1. This cohort study demonstrated that among patients with severe aortic stenosis and left ventricular ejection fraction (LVEF) less than 50% who underwent transcatheter aortic valve replacement, early LVEF improvement was associated with improved all-cause mortality and cardiac death at 5 years.

2. Early LVEF improvement occurred in approximately 1/3 of patients in this study and was less likely to occur in patients with any of the following baseline characteristics: previous myocardial infarction, diabetes, cancer, higher baseline LVEF, larger left ventricular end-diastolic diameter, and larger aortic valve area.

Evidence Rating Level: 2 (Good)

Study Rundown: Transcatheter aortic valve replacement (TAVR) can be used to treat patients with symptomatic severe aortic stenosis (AS). Failure to improve left ventricular ejection fraction (LVEF) following TAVR has been linked to poor outcomes. Previous studies have investigated the association between LVEF improvement post-TAVR and short-term follow-up (up to 1-year). This cohort study explored the association between early LVEF improvement and 5-year outcomes in patients with symptomatic severe aortic stenosis prior to TAVR. Among 659 patients included in the study, approximately 1/3 demonstrated LVEF improvement, which was defined as an increase of >10% from baseline LVEF at 30-days post-TAVR. Previous myocardial infarction (MI), diabetes, cancer, higher baseline LVEF, larger left ventricular end-diastolic diameter (LVEDD), and larger aortic valve area (AVA) were independently associated with a lower likelihood of early LVEF improvement; higher body mass index and higher stroke volume index (SVi) were independently associated with a greater likelihood of early LVEF improvement. In multivariable analyses, early LVEF improvement was significantly associated with lower all-cause death and cardiac death at 5 years post-TAVR. These associations were consistent regardless of patients’ previous history of coronary artery disease or MI. The association between early LVEF improvement and 5-year outcomes was only significant in female but not male patients. Overall, 1/3 of patients in this study experienced early LVEF improvement, which was associated with decreased 5-year all-cause mortality. Several baseline characteristics were associated with lower odds of improvement and the association between LVEF improvement and 5-year mortality was sex-dependent. This study was limited by its exclusion criteria, where those with LVEF <20% or low-gradient AS (mean gradient <40 mm Hg) at baseline were not included in the study; therefore, these results are not applicable to this population of patients. Further studies are required to understand the sex-dependent nature of these associations and physiologic mechanisms of reducing mortality after LVEF improvement.

Click to read the study in JAMA Cardiology

Relevant Reading: Impact of ejection fraction and aortic valve gradient on outcomes of transcatheter aortic valve replacement

In-Depth [retrospective cohort]: This cohort study investigated high- or intermediate-risk patients with symptomatic severe AS and LVEF less than 50% who underwent transfemoral TAVR and had 30-day follow-up LVEF assessment with echocardiography. The study population was drawn from the Placement of Aortic Transcatheter Valves (PARTNER) 1, 2, and S3 trials. Patients were excluded if they underwent transapical TAVR or had a previous surgical aortic valve replacement. LV dysfunction was defined as LVEF less than 50%, and early improvement was defined as whether there was an increase in >10% from baseline LVEF at 30-days post-TAVR. The primary endpoint was all-cause death at 5-years post-TAVR. All-cause death at 5-years occurred in 55.6% of patients, and early LVEF improvement occurred in 216/659 (32.8%) of patients. Patients with early LVEF improvement had significantly reduced all-cause mortality (50% [95% CI: 43.3-57.1] vs. 58.4% [95% CI: 53.6-63.2]; p= 0.04) and cardiac death (29.5% [95% CI: 23.2-37.1] vs. 38.1% [95% CI: 33.1-43.6]; p= 0.05) at 5-years post-TAVR compared to those without early LVEF improvement. In multivariable analyses, LVEF improvement (as a continuous variable) was associated with decreased risk of all-cause death (adjusted hazard ratio [aHR] per 5% LVEF increase: 0.94 [95% CI: 0.88-1.00]; p= 0.04) and cardiac death (aHR per 5% LVEF increase: 0.90 [95% CI: 0.82-0.98]; p= 0.02). When early LVEF was assessed as a dichotomous variable (>10% increase from baseline versus not), the association of early LVEF improvement was not significantly associated with reduced all-cause mortality (aHR: 0.79 [95% CI: 0.62-1.02]; p= 0.06) or cardiac death (aHR: 0.75 [95% CI: 0.53-1.05]; p= 0.09) at 5-years.

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