Introduction

In precapillary pulmonary hypertension (PH), an increase in right ventricular (RV) afterload causes hypertrophy, fibrosis, and stiffening of RV cardiomyocytes, resulting in increased RV diastolic stiffness and subsequent RV end-diastolic pressure (RVEDP) elevation [1, 2]. Recently, several researchers have highlighted the clinical significance of RV diastolic stiffness, demonstrating that it is an independent predictor of survival and is closely associated with disease severity in patients with precapillary PH [3,4,5]. RV pressure-volume loop analysis is the gold standard for evaluating RV diastolic stiffness (β) [2, 6]. However, assessing the end-diastolic pressure-volume relationship in daily clinical practice is difficult because of its invasive nature, high cost, and the need for specialized mathematical processing software [2].

The ratio of late-diastolic ventricular pressure increase to volume increase is also considered a measure of ventricular operating stiffness [7,8,9]. Based on this theory, we recently reported an echocardiographic method for the assessment of RV diastolic stiffness by dividing the descent of the pulmonary regurgitation (PR) pressure gradient during atrial contraction (PRPGDAC) by the tricuspid annular plane movement during atrial contraction (TAPMAC) [10]. Previous studies have shown that PRPGDAC/TAPMAC was correlated with the ratio of the late-diastolic RV pressure increase to the volume increase and RVEDP [10] and was useful for predicting prognoses in patients with heart failure. However, in these studies [10, 11], PRPGDAC/TAPMAC was not compared with β. Moreover, previous studies did not include patients with precapillary PH, in whom RV diastolic stiffness was related to clinical progression.

Therefore, this study aimed to determine the clinical usefulness of PRPGDAC/TAPMAC as an echocardiographically estimated index of RV diastolic stiffness by comparing it with β, the gold standard for RV diastolic stiffness, in patients with precapillary PH. Additionally, we examined the relationship between PRPGDAC/TAPMAC and the prognostic factors for precapillary PH.

Materials and methods

Participants

This retrospective, single-center, observational study examined the relationship between the echocardiographic estimation of RV diastolic stiffness based on the PR velocity waveform and β, as determined from the RV diastolic pressure-volume relationship. We included 73 consecutive patients with suspected or confirmed precapillary PH who underwent right heart catheterization, cardiac magnetic resonance imaging (MRI), and echocardiographic examination within a 1-week interval under stable clinical conditions at Hokkaido University Hospital between May 2020 and June 2022. Of these patients, we excluded those with poor RV pressure records by cardiac catheterization (n = 1), with atrial fibrillation during the examinations (n = 2), with frequent premature ventricular/atrial contractions (n = 2), and with tachycardia of heart rate ≥ 100 bpm (n = 1). Thus, 67 patients were included in the final analysis. Thirty-nine patients included in our previous study [12] were included in the present investigation; however, they were used for a different purpose. This retrospective observational study was approved by the institutional review board of our institution. Patients were allowed to opt out of participation on the hospital’s website.

Right heart catheterization

Right heart catheterization was performed using a Swan‒Ganz catheter. From the pressure records, we measured the mean right atrial (RA) pressure, pulmonary arterial (PA) systolic pressure, PA diastolic pressure, mean PA pressure, and mean PA wedge pressure. Immediately after the Swan‒Ganz catheter measurements, the Swan‒Ganz catheter was removed and a 5- or 6-F guiding catheter (Mach 1™ Coronary Guide Catheter, Boston Scientific) was inserted and advanced into the right ventricle. Subsequently, a pressure catheter (Micro-Cath™ pressure catheter; Millar Co., Ltd.) was inserted through the guiding catheter into the right ventricle [12]. From the RV pressure records, we measured RV systolic pressure, RV minimal pressure, RVEDP, and RV pressure increase during atrial contraction (ΔRVPAC) [10, 12]. The time constant of RV pressure decay, tau, was calculated using the Weiss method [13]. At least five continuous RV pressure curves were recorded at natural end expiration, and the mean of at least three measurements was used for the final analysis. An elevated RVEDP was defined as an RVEDP ≥ 8 mmHg [14]. Stroke volume (SV) and cardiac output were measured using the thermodilution method, and pulmonary vascular resistance was calculated as follows: (mean PA pressure – mean PA wedge pressure)/cardiac output. Left ventricular (LV) transmural pressure, which reflects external pericardial restraint, was estimated as mean PA wedge pressure – mean RA pressure based on a previous study [15].

Cardiac MRI

Cardiac MRI was performed using a 1.5-Tesla MRI scanner (Achieva or Achieva dStream, Philips Healthcare, Best, The Netherlands) or a 3.0-Tesla MRI scanner (Achieva Tx, Philips Medical Systems, Best, The Netherlands) with electrocardiogram gating. Image acquisition and analysis were performed using a previously described protocol, with high intra- and interobserver reproducibilities [16]. Briefly, cine MRI, with an axial plane covering the entire heart, was performed using a steady-state free-precession pulse sequence. Cine MRI images were analyzed using commercially available analysis software (Extended MR Work Space or IntelliSpace Portal, Philips Healthcare, Best, The Netherlands). Using cine MRI, the endocardial contours of the RV wall were manually traced from the most apical slice to the uppermost slice and the RV end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated. RV SV and ejection fraction (EF) were calculated as EDV − ESV and SV/EDV × 100, respectively. RV cavity enlargement was defined as RV EDV/BSA ≥ 123 mL/m2 in men, and RV EDV/BSA ≥ 104 mL/m2 in women [17].

Single-beat RV pressure-volume analysis

The details of the data analysis have been described previously [12]. Briefly, using the single-beat method, the end-systolic elastance (Ees) was calculated as follows: (RV isovolumic pressure – [1.65 × mean PA pressure – 7.79])/MRI-derived RV SV [12, 18, 19]. Arterial elastance (Ea) was calculated as the ratio of the (1.65 × mean PA pressure – 7.79) to the MRI-derived RV SV, and Ees/Ea was calculated as the ratio of Ees to Ea. β was calculated as a solution of the following simultaneous equations, as reported by Rain et al. [2]: RV pressure = α (eRV volume × β – 1), where α is a curve-fitting constant and β is a diastolic stiffness constant. The following three points of the RV pressure and volume were used to calculate α and β: RV pressure, RV volume (0, 0); RV minimal pressure, RV ESV; and RVEDP, RV EDV. To avoid measurement errors caused by the positioning of the RV catheter, the RV minimal pressure was normalized at 1 mmHg, and only in this calculation was RVEDP modified by the following formula: (1 + [RVEDP – RV minimal pressure]) [2, 12].

Echocardiography

Transthoracic echocardiography was performed using commercially available ultrasound machines: an Artida/Aplio i900 with a 3.0 MHz/i6SX1 probe (Canon Medical Systems, Otawara, Japan), a Vivid E9 ultrasound system with an M5S probe (GE Healthcare, Little Chalfont, UK), an iE33 ultrasound system with an S4 probe (Philips Medical Systems, Eindhoven, The Netherlands); an ACUSON SC2000 prime with a 4V1c probe (SIEMENS Healthcare, Erlangen, Germany), and a prosound F75 ultrasound system with a UST-52,127 probe (Hitachi Ltd., Tokyo, Japan). Cardiac chamber morphology and function were assessed according to the published guidelines [20,21,22]. LV EF and left atrial volume index were measured using the biplane disk summation method. Basal RV end-diastolic dimension and RA area were measured in an apical four-chamber view. End-diastolic RV wall thickness was measured from the subcostal four-chamber images of the RV free wall [20]. The inferior vena cava dimension was measured from the subcostal longitudinal view [20]. Tricuspid annular plane systolic excursion (TAPSE) was measured by placing an M-mode cursor through the tricuspid annulus of the RV free wall in the apical four-chamber image [20]. In four patients in whom M-mode images of the tricuspid annulus were not available, TAPSE was measured using a two-dimensional method in line with previous reports [23]. The LV eccentricity index, which reflects the degree of direct ventricular interaction due to RV pressure overload, was calculated as the ratio of the major axis to the minor axis of the basal short-axis view at the phase when the ratio was the highest from end systole to early diastole, in line with previous reports [24, 25].

PR flow velocity was recorded using continuous-wave Doppler echocardiography during breath-holding at shallow expiration or at the intermediate expiratory position under quiet respiration (Fig. 1a). To obtain an accurate PR flow velocity, the color flow signal of the PR jet was visualized in two mutually orthogonal planes and recorded from a window with the smallest incident angle and highest velocity [26, 27]. We measured the PR velocities just before RA contraction and at the bottom of the dip during RA contraction to calculate the PA-RV pressure gradients using a simplified Bernoulli Eqs. [10, 28]. We then calculated the descent of the PA-RV pressure gradient during atrial contraction derived from the PR velocity (PRPGDAC) by subtracting the latter from the former (Fig. 1a). M-mode echocardiography was used to measure the tricuspid annular plane movement during atrial contraction (TAPMAC) (Fig. 1b), which reflects the RV volume change associated with RA contraction [10]. Similar to TAPSE measurements [29], in four patients where M-mode images of the tricuspid annulus were not recorded, TAPMAC was measured using a two-dimensional method. Finally, PRPGDAC/TAPMAC was used as the echocardiographic index of RV diastolic stiffness (Fig. 2) [10, 11].

Fig. 1
figure 1

Evaluation of RV diastolic stiffness by echocardiography a The descent of pulmonary regurgitant pressure gradient during atrial contraction (PRPGDAC). b Tricuspid annular plane movement during atrial contraction measured by M-mode echocardiography (TAPMAC). The ratio of the two, PRPGDAC/TAPMAC, was calculated as an RV diastolic stiffness index. RV, right ventricular

Full size image

Statistical analyses

Statistical analyses were performed using the standard statistical software (IBM SPSS version 27 for Windows, IBM Co., Armonk, NY, USA). All numerical data are presented as means ± standard deviations, and categorical variables are expressed as numbers (percentages). Relationships between the two parameters were assessed using linear correlation and regression analyses. Invasive and estimated RV pressure increases during atrial contraction (ΔRVPAC and PRPGDAC, respectively) were compared using the Bland–Altman analysis to derive bias, agreement, and confidence intervals. Multiple linear regression analyses were performed to identify the relationships between the echocardiographic estimation of RV diastolic stiffness and the well-established risk factors for precapillary PH (SV index, RA area, mean RA pressure, and plasma natriuretic peptide [BNP] level) [30]. Logistic regression analysis was performed to assess the relationship between echocardiographic estimation of RV diastolic stiffness and advanced World Health Organization (WHO) functional classes. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic utility of the echocardiographic estimation of RV diastolic stiffness in predicting RVEDP elevation. Two-sided significance levels of 0.05 were used for all analyses. Intraobserver and interobserver variabilities for β were assessed in 10 randomly selected patients from the present study between 2 measurements by 1 observer (H. S.) and between 2 observers (H. S. and Y. N.). Intraobserver and interobserver variabilities for PRPGDAC/TAPMAC were also assessed in 10 randomly selected patients from the present study between 2 measurements by 1 observer (M. M.) and between 2 observers (M. M. and Y. N.).

Results

Patient characteristics

Among the 67 participants who met the inclusion criteria, PR flow velocity waveforms could not be measured because of poor imaging in 17 patients; thus, PRPGDAC/TAPMAC was measured in 50 (75%) patients. There was no difference between patients who could measure PRPGDAC/TAPMAC and those who could not (Online Resource 1). Table 1 summarizes patient characteristics. Of the 50 patients, 43 (86%) had PH (mean PA pressure > 20 mm Hg) [30]. The remaining 7 of the 50 (14%) patients did not meet the PH criteria, as their mean PA pressure and pulmonary vascular resistance were ≤ 20 mmHg and ≤ 3 Wood units, respectively. Most patients (48%) were classified as having group 1 PA hypertension (PAH), followed by 24% with group 4 PH (chronic thromboembolic PH). The RV cavity was enlarged in 15 (30%) patients [17], reduced RVEF (< 45%) was observed in 34 (68%) patients [21] elevated RVEDP and elevated mean RA pressure (≥ 8 mmHg) were observed in 6 (12%) and 4 (8%) patients, respectively [30]. Twenty (40%) patients had an enlarged RA area (> 18 cm2) [30]. More than moderate tricuspid regurgitation was observed in 9 (18%) patients. Approximately half of the patients showed a low 6-min walk distance (≤ 440 m) [30] and substantial PH symptoms (WHO functional classes III/IV).

Table 1 Clinical characteristics of the study patients
Full size table

Relationships between echocardiographic parameters regarding the RV diastolic stiffness and hemodynamic data

The continuous-wave Doppler-derived PRPGDAC was significantly correlated with the high-fidelity micromanometry-derived ΔRVPAC (r = 0.57, p < 0.001) (Fig. 2a), but a fixed bias (difference between the means, 1.35 mmHg; 95% confidence interval, 0.94–1.78 mmHg) was observed, indicating an overestimation of ΔRVPAC by PRPGDAC (Fig. 2b). The echocardiographic estimation of RV diastolic stiffness, PRPGDAC/TAPMAC, was significantly correlated with the gold standard method, β (r = 0.54, p < 0.001) (Fig. 3a). In addition, β was an independent determinant of PRPGDAC/TAPMAC even after adjustment for potential confounders, including WHO functional classes, heart rate, mean PA pressure, and RV wall thickness (β=−0.36, p = 0.008) (Online Resource 2).

Fig. 2
figure 2

Relationships between the descent of pulmonary regurgitant pressure gradient during atrial contraction (PRPGDAC) and catheterization measurements of RV pressure increase during atrial contraction (ΔRVPAC) A Correlation analyses. B Bland–Altman analyses. TAPMAC, tricuspid annular movement during atrial contraction; PRPGDAC, descent of the pulmonary regurgitant pressure gradient during atrial contraction RV, right ventricular

Full size image

PRPGDAC/TAPMAC also correlated well with RVEDP (r = 0.61, p < 0.001) (Fig. 3b). In the receiver operating characteristic analysis to identify patients with abnormal elevation of RVEDP, the area under the curve was 0.90 (95% confidence interval = 0.74–1.00, p = 0.002) for PRPGDAC/TAPMAC, which had 83% sensitivity, 93% specificity, 63% positive predictive value, 97% negative predictive value, and 94% accuracy at the optimal cut-off value of 0.74 mmHg/mm (Fig. 4).

Fig. 3
figure 3

Relationships between echocardiographic estimation of RV diastolic stiffness (PRPGDAC/TAPMAC) to β A and RV end-diastolic pressure (RVEDP) B TAPMAC, tricuspid annular movement during atrial contraction; PRPGDAC, descent of the pulmonary regurgitant pressure gradient during atrial contraction RV, right ventricular

Full size image
Fig. 4
figure 4

Receiver operating characteristic curves for the echocardiographic estimation of RV diastolic stiffness (PRPGDAC/TAPMAC) to distinguish patients with RV end-diastolic pressure ≥ 8 mmHg TAPMAC, tricuspid annular movement during atrial contraction; PRPGDAC, descent of the pulmonary regurgitant pressure gradient during atrial contraction RV, right ventricular

Full size image

Relationship between pressure gradient derived from pulmonary regurgitant velocity/tricuspid annular plane movement during atrial contraction and disease severity of precapillary pulmonary hypertension

Multivariate linear regression analyses were performed to assess the relationships between the four indices used for the risk assessment of precapillary PH (SV index, RA area, mean RA pressure, and plasma BNP level) [30] and PRPGDAC/TAPMAC. Consequently, PRPGDAC/TAPMAC was selected as an independent determinant of the above four risk factors after correcting for the possible confounding effects of age, sex, and body surface area (Table 2). In addition, a multivariate logistic regression analysis showed that the PRPGDAC/TAPMAC was an independent determinant of WHO functional classes III/IV after adjustment of age (adjusted odds ratio = 1.39, 95% confidence interval = 1.03–1.90, p < 0.001).

Table 2 Multivariable linear regression analysis to assess the associations between the PRPGDAC/TAPMAC and disease severity corrected for body surface area, age, and sex
Full size table

Hemodynamic and structural determinants of RV diastolic stiffness

The results of the linear regression analyses used to determine PRPGDAC/TAPMAC are shown in Fig. 5; Table 3. The RV wall thickness, LV eccentricity index, and LV transmural pressure were modestly correlated with PRPGDAC/TAPMAC (Fig. 5). Multivariate analysis revealed that the LV eccentricity index and transmural pressure were independent determinants of PRPGDAC/TAPMAC (Table 3).

Fig. 5
figure 5

Relationships between echocardiographic estimation of RV diastolic stiffness (PRPGDAC/TAPMAC) to hemodynamic and structural variables. (A) Correlation between RV diastolic stiffness and RV wall thickness. (B) Correlation between RV diastolic stiffness and left ventricular eccentricity index. (C) Correlation between RV diastolic stiffness and left ventricular transmural pressure. TAPMAC, tricuspid annular movement during atrial contraction; PRPGDAC, descent of the pulmonary regurgitant pressure gradient during atrial contraction RV, right ventricular

Full size image
Table 3 Hemodynamic and structural determinants of PRPGDAC/TAPMAC
Full size table

Analysis of invasive and noninvasive RV diastolic stiffness reproducibility

In the reproducibility analysis of β, interclass correlation coefficients were high at 0.980 for intraobserver reproducibility and 0.948 for interobserver reproducibility. In the reproducibility analysis of PRPGDAC/TAPMAC, interclass correlation coefficients were high at 0.976 for intraobserver reproducibility and 0.965 for interobserver reproducibility, indicating satisfactory reproducibility of the measurement of invasive and noninvasive RV diastolic stiffness.

Discussion

In this retrospective validation study, we demonstrated that an echocardiographic parameter for RV diastolic stiffness, PRPGDAC/TAPMAC, correlated well with β, a standard measure of RV diastolic stiffness based on RV pressure-volume analysis, in patients with precapillary PH. Additionally, PRPGDAC/TAPMAC was associated with elevated RVEDP, a hemodynamic abnormality associated with increased RV diastolic stiffness. Furthermore, PRPGDAC/TAPMAC was associated with prognostic risk factors and markers of disease severity in precapillary PH. This study is the first to establish the utility of an echocardiographic index of RV diastolic stiffness derived from PR velocity waveform analysis by comparison with RV pressure-volume analysis.

Mechanism of RV diastolic impairment in patients with precapillary PH

The stiffness of the ventricle has two properties: myocardial stiffness and chamber compliance [7]. In the right ventricle of precapillary PH, both abnormalities occur [1, 2]. Kwan et al. [1] conducted an experimental study using a male rat model of PAH and observed RV hemodynamic and morphological remodeling over 10 weeks. They observed an increase in RV thickness and mass by week 5, followed by a subsequent increase in RV diastolic stiffness and RVEDP, which were associated with increased passive myocardial stiffness [1]. In contrast to the RV end-diastolic mechanical abnormalities, RV contractility was maintained throughout week 10 because of RV hypertrophic wall thickening [1]. Diastolic RV stiffening has also been observed in animal models [1] and human studies [2]. Rain et al. reported intrinsic stiffening of the RV cardiomyocyte sarcomeres, resulting in increased RV diastolic stiffness and Ees, as determined by pressure-volume analysis in patients with PAH [2]. Similar to PAH, they also observed diastolic RV stiffening in patients with chronic thromboembolic PH.

In the context of a rapid increase in PA pressure or longstanding PH, RV-arterial coupling deteriorates, leading to subsequent enlargement of the right heart [31]. At this point, a markedly dilated right heart augments the pericardial constraint, causing increased RV chamber operating stiffness and subsequent RVEDP elevation [32]. In the present study, increased RV wall thickness, increased eccentricity index, and decreased transmural pressure were associated with increased RV diastolic stiffness in univariate analysis (Fig. 5). Multivariate analysis demonstrated that eccentricity index and transmural pressure were independent determinants of RV diastolic stiffness (Table 3). These results indicate that increased RV diastolic stiffness is strongly related to the augmentation of pericardial restraint, mainly due to the enlargement of the right heart in clinical patients.

Assessment of RV diastolic stiffness in a clinical setting

The gold standard method for calculating indices of RV diastolic stiffness, β or end-diastolic elastance, requires a simultaneous application of pressure and conductance catheterizations, which enable drawings of multiple RV pressure-volume loops [6]. However, in clinical patients, this technique cannot be performed because it requires intentional stepwise preload alteration, which is invasive and may even be hazardous to patients. A simpler method to assess RV diastolic stiffness is to use the single-beat RV end-diastolic pressure-volume relationship along with the application of a pressure catheter and cardiac MRI [2]. Despite validation of the single-beat method through comparison with the multiple-beat method [2], its practical application remains challenging in daily clinical practice because of the requirements for specialized pressure catheters and mathematical processing software. Therefore, the ratio of the pressure change during atrial contraction to the volume change during atrial contraction has been used to estimate ventricular stiffness in clinical settings [8, 9, 33].

The late-diastolic PR velocity pattern is distinctly modified by the late-diastolic RV pressure increase associated with RA contraction [28]. Based on this phenomenon, we previously reported the usefulness of echocardiographic parameter for RV diastolic stiffness, PRPGDAC/TAPMAC [10, 11]. PRPGDAC/TAPMAC significantly correlated with Otsuji’s partially invasive method [8] and RVEDP [10]. Furthermore, this noninvasive index of RV diastolic stiffness was associated with prognosis in patients with heart failure and demonstrated an incremental prognostic value over RV systolic function [11]. However, in these previous studies, the relationship between PRPGDAC/TAPMAC and the gold standard method for assessing RV diastolic stiffness could not be evaluated because of the unavailability of pressure-volume data. Moreover, previous studies did not include patients with precapillary PH, in whom diastolic RV stiffening has been a prognostic indicator of disease severity [2, 3]. Therefore, the present study is the first to validate the estimation of RV diastolic stiffness based on PR velocity waveform analysis compared with RV end-diastolic pressure-volume data. The reason for the moderate correlation between our noninvasive parameter and RV diastolic stiffness may be as follows: PRPGDAC/TAPMAC was based on estimation of the ratio of RV pressure change to volume change during late diastole, whereas β was assessed by nonlinear fitting of end-diastolic pressure-volume relationships. However, the present study demonstrated that our index would be useful in detecting RV diastolic dysfunction in daily practice.

Clinical implications

Recent studies have suggested that RV diastolic stiffness is important in the prognosis of precapillary PH. Rain et al. reported that increased RV diastolic stiffness was associated with disease severity, including SV, RA pressure, plasma BNP level, and 6-min walking distance, after controlling for pulmonary vascular resistance [2]. Following this study, Trip et al. showed that RV diastolic stiffness was more useful than RV contractility and RA pressure in predicting precapillary PH prognosis [4]. In a recent study, Nakaya et al. reported that increased RV diastolic stiffness was associated with cardiovascular events in patients with precapillary PH after adjusting for age [5]. The present study demonstrated that echocardiographically estimated RV diastolic stiffness was an independent determinant of prognostic risk factors for precapillary PH (Table 2). Therefore, the noninvasive parameter of RV diastolic stiffness, PRPGDAC/TAPMAC, might play an important role in risk stratification and as a prognostic marker for patients with precapillary PH in daily clinical practice. Further studies are needed to clarify whether the increase in RV diastolic stiffness is effectively dissociated from that in systolic stiffness and to elucidate the biology of diastolic dysfunction and its independent prognostic value in precapillary PH.

Limitations

This study has some limitations. First, cardiac catheterization, cardiac MRI, and echocardiography were not simultaneously performed: the median time difference between cardiac catheterization and MRI was 1 day (range, 1–5 days), between cardiac catheterization and echocardiography was 4 days (range, 1–5 days), and between MRI and echocardiography was 0 day (range, 0–3 days). Although we excluded patients with unstable hemodynamics and/or loading conditions between cardiac catheterization, MRI, and echocardiography, the possibility of hemodynamic changes could not be completely excluded. The Bland-Altman analysis in Fig. 2 showed that the accuracy of echocardiographic estimates of ΔRVPAC accuracy was not very robust, but this needs to be verified in a prospective simultaneous invasive echocardiographic study. Second, the relatively low feasibility (75% of the studied participants) indicated that our method requires some skill for the echocardiographer. Third, our method cannot be applied to patients lacking synchronized atrial activity due to arrhythmias, such as atrial fibrillation, atrial flutter, and complete atrioventricular block. In addition, the PRPGDAC may not correctly reflect the late-diastolic RV pressure increase in patients with severe PR because it impedes the estimation of the RV diastolic pressure curve from the PR velocity due to the huge, steep decline in the diastolic PA pressure. However, the present study did not include the patients with precapillary PH showing significant PR. Therefore, the impact of PR severity on the accuracy of our index remains unclear. Finally, future studies are expected to elucidate the additional prognostic value of PRPGDAC/TAPMAC over conventional echocardiographic parameters and its utility as a marker for assessing treatment efficacy.

Conclusion

In patients with precapillary PH, PRPGDAC/TAPMAC based on PR velocity waveform analysis can be useful for the noninvasive assessment of RV diastolic stiffness and discriminating RVEDP elevation associated with RV diastolic impairment. Furthermore, PRPGDAC/TAPMAC is associated with prognostic risk factors in precapillary PH.