Bicuspid Aortic Valve: Inconvenient Truths and Challenges in Clinical Management

A prospective cohort study conducted at Uppsala University Hospital in Sweden aimed to identify potential risk factors contributing to in-hospital heart failure and postoperative mortality following aortic valve replacement in patients with tricuspid and bicuspid valves.

It is well-known that aortic stenosis (AS) is the most prevalent valvular pathology globally, and the theoretical echocardiographic and symptomatic criteria for indicating surgical intervention are well-established. However, in patients with a bicuspid aortic valve (BAV), certain grey areas in its pathophysiology could prompt a reevaluation of the optimal “timing” for intervention in these cases. Thus, the authors proposed a study to delve into this aspect based on some lesser-known evidence. In 2021, in the Journal of the American College of Cardiology: Cardiovascular Imaging, Yang et al. observed that patients with BAV are associated with a higher risk of congestive heart failure (CHF) compared to the general population. A meta-analysis published that same year in Echocardiography by Chen et al. demonstrated that the hearts of BAV patients, even if asymptomatic and without valvular dysfunction, undergo structural left ventricular (LV) remodeling as early as adolescence and young adulthood. These findings corroborate evidence published in 2019 by Mahedevia et al. in the International Journal of Cardiovascular Imaging, showing that BAV patients typically experience increased afterload due to an eccentric BAV opening. This eccentric jet, over time, contributes to aortic remodeling, characterized by reduced elasticity of the ascending aorta and subsequent dilation.

Given the limited scientific evidence on the correlation between baseline left ventricular ejection fraction (LVEF), global longitudinal strain (a measure of ventricular function derived from two-dimensional echocardiographic imaging), and diastolic dysfunction in patients with severe AS, the purpose of the study by our colleagues in Uppsala was to analyze whether preoperative LVEF in 271 patients (152 with BAV) with severe AS (without coronary artery disease requiring revascularization or other associated valvulopathy) could influence an increase in mortality or hospitalizations. To exclude cases of CHF directly caused by surgery, patients readmitted for CHF within 30 days post-surgery were excluded from the study.

Patients were followed from January 2014 to May 2021, with a primary focus on the incidence of left ventricular failure. The statistical analyses showed that, compared with patients with tricuspid aortic valve (TAV), BAV patients presented preoperatively with the following:

Greater degree of left ventricular hypertrophy (LVH) and higher indexed left ventricular mass (LVMI)
Higher prevalence of LV diastolic dysfunction
Reduced LVEF
Elevated levels of pro-BNP and, consequently, greater presence of CHF
Higher prevalence of preoperative conditioning with levosimendan

An association was confirmed between higher LVMI and increased prevalence of diastolic dysfunction in both patient groups (BAV and TAV), whereas the presence of coronary artery disease was significantly more common in TAV patients (likely related to the more degenerative nature and higher atherogenic burden associated with TAV AS, not to mention the higher age in this cohort).

Logistic regression confirmed a direct association between LVMI or LVH and the degree of LV diastolic dysfunction. Additionally, Cox regression analysis showed a direct correlation between valve morphology (BAV) and CHF incidence. The explanation for these phenomena lies in the underlying pathophysiology: a stenotic aortic valve chronically increases afterload, resulting in ventricular remodeling with concentric hypertrophy, decreased compliance, increased LV stiffness, and ultimately LV diastolic dysfunction.

Lastly, another aspect that warrants attention is the “pressure recovery” (PR) phenomenon. This term refers to the pressure increase distal to the valvular stenosis due to the reconversion of the kinetic energy from the jet into potential energy, which could lead to an overestimation of echocardiographic valvular gradients that would differ from the lower (and actual) gradients measured by catheterization. Based on our colleagues’ findings, PR is more prevalent in patients with limited aortic remodeling, as typically seen in TAV patients, especially if the ascending aorta and/or the root are small (<30 mm). However, PR is not routinely used in AS studies. Therefore, it is logical to deduce that in BAV patients, who more frequently have associated aortic dilation, AS severity may be underestimated, potentially delaying the recommendation for invasive treatments until more advanced stages of the valvular disease. The clinical relevance of PR remains controversial. Some studies indicate it is negligible, with a maximum impact of 10 mmHg on peak gradients. However, in hypoplastic aortas (15-30 mm), it could be significant. Additionally, studies suggest that patients in whom PR was systematically incorporated into gradient calculations and who exhibited higher PR values showed lower CHF and sudden death rates, likely associated with lower true degrees of AS severity.

COMMENTARY:

Despite being a single-center study, the findings suggest that surgeons might consider revisiting the timing and echocardiographic criteria for early surgical indication in patients with AS, particularly in young BAV patients.

Could PR be a relevant phenomenon that might aid in decision-making? Opinions on this are divided. The majority of studies by echocardiographers and hemodynamicists suggest that PR is not impactful enough to cause significant discrepancies in severity assessment via Doppler echocardiography or hemodynamic study, as we previously discussed.

BAV remains a congenital heart disease warranting early diagnosis and patient follow-up from childhood, given the higher likelihood of developing AS earlier than TAV patients. We must recognize that delaying surgery for these patients results in operating on an “organized” and “hostile” structural heart disease, with poorer preoperative LVEF and an associated postoperative CHF that poses challenges for correcting established ventricular remodeling.

REFERENCE:

Wedin JO, Vedin O, Rodin S, Simonson OE, Hörsne Malmborg J, Pallin J, et al. Patients With Bicuspid Aortic Stenosis Demonstrate Adverse Left Ventricular Remodeling and Impaired Cardiac Function Before Surgery With Increased Risk of Postoperative Heart Failure. Circulation. 2022 Oct 25;146(17):1310-1322. doi: 10.1161/CIRCULATIONAHA.122.060125.