Background
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder and has a prevalence of 1/200 people [
1]. Patients with HCM usually have abnormal left atrial (LA) size and can develop atrial fibrillation (AF). Increased LA diameter has consistently been identified as a strong predictor of AF in HCM [
2,
3]. Some studies have shown that enlargement of the LA results from left ventricular (LV) diastolic dysfunction [
4,
5]. Elevated LV filling pressures from LV diastolic dysfunction are transmitted back to the LA, which results in LA enlargement and dysfunction [
6]. The normal function of the LA is to fill the LV and can be separated into three portions: (1) reservoir function (collection of pulmonary venous blood during LV systole); (2) conduit function (passage of pulmonary venous blood flow to LV during early LV diastole); (3) booster pump function (augment LV filling during late LV diastole/atrial systole) [
7].
HCM patients with obstructive hypertrophic cardiomyopathy (HOCM) tend to have associated LA enlargement and LA dysfunction likely from LV diastolic dysfunction [
6]. However, the impact of LV hypertrophy on the LA function in non-obstructive HCM (NOHCM) remains unknown. Previous publications investigating LA function in HCM patients have primarily focused on the LA size [
8] and volume [
9]. However, these two parameters alone may be insufficient to describe the complexity of the LA function in HCM [
10]. Thus, analysis of the LA functional parameters of strain and strain rate (SR) using non-invasive imaging modalities such as echocardiography speckle tracking (STE) and cardiovascular magnetic resonance (CMR) feature tracking (CMR-FT) have been proposed for further evaluation. STE has been proven to be a feasible and reproducible technique to evaluate LA function [
11] and has demonstrated significant LA function impairment in HCM [
12‐
14]. CMR-FT is a new quantitative method for wall motion assessment that is analogous to STE [
15]. CMR-FT is acquired on the routine CMR cine images and has the advantages of higher spatial resolution, larger field of view and better reproducibility when compared to STE [
16]. LA global and regional function in HCM patients have not yet been well studied by CMR-FT, especially in NOHCM. The aim of this study is to evaluate the feasibility and reproducibility of CMR-FT for the quantification of global and regional LA function in patients with NOHCM. In addition, we analyze the differences of global and regional LA function between NOHCM patients and healthy subjects to answer the question as to whether the alteration of LA function precedes LA enlargement.
Discussion
To the best of our knowledge, this is the first study evaluating both global and regional LA function by CMR-FT in NOHCM patients. This study elucidated several findings: CMR-FT is a promising method for quantification of the LA function in patients with NOHCM, LA global and regional reservoir dysfunction as well as LA conduit dysfunction was observed in NOHCM patients before LA dilation, the LA booster pump function did not show any significant difference between the patients with NOHCM and healthy control group, and regional function in the antero-roof LA wall was significantly decreased in NOHCM patients.
LA remodeling consists of both structural and functional changes. In HCM patients, LA structural remodeling has been shown to be related to LV diastolic dysfunction, degree of mitral regurgitation, and LVOT obstruction [
23]. LA enlargement has been proven to positively predict the risk of AF [
24]. Several studies have demonstrated that increased LA size in HCM patients is associated with impaired LA function [
25‐
27]. The incidence of AF in HCM patients is reported to be up to 20% of HCM patients (the annual incidence of AF is 2% per year) and has a poor prognosis [
28,
29]. The findings of our study show that LA dysfunction occurs prior to LA enlargement in NOHCM patients and thus suggests a relationship between LA dysfunction and AF occurrence in HCM patients prior to enlargement of the LA [
26]. However, it should be noted that the although the LA size of the enrolled NOHCM patients in our study was normal and not significantly different than our normal control group, it was larger than healthy controls in previous studies [
13,
23].
According to the results of our study, both LA reservoir and conduit dysfunction were observed NOHCM, which is consistent with findings of prior studies [
21,
30]. LA diastole (corresponding to the reservoir function) depends on both the atrial compliance and the LV base descent during LV systole [
31]. In patients with HCM, LA compliance is decreased due to increased wall stiffness caused by myocardial fibrosis [
23,
28,
32]. Additionally, Liu et al. previously demonstrated that decreased LV global longitudinal strain in HCM patients may reduce the systolic movement of the LV basal wall [
33], which would also decrease LA compliance and result in LA reservoir dysfunction. The LA conduit dysfunction is closely related to impaired LV compliance which is caused by a markedly thickened LV wall that often contains areas of myocardial fibrosis [
8,
34]. Thus, our study further validated previous studies by also detecting LA reservoir and conduit dysfunction in this group of NOHCM patients. However, in contrast to the Kowallick’s study, the LA booster pump function in our study was not statistically different between the NOHCM patients and the normal controls. The LA booster pump functions in previous HCM patient studies in the literature has not been consistent and has been separately reported as normal [
30], increased [
21] or reduced [
12]. LA contraction is influenced by pulmonary venous return (atrial pre-load), LV end-diastolic pressure (atrial after-load), and LV systolic reserve [
8]. This discrepancy between our study and Kowallick’s study may be due to patient selection criteria of current study: no LA enlargement, no LV systolic dysfunction and no LVOT obstruction.
Previous studies have investigated the global LA strain and SR in HCM patients. Our study took this one step further and also analyzed the segmental strain and SR. We found that the function of inferior, septal-roof and antero-roof were regionally abnormal. The LA inferior wall dysfunction was probably related to the gravity of blood which causes compression of the inferior wall as well as related to the LA conduction system. The LA conduction system is associated with a line of conduction block from the LA roof to the inferior wall. This line corresponds to a change in subendocardial fiber orientation. Subendocardial fibers located on the septal side of the line have a longitudinal orientation. Subendocardial fibers located lateral to this line are oblique and circumferential in orientation [
35]. The LA roof is fixed to the mediastinum by the pulmonary veins, which may account for the decreased LA roof wall function [
34]. As a result, although the global function of SRa was preserved in the NOHCM patients, there was regional deformation dysfunction. The regional deformation detected by the SR analysis could help monitor the changes in LA function (Fig.
2).
We found no significant correlations between the LA functional parameters and conventional LV functional parameters. One possible reason for this may be that LV conventional functional parameters mainly reflect the LV systolic function. However, the LA function is more related to LV diastolic function instead of LV systolic function [
36], which is exactly what our volumetric findings showed. Although LA maximal volume was similar to the normal controls, the volume of LA pre-contraction and after contraction were larger than those of the normal controls. Since the LA is directly exposed to the LV diastolic pressure during these two phases, the LA volume of these two phases could serve as an index in the assessment LV diastolic function. Furthermore, the majority of LA deformation parameters were significantly associated with LAEF, which might suggest potential correlation between LA wall deformation and LA size.
Limitations
Several limitations of our study should be acknowledged. Weonly calculated the LA strain and SR. Further investigation of additional parameters such as displacement and movement speed are required in future studies. Also, this is a single center with a relatively modest sample size. Thus, subgroup analysis for types of HCM such as asymmetric hypertrophy of interventricular septum and apical hypertrophy were not performed. Because of its invasiveness, cardiac catheterization was not performed and thus cardiac physiological parameters including atrial and ventricular pressure were not obtained.
Conclusions
CMR-FT technique is a reliable tool for quantitative assessment of LA function (volumetric and deformation parameters). Using CMR-FT, we found LA reservoir and conduit dysfunction occurs prior to LA enlargement in NOHCM patients. This suggests a relationship between LA dysfunction and AF risk in these patients. However, booster pump function in the NOHCM patients was not significantly different than normal controls. Additionally, deformation of the LA, in particular decreased regional function in the antero-roof LA wall, was also observed in the NOHCM patients. This LA regional deformation analysis may provide insight in assessing the LA performance over time in HCM patients.
Acknowledgements
The authors thank Dr. Arlene Sirajuddin, from National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), USA, for her expertise and language editing during the revision of the manuscript.
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