Introduction
Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by untreated thromboembolism of the pulmonary arteries, leading to right ventricular afterload, progression of pulmonary hypertension (PH), and life-threatening right heart failure [
1]. Pulmonary artery pressure measurement using right-sided heart catheterization (RHC) is considered the gold standard for diagnosing PH, but RHC can be challenging because of the invasiveness of the procedure. Echocardiography is routinely used for patients with suspected or diagnosed PH to roughly check the severity of PH and determine if they need RHC to manage PH.
Tricuspid regurgitant pressure gradient (TRPG) measured using echocardiography is among highly reliable parameters in the noninvasive measures for predicting actual systolic pulmonary arterial pressure measured using RHC (sPAP
RHC). Therefore, TRPG is widely used for estimating sPAP
RHC in clinical practice. However, we sometimes encounter PH patients in whom the systolic pulmonary arterial pressure estimated using TRPG (esPAP
TRPG) clearly differs from the sPAP
RHC, resulting in critical management errors. One reason for this discrepancy (i.e., between esPAP
TRPG and sPAP
RHC) is that esPAP
TRPG depends on the degree of the angle between the tricuspid regurgitation (TR) jet and Doppler beam [
2]. Another possible reason is that some patients have too trivial TR to measure TR velocity, resulting in seemingly normal TRPG values. Previous studies have reported that esPAP
TRPG might be significantly underestimated in some patients with severe PH because the modified Bernoulli equation cannot be used in such cases [
3‐
5]. Thus, esPAP
TRPG cannot always be helpful in evaluating the severity of PH. Therefore, other echocardiographic components are required for better management of patients with unreliable TRPG.
The 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines suggested grading the probability of PH based not only on TRPG but also on additional prespecified echocardiographic variables including left ventricular eccentricity index (LVEI) which is one of the parameters used to quantify the flattening of the interventricular septum (IVS) [
5]. The IVS curvature is also the parameter used to quantify IVS configuration. In the 1980s, King et al. [
6] first showed moderately high correlation between the IVS curvature on echocardiography and right ventricular systolic pressure qualitatively in children with congenital cardiac disorders. Studies on cardiac computed tomography (CT) and magnetic resonance imaging (MRI) have shown that quantified values of the IVS curvature correlate well with sPAP
RHC in patients with PH including CTEPH [
7‐
9]. In routine clinical echocardiography, most examiners check IVS displacement in addition to TRPG measurements to predict the severity of PH. However, evaluation related to the IVS is generally performed with visual assessment alone and has been rarely assessed quantitatively in echocardiography.
With the above background, this study aimed [
1] to investigate the correlation between the echocardiographic IVS curvature and sPAP
RHC in CTEPH patients and [
2] to evaluate the diagnostic performance of the IVS curvature in patients in whom accurate estimation of sPAP
RHC based on TRPG is difficult due to trivial TR and severe PH. We hypothesized that the IVS curvature could be a good echocardiographic parameter in addition to TRPG for evaluating sPAP
RHC in CTEPH patients especially with unreliable TRPG.
Discussion
To the best of our knowledge, this is the first study to assess the quantitative utility of the IVS curvature obtained using echocardiography for estimating sPAPRHC in patients with CTEPH.
The echocardiographic IVS curvature could compensate for the disadvantages of esPAPTRPG, especially in the management of patients with unreliable TRPG including trivial TR and severe PH.
In this study, the ICC for the IVS curvature and LVEI showed mild values (0.60 [0.41–0.74, 95% confidence interval] and 0.84 [0.75–0.90], respectively), suggesting that the IVS curvature measured using echocardiography could be as reliable as that measured using cardiac CT [
7].
Correlations of the IVS curvature with sPAP
RHC (r = − 0.55; Additional file
1: Fig. S1) in all CTEPH patients including them with trivial TR were less than those reported using CT [
7] and MRI [
15]. However, the echocardiographic IVS curvature should have the advantage of being a noninvasive, easy and low-cost tool unlike CT and MRI. From the viewpoint of safety, compared with MRI, it can be used for post-pulmonary endarterectomy patients with nontitanium wire. Moreover, the measurement of the echocardiographic IVS curvature can be performed easily using simple two-dimensional echocardiography without Doppler or three-dimensional echocardiography, unlike TRPG. This study excluded patients with insufficient TR jet for measuring TR velocity. Therefore, we suspected that the utility of the IVS curvature might be higher in the management of patients with CTEPH than predicted from this study.
Rich et al. [
2] and Fisher et al. [
16] both reported that the magnitude of pressure underestimation using esPAP
TRPG was greater than overestimation, particularly at high sPAP
RHC with fair or poor quality of Doppler TR jet. Mutlak et al. [
4] reported that severe TR is related to higher sPAP
RHC in general, but several patients with severe PH do not exhibit significant TR because of the remodeling of right heart cavities. Therefore, we focused on patients with trivial TR and severe PH regarded as unreliable TRPG and investigated the utility of the IVS curvature for estimating sPAP
RHC.
In patients with trivial TR, a significant correlation was found between sPAPRHC and esPAPcurv statistically, indicating that the IVS curvature could estimate their sPAPRHC to some extent even if their sPAPRHC cannot be estimated due to trivial TR. Moreover, the sensitivity of esPAPcurv to predict patients with sPAPRHC ≥ 70 mmHg was better than those of esPAPTRPG and esPAPLVEI. The sensitivity and specificity of esPAPcurv for detecting patients with sPAPRHC ≥ 70 do not appear particularly high. However, the sensitivity of esPAPTRPG with esPAPcurv was much higher than esPAPTRPG alone. Echocardiographic results are often required to determine the need for RHC, and underestimation can therefore lead to a critical mistake, especially during the first visit. We assessed the utility of the IVS curvature as an additional tool to TRPG to better manage patients with unreliable TRPG, including trivial TR and severe PH.
The 2015 ESC/ERS guidelines regarded LVEI > 1.1 in systole and/or diastole as an additional prespecified echocardiographic variable to predict the probability of PH in symptomatic patients suspected of PH [
5]. This study showed that the ICC of LVEI is higher than that of IVS curvature, indicating that LVEI have smaller interobserver error. However, as mentioned above, esPAP
LVEI has no significant correlation with sPAP
RHC in patients with trivial TR, and its sensitivity in estimating sPAP
RHC ≥ 70 mmHg is lower than that of esPAP
curv. It indicates that the IVS curvature in CTEPH patients would be a more useful tool for estimating the probability and severity of PH than LVEI which are similar parameters for evaluating the flattening of IVS.
The IVS curvature was measured in views showing the endocardial surface of the left ventricle at the papillary muscle level at the end systole. However, it was challenging to show the papillary muscle clearly in some patients. To confirm if the accuracy of the IVS curvature depends on the transverse section imaged, we divided patients into two groups based on the presence of clearly visible or invisible left ventricular papillary muscles in echocardiographic images used for measuring IVS curvature. As shown in Additional file
1: Table S1, The visible group (n = 65) showed a significant correlation between sPAP
RHC and IVS curvature (
P < 0.0001, r = − 0.55). However, there was no significant correlation in the invisible group (n = 7,
P = 0.17). The LVEI also showed the same result as the curvature (the visible group:
P = 0.0002, r = 0.43; the invisible group:
P = 0.11). This indicates that the accuracy of the IVS curvature and EI would depend on the transverse section imaged.
This study showed a linear relationship between the IVS curvature and sPAP
RHC as Roeleveld et al. [
13] reported in 379 adults suspected of PH and evaluated using MRI. However, the correlation value was lower in the present study (r = − 0.52,
P < 0.01) than in their study (r = 0.77,
P < 0.001). One possible reason for the lower correlation value in the present study is that echocardiographic IVS curvature might be dependent on patient’s physique and operator’s skill due to the use of local view in the heart instead of the whole heart in MRI. Another possible reason is that the present study included more patients with mild sPAP
RHC < 50 mmHg than the study by Roeleveld et al., Lopez-Candales et al. showed that LVEI measured at conventional papillary muscle level showed the best correlation with sPAP
RHC when the sPAP
RHC ranged between 45 and 60 mm [
17]. This indicates that the mechanical compliance of the IVS might be linear within a limited range of sPAP
RHC.
This study has some limitations. First, it was a single-center retrospective study with a small number of patients. Multicenter studies with a larger number of subjects are needed to increase the generalizability of our findings. Second, we analyzed only CTEPH as a representative of conditions involving PH. To test the broad utility of the IVS curvature in PH management, further studies with several conditions involving PH need to be performed using the methods in this study.
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