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.

Markers of Focal and Diffuse Nonischemic Myocardial Fibrosis Are Associated With Adverse Cardiac Remodeling and Prognosis in Patients With Hypertension: The REMODEL Study

“…27,28 As a consequence, they also have worse cardiac function and advanced hypertrophy, including elevated circulating biomarkers of myocardial wall stress and cardiac injury, which concurred and extended previous studies. 4,[29][30][31] Although nonischemic myocardial fibrosis has been reported in patients with hypertension, 30,32,33 the prognostic significance is not well understood. We observed that most CMR measures of nonischemic myocardial fibrosis (native T1, nonischemic LGE, ECV, and indexed interstitial volume) demonstrated prognostic associations in univariable analyses.…”

Strain Imaging and Ventricular Arrhythmia

“…GLS specifically evaluates longitudinal fiber function, which is more sensitive to ischemia since coronary perfusion extends from the subendocardium and outwards [36][37][38]. Finally, GLS has been shown to correlate closely with the neurohumoral response, infarct size, and myocardial fibrosis [39][40][41]. The primary impediment that has prevented GLS from earlier widespread clinical implementation has been its vendor dependency [42,43].…”

Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides

“…Myocardial fibrosis is, in general, one of the hallmarks of a failing heart [4]. Among subjects with severe AS, myocardial fibrosis initially develops as a response to pressure overload, exhibiting an interstitial and reversible nature.…”

“…Among subjects with severe AS, myocardial fibrosis initially develops as a response to pressure overload, exhibiting an interstitial and reversible nature. However, with the persistence of hemodynamic stress, it becomes an irreversible and substitutive process [4][5][6]. In fact, it is 2 of 14 well known that AS does not only affect the aortic valve but also impacts the myocardium, thereby elevating the risk of heart failure [4,6].…”

“…However, with the persistence of hemodynamic stress, it becomes an irreversible and substitutive process [4][5][6]. In fact, it is 2 of 14 well known that AS does not only affect the aortic valve but also impacts the myocardium, thereby elevating the risk of heart failure [4,6]. Finally, fibrosis may also play a role in the failure of valve replacement surgery [7][8][9].…”