Novel Biomarkers and Advanced Cardiac Imaging in Aortic Stenosis: Old and New

Abstract

Currently, the symptomatic status and left ventricular ejection fraction (LVEF) play a crucial role in aortic stenosis (AS) assessment. However, the symptoms are often subjective, and LVEF is not a sensitive marker of left ventricle (LV) decompensation. Over the past years, the cardiac structure and function research on AS has increased due to advanced imaging modalities and potential therapies. New imaging parameters emerged as predictors of disease progression in AS. LV global longitudinal strain has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF. The assessment of myocardial fibrosis by cardiac magnetic resonance is the most studied application and offers prognostic information on AS. Moreover, the usage of biomarkers in AS as objective measures of LV decompensation has recently gained more interest. The present review focuses on the transition from compensatory LV hypertrophy (H) to LV dysfunction and the biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement and provide insight into novel biomarkers for possible prognostic use in AS. However, data from randomized clinical trials are necessary to define their utility in daily practice.

Keywords: aortic stenosis; cardiac biomarkers; myocardial fibrosis; remodeling; risk assessment.

Figure 1

Left ventricular global longitudinal strain measured via speckle tracking echocardiography in an asymptomatic patient with severe aortic stenosis. The LVEF was normal (64%), and the mean transvalvular gradient was 48 mm Hg. The patient had concentric LV hypertrophy, more prominent in the interventricular septum. An impaired LV GLS (−17.8%) was found in this patient, with more severely reduced values of longitudinal deformation in the basal segments of the interventricular septum. Coronary angiography revealed no significant coronary artery disease. Abbreviations: LV, left ventricle; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction.

Figure 2

Left atrial longitudinal deformation in a 71-year-old patient with asymptomatic severe AS, preserved LVEF, and sinus rhythm. We observe in the right panel the LA longitudinal strain curve with a normal mean value of 24.7% (LAƐ). Abbreviations: AS, aortic stenosis; LVEF, left ventricular ejection fraction; LA, left atrium.

Figure 3

Left atrial longitudinal deformation in a 73-year-old patient with symptomatic severe AS, preserved LVEF, and sinus rhythm. We observe the LA longitudinal strain curve with a reduced mean value of 13% (LAƐ). Lower values of LA longitudinal strain (LA reservoir function) are observed in the symptomatic patient with severe AS compared to the asymptomatic one (Figure 2). Abbreviations: AS, aortic stenosis; AVC*, aortic valve closure; LVEF, left ventricular ejection fraction; LA, left atrium.

Figure 4

Late gadolinium enhancement on cardiac magnetic resonance imaging. The left and right panels represent LV three-chamber and, respectively, short axis CMR views of a patient with symptomatic severe aortic stenosis and moderate LV global systolic dysfunction (LVEF 38%). The LV was severely dilated, with thin walls, except for the IVS, which was hypertrophied. Coronary angiography revealed no significant coronary artery disease. The orange arrow indicates focal, non-ischemic (mid-wall) LGE in the IVS. Abbreviations: LGE, late gadolinium enhancement; CMR, cardiac magnetic resonance; LV, left ventricle; IVS, interventricular septum; LVEF, left ventricular ejection fraction.