Speckle-Tracking Echocardiography: History
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Contributor:
Yixia Lin
,
Li Zhang
,
Xiaoqing Hu
,
Lang Gao
,
Mengmeng Ji
,
Qing He
,
Mingxing Xie
,
Yuman Li

Heart failure with preserved ejection fraction (HFpEF) is defined as HF with left ventricular ejection fraction (LVEF) not less than 50%. HFpEF accounts for more than 50% of all HF patients, and its prevalence is increasing year to year with the aging population, with its prognosis worsening.

  • speckle-tracking echocardiography
  • heart failure with preserved ejection fraction

1. Introduction

Heart failure (HF) is a complex clinical heterogeneous syndrome characterized by the reduced capacity of the heart to pump blood, resulting in insufficient cardiac output to meet the body’s metabolic demands [1][2]. HF is also the terminal stage of various cardiovascular diseases, with symptoms (e.g., breathlessness, orthopnea, and fatigue) and signs (e.g., increased jugular venous pressure, hepatojugular reflux, and peripheral oedema) caused by cardiac abnormalities in the structure and/or function [3][4][5][6]. At present, left ventricular (LV) ejection fraction (LVEF) obtained via echocardiography remains a key indicator for the diagnosis and risk stratification of HF patients. However, LVEF has high variability and low repeatability. In various guidelines, the critical values of LVEF in different HF subtypes are different, and there is still a lack of definition of the normal range [7][8]. According to both European and American guidelines, HF is divided into three subtypes: heart failure with preserved ejection fraction (HFpEF, LVEF  ≥ 50%), heart failure with mid-range ejection fraction (HFmrEF, LVEF  ≥  40 and  < 50%), and heart failure with reduced ejection fraction (HFrEF, LVEF  <  40%) [6][9][10]. It is estimated that around 64.3 million people worldwide suffer from HF, of which, HFpEF is the most common subtype, accounting for more than half of all HF patients. The prevalence and incidence of HFpEF are growing with the aging of the population and the increasing prevalence of metabolic syndromes such as hypertension, obesity, and diabetes mellitus [11][12][13][14]. According to various etiologies, HFpEF can be divided into five subtypes: vascular-related HFpEF (hypertension, coronary artery disease, and coronary-microvascular-dysfunction-related HFpEF), cardiomyopathy-related HFpEF (HFpEF patients with hypertrophic cardiomyopathy or infiltrative cardiomyopathies, etc.), right-heart- and pulmonary-related HFpEF (HFpEF resulting from pulmonary hypertension with or without right ventricular dysfunction), valvular- and rhythm-related HFpEF (HFpEF due to valvular disease and atrial fibrillation), and extracardiac-disease-related HFpEF (HFpEF related to metabolic diseases, diseases that often cause high output states and chronic kidney disease, radiotherapy for cancer, etc.) [15]. Patients with HFpEF have LV diastolic dysfunction, increased filling pressure, and normal or slightly impaired systolic function, but LVEF within the normal range. Compared with HFrEF, the diagnosis of HFpEF is more challenging because of the normal LVEF [6]. The recent European Society of Cardiology (ESC) guidelines defined HFpEF as the presence of symptoms and/or signs of HF; preserved LVEF (LVEF > 50%); elevated levels of natriuretic peptide: brain natriuretic peptide (BNP) > 35 pg/mL and/or N-terminal pro-brain natriuretic peptide (NT-proBNP) > 125 pg/mL; and the evidence of diastolic dysfunction and/or structure heart disease (LV hypertrophy; left atrial (LA) enlargement) [6].
In general, objective evidence of a cardiac structural and functional abnormality is often obtained via imaging, and echocardiography is the preferred method for the clinical evaluation of cardiac structure and function at present [16]. Though LVEF is the most commonly used traditional echocardiographic parameter to assess cardiac performance and is readily available in daily practice, it is not sensitive to slight changes in LV systolic function [17][18][19][20]. The symptoms and signs of HFpEF patients are non-specific, and the LVEF is within normal range, which limits the estimation of cardiac function via conventional echocardiographic parameters. With the development of new techniques such as myocardial deformation imaging, early myocardial dysfunction can be identified before LVEF decreases to guide the diagnosis of HFpEF [19][21][22][23]. The early and accurate identification of cardiac dysfunction is essential for risk stratification, clinical management, and prognostic improvement in HFpEF patients. Myocardial strain obtained via cardiac magnetic resonance (CMR) and speckle-tracking echocardiography (STE) has been proven to be a sensitive parameter for the early detection of subclinical cardiac dysfunction, providing a new index for cardiac function evaluation in HFpEF patients [17][18][24][25]. CMR is the gold-standard imaging modality for quantifying volume and EF [26]. Furthermore, CMR allows for the accurate assessment of the structural changes in HFpEF patients, such as LA enlargement, LV hypertrophy and mitral inflow, and pulmonary venous velocity [26]. More recently, CMR has been used to describe the specific tissue composition of myocardial tissue in HFpEF patients through non-invasive methods, such as edema, fat, iron overload, and focal fibrosis [27]. CMR feature tracking imaging can accurately assess myocardial deformation and help find potential causes of HFpEF [26][27]; however, CMR has a variety of contraindications, such as metal implantation, a long scanning time, and being inappropriate for individuals with claustrophobia, which limits the application of CMR in clinical practice [25]. Currently, echocardiography remains the preferred imaging examination technique for the initial evaluation of HFpEF patients, and STE has emerged as a potential technique for evaluating LV function [28].

2. Clinical Application of Speckle-Tracking Echocardiography in Patients with HFpEF

2.1. Left Ventricular Function

LV myocardial structure and movement patterns are complex. LV myocardial fibers consist of three layers: subendocardial, middle, and subepicardial. The subepicardial myocardial fibers are longitudinally oriented in the right-handed helix; the mid-myocardial fibers are circumferentially oriented; and the subendocardial fibers are longitudinally oriented in the left-handed helix, which allows the LV movement to be divided into longitudinal shortening, radial thickening, and circumferential movement [17][29]. Therefore, the LV strain is described as myocardial deformation occurring in the longitudinal, radial, and circumferential planes during the cardiac cycle, corresponding to the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), respectively [17][30][31]. The subendocardial myocardium is most sensitive to ischemia and is the first to undergo dysfunction during myocardial ischemia, namely, the first to change GLS.
In the past, it was considered that patients with HFpEF had LV diastolic dysfunction and normal systolic function. However, recent studies have found that the symptoms of HFpEF patients are not completely caused by diastolic dysfunction, and patients already have systolic dysfunction in the early stage of HFpEF [32][33][34]. The longitudinal myocardium contracts in coordination with the circular myocardium, and ventricular torsion compensation increases, keeping LVEF within the normal range in HFpEF patients [6]. Consequently, the early identification of LV systolic dysfunction provides a basis for risk stratification and clinical management in patients with HFpEF. Hashemi et al., used CMR to evaluate LV function in HFpEF patients, and the results showed that there was no significant difference in LVEF between controls and HFpEF patients, but GLS and GCS were significantly impaired in HFpEF patients. The LV septum was found to be the most affected location by regional strain analysis [25]. However, the high price, long scanning time, and inability to be used in patients with metal implants may limit the wide application of CMR in clinical practice. STE remains a promising technique for the evaluation of LV function. Liu et al., found that LVGLS obtained by 2D-STE was significantly lower in patients with HFpEF compared with healthy controls, while LVEF was not significantly different, suggesting the higher sensitivity of LVGLS over LVEF for the detection of LV dysfunction [35]. The research by Smith et al., suggested that subendocardial and subepicardial LVGLS of the basal, middle, and apical segments is significantly reduced in HFpEF patients, indicating that HFpEF not only affects the subendocardial myocardial fibers but all layers of the myocardium [36]. Kosmala et al., used 2D-STE to investigate the cardiac function in 207 symptomatic HFpEF subjects and 60 HFpEF asymptomatic patients, as well as exploring the predictors of adverse outcomes in patients with HFpEF. Their study showed that LVGLS was significantly decreased in both symptomatic and asymptomatic patients. Receiver operator characteristic (ROC) curves showed that LVGLS during exercise (AUC 0.78) could predict symptomatic HFpEF most accurately, and its predictive value was better than that of E/e’ and LVEF [37]. In a prospective investigation of HFpEF patients followed for three years, Wang et al., proved that impaired LVGLS was associated with adverse events, but only the reduction in LVGLS during exercise was an independent predictor of adverse clinical outcomes, showing that LVGLS is of great value in the prognostic evaluation of HFpEF patients [38]. However, the changes in GCS and GRS in patients with HFpEF and their effects on prognosis are contradictory [29]. Some studies showed that there was no significant difference in GCS in patients with HFpEF compared with healthy controls and that GCS was not associated with the occurrence of adverse outcome events in patients. However, other studies reported a reduction in GCS in patients with HFpEF [36][39][40]. Among them, Smith et al., showed that the GCS of subendocardial and subepicardial LV basal, middle, and apical segments in HFpEF patients was significantly reduced, which again confirmed that the LV full-thickness myocardial wall in HFpEF patients was affected [36]. GRS is rarely investigated in patients with HFpEF. Studies observed the absence of difference in GRS between healthy controls and HFpEF patients, although other research suggested a significantly reduction in GRS in HFpEF patients [38][41][42]. Some studies revealed that GRS was not associated with the occurrence of adverse events in HFpEF patients, but additional studies are needed to explore the effect of GRS on prognosis [38]. In recent years, 3D-STE has been increasingly used in patients with HFpEF and is of great value for the comprehensive evaluation of cardiac function. Fan et al., applied 3D-STE to analyze LV function in patients with and without HFpEF; they reported that the area strain (AS) of the LV was significantly impaired in HFpEF patients and negatively correlated with LVEF, indicating that the change in AS occurred sooner than that in LVEF [43]. Luo et al., used 3D-STE to measure the three-dimensional strain of the left ventricle; their results demonstrated that GLS, GCS, GRS, and AS were progressively impaired in HFpEF patients and that AS combined with GLS and GCS was a predictor of LV systolic dysfunction [44].

2.2. Left Atrial Function

LV diastolic dysfunction and increased LV filling pressure in HFpEF patients lead to ineffective LA emptying and increased LA volume and afterload, finally resulting in LA remodeling and function impairment. LA enlargement is a recognized indicator of LV diastolic dysfunction and an independent predictor of poor prognosis in patients with HFpEF [45]. The LA volume index (LAVI) is an essential part of the evaluation of LV diastolic function and is an integral component of the diagnostic criteria of HFpEF [46][47]. LA dysfunction usually precedes the occurrence of LA remodeling and plays an important role in evaluating patients’ prognosis [48][49][50]. According to the different roles of the left atrium in different phases of the cardiac cycle, LA function is divided into reservoir, conduit, and booster functions. LA deformation in different phases was quantified by STE to evaluate LA function. LA peak strain occurs during ventricular contraction, representing reservoir function. LA conduit strain appears during LV early diastole, representing passive LA emptying. LA booster strain appears during LA systole, representing active LA emptying [48][51]. The impaired of LA peak strain is associated with LV systolic and diastolic dysfunction and is highly correlated with LVGLS. Left ventricular systolic longitudinal dysfunction leads to a reduction in displacement from the mitral valve to the apex and thus a reduction in passive LA stretch [52]. Santos et al., used 2D-STE to compare 135 HFpEF patients with sinus rhythm and 40 healthy controls and found the impairment of LA reservoir, conduit, and booster strain in HFpEF patients, as well as the fact that LA reservoir dysfunction was independent of LA size. In addition, they reported that patients with lower LA peak strain had a higher rate of heart failure hospitalization and worse left ventricular systolic function, indicating that LA dysfunction is related to the severity and pathophysiology of HFpEF patients [53]. Using 2D-STE, Morris et al., revealed that the sensitivity of LA strain in the diagnosis of early LA dysfunction in HFpEF patients was higher than that of LAVI, confirming that LA strain is a reliable indicator of LA dysfunction. Moreover, LA strain abnormalities were still significantly associated with worse New York Heart Association (NYHA) class and a higher risk of hospitalization for HF after adjusting for gender, age, and LAVI [54]. Tells et al., simultaneously performed right heart catheterization and echocardiography on the study subjects and found impaired LA peak and booster strain in patients with HFpEF. Further, they investigated the relationship between LA strain and hemodynamics in HFpEF, and the results showed that LA peak strain was negatively correlated with pulmonary capillary wedge pressure (r = −0.64, p < 0.001) and that LA booster strain was positively correlated with pulmonary capillary wedge pressure (r = 0.72, p < 0.001). The study also found that when LA peak strain was less than 33%, the sensitivity and specificity of non-invasive diagnosis of HFpEF were 87% and 77%, respectively. In summary, LA strain can be used as a non-invasive indicator to evaluate the pressure of the cardiac chamber in HFpEF patients [55]. Freed et al., measured LA strain parameters in HFpEF patients by 2D-STE and followed up these patients. They found that LA function was impaired in HFpEF patients at all phases and LA strain (especially LA reservoir strain) was an independent predictor of adverse outcomes. Moreover, LA reservoir strain was significantly associated with reduced exercise capacity, decreased cardiac output, and the increased risk of poor prognosis. Therefore, therapies that enhance LA function may be beneficial for HFpEF patients [56]. Because of the out-of-plane motion of the speckles and the segmentation of LA following the segmentation of LV, LA structure and function cannot be comprehensively evaluated by 2D-STE. The newly developed 3D-STE more objectively quantifies LA deformation and function and compensates for the shortcomings of 2D-STE. Liu et al., evaluated the LA function in 43 HFpEF patients and 18 healthy subjects. The results of this study showed that LA strain reduction in HFpEF patients with normal LA size predominantly occurred in the middle part of the LA, and strain of basal and roof levels also significantly decreased with the increase in LA size. The reproducibility of strain at the LA middle level was satisfactory (ICC > 0.8), which is an ideal indicator to evaluate LA function. In addition, they also reported that LA reservoir, conduit, and booster function were significantly impaired in HFpEF patients, and these changes were more significant in patients with LA enlargement [57].

This entry is adapted from the peer-reviewed paper 10.3390/diagnostics13182923

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