Hemodynamics assessment using 4D flow CMR before and after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: A retrospective observational study

Hemodynamics assessment using 4D flow CMR before and after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: A retrospective observational study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Hemodynamics assessment using 4D flow CMR before and after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: A retrospective observational study Kazuto Ohno, Kenichiro Suwa, Keitaro Akita, Ryota Sato, Terumori Satoh, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6184673/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Aug, 2025 Read the published version in BMC Cardiovascular Disorders → Version 1 posted 12 You are reading this latest preprint version Abstract Background The effect of balloon pulmonary angioplasty (BPA) for hemodynamics in chronic thromboembolic pulmonary hypertension (CTEPH), assessed using time-resolved three-dimensional cine phase-contrast cardiac magnetic resonance (4D flow CMR), remains unclear. Therefore, the present study aimed to investigate the hemodynamic features of the pulmonary artery (PA) before and after BPA and the diagnostic performance of 4D flow CMR-derived hemodynamics before BPA to predict the achievement of mean PA pressure (mPAP) < 30 mmHg after BPA. Methods Twenty-one patients with CTEPH who underwent 4D flow CMR before and after BPA were retrospectively enrolled. Regarding 4D flow CMR, the analysis included peak flow volume and velocity at the main PA and peak systolic wall shear stress (WSS). Results Peak flow velocity at the main PA (262.8 ± 52.3 mm/s vs. 298.5 ± 68.3 mm/s, p = 0.015) and peak WSS (0.61 ± 0.14 Pa vs. 0.76 ± 0.20 Pa, p = 0.002) both increased after BPA compared to their values before BPA. Receiver operating characteristic analysis was performed to predict mPAP ≥ 30 mmHg after BPA based on peak flow velocity before BPA. The analysis revealed an area under the curve of 0.926 ( p < 0.001) for peak flow velocity before BPA (sensitivity, 0.765; specificity 0.750; cut-off, < 251 mm/s) and 1.00 ( p < 0.001) for peak WSS before BPA (sensitivity, 1.00; specificity, 1.00; cut-off, < 0.48 Pa). Conclusions Based on the study results, 4D flow CMR imaging showed improvement in hemodynamics after BPA. Furthermore, peak flow velocity and peak WSS were useful metrics for predicting the achievement of catheter-based BPA goal of mPAP < 30 mmHg with a better prognosis. chronic thromboembolic pulmonary hypertension 4D flow CMR wall shear stress Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by pulmonary hypertension, with an organized thrombus due to an incompletely resolved acute pulmonary embolism c. Persistent thromboembolism in the pulmonary artery (PA) elevates pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP), eventually resulting in right heart failure or death, if left untreated [ 2 ]. Patients with CTEPH with mPAP ≥ 30 mmHg have poor prognoses [ 3 ]. Invasive treatments are typically considered for symptomatic drug-refractory CTEPH [ 2 ]. For patients with peripheral vasculopathy of segmental or subsegmental vessels unsuitable for pulmonary artery endarterectomy (PEA) [ 3 ], balloon pulmonary angioplasty (BPA) is indicated [ 4 ]. BPA reduces PVR and mPAP, resulting in symptom relief [ 2 , 5 ]. Therefore, mPAP < 30 mmHg is considered one of the goals following BPA. Time-resolved three-dimensional cine phase-contrast cardiac magnetic resonance (4D flow CMR) visualizes and quantifies the blood flow in large vessels and heart [ 6 ]. Few studies have investigated the hemodynamics in patients with CTEPH; however, the efficacy of BPA assessed using 4D flow CMR remains unclear. Therefore, the present study aimed (1) to investigate the hemodynamic features of PA before and after BPA and (2) evaluate the diagnostic performance of 4D flow CMR-derived hemodynamics before BPA to predict the achievement of mPAP < 30 mmHg after BPA in patients with CTEPH. Methods Patients As presented in Fig. 1 , this retrospective observational study initially recruited 25 consecutive patients with CTEPH scheduled for BPA at Hamamatsu University Hospital between December 2017 and December 2022. All patients underwent an initial right heart catheterization (RHC) and CMR, including 4D flow CMR, before BPA. After the exclusion of four patients without follow-up CMR, the remaining 21 patients who underwent follow-up RHC and 4D flow CMR were selected for the analysis. The diagnosis of CTEPH was based on the latest guidelines of the European Society of Cardiology [ 7 , 8 ] and Japanese Circulation Society [ 9 ] as appropriately. The time courses of the examinations were as follows: initial RHC and CMR within 1 month before the first BPA session, following serial BPA sessions, and follow-up RHC and CMR 3 months after the final BPA session. The decision to terminate any further additional BPA sessions was based on a comprehensive assessment, considering symptom improvement, the absence of treatable vessels, and mPAP levels after BPA. This study complied with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Hamamatsu University School of Medicine (approval ID 17–293). Written informed consent was obtained from all patients. Serological tests, transthoracic echocardiography, and RHC All patients underwent serological tests and transthoracic echocardiography (TTE) within 1 month before the first BPA session and 3 months after the final BPA session. Serological test included N-terminal pro-brain natriuretic peptide (NT-proBNP). Using TTE, we assessed the degree of tricuspid regurgitation (TR) and maximum TR pressure gradient (TRPG). RHC parameters included mean pulmonary artery wedge pressure (PAWP), mPAP, PVR, cardiac output, and cardiac index measured using the Fick principle. CMR CMR examinations were performed using a 3T scanner (Discovery MR750, GE Healthcare, Waukesha, WI, USA), with a maximum gradient strength of 50 mT/m and a maximum slew rate of 200 mT/m/ms; the scanner was used in combination with a commercially available 12-channel phased array body coil. Typically, two-dimensional (2D) cine images were obtained by fast imaging employing steady-state acquisition (FIESTA) and late gadolinium enhancement (LGE) images acquired using inversion recovery-prepared fast gradient echo (IR-FGRE) sequences in short-axis and vertical and horizontal long-axis orientations, with a slice thickness/gap of 10 mm/0 mm (6–9 slices). Contrast-enhanced three-dimensional (3D) fast spoiled gradient echo (FSPGR) magnetic resonance angiography (MRA) was performed for geometric information of 4D flow CMR and area quantification of the PA. The following parameters were set: repetition time 2.7 ms; echo time 1.0 ms; flip angle 12 degrees, number of excitations, 1; field of view, 32 cm; matrix size reconstructed with the aid of zero fill interpolation, 224 × 224; receiver bandwidth, 83.3 kHz; and imaging time, 33 s for 4 phases. A bolus injection of 0.1 mmol/kg gadobutrol (Gadovist, Bayer AG, Berlin, Germany) was administered at an injection rate of 2.0 mL/s, followed by the administration of 20 mL of saline. 4D flow CMR provides time-resolved 3D voxel data, each with 3D flow velocity components. Imaging parameters used for coronal 3D Fourier transform FSPGR-based 4D flow CMR were as follows: repetition time 4.5–5.0 ms; echo time 2.0 ms; flip angle 15 degrees; number of excitations 1; field of view, 32 cm; matrix, 224 × 224; 2-mm thickness; 60 partitions; 20 phases per cardiac cycle; velocity encoding, 200 cm/s; and receiver bandwidth, 83.3 kHz. The temporal resolution was 58.8 ± 10.8 msec. Respiratory-compensated retrospective cardiac gating was performed. The resulting imaging time was approximately 10 min, with a reduction factor of two for auto-calibrating the reconstruction for Cartesian sampling. Raw data of the 4D flow CMR were transferred to a personal computer (Intel Xeon E3-1270 [3.4 GHz/Quad-core] DDR3, 16 GB ECC, Linux) and reconstructed. Conventional CMR parameters Right ventricular (RV) end-diastolic volume index (RVEdVI), RV end-systolic volume index (RVEsVI), and RV stroke volume index (RVSVI), all indexed with body surface area using the Du Bois formula, and RV ejection fraction (RVEF) and main PA diameter just above the pulmonary valve at the end-diastolic phase were measured using Cardiac VX software (GE Healthcare). RV stroke volume divided by RV end-systolic volume (RVSV/RVEsV), as a right ventricular-pulmonary arterial (RV-PA) coupling parameter [ 10 ], was calculated. Post-processing for 4D flow CMR 4D flow CMR and MRA datasets were formatted using Digital Imaging and Communications in Medicine and analyzed on a personal computer. Segmentation, visualization of flow patterns, and calculations of flow velocity and volume and wall shear stress (WSS) were performed using commercially available software (Flova; R’-Tech Co., Hamamatsu, Japan). In particular, the regions of interest, including the main, right, and left PAs, were determined for the 4D flow CMR and MRA datasets. Segmentation was performed for vascular wall structures from 3D MRA datasets at the peak of the R wave, with magnitude images of 4D flow CMR, using the region growing method. The shapes were created using the marching cubes method. The 3D flow information was interpolated with a spatial resolution of 2 × 2 × 2 mm 3 using the 3D datasets. Three emitter planes traversing the bases of the main, right, and left PAs were manually set, and 3D streamline images were subsequently generated using the Runge–Kutta method. PA flow was evaluated based on the 3D streamline in each timeframe. In addition, PA flow patterns were evaluated in the main, right, and left PAs for the presence of vortical or helical flow in the entire cardiac cycle, the duration of vortical or helical flow, and the presence of vortical or helical flow in systole, respectively. Vortical flow was defined as a rotational streamline with an axis orthogonal to the centerline of the vessel. Helical flow was defined as regional fluid circulation along the longitudinal axis of the vessel centerline, thereby revealing a corkscrew-like motion [ 11 , 12 ]. The flow volume curve at the base of the main PA was obtained using Flova. Blood flow parameters included peak flow volume and velocity at the base of the main PA, peak systolic WSS, and mean oscillatory shear index (OSI). Both WSS and OSI distribution maps of the PAs were color-coded and visualized as 3D images. Temporal changes in the entire surface area-averaged WSS at the PA wall during one cardiac cycle were described, and peak systolic WSS and mean OSI were estimated. The Reynolds number (Re), fluid characteristics to predict the flow pattern of laminar flow or turbulence, was calculated at the main PA in each patient using the following equation: Re = ρVL/µ, where ρ: density = 1.05 g/cm 3 , µ: viscosity = 4.0 × 10 − 3 Pa × s, V = area-averaged peak velocity, and L = vessel diameter at the base of main PA. Statistical analysis Continuous data were expressed as means ± standard deviation (SD) or as medians with interquartile range (IQR), as appropriate. Categorical data were presented as numbers and percentages. Continuous variables were compared using the two-sided t-test, Wilcoxon signed-rank test, or Mann–Whitney U test. Categorical variables were compared using the McNemar’s test. PA flow patterns were evaluated by one observer (KO) and another independent observer (KS) to assess interobserver variability, and Cohen's Kappa (κ) coefficient was calculated for qualitative evaluation and the intraclass coefficient for quantitative evaluation. Correlations were assessed using the Pearson’s correlation coefficient (r) and linear regression analysis. Statistical significance was set at p < 0.05. All statistical analyses were performed using the SPSS 30.0 statistical software package (SPSS Inc., Armonk, NY, USA). Results Patient characteristics The baseline characteristics of the study participants are shown in Table 1 . The mean age of the participants was 60.7 ± 14.8 years, and 90.5% of all patients were women. Ten patients (47.6%) had moderate or greater TR. All patients were administered riociguat and oral anticoagulants (OACs), and one patient additionally received selexipag. Serum NT-proBNP level was 137.0 (86.0‒975.5) pg/mL before BPA and significantly decreased after BPA [59.0 (34.5‒151.0) pg/mL, p < 0.001]. The median (IQR) number of BPA sessions was 5.00 (4.00‒7.00). The distribution of patients according to the World Health Organization functional classification (WHO-FC) was as follows: 0 (0.0%) in class Ⅰ, 10 (47.5%) in class Ⅱ, 10 (47.5%) in class Ⅲ, and 1 (4.8%) in class Ⅳ, while it improved significantly ( p < 0.001) to 14 (66.7%) in class Ⅰ, 5 (23.8%) in class Ⅱ, 2 (9.5%) in class Ⅲ, and 0 (0.0%) in class Ⅳ, respectively. Table 1 Baseline characteristics Number of patients n = 21 Age, years 60.7 ± 14.8 Female, n (%) 19 (90.5) Height, cm 156.0 ± 5.6 Weight, kg 55.1 (45.6 ‒ 66.3) Body Surface Area, m 2 1.56 ± 0.17 Acute pulmonary thromboembolism, n (%) 12 (57.1) Pulmonary endarterectomy, n (%) 0 (0.0) Medication Soluble guanylate cyclase stimulator, n (%) 21 (100.0) Selective prostacyclin receptor agonist, n (%) 1 (4.8) DOACs, n (%) 14 (66.7) Warfarin, n (%) 7 (33.3) HOT, n (%) 16 (76.2) WHO-FC I 0 (0.0) II 10 (47.6) III 10 (47.6) IV 1 (4.8) Laboratory data Serum uric acid, mg/dL 5.7 ± 1.8 Serum creatinine, mg/dL 0.70 (0.63 ‒ 0.81) eGFR, mL/min/1.73 m 2 66.4 ± 16.8 Serum NT-proBNP, pg/mL 137 (86 ‒ 976) D-dimer > 1.0 µg/mL, n (%) 4 (19.0) Number of BPA sessions per person 5.0 (4.0 ‒ 7.0) Data are expressed as mean ± standard deviation, median (interquartile range), or number (%). CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DOACs, direct oral anticoagulants; eGFR, estimated glomerular filtration rate; HOT, home oxygen therapy; TR, tricuspid regurgitation; NT-proBNP, N-terminal prohormone of B-type natriuretic peptide; WHO-FC, World Health Organization functional classification TTE, RHC, and conventional CMR TRPG, as measured by TTE, significantly reduced 3 months after BPA compared to before BPA (59.9 ± 25.7 mmHg vs. 26.5 ± 13.3 mmHg, p < 0.001). mPAP (36.0 [32.0‒47.5] mmHg vs. 24.0 [21.0‒28.0] mmHg, p < 0.001) and PVR (6.1 [4.5‒11.9] Wood units vs. 3.4 [2.5‒4.4] Wood units, p 30 mmHg 3 months after the final BPA. RVEdVI (95.2 ± 17.8 mL/m 2 vs. 71.3 ± 17.9 mL/m 2 , p < 0.001), and RVEsVI (54.3 ± 17.6 mL/m 2 vs. 31.8 ± 12.0 mL/m 2 , p < 0.001) significantly reduced 3 months after BPA compared to before BPA. Furthermore, RVEF significantly increased 3 months after BPA compared to before BPA (44.1 ± 10.8 mmHg vs. 56.2 ± 8.5 mmHg, p < 0.001). RVSV/RVEsV significantly increased 3 months after BPA compared to before BPA (0.68 [0.56 ‒ 1.23] vs. 1.29 [1.07 ‒ 1.69], p < 0.001). Main PA diameter significantly reduced 3 months after BPA compared to before BPA (33.0 ± 4.0 mm vs. 30.6 ± 4.1 mm, p < 0.001). LGE was observed at the RV insertion point in 21 (100%) patients before BPA and did not change 3 months after BPA. Table 2 RHC and CMR before and 3 months after the BPA Before BPA 3 months after BPA P TTE TRPG, mmHg 59.9 ± 25.7 26.5 ± 13.3 < 0.001 RHC Mean PAP, mmHg 36.0 (32.0 ‒ 47.5) 24.0 (21.0 ‒ 28.0) < 0.001 Mean PAWP, mmHg 11.0 (7.5 ‒ 15.0) 11.0 (6.0 ‒ 13.0) 0.243 PVR, Wood Unit 6.1 (4.5 ‒ 11.9) 3.4 (2.5 ‒ 4.4) < 0.001 Cardiac output, L/min 3.9 ± 1.3 4.2 ± 1.1 0.230 Cardiac index, L/min/m 2 2.5 ± 0.7 2.7 ± 0.6 0.227 CMR Heart rate, beat/min 68.9 ± 10.9 68.1 ± 10.8 0.748 RVEdVI, mL/m 2 95.2 ± 17.8 71.3 ± 17.9 < 0.001 RVEsVI, mL/m 2 54.3 ± 17.6 31.8 ± 12.0 < 0.001 RVSVI, mL/m 2 40.9 ± 9.1 39.5 ± 9.4 0.509 RVEF, % 44.1 ± 10.8 56.2 ± 8.5 < 0.001 RVSV/RVEsV 0.68 (0.56 ‒ 1.23) 1.29 (1.07 ‒ 1.69) < 0.001 Main PA diameter, mm 33.0 ± 4.0 30.6 ± 4.1 < 0.001 4D flow CMR Peak flow volume, 10 3 mm 3 /s 200.6 ± 43.3 203.6 ± 54.2 0.757 Peak flow velocity, mm/s 262.8 ± 52.3 298.5 ± 68.3 0.015 Peak WSS, Pa 0.61 ± 0.14 0.76 ± 0.20 0.002 Mean OSI 0.11 (0.10 ‒ 0.13) 0.12 (0.09 ‒ 0.13) 0.794 Reynolds number 2244 ± 381 2359 ± 487 0.266 Data are expressed as means ± standard deviation, medians (interquartile range), or numbers (%). BPA, balloon pulmonary angioplasty; CMR, cardiac magnetic resonance imaging; OSI, oscillatory shear index; PA, pulmonary artery; PAP, pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; RHC, right heart catheterization; RVEdVI, right ventricular end-diastolic volume index; RVEF, right ventricular ejection fraction; RVEsVI, right ventricular end-systolic volume index; RVSVI, right ventricular stroke volume index; RVSV/RVEsV, right ventricular stroke volume divided by right ventricular end-systolic volume; TRPG, tricuspid regurgitation pressure gradient; TTE, transthoracic echocardiography; WSS, wall shear stress; 4D flow: three-dimensional cine phase-contrast Visualization of PA streamline, WSS, and OSI using 4D flow CMR Representative streamline images of PA flow at the peak systolic phase before (Fig. 2 a) and after (Fig. 2 b) BPA revealed that the vortical flow pattern in the main PA did not change significantly, whereas flow velocity at the main PA increased after BPA. Three-dimensional WSS at peak systole revealed a relatively elevated WSS distribution in the anterior wall of the main PA before BPA (Fig. 2 c) and elevated WSS after BPA (Fig. 2 d). In addition, 3D OSI revealed relatively low values and similar distributions before (Fig. 2 e) and after (Fig. 2 f) BPA. 4D flow CMR-derived hemodynamics As presented in Table 2 , peak flow velocity (262.8 ± 52.3 mm/s vs. 298.5 ± 68.3 mm/s, p = 0.015) and peak WSS (0.61 ± 0.14 Pa vs. 0.76 ± 0.20 Pa, p = 0.002) significantly increased after BPA compared to before BPA, whereas the mean OSI remained unchanged. There was no significant change in the Reynolds number before and after BPA. As summarized in Table 3 , streamline images before BPA developed a vortical or helical flow in the main PA (n = 21, 100%), right PA (n = 16, 76.2%), and left PA (n = 14, 66.7%). The prevalence of vortical or helical flow during an entire cardiac cycle and only in systole and the duration of vortical or helical flow did not change after BPA. Interobserver variabilities in the presence of vortical or helical flow (kappa = 0.96) and the duration of the vortex or helix (intraclass correlation coefficient = 0.99) were excellent. Table 3 Visual evaluation of vortical flow and helical flow in the main, right, and left PA Before BPA 3 months after BPA P Presence of vortical or helical flow in an entire cardiac cycle, n (%) Vortical or helical flow 21 (100) 21 (100) - MPA Vortical flow 21 (100) 20 (95.2) - Helical flow 11 (52.3) 12 (57.1) 1.000 Vortical or helical flow 16 (76.2) 14 (66.7) 0.453 RPA Vortical flow 12 (57.1) 9 (42.9) 0.508 Helical flow 11 (52.3) 13 (61.9) 0.727 Vortical or helical flow 14 (66.7) 11 (52.3) 0.508 LPA Vortical flow 9 (42.9) 9 (42.9) 1.000 Helical flow 11 (52.3) 9 (42.9) 0.687 Vortical or helical flow duration, phase number MPA 13.0 ± 5.2 11.7 ± 5.5 0.165 RPA 7.4 ± 6.4 7.3 ± 6.6 0.928 LPA 6.3 ± 5.6 5.4 ± 5.6 0.550 Presence of vortical or helical flow in systole, n (%) MPA 21 (100) 21 (100) - RPA 15 (71.4) 13 (61.9) 0.687 LPA 7 (33.3) 6 (28.6) 1.000 Data are expressed as means ± standard deviation or numbers (%). BPA, balloon pulmonary angioplasty; LPA, left pulmonary artery; MPA, main pulmonary artery; PA, pulmonary artery; RPA, right pulmonary artery 4D flow CMR-derived hemodynamics parameters based on the reference mPAP value of 30 mmHg The intergroup comparisons based on mPAP value of 30 mmHg after BPA are summarized in Table 4 . Peak flow velocity before BPA (278.4 ± 40.0 mm/s vs. 196.7 ± 50.0 mm/s, p = 0.039), peak flow velocity after BPA (321.5 ± 49.8 mm/s vs. 200.65 ± 46.4, p = 0.006), peak WSS before BPA (0.65 ± 0.12 Pa vs. 0.43 ± 0.04 Pa, p < 0.001), and peak WSS after BPA (0.80 ± 0.19 Pa vs. 0.57 ± 0.15 Pa, p = 0.041) were significantly higher in patients with mPAP < 30 mmHg than in patients with mPAP ≥ 30 mmHg. Patients with mPAP ≥ 30 mmHg were older (57.2 ± 13.3 years vs. 75.5 ± 12.5 years, p = 0.050). Table 4 4D flow CMR-derived hemodynamic parameters with respect to the reference mPAP value of 30 mmHg mPAP after BPA < 30 mmHg (n = 17) mPAP after BPA ≥ 30 mmHg (n = 4) P Peak flow volume before BPA, 10 3 mm 3 /s 202.6 ± 36.0 192.1 ± 74.0 0.800 Peak flow volume after BPA, 10 3 mm 3 /s 212.4 ± 55.1 166.6 ± 33.6 0.068 Peak flow velocity before BPA, mm/s 278.4 ± 40.0 196.7 ± 50.0 0.039 Peak flow velocity after BPA, mm/s 321.5 ± 49.8 200.6 ± 46.4 0.006 Peak WSS before BPA, Pa 0.65 ± 0.12 0.43 ± 0.04 < 0.001 Peak WSS after BPA, Pa 0.80 ± 0.19 0.57 ± 0.15 0.041 Mean OSI before BPA 0.11 (0.10‒0.13) 0.12 (0.10‒0.13) 1.000 Mean OSI after BPA 0.12 (0.09‒0.13) 0.11 (0.09‒0.13) 1.000 Main PA diameter before BPA, mm 32.0 ± 3.0 37.0 ± 5.9 0.193 Main PA diameter after BPA, mm 29.6 ± 2.9 35.2 ± 5.8 0.147 Reynolds number before BPA 2326 ± 296 1893 ± 546 0.212 Reynolds number after BPA 2490 ± 440 1803 ± 186 < 0.001 Data are expressed as means ± standard deviation or medians (interquartile range). BPA, balloon pulmonary angioplasty; CMR, cardiac magnetic resonance imaging; mPAP, mean pulmonary arterial pressure; OSI, Oscillatory shear index; PA, pulmonary artery; WSS, wall shear stress Furthermore, intragroup comparisons before and after BPA based on mPAP of 30 mmHg after BPA are shown in Fig. 3 . In patients with mPAP < 30 mmHg, peak flow velocity (278.4 ± 40.0 mmHg vs. 321.5 ± 49.8 mmHg, p = 0.012) and peak WSS (0.65 ± 0.12 Pa vs. 0.80 ± 0.19 Pa, p = 0.008) were significantly increased after BPA. Main PA diameter was significantly reduced after BPA in patients with mPAP < 30 mmHg (32.0 ± 3.0 mm vs. 29.6 ± 2.9 mm, p < 0.001) and patients with mPAP ≥ 30 mmHg (37.0 ± 5.9 mm vs. 35.2 ± 5.8 mm, p = 0.017). Correlation between 4D flow CMR parameters before BPA and mPAP after BPA Peak velocity before BPA and mPAP after BPA (Fig. 4 a, R = -0.695, p < 0.001) and peak WSS before BPA and mPAP after BPA (Fig. 4 b, R = -0.633, p = 0.002) had significant negative correlations. Diagnostic performance of peak flow velocity and peak WSS before BPA in predicting mPAP ≥ 30 mmHg after BPA Receiver operating characteristic analysis to predict mPAP ≥ 30 mmHg after BPA using peak flow velocity and peak WSS before BPA revealed an area under the curve of 0.926 ( p < 0.001) for peak flow velocity before BPA (Fig. 4 C) and 1.00 (p < 0.001) for peak WSS before BPA (Fig. 4 D). The sensitivity and specificity were 0.765 and 0.750, respectively, for peak flow velocity before BPA, with a cutoff value of < 251 mm/s. The sensitivity and specificity were 1.000 and 1.000, respectively, for peak WSS before BPA, with a cutoff value of < 0.48 Pa. Discussion In the present study, we demonstrated serial changes in PA hemodynamics using 4D flow CMR imaging in patients with CTEPH before and after BPA. Briefly, RVEdVI and RVEsVI decreased, RVEF increased, peak flow velocity at the main PA increased, and peak WSS increased after BPA compared to before BPA. When comparing patients with a post-BPA mPAP exceeding the reference value of 30 mmHg to those with mPAP ≤ 30 mmHg, significant differences were observed in peak flow velocity and peak WSS both before and after BPA. In addition, we demonstrated the utility of peak flow velocity and peak WSS before BPA in predicting the achievement of mPAP < 30 mmHg after BPA. In this study cohort, we demonstrated the effect of BPA on RV-PA hemodynamics and cardiac function, namely, BPA reduced PVR and mPAP; however it did not increase cardiac output. In addition, we demonstrated changes in PA hemodynamics using 4D flow CMR, which showed an increase in peak flow velocity but not in peak flow volume. This finding is consistent with the cardiac output measured using RHC and stroke volume in cine CMR. Another insight from this study is that achievement of mPAP < 30 mmHg after BPA may be predicted by peak flow velocity before BPA using 4D flow CMR, even though pressure cannot be measured using 4D flow CMR. Previous studies [ 2 , 13 , 14 ] have reported that BPA in patients with CTEPH improved WHO-FC, reduced BNP, reduced mPAP and PVR measured using RHC, reduced RVEdV and RVEsV, and increased RVEF measured using conventional CMR. Our results are consistent with those of the aforementioned studies. In addition, we observed an increase in RVSV/RVEsV and a decrease in the main PA diameter, which were associated with morphological reverse remodeling of the right ventricle and PA. RVSV/RVEsV has prognostic value in patients with pulmonary hypertension. Thus, an increase in RVSV/RVEsV may suggest improved outcomes in patients undergoing BPA. A characteristic endpoint of 4D flow CMR is the visualization of a 3D flow in a time course of a cardiac cycle. Non-laminar flow patterns, including vortical and helical flows in the PA, have been reported in patients with pulmonary hypertension, whereas flow patterns seem to be more prone to laminar flow in healthy participants [ 15 – 17 ]. The effect of BPA on flow patterns remains unclear. A significantly diminished vortical flow has been reported in a patient after BPA [ 18 ] and another patient after PEA [ 19 ]. However, in the present study, the prevalences of vortical and helical flows and their duration did not decrease after BPA, even though mPAP decreased and WHO-FC symptoms were relieved. In this regard, considering the mPAP cut-off value of 16.0 mmHg for the appearance of vortical flow [ 20 ], the mPAP after BPA in this study (24.0 [21.0–28.0] mmHg) was relatively high. WSS is proportional to velocity and inversely proportional to vessel diameter under laminar flow conditions [ 21 , 22 ]. Although PA blood flow in patients with CTEPH was generally non-laminar, the relationship between velocity, vessel diameter, and WSS remained consistent with the laminar flow model mentioned above, where higher velocity and smaller vessel diameter both led to increased WSS. However, the WSS on the PA surface was heterogeneous, with an uneven PA surface and diameter, complex bifurcation anatomy, and complex hemodynamics with non-laminar flow. Therefore, actual measurement of WSS using 4D flow CMR is vital for accurate assessments. Physiological WSS in healthy individuals has a favorable effect on endothelial function [ 21 ]. In contrast, WSS in patients with pulmonary hypertension is lower than that in healthy individuals [ 15 , 23 – 26 ]. Therefore, abnormally decreased WSS is associated with the overexpression of inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, leading to thickening and fibrotic change in the PA endothelium and suppression of nitric oxide production, which causes vasoconstriction, and finally results in PA remodeling [ 27 – 29 ]. Schäfer et al. reported that the WSS of the PA correlated with stiffness and elasticity in the PA [ 30 ]. Thus, before BPA, the PA may be exposed to worse conditions with subsequent PA remodeling, whereas the increased WSS after BPA, as shown in this study, may prevent further PA remodeling in patients with CTEPH. In such cases, invasive RHC is performed 3 months after BPA to assess whether mPAP had decreased sufficiently. In the present study, we predicted the achievement of the BPA goal using peak flow velocity and peak WSS derived from non-invasive 4D flow CMR. Therefore, 4D flow CMR may help to understand the clinical course and decide the treatment strategy of CTEPH including additional vasodilator or further BPA sessions. This study had several limitations. First, this was a single-center study with a small sample size. However, we believe that the patient characteristics in this study represent the characteristics of patients with CTEPH who undergo BPA because patients with CTEPH in our institution were consecutively recruited. Second, this study did not include healthy participants; instead, we focused on the differences in variables before and after BPA. Third, all the patients were administered pulmonary vasodilators, which may have affected their PA hemodynamics. However, the medication dose was maintained throughout the study. Finally, we could not determine the benefits of hemodynamic changes after BPA owing to the study design. Conclusion In the present study, 4D flow CMR showed an improvement in the hemodynamics of patients with CTEPH before and after BPA. Finally, peak flow velocity and peak WSS were useful metrics for predicting the achievement of the BPA goal with a better prognosis. Therefore, non-invasive 4D flow CMR potentially predict invasive RHC. A large-scale follow-up study is warranted to determine the benefits of BPA and hemodynamic assessment using 4D flow CMR for further PA remodeling. Abbreviations BPA balloon pulmonary angioplasty CMR cardiac magnetic resonance CTEPH chronic thromboembolic pulmonary hypertension FIESTA 2D-fast imaging employing steady-state acquisition FSPGR fast spoiled gradient echo IR-FGRE inversion recovery prepared fast gradient echo IQR interquartile range LGE late gadolinium enhancement mPAP mean pulmonary arterial pressure MR magnetic resonance NT-proBNP N-terminal pro-brain natriuretic peptide OSI oscillatory shear index PAP pulmonary arterial pressure PCR pulmonary vascular resistance PA pulmonary artery PAWP pulmonary artery wedge pressure PEA pulmonary artery endarterectomy PVR pulmonary vascular resistance RHC right heart catheterization RVEF right ventricular ejection fraction RVEdVI right ventricular end-diastolic volume index RVEsVI right ventricular end-systolic volume index RV‒PA right ventricular-pulmonary arterial RVSVI right ventricular stroke volume index SD standard deviation TR tricuspid regurgitation TRPG tricuspid regurgitation pressure gradient TTE transthoracic echocardiography WHO-FC The World Health Organization functional classification WSS wall shear stress 4D flow three-dimensional cine phase-contrast Declarations Ethics approval and consent to participate This study only included human participants. This study was approved by the Institutional Review Board (approval number 17–293). All patients provided written informed consent prior to participation. Consent for publication All the patients provided written informed consent for publication. Availability of data and materials Datasets supporting the conclusions of this study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by HUSM Grant-in-Aid. Authors’ Contributions KO was involved in the methodology, investigation, writing of the original draft, and the acquisition of funding. KS was involved in investigation, data validation, and manuscript editing. KA, RS and TS were involved in investigation and manuscript editing. YM was involved in conceptualization, supervision, and manuscript editing. All authors read and approved the final manuscript Acknowledgements Not applicable. 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Right ventricular reverse remodelling after balloon pulmonary angioplasty. Eur Respir J. 2014;43:1394–402. Markl M, Kilner PJ, Ebbers T. Comprehensive 4D velocity mapping of the heart and great vessels by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2011;13:7. Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015;46:903–75. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618–731. Fukuda K, Date H, Doi S, Fukumoto Y, Fukushima N, Hatano M, et al. Guidelines for the Treatment of Pulmonary Hypertension (JCS 2017/JPCPHS 2017). Circ J. 2019;83:842–945. Tello K, Dalmer A, Axmann J, Vanderpool R, Ghofrani HA, Naeije R, et al. Reserve of right ventricular-arterial coupling in the setting of chronic overload. Circ Heart Fail. 2019;12:e005512. von Knobelsdorff-Brenkenhoff F, Trauzeddel RF, Barker AJ, Gruettner H, Markl M, Schulz-Menger J. Blood flow characteristics in the ascending aorta after aortic valve replacement–a pilot study using 4D-flow MRI. Int J Cardiol. 2014;170:426–33. Komoriyama H, Kamiya K, Nagai T, Oyama-Manabe N, Tsuneta S, Kobayashi Y, et al. Blood flow dynamics with four-dimensional flow cardiovascular magnetic resonance in patients with aortic stenosis before and after transcatheter aortic valve replacement. J Cardiovasc Magn Reson. 2021;23:81. Schoenfeld C, Hinrichs JB, Olsson KM, Kuettner M-A, Renne J, Kaireit T, et al. Cardio-pulmonary MRI for detection of treatment response after a single BPA treatment session in CTEPH patients. Eur Radiol. 2019;29:1693–702. Kawakubo M, Yamasaki Y, Kamitani T, Sagiyama K, Matsuura Y, Hino T, et al. Clinical usefulness of right ventricular 3D area strain in the assessment of treatment effects of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: comparison with 2D feature-tracking MRI. Eur Radiol. 2019;29:4583–92. Odagiri K, Inui N, Hakamata A, Inoue Y, Suda T, Takehara Y, et al. Non-invasive evaluation of pulmonary arterial blood flow and wall shear stress in pulmonary arterial hypertension with 3D phase contrast magnetic resonance imaging. Springerplus. 2016;5:1071. Sieren MM, Berlin C, Oechtering TH, Hunold P, Drömann D, Barkhausen J, et al. Comparison of 4D Flow MRI to 2D Flow MRI in the pulmonary arteries in healthy volunteers and patients with pulmonary hypertension. PLoS ONE. 2019;14:e0224121. Ota H, Kamada H, Higuchi S, Takase K. Clinical application of 4D Flow MR imaging to pulmonary hypertension. Magn Reson Med Sci. 2022;21:309–18. Ota H, Sugimura K, Miura M, Shimokawa H. Four-dimensional flow magnetic resonance imaging visualizes drastic change in vortex flow in the main pulmonary artery after percutaneous transluminal pulmonary angioplasty in a patient with chronic thromboembolic pulmonary hypertension. Eur Heart J. 2015;36:1630. Han QJ, Contijoch F, Forfia PR, Han Y. Four-dimensional flow magnetic resonance imaging visualizes drastic changes in the blood flow in a patient with chronic thromboembolic pulmonary hypertension after pulmonary thromboendarterectomy. Eur Heart J. 2016;37:2802. Reiter G, Reiter U, Kovacs G, Olschewski H, Fuchsjäger M. Blood flow vortices along the main pulmonary artery measured with MR imaging for diagnosis of pulmonary hypertension. Radiology. 2014;275:71–9. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282:2035–42. Roux E, Bougaran P, Dufourcq P, Couffinhal T. Fluid shear stress sensing by the endothelial layer. Front Physiol. 2020;11:861. Tang BT, Pickard SS, Chan FP, Tsao PS, Taylor CA, Feinstein JA. Wall shear stress is decreased in the pulmonary arteries of patients with pulmonary arterial hypertension: an image-based, computational fluid dynamics study. Pulm Circ. 2012;2:470–6. Barker AJ, Roldán-Alzate A, Entezari P, Shah SJ, Chesler NC, Wieben O, et al. Four-dimensional flow assessment of pulmonary artery flow and wall shear stress in adult pulmonary arterial hypertension: results from two institutions. Magn Reson Med. 2015;73:1904–13. Terada M, Takehara Y, Isoda H, Uto T, Matsunaga M, Alley M. Low WSS and high OSI measured by 3D cine PC MRI reflect high pulmonary artery pressures in suspected secondary pulmonary arterial hypertension. Magn Reson Med Sci. 2016;15:193–202. Ikoma T, Suwa K, Sano M, Ushio T, Saotome M, Ogawa N, et al. Early changes of pulmonary arterial hemodynamics in patients with systemic sclerosis: flow pattern, WSS, and OSI analysis with 4D flow MRI. Eur Radiol. 2021;31:4253–63. Matura LA, Ventetuolo CE, Palevsky HI, Lederer DJ, Horn EM, Mathai SC, et al. Interleukin-6 and tumor necrosis factor-alpha are associated with quality of life-related symptoms in pulmonary arterial hypertension. Ann Am Thorac Soc. 2015;12:370–5. Xu WJ, Wu Q, He WN, Wang S, Zhao YL, Huang JX, et al. Interleukin-6 and pulmonary hypertension: from physiopathology to therapy. Front Immunol. 2023;14:1181987. Chester AH, Yacoub MH, Moncada S. Nitric oxide and pulmonary arterial hypertension. Glob Cardiol Sci Pract. 2017;2017:14. Schäfer M, Kheyfets VO, Schroeder JD, Dunning J, Shandas R, Buckner JK, et al. Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension. Pulm Circ. 2016;6:37–45. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Aug, 2025 Read the published version in BMC Cardiovascular Disorders → Version 1 posted Editorial decision: Revision requested 22 May, 2025 Reviews received at journal 17 May, 2025 Reviewers agreed at journal 14 May, 2025 Reviewers agreed at journal 08 May, 2025 Reviews received at journal 20 Apr, 2025 Reviewers agreed at journal 17 Mar, 2025 Reviewers agreed at journal 16 Mar, 2025 Reviewers invited by journal 16 Mar, 2025 Editor invited by journal 13 Mar, 2025 Editor assigned by journal 12 Mar, 2025 Submission checks completed at journal 12 Mar, 2025 First submitted to journal 08 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6184673","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":428234894,"identity":"79def99f-baaa-4569-b925-ed0b4b2eb6a7","order_by":0,"name":"Kazuto Ohno","email":"","orcid":"","institution":"Hamamatsu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kazuto","middleName":"","lastName":"Ohno","suffix":""},{"id":428234895,"identity":"7eeebc28-e0bc-4316-8d68-df7580181996","order_by":1,"name":"Kenichiro Suwa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYBACCQhlkwDlM4NJAyK0pJGu5TCqFrxAsoH9mTRPzfk8/mmHHzDdqLBm4G8/wFBcgEeLNAOPmTTPsdvFErfTDJhzzqQzSJxJYDCegUeLnPwbNukcttuJDbcTzH/nth1mYLjBwGDMg08LA9BhOf/OJc6/nf6BOfffYQZ5QlqkGRjMpHPbDiRuuJ1jwJzbcJjBgJAWyQYeY+u/fcmJG2/nFDDnHEvnMTyT2IDXLxIH2B/enPHNLnHe7fQNzDk11nJyxw8fM8YXYhgA6CTGNmNSdIAB82OStYyCUTAKRsFwBgCvLUY5y/1GtAAAAABJRU5ErkJggg==","orcid":"","institution":"Hamamatsu University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kenichiro","middleName":"","lastName":"Suwa","suffix":""},{"id":428234896,"identity":"9b624c97-49ec-4c4c-b521-8cd0e68d66f2","order_by":2,"name":"Keitaro Akita","email":"","orcid":"","institution":"Columbia University Irving Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Keitaro","middleName":"","lastName":"Akita","suffix":""},{"id":428234897,"identity":"75846b17-3de0-432e-ae43-25ff1e7a0640","order_by":3,"name":"Ryota Sato","email":"","orcid":"","institution":"Hamamatsu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ryota","middleName":"","lastName":"Sato","suffix":""},{"id":428234898,"identity":"eb78be63-49d0-4be8-b956-c589bddeeb14","order_by":4,"name":"Terumori Satoh","email":"","orcid":"","institution":"Hamamatsu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Terumori","middleName":"","lastName":"Satoh","suffix":""},{"id":428234901,"identity":"5c638978-f2ee-46ee-8ba1-1f1fe389124a","order_by":5,"name":"Yuichiro Maekawa","email":"","orcid":"","institution":"Hamamatsu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuichiro","middleName":"","lastName":"Maekawa","suffix":""}],"badges":[],"createdAt":"2025-03-08 14:38:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6184673/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6184673/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12872-025-05068-x","type":"published","date":"2025-08-21T16:29:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":78690889,"identity":"762f72d1-b47f-448c-834c-c3ea881ccdec","added_by":"auto","created_at":"2025-03-17 16:15:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29172,"visible":true,"origin":"","legend":"\u003cp\u003ePatient selection. All 25 patients with CTEPH scheduled to undergo BPA underwent initial RHC and 4D flow CMR and proceeded to BPA. After the exclusion of four patients without follow-up 4D flow CMR, the remaining 21 patients who underwent follow-up RHC and CMR studies 3 months after BPA were recruited for the analysis. BPA, balloon pulmonary angioplasty; 4D flow: three-dimensional cine phase-contrast; CMR, cardiac magnetic resonance imaging; CTEPH, chronic thromboembolic pulmonary hypertension; RHC, right heart catheterization.\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-6184673/v1/05f06e4121d224f8b7fef008.png"},{"id":78690892,"identity":"5bca5ccc-0622-4817-a4bd-2be671648a58","added_by":"auto","created_at":"2025-03-17 16:15:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":326489,"visible":true,"origin":"","legend":"\u003cp\u003eUpper row. Streamline images of PA flow at peak systolic phase before (a) and 3 months after BPA (b). Middle row. Three-dimensional WSS distribution maps of the PA at peak systole before (c) and 3 months after BPA (d). Lower row. Three-dimensional OSI distribution maps of the PA before (e) and 3 months after BPA (f).\u003c/p\u003e\n\u003cp\u003eBPA, balloon pulmonary angioplasty; OSI, oscillatory shear index; PA, pulmonary artery; WSS, wall shear stress\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-6184673/v1/df33dc08b455c2064aac5d1a.png"},{"id":78690890,"identity":"07131a96-03bc-428d-a24b-64302861c65b","added_by":"auto","created_at":"2025-03-17 16:15:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41762,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of parameters before and after BPA between the two groups: mPAP after BPA \u0026lt; 30 mmHg and mPAP after BPA ≥ 30 mmHg. (a) Peak flow volume, (b) peak flow velocity, (c) peak WSS, (d) mean OSI, (e) main PA diameter, and (f) Reynolds number.\u003c/p\u003e\n\u003cp\u003emPAP, mean pulmonary artery pressure; BPA, balloon pulmonary angioplasty; WSS, wall shear stress; OSI, oscillatory shear index; PA, pulmonary artery; n.s., not significant.\u003c/p\u003e","description":"","filename":"Slide3.png","url":"https://assets-eu.researchsquare.com/files/rs-6184673/v1/cd9fa82484b92b9f2b51b727.png"},{"id":78692272,"identity":"ddeb447a-4dcb-485c-aa4e-86efa17d651e","added_by":"auto","created_at":"2025-03-17 16:23:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":76592,"visible":true,"origin":"","legend":"\u003cp\u003eUpper row. Scatter plots showing the correlation between mPAP after BPA and 4D flow CMR parameters before BPA. (a) Correlation between mPAP after BPA and peak velocity before BPA and (b) between mPAP after BPA and peak WSS before BPA.\u003c/p\u003e\n\u003cp\u003eLower row. The ROC for prediction of mPAP after BPA ≥ 30 mmHg by peak flow velocity before BPA (c) and peak WSS before BPA (d).\u003c/p\u003e\n\u003cp\u003eAUC, area under the curve; CI, confidence interval; mPAP, mean pulmonary artery pressure; ROC: receiver operating characteristic; WSS, wall shear stress.\u003c/p\u003e","description":"","filename":"Slide4.png","url":"https://assets-eu.researchsquare.com/files/rs-6184673/v1/3f2401543f6dd80e63250f11.png"},{"id":89847203,"identity":"7e1e8c2f-bec3-4fa8-8a49-7daf1a8ba9fe","added_by":"auto","created_at":"2025-08-25 16:42:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1559253,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6184673/v1/de66242d-b6c7-4502-b8bf-e11b4e73eb39.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hemodynamics assessment using 4D flow CMR before and after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: A retrospective observational study","fulltext":[{"header":"Background","content":"\u003cp\u003eChronic thromboembolic pulmonary hypertension (CTEPH) is characterized by pulmonary hypertension, with an organized thrombus due to an incompletely resolved acute pulmonary embolism c. Persistent thromboembolism in the pulmonary artery (PA) elevates pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP), eventually resulting in right heart failure or death, if left untreated [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients with CTEPH with mPAP \u0026ge; 30 mmHg have poor prognoses [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Invasive treatments are typically considered for symptomatic drug-refractory CTEPH [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. For patients with peripheral vasculopathy of segmental or subsegmental vessels unsuitable for pulmonary artery endarterectomy (PEA) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], balloon pulmonary angioplasty (BPA) is indicated [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. BPA reduces PVR and mPAP, resulting in symptom relief [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg is considered one of the goals following BPA.\u003c/p\u003e \u003cp\u003eTime-resolved three-dimensional cine phase-contrast cardiac magnetic resonance (4D flow CMR) visualizes and quantifies the blood flow in large vessels and heart [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Few studies have investigated the hemodynamics in patients with CTEPH; however, the efficacy of BPA assessed using 4D flow CMR remains unclear.\u003c/p\u003e \u003cp\u003eTherefore, the present study aimed (1) to investigate the hemodynamic features of PA before and after BPA and (2) evaluate the diagnostic performance of 4D flow CMR-derived hemodynamics before BPA to predict the achievement of mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg after BPA in patients with CTEPH.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eAs presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, this retrospective observational study initially recruited 25 consecutive patients with CTEPH scheduled for BPA at Hamamatsu University Hospital between December 2017 and December 2022. All patients underwent an initial right heart catheterization (RHC) and CMR, including 4D flow CMR, before BPA. After the exclusion of four patients without follow-up CMR, the remaining 21 patients who underwent follow-up RHC and 4D flow CMR were selected for the analysis. The diagnosis of CTEPH was based on the latest guidelines of the European Society of Cardiology [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and Japanese Circulation Society [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] as appropriately. The time courses of the examinations were as follows: initial RHC and CMR within 1 month before the first BPA session, following serial BPA sessions, and follow-up RHC and CMR 3 months after the final BPA session. The decision to terminate any further additional BPA sessions was based on a comprehensive assessment, considering symptom improvement, the absence of treatable vessels, and mPAP levels after BPA. This study complied with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Hamamatsu University School of Medicine (approval ID 17\u0026ndash;293). Written informed consent was obtained from all patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSerological tests, transthoracic echocardiography, and RHC\u003c/h3\u003e\n\u003cp\u003eAll patients underwent serological tests and transthoracic echocardiography (TTE) within 1 month before the first BPA session and 3 months after the final BPA session. Serological test included N-terminal pro-brain natriuretic peptide (NT-proBNP). Using TTE, we assessed the degree of tricuspid regurgitation (TR) and maximum TR pressure gradient (TRPG). RHC parameters included mean pulmonary artery wedge pressure (PAWP), mPAP, PVR, cardiac output, and cardiac index measured using the Fick principle.\u003c/p\u003e\n\u003ch3\u003eCMR\u003c/h3\u003e\n\u003cp\u003eCMR examinations were performed using a 3T scanner (Discovery MR750, GE Healthcare, Waukesha, WI, USA), with a maximum gradient strength of 50 mT/m and a maximum slew rate of 200 mT/m/ms; the scanner was used in combination with a commercially available 12-channel phased array body coil. Typically, two-dimensional (2D) cine images were obtained by fast imaging employing steady-state acquisition (FIESTA) and late gadolinium enhancement (LGE) images acquired using inversion recovery-prepared fast gradient echo (IR-FGRE) sequences in short-axis and vertical and horizontal long-axis orientations, with a slice thickness/gap of 10 mm/0 mm (6\u0026ndash;9 slices). Contrast-enhanced three-dimensional (3D) fast spoiled gradient echo (FSPGR) magnetic resonance angiography (MRA) was performed for geometric information of 4D flow CMR and area quantification of the PA. The following parameters were set: repetition time 2.7 ms; echo time 1.0 ms; flip angle 12 degrees, number of excitations, 1; field of view, 32 cm; matrix size reconstructed with the aid of zero fill interpolation, 224 \u0026times; 224; receiver bandwidth, 83.3 kHz; and imaging time, 33 s for 4 phases. A bolus injection of 0.1 mmol/kg gadobutrol (Gadovist, Bayer AG, Berlin, Germany) was administered at an injection rate of 2.0 mL/s, followed by the administration of 20 mL of saline. 4D flow CMR provides time-resolved 3D voxel data, each with 3D flow velocity components. Imaging parameters used for coronal 3D Fourier transform FSPGR-based 4D flow CMR were as follows: repetition time 4.5\u0026ndash;5.0 ms; echo time 2.0 ms; flip angle 15 degrees; number of excitations 1; field of view, 32 cm; matrix, 224 \u0026times; 224; 2-mm thickness; 60 partitions; 20 phases per cardiac cycle; velocity encoding, 200 cm/s; and receiver bandwidth, 83.3 kHz. The temporal resolution was 58.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 msec. Respiratory-compensated retrospective cardiac gating was performed. The resulting imaging time was approximately 10 min, with a reduction factor of two for auto-calibrating the reconstruction for Cartesian sampling. Raw data of the 4D flow CMR were transferred to a personal computer (Intel Xeon E3-1270 [3.4 GHz/Quad-core] DDR3, 16 GB ECC, Linux) and reconstructed.\u003c/p\u003e\n\u003ch3\u003eConventional CMR parameters\u003c/h3\u003e\n\u003cp\u003eRight ventricular (RV) end-diastolic volume index (RVEdVI), RV end-systolic volume index (RVEsVI), and RV stroke volume index (RVSVI), all indexed with body surface area using the Du Bois formula, and RV ejection fraction (RVEF) and main PA diameter just above the pulmonary valve at the end-diastolic phase were measured using Cardiac VX software (GE Healthcare). RV stroke volume divided by RV end-systolic volume (RVSV/RVEsV), as a right ventricular-pulmonary arterial (RV-PA) coupling parameter [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], was calculated.\u003c/p\u003e\n\u003ch3\u003ePost-processing for 4D flow CMR\u003c/h3\u003e\n\u003cp\u003e4D flow CMR and MRA datasets were formatted using Digital Imaging and Communications in Medicine and analyzed on a personal computer. Segmentation, visualization of flow patterns, and calculations of flow velocity and volume and wall shear stress (WSS) were performed using commercially available software (Flova; R\u0026rsquo;-Tech Co., Hamamatsu, Japan). In particular, the regions of interest, including the main, right, and left PAs, were determined for the 4D flow CMR and MRA datasets. Segmentation was performed for vascular wall structures from 3D MRA datasets at the peak of the R wave, with magnitude images of 4D flow CMR, using the region growing method. The shapes were created using the marching cubes method. The 3D flow information was interpolated with a spatial resolution of 2 \u0026times; 2 \u0026times; 2 mm\u003csup\u003e3\u003c/sup\u003e using the 3D datasets. Three emitter planes traversing the bases of the main, right, and left PAs were manually set, and 3D streamline images were subsequently generated using the Runge\u0026ndash;Kutta method.\u003c/p\u003e \u003cp\u003ePA flow was evaluated based on the 3D streamline in each timeframe. In addition, PA flow patterns were evaluated in the main, right, and left PAs for the presence of vortical or helical flow in the entire cardiac cycle, the duration of vortical or helical flow, and the presence of vortical or helical flow in systole, respectively. Vortical flow was defined as a rotational streamline with an axis orthogonal to the centerline of the vessel. Helical flow was defined as regional fluid circulation along the longitudinal axis of the vessel centerline, thereby revealing a corkscrew-like motion [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe flow volume curve at the base of the main PA was obtained using Flova. Blood flow parameters included peak flow volume and velocity at the base of the main PA, peak systolic WSS, and mean oscillatory shear index (OSI). Both WSS and OSI distribution maps of the PAs were color-coded and visualized as 3D images. Temporal changes in the entire surface area-averaged WSS at the PA wall during one cardiac cycle were described, and peak systolic WSS and mean OSI were estimated. The Reynolds number (Re), fluid characteristics to predict the flow pattern of laminar flow or turbulence, was calculated at the main PA in each patient using the following equation: Re\u0026thinsp;=\u0026thinsp;ρVL/\u0026micro;, where ρ: density\u0026thinsp;=\u0026thinsp;1.05 g/cm\u003csup\u003e3\u003c/sup\u003e, \u0026micro;: viscosity\u0026thinsp;=\u0026thinsp;4.0 \u0026times; 10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e Pa \u0026times; s, V\u0026thinsp;=\u0026thinsp;area-averaged peak velocity, and L\u0026thinsp;=\u0026thinsp;vessel diameter at the base of main PA.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous data were expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or as medians with interquartile range (IQR), as appropriate. Categorical data were presented as numbers and percentages. Continuous variables were compared using the two-sided t-test, Wilcoxon signed-rank test, or Mann\u0026ndash;Whitney U test. Categorical variables were compared using the McNemar\u0026rsquo;s test.\u003c/p\u003e \u003cp\u003ePA flow patterns were evaluated by one observer (KO) and another independent observer (KS) to assess interobserver variability, and Cohen's Kappa (κ) coefficient was calculated for qualitative evaluation and the intraclass coefficient for quantitative evaluation. Correlations were assessed using the Pearson\u0026rsquo;s correlation coefficient (r) and linear regression analysis.\u003c/p\u003e \u003cp\u003eStatistical significance was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using the SPSS 30.0 statistical software package (SPSS Inc., Armonk, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThe baseline characteristics of the study participants are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of the participants was 60.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8 years, and 90.5% of all patients were women. Ten patients (47.6%) had moderate or greater TR. All patients were administered riociguat and oral anticoagulants (OACs), and one patient additionally received selexipag. Serum NT-proBNP level was 137.0 (86.0‒975.5) pg/mL before BPA and significantly decreased after BPA [59.0 (34.5‒151.0) pg/mL, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001]. The median (IQR) number of BPA sessions was 5.00 (4.00‒7.00). The distribution of patients according to the World Health Organization functional classification (WHO-FC) was as follows: 0 (0.0%) in class Ⅰ, 10 (47.5%) in class Ⅱ, 10 (47.5%) in class Ⅲ, and 1 (4.8%) in class Ⅳ, while it improved significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) to 14 (66.7%) in class Ⅰ, 5 (23.8%) in class Ⅱ, 2 (9.5%) in class Ⅲ, and 0 (0.0%) in class Ⅳ, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (90.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight, kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.1 (45.6 ‒ 66.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody Surface Area, m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute pulmonary thromboembolism, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (57.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary endarterectomy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSoluble guanylate cyclase stimulator, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelective prostacyclin receptor agonist, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDOACs, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWarfarin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHOT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO-FC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (47.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (47.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum uric acid, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.70 (0.63 ‒ 0.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR, mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum NT-proBNP, pg/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137 (86 ‒ 976)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer\u0026thinsp;\u0026gt;\u0026thinsp;1.0 \u0026micro;g/mL, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (19.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of BPA sessions per person\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.0 (4.0 ‒ 7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median (interquartile range), or number (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eCKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DOACs, direct oral anticoagulants; eGFR, estimated glomerular filtration rate; HOT, home oxygen therapy; TR, tricuspid regurgitation; NT-proBNP, N-terminal prohormone of B-type natriuretic peptide; WHO-FC, World Health Organization functional classification\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTTE, RHC, and conventional CMR\u003c/h2\u003e \u003cp\u003eTRPG, as measured by TTE, significantly reduced 3 months after BPA compared to before BPA (59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;25.7 mmHg vs. 26.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3 mmHg, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). mPAP (36.0 [32.0‒47.5] mmHg vs. 24.0 [21.0‒28.0] mmHg, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and PVR (6.1 [4.5‒11.9] Wood units vs. 3.4 [2.5‒4.4] Wood units, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) significantly decreased 3 months after BPA compared to before BPA (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, four patients showed mPAP\u0026thinsp;\u0026gt;\u0026thinsp;30 mmHg 3 months after the final BPA. RVEdVI (95.2\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 mL/m\u003csup\u003e2\u003c/sup\u003e vs. 71.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9 mL/m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and RVEsVI (54.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.6 mL/m\u003csup\u003e2\u003c/sup\u003e vs. 31.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0 mL/m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) significantly reduced 3 months after BPA compared to before BPA. Furthermore, RVEF significantly increased 3 months after BPA compared to before BPA (44.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 mmHg vs. 56.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5 mmHg, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). RVSV/RVEsV significantly increased 3 months after BPA compared to before BPA (0.68 [0.56 ‒ 1.23] vs. 1.29 [1.07 ‒ 1.69], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Main PA diameter significantly reduced 3 months after BPA compared to before BPA (33.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 mm vs. 30.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). LGE was observed at the RV insertion point in 21 (100%) patients before BPA and did not change 3 months after BPA.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRHC and CMR before and 3 months after the BPA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore BPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 months after BPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTTE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTRPG, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;25.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean PAP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.0 (32.0 ‒ 47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.0 (21.0 ‒ 28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean PAWP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.0 (7.5 ‒ 15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.0 (6.0 ‒ 13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVR, Wood Unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1 (4.5 ‒ 11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.4 (2.5 ‒ 4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac output, L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac index, L/min/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.227\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate, beat/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.748\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVEdVI, mL/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.2\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVEsVI, mL/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVSVI, mL/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.509\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVEF, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVSV/RVEsV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.68 (0.56 ‒ 1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.29 (1.07 ‒ 1.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain PA diameter, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4D flow CMR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak flow volume, 10\u003csup\u003e3\u003c/sup\u003e mm\u003csup\u003e3\u003c/sup\u003e/s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200.6\u0026thinsp;\u0026plusmn;\u0026thinsp;43.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e203.6\u0026thinsp;\u0026plusmn;\u0026thinsp;54.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.757\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak flow velocity, mm/s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e262.8\u0026thinsp;\u0026plusmn;\u0026thinsp;52.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e298.5\u0026thinsp;\u0026plusmn;\u0026thinsp;68.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak WSS, Pa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean OSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.10 ‒ 0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12 (0.09 ‒ 0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.794\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReynolds number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2244\u0026thinsp;\u0026plusmn;\u0026thinsp;381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2359\u0026thinsp;\u0026plusmn;\u0026thinsp;487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.266\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, medians (interquartile range), or numbers (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBPA, balloon pulmonary angioplasty; CMR, cardiac magnetic resonance imaging; OSI, oscillatory shear index; PA, pulmonary artery; PAP, pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; RHC, right heart catheterization; RVEdVI, right ventricular end-diastolic volume index; RVEF, right ventricular ejection fraction; RVEsVI, right ventricular end-systolic volume index; RVSVI, right ventricular stroke volume index; RVSV/RVEsV, right ventricular stroke volume divided by right ventricular end-systolic volume; TRPG, tricuspid regurgitation pressure gradient; TTE, transthoracic echocardiography; WSS, wall shear stress; 4D flow: three-dimensional cine phase-contrast\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eVisualization of PA streamline, WSS, and OSI using 4D flow CMR\u003c/h2\u003e \u003cp\u003eRepresentative streamline images of PA flow at the peak systolic phase before (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea) and after (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb) BPA revealed that the vortical flow pattern in the main PA did not change significantly, whereas flow velocity at the main PA increased after BPA. Three-dimensional WSS at peak systole revealed a relatively elevated WSS distribution in the anterior wall of the main PA before BPA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec) and elevated WSS after BPA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). In addition, 3D OSI revealed relatively low values and similar distributions before (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee) and after (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef) BPA.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4D flow CMR-derived hemodynamics\u003c/h2\u003e \u003cp\u003eAs presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, peak flow velocity (262.8\u0026thinsp;\u0026plusmn;\u0026thinsp;52.3 mm/s vs. 298.5\u0026thinsp;\u0026plusmn;\u0026thinsp;68.3 mm/s, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015) and peak WSS (0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14 Pa vs. 0.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20 Pa, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) significantly increased after BPA compared to before BPA, whereas the mean OSI remained unchanged. There was no significant change in the Reynolds number before and after BPA. As summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, streamline images before BPA developed a vortical or helical flow in the main PA (n\u0026thinsp;=\u0026thinsp;21, 100%), right PA (n\u0026thinsp;=\u0026thinsp;16, 76.2%), and left PA (n\u0026thinsp;=\u0026thinsp;14, 66.7%). The prevalence of vortical or helical flow during an entire cardiac cycle and only in systole and the duration of vortical or helical flow did not change after BPA. Interobserver variabilities in the presence of vortical or helical flow (kappa\u0026thinsp;=\u0026thinsp;0.96) and the duration of the vortex or helix (intraclass correlation coefficient\u0026thinsp;=\u0026thinsp;0.99) were excellent.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVisual evaluation of vortical flow and helical flow in the main, right, and left PA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore BPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 months after BPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003ePresence of vortical or helical flow in an entire cardiac cycle, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVortical or helical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVortical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHelical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVortical or helical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.453\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVortical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHelical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVortical or helical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVortical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHelical flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eVortical or helical flow duration, phase number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.928\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003ePresence of vortical or helical flow in systole, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or numbers (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eBPA, balloon pulmonary angioplasty; LPA, left pulmonary artery; MPA, main pulmonary artery; PA, pulmonary artery; RPA, right pulmonary artery\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4D flow CMR-derived hemodynamics parameters based on the reference mPAP value of 30 mmHg\u003c/h2\u003e \u003cp\u003eThe intergroup comparisons based on mPAP value of 30 mmHg after BPA are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Peak flow velocity before BPA (278.4\u0026thinsp;\u0026plusmn;\u0026thinsp;40.0 mm/s vs. 196.7\u0026thinsp;\u0026plusmn;\u0026thinsp;50.0 mm/s, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039), peak flow velocity after BPA (321.5\u0026thinsp;\u0026plusmn;\u0026thinsp;49.8 mm/s vs. 200.65\u0026thinsp;\u0026plusmn;\u0026thinsp;46.4, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006), peak WSS before BPA (0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 Pa vs. 0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 Pa, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and peak WSS after BPA (0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19 Pa vs. 0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15 Pa, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041) were significantly higher in patients with mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg than in patients with mPAP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg. Patients with mPAP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg were older (57.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3 years vs. 75.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5 years, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.050).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e4D flow CMR-derived hemodynamic parameters with respect to the reference mPAP value of 30 mmHg\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003emPAP after BPA\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003emPAP after BPA\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak flow volume before BPA, 10\u003csup\u003e3\u003c/sup\u003e mm\u003csup\u003e3\u003c/sup\u003e/s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202.6\u0026thinsp;\u0026plusmn;\u0026thinsp;36.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e192.1\u0026thinsp;\u0026plusmn;\u0026thinsp;74.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak flow volume after BPA, 10\u003csup\u003e3\u003c/sup\u003e mm\u003csup\u003e3\u003c/sup\u003e/s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e212.4\u0026thinsp;\u0026plusmn;\u0026thinsp;55.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166.6\u0026thinsp;\u0026plusmn;\u0026thinsp;33.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak flow velocity before BPA, mm/s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e278.4\u0026thinsp;\u0026plusmn;\u0026thinsp;40.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e196.7\u0026thinsp;\u0026plusmn;\u0026thinsp;50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak flow velocity after BPA, mm/s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e321.5\u0026thinsp;\u0026plusmn;\u0026thinsp;49.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200.6\u0026thinsp;\u0026plusmn;\u0026thinsp;46.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak WSS before BPA, Pa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak WSS after BPA, Pa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean OSI before BPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.10‒0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12 (0.10‒0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean OSI after BPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.12 (0.09‒0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.11 (0.09‒0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain PA diameter before BPA, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain PA diameter after BPA, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReynolds number before BPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2326\u0026thinsp;\u0026plusmn;\u0026thinsp;296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1893\u0026thinsp;\u0026plusmn;\u0026thinsp;546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReynolds number after BPA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2490\u0026thinsp;\u0026plusmn;\u0026thinsp;440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1803\u0026thinsp;\u0026plusmn;\u0026thinsp;186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or medians (interquartile range).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBPA, balloon pulmonary angioplasty; CMR, cardiac magnetic resonance imaging; mPAP, mean pulmonary arterial pressure; OSI, Oscillatory shear index; PA, pulmonary artery; WSS, wall shear stress\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFurthermore, intragroup comparisons before and after BPA based on mPAP of 30 mmHg after BPA are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In patients with mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg, peak flow velocity (278.4\u0026thinsp;\u0026plusmn;\u0026thinsp;40.0 mmHg vs. 321.5\u0026thinsp;\u0026plusmn;\u0026thinsp;49.8 mmHg, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) and peak WSS (0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 Pa vs. 0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19 Pa, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) were significantly increased after BPA. Main PA diameter was significantly reduced after BPA in patients with mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg (32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0 mm vs. 29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and patients with mPAP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg (37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 mm vs. 35.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation between 4D flow CMR parameters before BPA and mPAP after BPA\u003c/h2\u003e \u003cp\u003ePeak velocity before BPA and mPAP after BPA (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea, R = -0.695, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and peak WSS before BPA and mPAP after BPA (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb, R = -0.633, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) had significant negative correlations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eDiagnostic performance of peak flow velocity and peak WSS before BPA in predicting mPAP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg after BPA\u003c/b\u003e \u003c/p\u003e \u003cp\u003eReceiver operating characteristic analysis to predict mPAP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg after BPA using peak flow velocity and peak WSS before BPA revealed an area under the curve of 0.926 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for peak flow velocity before BPA (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC) and 1.00 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for peak WSS before BPA (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD). The sensitivity and specificity were 0.765 and 0.750, respectively, for peak flow velocity before BPA, with a cutoff value of \u0026lt;\u0026thinsp;251 mm/s. The sensitivity and specificity were 1.000 and 1.000, respectively, for peak WSS before BPA, with a cutoff value of \u0026lt;\u0026thinsp;0.48 Pa.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we demonstrated serial changes in PA hemodynamics using 4D flow CMR imaging in patients with CTEPH before and after BPA. Briefly, RVEdVI and RVEsVI decreased, RVEF increased, peak flow velocity at the main PA increased, and peak WSS increased after BPA compared to before BPA. When comparing patients with a post-BPA mPAP exceeding the reference value of 30 mmHg to those with mPAP\u0026thinsp;\u0026le;\u0026thinsp;30 mmHg, significant differences were observed in peak flow velocity and peak WSS both before and after BPA. In addition, we demonstrated the utility of peak flow velocity and peak WSS before BPA in predicting the achievement of mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg after BPA.\u003c/p\u003e \u003cp\u003eIn this study cohort, we demonstrated the effect of BPA on RV-PA hemodynamics and cardiac function, namely, BPA reduced PVR and mPAP; however it did not increase cardiac output. In addition, we demonstrated changes in PA hemodynamics using 4D flow CMR, which showed an increase in peak flow velocity but not in peak flow volume. This finding is consistent with the cardiac output measured using RHC and stroke volume in cine CMR. Another insight from this study is that achievement of mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg after BPA may be predicted by peak flow velocity before BPA using 4D flow CMR, even though pressure cannot be measured using 4D flow CMR.\u003c/p\u003e \u003cp\u003ePrevious studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] have reported that BPA in patients with CTEPH improved WHO-FC, reduced BNP, reduced mPAP and PVR measured using RHC, reduced RVEdV and RVEsV, and increased RVEF measured using conventional CMR. Our results are consistent with those of the aforementioned studies. In addition, we observed an increase in RVSV/RVEsV and a decrease in the main PA diameter, which were associated with morphological reverse remodeling of the right ventricle and PA. RVSV/RVEsV has prognostic value in patients with pulmonary hypertension. Thus, an increase in RVSV/RVEsV may suggest improved outcomes in patients undergoing BPA.\u003c/p\u003e \u003cp\u003eA characteristic endpoint of 4D flow CMR is the visualization of a 3D flow in a time course of a cardiac cycle. Non-laminar flow patterns, including vortical and helical flows in the PA, have been reported in patients with pulmonary hypertension, whereas flow patterns seem to be more prone to laminar flow in healthy participants [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The effect of BPA on flow patterns remains unclear. A significantly diminished vortical flow has been reported in a patient after BPA [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and another patient after PEA [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, in the present study, the prevalences of vortical and helical flows and their duration did not decrease after BPA, even though mPAP decreased and WHO-FC symptoms were relieved. In this regard, considering the mPAP cut-off value of 16.0 mmHg for the appearance of vortical flow [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], the mPAP after BPA in this study (24.0 [21.0\u0026ndash;28.0] mmHg) was relatively high.\u003c/p\u003e \u003cp\u003eWSS is proportional to velocity and inversely proportional to vessel diameter under laminar flow conditions [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although PA blood flow in patients with CTEPH was generally non-laminar, the relationship between velocity, vessel diameter, and WSS remained consistent with the laminar flow model mentioned above, where higher velocity and smaller vessel diameter both led to increased WSS. However, the WSS on the PA surface was heterogeneous, with an uneven PA surface and diameter, complex bifurcation anatomy, and complex hemodynamics with non-laminar flow. Therefore, actual measurement of WSS using 4D flow CMR is vital for accurate assessments. Physiological WSS in healthy individuals has a favorable effect on endothelial function [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In contrast, WSS in patients with pulmonary hypertension is lower than that in healthy individuals [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Therefore, abnormally decreased WSS is associated with the overexpression of inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, leading to thickening and fibrotic change in the PA endothelium and suppression of nitric oxide production, which causes vasoconstriction, and finally results in PA remodeling [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Sch\u0026auml;fer et al. reported that the WSS of the PA correlated with stiffness and elasticity in the PA [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Thus, before BPA, the PA may be exposed to worse conditions with subsequent PA remodeling, whereas the increased WSS after BPA, as shown in this study, may prevent further PA remodeling in patients with CTEPH.\u003c/p\u003e \u003cp\u003eIn such cases, invasive RHC is performed 3 months after BPA to assess whether mPAP had decreased sufficiently. In the present study, we predicted the achievement of the BPA goal using peak flow velocity and peak WSS derived from non-invasive 4D flow CMR. Therefore, 4D flow CMR may help to understand the clinical course and decide the treatment strategy of CTEPH including additional vasodilator or further BPA sessions.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, this was a single-center study with a small sample size. However, we believe that the patient characteristics in this study represent the characteristics of patients with CTEPH who undergo BPA because patients with CTEPH in our institution were consecutively recruited. Second, this study did not include healthy participants; instead, we focused on the differences in variables before and after BPA. Third, all the patients were administered pulmonary vasodilators, which may have affected their PA hemodynamics. However, the medication dose was maintained throughout the study. Finally, we could not determine the benefits of hemodynamic changes after BPA owing to the study design.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the present study, 4D flow CMR showed an improvement in the hemodynamics of patients with CTEPH before and after BPA. Finally, peak flow velocity and peak WSS were useful metrics for predicting the achievement of the BPA goal with a better prognosis. Therefore, non-invasive 4D flow CMR potentially predict invasive RHC. A large-scale follow-up study is warranted to determine the benefits of BPA and hemodynamic assessment using 4D flow CMR for further PA remodeling.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBPA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eballoon pulmonary angioplasty\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiac magnetic resonance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTEPH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic thromboembolic pulmonary hypertension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFIESTA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e2D-fast imaging employing steady-state acquisition\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFSPGR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efast spoiled gradient echo\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIR-FGRE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einversion recovery prepared fast gradient echo\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLGE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elate gadolinium enhancement\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emPAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emean pulmonary arterial pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emagnetic resonance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNT-proBNP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eN-terminal pro-brain natriuretic peptide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOSI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoscillatory shear index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary arterial pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary vascular resistance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAWP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary artery wedge pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePEA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary artery endarterectomy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePVR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary vascular resistance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright heart catheterization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRVEF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright ventricular ejection fraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRVEdVI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright ventricular end-diastolic volume index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRVEsVI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright ventricular end-systolic volume index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRV‒PA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright ventricular-pulmonary arterial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRVSVI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright ventricular stroke volume index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etricuspid regurgitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTRPG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etricuspid regurgitation pressure gradient\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTTE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etransthoracic echocardiography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO-FC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe World Health Organization functional classification\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewall shear stress\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e4D flow\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethree-dimensional cine phase-contrast\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study only included human participants. This study was approved by the Institutional Review Board (approval number 17\u0026ndash;293). All patients provided written informed consent prior to participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the patients provided written informed consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDatasets supporting the conclusions of this study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by HUSM Grant-in-Aid.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKO was involved in the methodology, investigation, writing of the original draft, and the acquisition of funding. KS was involved in investigation, data validation, and manuscript editing. KA, RS and TS were involved in investigation and manuscript editing. YM was involved in conceptualization, supervision, and manuscript editing. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePapamatheakis DG, Poch DS, Fernandes TM, Kerr KM, Kim NH, Fedullo PF. Chronic thromboembolic pulmonary hypertension: JACC focus seminar. J Am Coll Cardiol. 2020;76:2155\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Yang T, Quan RL, Chen XX, An J, Zhao ZH, et al. Balloon pulmonary angioplasty reverse right ventricular remodelling and dysfunction in patients with inoperable chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis. Eur Radiol. 2021;31:3898\u0026ndash;908.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJenkins D. Pulmonary endarterectomy: the potentially curative treatment for patients with chronic thromboembolic pulmonary hypertension. Eur Respir Rev. 2015;24:263\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJapanese Circulation Society Joint Working Group. Statement for balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension (JCS 2014) [in Japanese] \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.j-circ.or.jp/guideline/pdf/JCS2014_ito_d.pdf\u003c/span\u003e\u003cspan address=\"http://www.j-circ.or.jp/guideline/pdf/JCS2014_ito_d.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed January 7 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFukui S, Ogo T, Morita Y, Tsuji A, Tateishi E, Ozaki K, et al. Right ventricular reverse remodelling after balloon pulmonary angioplasty. Eur Respir J. 2014;43:1394\u0026ndash;402.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkl M, Kilner PJ, Ebbers T. Comprehensive 4D velocity mapping of the heart and great vessels by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2011;13:7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGali\u0026egrave; N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015;46:903\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHumbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618\u0026ndash;731.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFukuda K, Date H, Doi S, Fukumoto Y, Fukushima N, Hatano M, et al. Guidelines for the Treatment of Pulmonary Hypertension (JCS 2017/JPCPHS 2017). Circ J. 2019;83:842\u0026ndash;945.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTello K, Dalmer A, Axmann J, Vanderpool R, Ghofrani HA, Naeije R, et al. Reserve of right ventricular-arterial coupling in the setting of chronic overload. Circ Heart Fail. 2019;12:e005512.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Knobelsdorff-Brenkenhoff F, Trauzeddel RF, Barker AJ, Gruettner H, Markl M, Schulz-Menger J. Blood flow characteristics in the ascending aorta after aortic valve replacement\u0026ndash;a pilot study using 4D-flow MRI. Int J Cardiol. 2014;170:426\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKomoriyama H, Kamiya K, Nagai T, Oyama-Manabe N, Tsuneta S, Kobayashi Y, et al. Blood flow dynamics with four-dimensional flow cardiovascular magnetic resonance in patients with aortic stenosis before and after transcatheter aortic valve replacement. J Cardiovasc Magn Reson. 2021;23:81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoenfeld C, Hinrichs JB, Olsson KM, Kuettner M-A, Renne J, Kaireit T, et al. Cardio-pulmonary MRI for detection of treatment response after a single BPA treatment session in CTEPH patients. Eur Radiol. 2019;29:1693\u0026ndash;702.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawakubo M, Yamasaki Y, Kamitani T, Sagiyama K, Matsuura Y, Hino T, et al. Clinical usefulness of right ventricular 3D area strain in the assessment of treatment effects of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: comparison with 2D feature-tracking MRI. Eur Radiol. 2019;29:4583\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOdagiri K, Inui N, Hakamata A, Inoue Y, Suda T, Takehara Y, et al. Non-invasive evaluation of pulmonary arterial blood flow and wall shear stress in pulmonary arterial hypertension with 3D phase contrast magnetic resonance imaging. Springerplus. 2016;5:1071.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSieren MM, Berlin C, Oechtering TH, Hunold P, Dr\u0026ouml;mann D, Barkhausen J, et al. Comparison of 4D Flow MRI to 2D Flow MRI in the pulmonary arteries in healthy volunteers and patients with pulmonary hypertension. PLoS ONE. 2019;14:e0224121.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOta H, Kamada H, Higuchi S, Takase K. Clinical application of 4D Flow MR imaging to pulmonary hypertension. Magn Reson Med Sci. 2022;21:309\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOta H, Sugimura K, Miura M, Shimokawa H. Four-dimensional flow magnetic resonance imaging visualizes drastic change in vortex flow in the main pulmonary artery after percutaneous transluminal pulmonary angioplasty in a patient with chronic thromboembolic pulmonary hypertension. Eur Heart J. 2015;36:1630.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan QJ, Contijoch F, Forfia PR, Han Y. Four-dimensional flow magnetic resonance imaging visualizes drastic changes in the blood flow in a patient with chronic thromboembolic pulmonary hypertension after pulmonary thromboendarterectomy. Eur Heart J. 2016;37:2802.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReiter G, Reiter U, Kovacs G, Olschewski H, Fuchsj\u0026auml;ger M. Blood flow vortices along the main pulmonary artery measured with MR imaging for diagnosis of pulmonary hypertension. Radiology. 2014;275:71\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282:2035\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoux E, Bougaran P, Dufourcq P, Couffinhal T. Fluid shear stress sensing by the endothelial layer. Front Physiol. 2020;11:861.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang BT, Pickard SS, Chan FP, Tsao PS, Taylor CA, Feinstein JA. Wall shear stress is decreased in the pulmonary arteries of patients with pulmonary arterial hypertension: an image-based, computational fluid dynamics study. Pulm Circ. 2012;2:470\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarker AJ, Rold\u0026aacute;n-Alzate A, Entezari P, Shah SJ, Chesler NC, Wieben O, et al. Four-dimensional flow assessment of pulmonary artery flow and wall shear stress in adult pulmonary arterial hypertension: results from two institutions. Magn Reson Med. 2015;73:1904\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTerada M, Takehara Y, Isoda H, Uto T, Matsunaga M, Alley M. Low WSS and high OSI measured by 3D cine PC MRI reflect high pulmonary artery pressures in suspected secondary pulmonary arterial hypertension. Magn Reson Med Sci. 2016;15:193\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIkoma T, Suwa K, Sano M, Ushio T, Saotome M, Ogawa N, et al. Early changes of pulmonary arterial hemodynamics in patients with systemic sclerosis: flow pattern, WSS, and OSI analysis with 4D flow MRI. Eur Radiol. 2021;31:4253\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatura LA, Ventetuolo CE, Palevsky HI, Lederer DJ, Horn EM, Mathai SC, et al. Interleukin-6 and tumor necrosis factor-alpha are associated with quality of life-related symptoms in pulmonary arterial hypertension. Ann Am Thorac Soc. 2015;12:370\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu WJ, Wu Q, He WN, Wang S, Zhao YL, Huang JX, et al. Interleukin-6 and pulmonary hypertension: from physiopathology to therapy. Front Immunol. 2023;14:1181987.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChester AH, Yacoub MH, Moncada S. Nitric oxide and pulmonary arterial hypertension. Glob Cardiol Sci Pract. 2017;2017:14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSch\u0026auml;fer M, Kheyfets VO, Schroeder JD, Dunning J, Shandas R, Buckner JK, et al. Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension. Pulm Circ. 2016;6:37\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"chronic thromboembolic pulmonary hypertension, 4D flow CMR, wall shear stress","lastPublishedDoi":"10.21203/rs.3.rs-6184673/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6184673/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe effect of balloon pulmonary angioplasty (BPA) for hemodynamics in chronic thromboembolic pulmonary hypertension (CTEPH), assessed using time-resolved three-dimensional cine phase-contrast cardiac magnetic resonance (4D flow CMR), remains unclear. Therefore, the present study aimed to investigate the hemodynamic features of the pulmonary artery (PA) before and after BPA and the diagnostic performance of 4D flow CMR-derived hemodynamics before BPA to predict the achievement of mean PA pressure (mPAP)\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg after BPA.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eTwenty-one patients with CTEPH who underwent 4D flow CMR before and after BPA were retrospectively enrolled. Regarding 4D flow CMR, the analysis included peak flow volume and velocity at the main PA and peak systolic wall shear stress (WSS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePeak flow velocity at the main PA (262.8\u0026thinsp;\u0026plusmn;\u0026thinsp;52.3 mm/s vs. 298.5\u0026thinsp;\u0026plusmn;\u0026thinsp;68.3 mm/s, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015) and peak WSS (0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14 Pa vs. 0.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20 Pa, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) both increased after BPA compared to their values before BPA. Receiver operating characteristic analysis was performed to predict mPAP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg after BPA based on peak flow velocity before BPA. The analysis revealed an area under the curve of 0.926 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for peak flow velocity before BPA (sensitivity, 0.765; specificity 0.750; cut-off, \u0026lt; 251 mm/s) and 1.00 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for peak WSS before BPA (sensitivity, 1.00; specificity, 1.00; cut-off, \u0026lt; 0.48 Pa).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBased on the study results, 4D flow CMR imaging showed improvement in hemodynamics after BPA. Furthermore, peak flow velocity and peak WSS were useful metrics for predicting the achievement of catheter-based BPA goal of mPAP\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg with a better prognosis.\u003c/p\u003e","manuscriptTitle":"Hemodynamics assessment using 4D flow CMR before and after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: A retrospective observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-17 16:15:24","doi":"10.21203/rs.3.rs-6184673/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-22T10:50:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-17T04:22:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335207414202369350288664385509263960376","date":"2025-05-15T03:02:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"56281788406284847449965657945763651860","date":"2025-05-08T15:33:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-20T14:43:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309661985852904035654467484177441307796","date":"2025-03-17T11:20:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332477632891810814949827521346258887110","date":"2025-03-17T02:20:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-16T18:20:08+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-13T06:57:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-12T10:12:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-12T10:09:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-03-08T14:36:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cd13e7ab-5978-422c-9071-101fa8d34adc","owner":[],"postedDate":"March 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T16:32:38+00:00","versionOfRecord":{"articleIdentity":"rs-6184673","link":"https://doi.org/10.1186/s12872-025-05068-x","journal":{"identity":"bmc-cardiovascular-disorders","isVorOnly":false,"title":"BMC Cardiovascular Disorders"},"publishedOn":"2025-08-21 16:29:05","publishedOnDateReadable":"August 21st, 2025"},"versionCreatedAt":"2025-03-17 16:15:24","video":"","vorDoi":"10.1186/s12872-025-05068-x","vorDoiUrl":"https://doi.org/10.1186/s12872-025-05068-x","workflowStages":[]},"version":"v1","identity":"rs-6184673","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6184673","identity":"rs-6184673","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}