The risk of adverse health outcomes increases significantly in patients with bicuspid aortic valve (BAV) disease if left ventricular ejection fraction (LVEF) falls below 60%, according to researchers. The study team suggested that LVEF cutoff values outlined in current intervention guidelines should be raised from 50% to 60% in isolated aortic stenosis (AS) or isolated aortic regurgitation (AR), and 55% in mixed aortic valve disease (MAVD). “Furthermore, our study extends the previously reported results from series predominantly composed of patients with tricuspid aortic valve to patients with BAV disease,” said the research team, led by Sébastien Hecht, MSc, from the Quebec Heart and Lung Institute at Laval University. “Ideally, randomized strategy trials would be necessary to determine if asymptomatic patients with severe BAV disease and LVEF <60% benefit of early aortic valve replacement or repair (AVR).” In the study, published online Monday and in the Sept. 12 issue of the Journal of the American College of Cardiology, the team set out to investigate the prognostic impact of LVEF in BAV disease. Study methodology Here, the team retrospectively analyzed data collected in 2,672 patients that included an international registry of patients with BAV. Of the 1,493 patients with BAV disease, 269 (18.0%) had LVEF >70%, 679 (45.5%) had LVEF between 60% and 70%, and 316 (21.2%) had LVEF between 50% and 59%. Further baseline characteristics of the study population included 182 (12.2%) with LVEF between 30% and 49%, and 47 (3.1%) with LVEF <30%. In the total cohort, the median age was 51 years (interquartile range [IQR]: 37-63 years) and 70% were men. Overall, patients with reduced LVEF (<50%) were older, were more often men, and had worse cardiovascular profiles. The study population was first divided according to the type of LVEF strata (LVEF >70%, n = 269; 60%-70%, n = 679; 50%-59%, n = 316; 30%-49%, n = 182; <30%, n = 47). Then, to study LVEF effect on clinical outcomes in each type of aortic valve dysfunction, the BAV cohort was divided into four groups: whole cohort (BAV patients with significant aortic valve dysfunction, n = 1,493) and isolated AS (significant AS [≥ moderate] and less than moderate AR, n = 749). The remaining two groups were isolated AR (significant AR [≥ moderate] and less than moderate AS, n = 554), and MAVD, (both AS and AR ≥ moderate, n = 190). While AS severity was classified according to actual guideline recommendations, AR severity was assessed using a multiparametric approach. MAVD was defined as the coexistence of moderate AS and moderate AR with severe MAVD identified if AS and/or AR was equal or greater than moderate. The study’s primary endpoint was all-cause mortality occurring before or after AVR, with the secondary endpoint considered the composite of AVR and all-cause mortality. The end-of-study follow-up date was September 2019, with follow-up data available for 1,334 (89.3%) patients: 693 (92.5%) patients with isolated AS, 176 (92.6%) patients with MAVD and 465 (83.9%) patients with isolated AR. Key results In the whole cohort, the primary endpoint of all-cause mortality occurred in 117 (8.8%) patients over a median follow-up of 56 months (IQR: 22-102 months). The secondary endpoint occurred in 675 (51%) patients: i.e., 602 (45%) patients underwent AVR and 73 (5.5%) died over a median follow-up of 21 months (IQR: 3-67 months). In multivariable analysis, when compared with the LVEF using the 60% to 70% stratum as a reference group, each decrease in LVEF stratum was significantly associated with incremental increases in the rate of mortality: in the LVEF stratum 50% to 59% (hazard ratio [HR]: 1.83; 95% confidence interval [CI]: 1.09-3.07; P = 0.022), LVEF 30% to 49% (HR: 1.97; 95% CI: 1.13-3.41; P = 0.016), and LVEF <30% (HR: 4.20; 95% CI: 2.01-8.75; P < 0.001). The same was true of the composite endpoint of AVR and mortality, with each decrease in LVEF stratum significantly associated with incremental increases in incidence of the endpoint (LVEF 60% to 70% vs. LVEF 50% to 59%, HR: 1.35 [95% CI: 1.09-1.67]; P = 0.007; vs. LVEF 30% to 49%, HR: 1.69 [95% CI: 1.33-2.16]; P < 0.001; and vs. LVEF <30%, HR: 1.82 [95% CI: 1.17-2.81]; P = 0.007). Editorial commentary In an accompanying editorial, authors Erwan Donal MD, PhD, of the University of Rennes, France; Julien Magne, MD, PhD, of the Université de Limoges and CHU Limoges, France, and Bernard Cosyns, MD, PhD, of Universitair Ziekenhuis Brussel and Vrij Univeristeit van Brussel, Brussels, said the choice to raise LVEF cutoff values from 50% to 55%-60% was “empiric, resulting from consensus, and the level of evidence remained low.” “Furthermore, the cutoffs proposed in guidelines are mainly based on studies including patients with isolated tricuspid aortic regurgitation or stenosis,” Donal and colleagues added. “Given that patients with BAV may have a mixed form of valvular heart disease and particular natural history, there is a profound need for data on outcome and on the impact of LVEF (specifically derived from patients with BAV).” The editorialists also pointed out in previous demonstrations that LVEF is of crucial importance in stenotic and regurgitant aortic valve diseases, and recent guidelines took into consideration the new cutoff of 55% instead of 50%. However, Donal and colleagues said LVEF is not left ventricular systolic function and that other imaging opportunities exist to best manage patients. Commenting on certain study limitations, the editorial highlighted the need to more accurately define the data collection process and quality control of the epidemiological registry employed. While the sample size was a study strength, including 1990s and early 2000s patients implied that management strategies might have impacted outcome and on AVR indication. Despite this, he believed the study should be highlighted and could, with other studies, potentially influence the next set of guidelines. “The myocardial damage assessment is crucial and should help in promoting earlier interventions,” they stated. “We should look at the valve but not only at the valve. We should look at the consequences of heart valve diseases.” Sources: Hecht S, Butcher SC, Stephan MP, et al. Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease. J Am Coll Cardiol 2022;80:1071-1084. Donal E, Magne J, Cosyns B, Left Ventricular Ejection Fraction Thresholds Reappraisal: Also for Bicuspid Valve Disease? J Am Coll Cardiol 2022;80:1085–1087. Image Credit: iushakovsky– stock.adobe.com