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.