DISCUSSION
In our study, we aim to demonstrate the invasive validation of LV GLS in estimating elevated LV filling pressure. We confirmed that the LV GLS highly predicts the elevated LAP in patients with preserved EF such as E/e’ and TR jet velocity. We also demonstrated that -18.1% of LV GLS had higher sensitivity to estimate LV filling pressure compared with the 2016 ASE/ EACVI algorithm.
As it is known, increased myocardial stiffness and prolongation of active myocardial relaxation are the main reasons for HFpEF, which leads to elevated LV filling pressure. Thus, invasive evaluation of elevated LV filling pressure is the gold standard method to define diastolic dysfunction in patients with HF symptoms. However, invasive assessment is not practical and reproducible for all patients with HF symptoms. For this reason, the 2009 American Society of Echocardiography (ASE) and the European Association of Echocardiography (now European Association of Cardiovascular Imaging [EACVI]) guideline simplified and developed a practical algorithm in 2016 guideline to estimate LV filling pressure. However, the studies designed to validate the 2016 ASE/EACVI algorithm with invasive LV filling pressure provided conflicting results. Some of them demonstrated good agreement with invasive LV pressure[2, 3].
Furthermore, the Euro-Filling study demonstrated a substantial sensitivity to diagnose elevated LV filling pressures with the 2016 recommendations in patients undergoing invasive LV end-diastolic pressure measurement. However, they concluded that the algorithm was suboptimal in patients with preserved ejection fraction [4]. On the other contrary, Obokata et al. reported that the new algorithm was specific but poorly sensitive, being able to identify only 34% of individuals with HFpEF diagnosis [5]. Our study also presented that the new algorithm had good specificity but lower sensitivity to predict LV filling pressure.
Even though transthoracic echocardiography is practical and reproducible to determine the diastolic dysfunction, it is not feasible in some instances, including atrial fibrillation, mitral annular calcification, and indeterminate group defined in the guideline. Almedia et al. showed the increase of indeterminate cases using the 2016 algorithm compared with the 2009 guideline[6]. The inclusion of TR velocity to the new algorithm might be an essential reason for increased indeterminate cases. TR velocity generally reflects severe HFpEF; therefore, the early stage of disease may not be evaluated. Moreover, 30% of patients show normal resting diastolic function by standard echocardiographic assessment [7, 8]. Although the parameters’ cumulative effect using the algorithm gives substantial information about LV filling pressure, individual parameters have some limitations. Especially E/e’ is load-dependent and might affect from angle intonation also have poor predictivity to detect the elevation of LV filling pressures with 37% estimation [9].
Nevertheless, LAVi is an adequate parameter to estimate the cumulative effect of increased LV filling pressures [10-12]. It might be inadequate to detect early LV diastolic dysfunction since this volumetric parameter reflects essentially the chronic effect of elevated LV filling pressure[13]. Our study observed a week correlation between TR jet velocity, E/e’, and invasive pre-A pressure and no correlation between LAVi and invasive pre-A pressure. Additionally, LAVi had lower sensitivity (specificity 73.40%, sensitivity 65%) compared with E/e’ and TR jet velocity.
Left ventricular Speckle-tracking global longitudinal strain is a valuable parameter to assess global and regional left ventricular systolic dysfunction. Moreover, LV GLS reflects the longitudinally arranged sub-endocardial fibers function that is influenced early in disease pathogenesis, allowing detection of even subtle impairment; in contrast, EF only detects overt systolic failure [14]. It was believed that diastolic impairment of LV is the main mechanism of HFpEF[15, 16]. However, pathophysiological features of HFpEF, including myocardial fibrosis and microvascular dysfunction, can impair both diastolic and systolic function. There is now clear evidence of significant systolic impairment in patients with HFpEF, such as decreased contractility, which is associated with greater mortality [17].
Furthermore, PARAMOUNT study has demonstrated an independent association between NT-proBNP levels and LV GLS and impaired LV GLS as highly predicted adverse outcomes[18, 19]. The 2016 ASE/ESC guideline recommended assessing LV GLS for patients with atrial fibrillation and severe mitral annular calcification. They also recommended LV GLS to provide the discriminative diagnostic capacity in indeterminate groups[12]. Biering-Sørensen, et al. reported that LV GLS for noninvasive evaluation of LV filling pressure acquired good correlation with PCWP both with rest and exertion[20]. Besides, a cut point of <16% for LV GLS was included in the HFA-PEFF algorithm as minor criteria for diagnosing HFpEF recommended by the Heart Failure Association of the ESC in 2019 [1]. Considering all of these, we investigated whether the LV GLS is more sensitive in predicting elevated LV filling pressure. We showed that LV GLS had better sensitivity than the 2016 echocardiography algorithm for estimating LV filling pressure. We thought that LV GLS might be added echocardiography algorithm to improve the estimation of LAP pressure. Moreover, deficiency of algorithm, including indeterminate group, atrial fibrillation, and mitral annulus calcification might be evaluated with LV GLS. We also believed that LV GLS may be used as major echocardiographic criteria for the HFA-PEFF algorithm and may add incremental value on HFpEF diagnosis.