Echocardiographic Global Longitudinal Strain Is Associated With Myocardial Fibrosis and Predicts Outcomes in Aortic Stenosis

Abstract

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ² = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.

Keywords: aortic stenosis (AS); cardiovascular magnetic resonance; global longitudinal strain (GLS); hypertensive heart disease (HHD); myocardial fibrosis.

Figure 1

Replacement myocardial fibrosis on cardiovascular magnetic resonance in patients with hypertension. Despite similar left ventricular (LV) ejection fraction (A), patients with replacement myocardial fibrosis had increased indexed LV mass (B) and worse global longitudinal strain on echocardiography (C). All values in mean and standard deviation.

Figure 2

Event-free survival curves in patients with aortic stenosis risk-stratified by global longitudinal strain. High-risk patients with aortic stenosis (global longitudinal strain; GLS > −15.0%) had worse prognosis compared to those at intermediate and low-risk (GLS < −21.0%) for both primary (A) and secondary (B) outcome. Similar prognostic findings were observed regardless of sex (C,D) and excluding those with coronary artery disease (E).

Figure 3

Prognostic value of global longitudinal strain in aortic stenosis. Hazard ratios (HR) predicting time to adverse cardiovascular events for global longitudinal strain in unadjusted and adjusted cox models. BMI, body mass index; HTN, history of hypertension; DM, history of diabetes mellitus; CAD, history of coronary artery disease; AVA, aortic valve area; LV, left ventricular.