Application of left atrial strain assessment by 2D echocardiography in cardiac conditions involving the left atrium including cardiac amyloidosis

Abstract

The left atrium (LA) plays an important role in the modulation of LV filling and contributes to LV stroke volume with atrial contraction. Despite this important role, much research to date has been focused on the ventricles in disease, rather than the atria. In recent years there has been increasing interest and excitement in the function of the LA in normal and disease states – no longer is the LA secondary to the left ventricle (LV). The LA has three major functions: reservoir, conduit and contractile. The LA acts as a reservoir during ventricular systole as it fills with blood via the pulmonary veins and expands in size, subsequently, the mitral valve opens and the conduit phase is this passing of blood from the LA to the LV due to a small pressure gradient. Lastly, atrial systole, or the ‘atrial kick’, provides further augmentation of the LV stroke volume at the end of ventricular diastole. Methods for non-invasive assessment of these LA functions have been limited due to echocardiographic technology and the cumbersome nature data collection for these parameters. Prior techniques included assessment of LA size, phasic changes in LA size or volume as well as a variety of Doppler parameters which provided a cruder assessment of the LA functions. Strain is a unitless measurement of myocardial deformation and can be applied to assess the three LA functions in more detail. Contemporary strain research uses 2D-speckle tracking echocardiography (STE), where strain represents a fraction change in myocardial length relative to baseline and is expressed as a percentage. As strain technology surges forward with now dedicated LA strain software packages, the importance of the left atrium has become increasingly recognised. Improved strain technology has allowed easier and more widely available assessment of the three LA functions. Several studies have now documented normal LA strain values in large populations, and specifically, variations due to age and gender. Multiple literature reviews and guideline documents from cardiac imaging bodies have provided a standardised basis for acquisition of LA strain and the language used to describe LA functions and strain values. Previously, different gating techniques, software and terminology made comparison of literature more challenging. Interest and guidance from these peak bodies such as the European society of cardiovascular imaging confirms the importance of LA strain moving forward. There are many disease states which impact upon LA function and further study of LA strain in these areas may allow identification of subclinical atrial disease and impact on diagnostic or treatment pathways. In reviewing the literature, this thesis examines the current knowledge for clinical applications of LA strain in various pathologies/disease states. To contribute to current LA strain research, this thesis goes on to investigate the reproducibility of the LA strain technique, comparing strain readers of different expertise. This is an important step for uptake of LA strain into widespread use. The study showed LA strain was highly reproducible by a novice strain reader using multi-vendor analysis software and secondly, that there was good interobserver reproducibility between novice and experts. The thesis goes on to investigate the use of LA strain in a specific clinical scenario - cardiac amyloidosis (CA). Cardiac amyloidosis is a condition leading to amyloid protein deposition in cardiac tissue and subsequent organ dysfunction. Recent studies have shown that CA leads to LA dysfunction and abnormal LA strain and strain rate values. Given many different conditions can lead to reduction in LA strain, further investigation into changes and degree of LA dysfunction with CA compared to mimicking pathologies is of importance. Ventricular hypertrophy due hypertension can make differentiation of cardiac amyloidosis difficult using echocardiography alone – particularly when clinical history of hypertension is not previously known. The second original research study confirms a severe reduction in LA function in patients with cardiac amyloidosis, concordant with that seen in other studies. Additionally, LA function in CA was significantly worse compared to the hypertensive group, despite similar increases in LV wall thickness. Therefore, LA strain may provide incremental value in differentiating cardiac amyloidosis from increased LV wall thickness secondary to hypertension. Further investigation with larger cohorts and comparison between strain values in CA and other infiltrative pathologies should be considered to improve observe how specific this severe reduction in LA strain values is for CA compared to other infiltrative pathologies causing increased LV wall thickness. LA strain is a promising emerging tool, the applications of which will be further explored in this thesis.