Left Ventricular Global Longitudinal Strain: An Imaging Marker Associated with Outcomes in Paradoxical Low-Flow,...

The clinical management and optimal timing of intervention in paradoxical low-flow, low-gradient severe aortic stenosis (PLFLG AS) is unclear. Left ventricular (LV) global longitudinal strain (GLS) has been shown to predict outcomes in high-flow severe AS, but there is a lack of data in patients with PLFLG AS. Given the exaggerated LV hypertrophy and remodeling pattern in PLFLG AS, LV GLS may be a mechanistic imaging parameter for outcomes by being a surrogate marker for subclinical myocardial fibrosis. We aimed to examine whether LV GLS in patients with PLFLG AS is associated with adverse outcomes.

We examined patients with PLFLG AS defined as aortic valve area <1.0 cm², mean gradient <40 mm Hg, and preserved left ventricular ejection fraction ≥50%, with low-flow state defined as transvalvular flow rate (Q) ≤210 mL/sec. Exclusion criteria included moderate or greater mitral or aortic regurgitation and presence of atrial fibrillation at the time of echocardiogram. Left ventricular strain analysis was performed using two-dimensional strain imaging software. The primary outcomes were all-cause mortality censored for aortic valve replacement (AVR) and AVR via either surgical or transcatheter approach. The composite outcome was all-cause mortality and AVR. Patients were stratified by LV GLS above and below the optimal cutoff value based on spline curve analysis.

A total of 209 patients were included in the analysis, with an optimal cutoff LV GLS of -14.6%. Over a median follow-up time of 1.2 years (interquartile range, 3.1 years), 110 deaths (52.6%) were identified. Patients with less negative LV GLS had a higher incidence of all-cause mortality than those with more negative LV GLS (82 vs 28, P = .014). There was no significant difference in the incidence of AVR between both groups (17 vs 27, P = .526). Kaplan-Meier analysis showed that patients with less negative LV GLS had a worse 5-year survival rate than those with more negative LV GLS (22% vs 48%, P = .003). There was no significant difference in the 5-year rate of freedom from AVR between both groups (64% vs 65%, P = .73). After multivariable adjustment for potential confounders (stroke volume index, aortic valve mean gradient, relative wall thickness, age, male gender, heart failure, hypertension, coronary artery disease, and diabetes), less negative LV GLS was independently associated with all-cause mortality (hazard ratio [HR] = 1.93; 95% CI [1.24-3.01]; P = .004), whereas hypertension was associated with improved survival (HR = 0.60; 95% CI [0.36-0.99]; P = .04). Continuous variable analysis demonstrated an 8% increase in the risk of all-cause mortality for every 1% less negative change in LV GLS (HR = 1.08; P = .005).

In patients with PLFLG AS defined by a flow rate (Q) ≤210 mL/sec, reduced LV GLS is associated with increased all-cause mortality. Left ventricular GLS may serve as an imaging marker for optimal timing of management.