promote health; hence, there is an urgent need to report Asian data. In Taiwan, health care is provided by National Health        Table 2). Comparison between those with and without concomitant aorta surgery is shown in Supplemental Table 2; the former had a higher prevalence of connective tissue disease and Marfan syndrome, were less symptomatic, and apparently had larger aorta size.
Regarding surgical indications ( Table 2) Figure 3A). Cox proportional hazards model revealed that baseline maximal aorta size (absolute or indexed to BSA) was independently associated with death under medical surveillance (Supplemental Table 4).
Compared with an age-and sex-matched general population in Taiwan  Values are n (%) or mean AE SD. The study used 2014 American College of Cardiology/American Heart Association guidelines. a Analysis excluded 3 patients: 1 underwent cardiac transplantation, and 2 died intraoperatively. b Of 241 patients having aortic valve replacement, valve size were unknown in 27 patients who received aortic valve surgery other than at the study hospital. Bold value indicates P value #0.05. Table 1.

Abbreviations as in
regarding AVS in young patients with BAV-AR. In the current study, we observed excess risk of death in TAV-AR compared with that in the general popula- tion, yet the TAV-AR survival-gap was larger herein compared with our prior work 3 ( Figure 1E). This may be explained (Supplemental Table 5 The incidence of AD in Taiwan was reported as 5.6 per 100,000 persons, 16 which was conceivably lower than what we reported herein in patients with significant AR because our patients tended to have larger aorta size and more hypertension, placing them at higher risk of AD. Of note, Asian patients exhibited larger absolute and indexed aorta size, reflected by a higher rate of concomitant aorta surgery (46%) compared with our prior report in the United States (30%). 3 Although we showed that baseline maximal aorta size (absolute or BSA-indexed) was linked to poor survival in TAV-AR, it is encouraging that AVS with concomitant aorta surgery seemed beneficial to survival (Supplemental Table 4, Supplemental Figure 3); this observation was also supported by a prior study. 17 Most importantly, we showed that aorta size $45 mm (

Similarity Between Asians and Westerners
Low incidence of dissection in BAV Taiwanese patients had smaller body size, more non-right-left coronary fusion in bicuspid aortic valve (BAV), larger aorta size, and less cusp prolapse in tricuspid aortic valve (TAV). Baseline symptoms correlated better with chamber remodeling in TAV. Surgery-wise, aortic valve surgery (AVS) incidence was higher in TAV-AR than in BAV-AR, surgery was mainly driven by symptoms, repair rate was low, and a smaller prosthesis was used. 2 Similarities between the Asian and U.S. cohort include comparable post-AVS survival, post-AVS left ventricular recovery, and low aortic dissection incidence in BAV patients. cohort; this phenomenon could be explained by late presentation in our cohort. We cannot rule out, however, the possibility of other causes for aorta disease as not every patient received genetic testing.
Causes for symptoms were multifactorial (eg, comorbid conditions, AR severity). Also, the changes in LVEF and dimensions postsurgery, albeit significant, could be partially attributed to measurement variations. Finally, our national death records provided cause of death in all patients and allowed us to evaluate AD cumulative incidence although not every deceased patient underwent autopsy.

CONCLUSIONS
Findings from this large contemporary Asian cohort comparing TAV-AR and BAV-AR are both reassuring and concerning. We showed that post-AVS survival in both groups and overall survival in BAV-AR were comparable to those of the U.S. cohort (Supplemental Table 5). However, compared with the U.S. cohort, TAV-AR patients had a larger survival gap; both BAV-AR and TAV-AR had larger absolute and indexed aorta size, larger indexed LV size, and lower AVS incidence.
Also, the cumulative incidence of AD, which was reported for the first time in a significant AR cohort, was higher in TAV and seemed to be related to aorta size $45 mm. Therefore, in patients with AR (especially Asian subjects), more must be done to improve survival; use of indexed rather than absolute LV size to guide surgical referral merits re-emphasis, especially in TAV-AR. Aorta surgery could be considered, but more evidence is needed once the maximal aortic dimension is >45 mm to prevent fatal AD. patients, who had a higher surgical incidence. Cumulative 10year incidence of AD was higher in TAV-AR and was associated with baseline aorta size >45 mm.

FUNDING SUPPORT AND AUTHOR DISCLOSURES
TRANSLATIONAL OUTLOOK: Future research should explore whether a lower cutoff prompting concomitant aorta surgery in Asian patients with TAV-AR could improve outcomes by lowering the rate of AD.