Evaluating the Efficacy of Pressure Microcatheters for Fractional Flow Reserve Measurement in Chronic Thromboembolic Pulmonary Hypertension: A Comparative Study

Evaluating the Efficacy of Pressure Microcatheters for Fractional Flow Reserve Measurement in Chronic Thromboembolic Pulmonary Hypertension: A Comparative 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 Evaluating the Efficacy of Pressure Microcatheters for Fractional Flow Reserve Measurement in Chronic Thromboembolic Pulmonary Hypertension: A Comparative Study Jinzhi Wang, Haobo Li, Lu Sun, Ruzetuoheti Yiminniyaze, Xincheng Li, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8896926/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background This study aimed to compare the efficacy and procedural performance of pressure microcatheters and pressure guidewires for fractional flow reserve (FFR) measurement in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA). Methods This prospective observational study enrolled patients with CTEPH undergoing BPA between April 2022 and December 2025. FFR was sequentially measured using a pressure microcatheter (PMC) followed by a pressure guidewire (PW). Agreement between methods was evaluated using Bland–Altman analysis. Diagnostic performance of FFR (PMC) was assessed using receiver operating characteristic analysis, with FFR(PW) ≤ 0.80 as the reference standard. Results Seventy-five vessels were included. The mean FFR (PW) was 0.60 ± 0.17; the mean FFR (PMC) was 0.59 ± 0.18. The mean bias between methods was − 0.010, with 95% limits of agreement from − 0.071 to 0.052. FFR (PMC) demonstrated a sensitivity of 98.4% and specificity of 90.9%, with an area under the curve of 0.992 (p < 0.001). Conclusion FFR (PMC) shows excellent agreement and diagnostic accuracy compared with FFR (PW), supporting its use as an alternative physiological assessment during BPA in CTEPH. Chronic thromboembolic pulmonary hypertension Balloon pulmonary angioplasty Fractional flow reserve Pressure microcatheter Physiologic assessment Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive and potentially curable form of pulmonary hypertension characterized by persistent thromboembolic obstruction ( 1 – 4 ) and pulmonary vascular remodeling ( 5 – 8 ). For patients who are ineligible for pulmonary endarterectomy (PEA) or have residual pulmonary hypertension after surgery, balloon pulmonary angioplasty (BPA) has emerged as an established interventional therapy that improves hemodynamics, alleviates symptoms, and enhances long-term outcomes ( 9 – 12 ). As BPA techniques continue to advance, precise lesion selection and functional guidance have become increasingly important to maximize therapeutic benefit while minimizing procedural risk. Invasive physiological assessment using pressure-derived fractional flow reserve (FFR) has been proposed as an approach to quantify the functional significance of pulmonary arterial stenoses in CTEPH ( 13 – 15 ). Compared with coronary arteries, CTEPH lesions are often fibrotic, web-like, or band lesion, making wire manipulation challenging. Passage of the pressure wire across tight or irregular lesions carries a higher risk of vascular injury, including dissection and hemorrhage. Furthermore, the stability and reproducibility of pressure measurements can be affected by wire position and micro-instability in the low-pressure pulmonary artery system. A novel pressure microcatheter system, designed to be compatible with any 0.014-inch guidewire, has achieved widespread use in coronary physiological assessment. By incorporating a miniaturized pressure sensor within a low-profile catheter structure, this technology allows pressure measurements without relying on the mechanical characteristics of the wire itself ( 16 ). Consequently, the microcatheter can be advanced over a standard guidewire that has already safely crossed the lesion, thereby reducing crossing difficulty, minimizing trauma to delicate vessel segments, and potentially improving measurement consistency. Despite its success in coronary interventions ( 17 – 19 ), the applicability and clinical utility of pressure microcatheter–derived physiological assessment in the pulmonary arteries have not been systematically investigated. CTEPH lesion morphology, vessel compliance, and hemodynamic conditions differ substantially from the coronary circulation, making direct extrapolation uncertain. Establishing whether microcatheter-derived FFR correlates with standard pressure-wire measurements and whether it can be applied safely and efficiently during BPA is essential for determining its role as an alternative or improved physiological tool in this unique vascular territory. Accordingly, this study aims to evaluate the feasibility, diagnostic agreement, and safety of pressure microcatheter–based functional assessment in patients undergoing BPA for CTEPH. By comparing microcatheter-derived FFR measurements with those obtained using conventional pressure wires, we seek to determine whether this technology can overcome existing procedural limitations and offer a more reliable and practical physiological assessment method in pulmonary artery interventions. Methods Study Design and Cohort This prospective observational study was approved by the institutional review board of the China-Japan Friendship Hospital (No. 2021-136-K94) and in compliance with the Declaration of Helsinki. We enrolled patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital between April 2022 and December 2025. Inclusion criteria: ( 1 ) patients were between 18 and 75 years of age; ( 2 ) willing to conduct FFR (PW) measurements and FFR (PMC) measurements in the pulmonary artery; ( 3 ) signed informed consent. Exclusion criteria: incomplete clinical data. Clinical Characteristics The baseline information, including sex, age, medical history was collected. Cardiopulmonary assessment revealed NT-proBNP, with WHO functional class distribution and a 6-minute walk distance (6MWD). Hemodynamic parameters measured and calculated via RHC included mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance (PVR), and mixed venous oxygen saturation (SvO 2 ). Physiologic assessment Pressure Wire Derived FFR A standard 0.014-inch pressure wire (Verrata, Philips Volcano, San Diego, California, USA) was calibrated according to previously reported procedures ( 14 ), equalized to the guiding catheter pressure, and advanced across the target lesion. FFR was calculated as the ratio of distal to proximal pressure (Pd/Pa). Pressure Microcatheter Derived FFR Following standard guidewire crossing, a pressure microcatheter (TruePhysio, Insight Lifetech, Shenzhen, China) was advanced over the guidewire to the distal segment of the target lesion (Fig. 1 ). Calibration and equalization were performed per manufacturer instructions. Microcatheter-based Pd/Pa measurements were recorded under the same state as the pressure-wire assessment. If the pressure wire was used first, it was withdrawn while leaving the guidewire in place before advancing the microcatheter. If the microcatheter was used first, the guidewire remained unchanged to avoid bias from repeated crossing. Primary and secondary endpoints The primary endpoint for this study is the mean bias between FFR of MEMS-PMC and PW, as assessed by Bland–Altman analysis. Using FFR (PW) ≤ 0.80 as the dichotomous threshold for physiological significance. Other endpoints include the Pearson correlation coefficient, vessel diagnostic performance, the independent predictors for diagnostic agreement, Passing-Bablok regression, ROC analysis, device success and drift. Statistical analyses All statistical analyses were performed using R software. Continuous variables were assessed for normality using the Shapiro–Wilk test. Normally distributed data are expressed as mean ± SD, and non-normally distributed variables as median (IQR). Categorical variables are presented as counts and percentages. Group comparisons were performed with the unpaired t-test or Mann–Whitney U test, as appropriate. Changes in paired measurements were evaluated using the paired t-test or Wilcoxon signed-rank test. Categorical data were compared using the chi-square test or Fisher’s exact test, depending on expected frequencies. Correlation between FFR (PMC) and FFR (PW) was examined using Pearson correlation analysis. Agreement between the two measurements was assessed using Bland–Altman analysis, including the mean bias and 95% limits of agreement. Diagnostic performance metrics—sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy—were calculated using FFR(PW) ≤ 0.80 as the reference. The discriminatory ability of FFR (PMC) was evaluated using receiver operating characteristic (ROC) analysis, and the area under the curve (AUC) was reported with 95% confidence intervals. p -value < 0.05 was considered statistically significant. Results Baseline clinical and lesion Characteristics A total of 31 patients with CTEPH were analyzed in this study (Figure 2), with a mean age of 57.8±12.4 years. There were 17 male patients (54.8%). Medical history showed that 17 patients (54.8%) had pulmonary embolism, 18 patients (58.1%) had deep vein thrombosis, 5 patients (16.1%) had hypertension, and 3 patient each had coronary artery disease and diabetes mellitus (9.7% each). Oral anticoagulant medications included warfarin in 8 cases (25.8%) and rivaroxaban in 23 cases (74.2%). Other medications used were riociguat in 10 cases (32.3%), macitentan in 3 cases (9.7%), and sildenafil in 3 cases (9.7%). Additionally, the hemodynamics, exercise capacity, NT-proBNP levels, World Health Organization functional class (WHO FC) and 6MWD, are detailed in Table 1. Table 1 Baseline characteristics All patients (n=31) Age, years 57.8±12.4 Male, n (%) 17(54.8) History of PE, n (%) 17(54.8) History of DVT, n (%) 18 (58.1) Comorbidities, n (%) Coronary heart disease 3 (9.7) Diabetes 3(9.7) Hypertension 5 (16.1) Anticoagulants, n (%) Warfarin 8 (25.8) Rivaroxaban 23 (74.2) Targeted therapy, n (%) PDE5i 3 (9.7) ERA 3 (9.7) sGC stimulator 10 (32.3) Mean PAP (mmHg) 31.41±11.04 Cardiac output (L/min) 3.83±0.64 PVR (Wood Unit） 5.63±3.57 SvO2 (%） 73.47±8.05 NT-proBNP (pg/ml) 245.50 (44.51, 291.00) WHO-FC (n%) I 0 (0.00） II 16 (51.60） III 15 (48.40） IV 0 (0.00) 6MWD (m) 440.15±92.65 Abbreviation: PE, pulmonary embolism; DVT, deep vein thrombosis; PDE5i, phosphodiesterase 5 inhibitor; ERA, endothelin receptor antagonist; sGC, soluble guanylate cyclase; PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance; SvO 2 , mixed venous oxygen saturation; NT-proBNP, N-terminal pro-B-type natriuretic peptide; WHO-FC, World Health Organization functional class; 6MWD, 6-minute walking distance. This study included a total of 75 vessels with lesions. The mean FFR (PW) was 0.60±0.17; the mean FFR (PMC) was 0.59±0.18. The anatomical distribution of the lesioned vessels was as follows: 2 cases (2.7%) in the left upper lobe, 30 cases (40.0%) in the left lower lobe, 8 cases (10.7%) in the right upper lobe, 9 cases (12.0%) in the right middle lobe, and 26 cases (34.6%) in the right lower lobe. Selective pulmonary angiography (SPA) showed 29 cases (38.7%) of ring-like stenotic lesions, 44 cases (58.7%) of web lesions, and 2 cases (2.6%) of subtotal lesions. Detailed characteristics are summarized in Table 2. Table 2 Baseline characteristics of FFR, Vessel number, vascular location and Pulmonary artery lesions Vessel number (n) 75 Fractional flow reserve (PW) (`x±s) 0.60±0.17 FFR-Pa (PW) (mmHg) 38.30±10.96 FFR-Pd (PW) (mmHg) 21.26±7.42 Fractional flow reserve (PMC) (`x±s) 0.59±0.18 FFR-Pa (PMC) (mmHg) 37.12±10.73 FFR-Pd (PMC) (mmHg) 21.07±7.44 Vascular location, n (%) Left lung 32 (42.7) left lung upper lobe 2 (2.7) left lung lower lobe 30 (40.0) Right lung 43 (57.3) right lung upper lobe 8 (10.7) right lung middle lobe 9 (12.0) right lung lower lobe 26 (34.6) Pulmonary artery lesions, n (%) ring-like stenosis lesion 29 (38.7) web lesion 44 (58.7) subtotal lesion 2 (2.6) total occlusion lesion 0 (0.0) tortuous lesion 0 (0.0) Abbreviation: FFR, fractional flow reserve; PW, pressure wire; Pa, proximal pressure; Pd, distal pressure;PMC, pressure microcatheter. Primary endpoints Agreement Between FFR (PW) and FFR (PMC) A total of 75 paired FFR measurements obtained using a pressure wire and a microcatheter were included in the analysis. Bland–Altman analysis demonstrated a high level of agreement between the two measurement techniques. The mean difference (bias) between microcatheter FFR and pressure-wire FFR was −0.010, indicating a minimal systematic difference between the two methods. The standard deviation of the differences was 0.032. The 95% limits of agreement ranged from −0.071 to 0.052, with the vast majority of paired measurements lying within these limits (Figure 3). Bland–Altman plot showed no apparent trend in the differences across the range of mean FFR values, suggesting the absence of proportional bias. Agreement was consistent across both lower and higher FFR values, indicating stable measurement performance of the microcatheter-based approach throughout the clinically relevant FFR spectrum. Secondary endpoints Correlation, regression, diagnostic performance, and ROC analysis Using FFR (PW) ≤ 0.80 as the reference, FFR (PMC) demonstrated a sensitivity of 98.4% (95% CI: 91.7–99.7%), specificity of 90.9% (95% CI: 62.3–98.4%), positive predictive value of 98.4% (95% CI: 91.7–99.7%), and negative predictive value of 90.9% (95% CI: 62.3–98.4%). The diagnostic accuracy was 97.3% (95% CI: 90.8–99.3%) (Figure 4). The McNemar test showed no statistically significant difference in the diagnostic distribution between the two methods ( p =1.000), further confirming the interchangeability of the microcatheter system with the conventional pressure wire. The overall diagnostic accuracy of FFR (PMC) was further evaluated using receiver operating characteristic (ROC) analysis. The ROC curve demonstrated an area under the curve (AUC) of 0.992 (95% CI: 0.976–1.000, p < 0.001), indicating excellent diagnostic performance and near-perfect agreement between the two measurement methods (Figure 5). In addition, a strong linear relationship was observed between FFR (PMC) and FFR (PW)values (r = 0.983, p < 0.001), suggesting a very high level of consistency between the two measurement methods (Figure 6). Discussion This clinical study compared the performance of pressure wire-derived and pressure microcatheter-derived fractional flow reserve (FFR) in evaluating pulmonary arterial lesions in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The two techniques showed a high degree of agreement, as reflected by a strong correlation, minimal bias on Bland–Altman analysis, and consistently excellent diagnostic performance. Bland–Altman analysis shows the mean bias between the two systems is −0.010, with 95% limits of agreement (LoA) of 0.071 to 0.052. With respect to diagnostic agreement, using the cutoff FFR ≤ 0.80 as the reference, the FFR (PMC) demonstrated an accuracy of 97.3%, sensitivity of 98.4%, and specificity of 90.9%. These findings indicate that microcatheter-based FFR can reliably reflect physiological lesion severity in the pulmonary artery. In clinical practice, precise guidance and evaluation methods for BPA therapy in patients who were eligible for intervention remain lacking. Conventional approaches based on right heart catheterization (RHC) data and (PFG) (20, 21) lack quantification and depend on operators’ judgement. Studies have shown pressure wires to evaluate pulmonary artery lesions, which showed an accurate assessment for clinical treatment effects (22, 23). However, in complex pulmonary arterial lesions, advancing a pressure wire across the stenotic segment may carry risks such as vascular injury or wire deformation. In the coronary arteries field, pressure microcatheters have been widely adopted in clinical practice (24-26). Compared with pressure wires, pressure microcatheters provide several practical advantages. They are easier to handle, eliminate the need for wire exchanges, shorten procedural time, reduce radiation exposure, forward support force and streamline the workflow during BPA procedures in which multiple vessels are typically evaluated within a single session. Although concerns have been raised that the larger diameter of microcatheters may alter flow or artificially elevate pressure readings, the negligible average bias observed in this study suggests that such effects are minimal in the pulmonary arterial system. This may be attributable to the larger vessel caliber and lower baseline resistance of the pulmonary artery compared with coronary arteries. The consistency of FFR measurements across these lesion types further supports the robustness of the microcatheter method. These findings imply that physiological assessment using a microcatheter may enhance lesion selection, reduce unnecessary dilatation of hemodynamically insignificant segments, and potentially improve procedural efficiency and patient outcomes. Several limitations warrant consideration. First, this was a single-center analysis with a relatively small number of patients, which may limit broader applicability. Second, all measurements were obtained at rest. The optimal physiological testing conditions for the pulmonary artery remain debated, and whether additional stimuli could refine assessment is yet to be determined. Third, this study did not include follow-up data on BPA response or long-term hemodynamic improvement, preventing direct evaluation of whether FFR-guided strategies translate into clinical benefit. Larger, multicenter studies with longitudinal follow-up will be important to verify these findings and clarify the role of microcatheter-derived FFR in procedural planning. Conclusion In summary, this study demonstrates that microcatheter-derived FFR provides reliable and accurate physiological assessment of pulmonary arterial lesions in CTEPH, showing strong agreement with the pressure wire standard. Given its operational advantages and stable measurement characteristics, the pressure microcatheter represents a promising tool for more precise, physiology-based guidance during BPA. Declarations Author contributions Jinzhi Wang and Ruzetuoheti Yiminniyaze collected the clinical information and completed the manuscript. Wanmu Xie, Qian Gao, Shuai Zhang, Yunxia Zhang, Dingyi Wang, Zhu Zhang, Yu Zhang, Jixiang Liu, Linfeng Xi, Yuzhi Tao and Yanhua Kong completed data analysis and revised manuscript. Xincheng Li, Lu Sun, Haobo Li and Hanyu Zheng completed data analysis, Peiran Yang, Qiang Huang and Zhenguo Zhai were conception and design of the study. All authors approved the final version. Funding This study is supported by The National Key Research and Development Program of China (2023YFC2507200), CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-049). National High Level Hospital Clinical Research Funding（2022-NHLHCRF-LX-01-0203）. Data availability statement The data that support the findings of this study are available on request from the corresponding author. Competing interests None declared. Ethics approval and consent to participate This study was approved by the Institutional Review Board of China-Japan Friendship Hospital (No. 2021-136-K94). All patients provided written informed consent to participate in the study, and the study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Clinical trial number Not applicable. References Khangoora VS, Shlobin OA. Evolving spectrum of treatment for CTEPH. Curr Opin Pulm Med. 2020;26(5):406–13. Yang JZ, Poch DS, Ang L, Mahmud E, Kim NH. 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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-8896926","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":610065429,"identity":"1da67a45-b500-4ece-b5ad-3941ebd2fcd1","order_by":0,"name":"Jinzhi Wang","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinzhi","middleName":"","lastName":"Wang","suffix":""},{"id":610065430,"identity":"8644a550-3a06-4309-b35e-7d58ddff49eb","order_by":1,"name":"Haobo Li","email":"","orcid":"","institution":"China-Japan Friendship 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yunxia","middleName":"","lastName":"Zhang","suffix":""},{"id":610065440,"identity":"8dcb5a13-a51c-4f7a-b428-94b0bfc7ede2","order_by":11,"name":"Yanhua Kong","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanhua","middleName":"","lastName":"Kong","suffix":""},{"id":610065441,"identity":"93624b8d-986c-45b4-a9d8-ca598b676291","order_by":12,"name":"Dingyi Wang","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dingyi","middleName":"","lastName":"Wang","suffix":""},{"id":610065442,"identity":"3c82b581-7e82-42a6-84f6-922c1d8e807f","order_by":13,"name":"Zhu Zhang","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhu","middleName":"","lastName":"Zhang","suffix":""},{"id":610065443,"identity":"0ddcedb5-7372-4a2b-a982-af854d0338d0","order_by":14,"name":"Yu Zhang","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhang","suffix":""},{"id":610065444,"identity":"e5129b6e-cc38-4b42-ab55-51c80fb7eeb8","order_by":15,"name":"Jixiang Liu","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jixiang","middleName":"","lastName":"Liu","suffix":""},{"id":610065445,"identity":"b56830c6-b49a-4649-b5a1-8686b2101f9c","order_by":16,"name":"Linfeng Xi","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Linfeng","middleName":"","lastName":"Xi","suffix":""},{"id":610065446,"identity":"41d00dc3-9472-44c6-a31b-aa97c6be61ed","order_by":17,"name":"Peiran Yang","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Peiran","middleName":"","lastName":"Yang","suffix":""},{"id":610065447,"identity":"cea2217d-f484-4970-8d08-3fb964c01101","order_by":18,"name":"Qiang Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYBACAwbG9h8JP2x4+PkbiNbCfEDiYU+ajOSMA0RrYUuQfMB22MagIYFILebsOQYGCTzneQwYDjB++JhDhBbLnjcGCQkWt3nMmRuYJWduI8ZhN3IMDiTw3OaxbDjAxsxLpBbDhgS2czxAjURrSUtmSGA7QIqWM4+PMST2JPNIzjjYTKRfjie2Mf74YWfPz9988MNHYrQwMCTAGIwNRKlH1jIKRsEoGAWjAAcAAJsBOPJajTKgAAAAAElFTkSuQmCC","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":true,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Huang","suffix":""},{"id":610065448,"identity":"bca2412b-be1b-4c18-8d1e-945d7f470e05","order_by":19,"name":"Zhenguo Zhai","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhenguo","middleName":"","lastName":"Zhai","suffix":""}],"badges":[],"createdAt":"2026-02-17 01:53:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8896926/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8896926/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105351107,"identity":"b5fb4f78-cfe7-4eca-8a9a-fa04f47044fb","added_by":"auto","created_at":"2026-03-25 05:53:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":398394,"visible":true,"origin":"","legend":"\u003cp\u003eThe FFR (PMC) measuring procedure. Right anterior oblique 45°(a) and supine position (b). Selective pulmonary angiography of the left A9 pulmonary artery, with the white arrow indicating the pressure microcatheter positioned distal to the lesion for hemodynamic assessment. (c) Sequential pull-back of the pressure microcatheter from the distal to the proximal segment across the lesion.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/eae70b8a326bd8b45652f85a.png"},{"id":105351117,"identity":"f18d3c27-d0eb-45e7-a0dc-989ff4785a02","added_by":"auto","created_at":"2026-03-25 05:53:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":142438,"visible":true,"origin":"","legend":"\u003cp\u003eStudy Flowchart\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/83e9c2463c798332278d16ee.png"},{"id":105351129,"identity":"d8526f62-89b2-4f24-a60e-3424aebd2ce6","added_by":"auto","created_at":"2026-03-25 05:53:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33576,"visible":true,"origin":"","legend":"\u003cp\u003eThe Bland–Altman Plot. Bland–Altman plot showing the mean bias and limits of agreement (LOA) between the two FFR measurements. The mean bias was −0.010, with 95% LOA = [−0.071, 0.052], confirming negligible systematic difference and narrow agreement range.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/a899b855f078cd0bc29daf79.png"},{"id":105351191,"identity":"0a452a6a-ed65-4734-a296-b41f00667d0b","added_by":"auto","created_at":"2026-03-25 05:54:11","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":280256,"visible":true,"origin":"","legend":"\u003cp\u003eDiagnostic Performance of Microcatheter FFR (PMC). Sensitivity of 98.4% (95% CI: 91.7–99.7%), specificity of 90.9% (95% CI: 62.3–98.4%), positive predictive value (PPV) of 98.4% (95% CI: 91.7–99.7%), and negative predictive value (NPV) of 90.9% (95% CI: 62.3–98.4%) were calculated using pressure-wire FFR (≤0.80) as the reference standard. The diagnostic accuracy was 97.3% (95% CI: 90.8–99.3%)\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/2f5bf5e794b7deaf7047a6fb.png"},{"id":105351103,"identity":"fc4c6ee4-49ba-4f3b-bec3-0f3894c8394e","added_by":"auto","created_at":"2026-03-25 05:53:28","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":361524,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operator characteristic area under the curve. The receiver-operating characteristic (ROC) curve for FFR (PW) in detecting physiologically significant lesions defined by pressure wire FFR ≤ 0.80. The area under the curve (AUC) was 0.992 (95% CI: 0.976–1.000, \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001), indicating outstanding diagnostic accuracy.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/b53be44bbaa8f6b3122cc430.png"},{"id":105351113,"identity":"ed5f4b04-ae75-420d-8ced-276008accb82","added_by":"auto","created_at":"2026-03-25 05:53:32","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":632173,"visible":true,"origin":"","legend":"\u003cp\u003eThe correlation between FFR(PMC) and FFR(PW). A strong linear correlation was observed between the microcatheter FFR and the pressure wire FFR (r = 0.983, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/a79e9e5a17ee7cc05b6c1daf.png"},{"id":105565298,"identity":"22fccb81-2056-4dbb-827c-d31ffc0fe1fb","added_by":"auto","created_at":"2026-03-27 12:52:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2706873,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8896926/v1/275ffe21-ba2b-41f7-8aa8-7e24810f5607.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating the Efficacy of Pressure Microcatheters for Fractional Flow Reserve Measurement in Chronic Thromboembolic Pulmonary Hypertension: A Comparative Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic thromboembolic pulmonary hypertension (CTEPH) is a progressive and potentially curable form of pulmonary hypertension characterized by persistent thromboembolic obstruction (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) and pulmonary vascular remodeling (\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). For patients who are ineligible for pulmonary endarterectomy (PEA) or have residual pulmonary hypertension after surgery, balloon pulmonary angioplasty (BPA) has emerged as an established interventional therapy that improves hemodynamics, alleviates symptoms, and enhances long-term outcomes (\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). As BPA techniques continue to advance, precise lesion selection and functional guidance have become increasingly important to maximize therapeutic benefit while minimizing procedural risk.\u003c/p\u003e \u003cp\u003eInvasive physiological assessment using pressure-derived fractional flow reserve (FFR) has been proposed as an approach to quantify the functional significance of pulmonary arterial stenoses in CTEPH (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Compared with coronary arteries, CTEPH lesions are often fibrotic, web-like, or band lesion, making wire manipulation challenging. Passage of the pressure wire across tight or irregular lesions carries a higher risk of vascular injury, including dissection and hemorrhage. Furthermore, the stability and reproducibility of pressure measurements can be affected by wire position and micro-instability in the low-pressure pulmonary artery system.\u003c/p\u003e \u003cp\u003eA novel pressure microcatheter system, designed to be compatible with any 0.014-inch guidewire, has achieved widespread use in coronary physiological assessment. By incorporating a miniaturized pressure sensor within a low-profile catheter structure, this technology allows pressure measurements without relying on the mechanical characteristics of the wire itself (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Consequently, the microcatheter can be advanced over a standard guidewire that has already safely crossed the lesion, thereby reducing crossing difficulty, minimizing trauma to delicate vessel segments, and potentially improving measurement consistency.\u003c/p\u003e \u003cp\u003eDespite its success in coronary interventions (\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), the applicability and clinical utility of pressure microcatheter\u0026ndash;derived physiological assessment in the pulmonary arteries have not been systematically investigated. CTEPH lesion morphology, vessel compliance, and hemodynamic conditions differ substantially from the coronary circulation, making direct extrapolation uncertain. Establishing whether microcatheter-derived FFR correlates with standard pressure-wire measurements and whether it can be applied safely and efficiently during BPA is essential for determining its role as an alternative or improved physiological tool in this unique vascular territory.\u003c/p\u003e \u003cp\u003eAccordingly, this study aims to evaluate the feasibility, diagnostic agreement, and safety of pressure microcatheter\u0026ndash;based functional assessment in patients undergoing BPA for CTEPH. By comparing microcatheter-derived FFR measurements with those obtained using conventional pressure wires, we seek to determine whether this technology can overcome existing procedural limitations and offer a more reliable and practical physiological assessment method in pulmonary artery interventions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Cohort\u003c/h2\u003e \u003cp\u003eThis prospective observational study was approved by the institutional review board of the China-Japan Friendship Hospital (No. 2021-136-K94) and in compliance with the Declaration of Helsinki. We enrolled patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital between April 2022 and December 2025. Inclusion criteria: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) patients were between 18 and 75 years of age; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) willing to conduct FFR (PW) measurements and FFR (PMC) measurements in the pulmonary artery; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) signed informed consent. Exclusion criteria: incomplete clinical data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical Characteristics\u003c/h3\u003e\n\u003cp\u003eThe baseline information, including sex, age, medical history was collected. Cardiopulmonary assessment revealed NT-proBNP, with WHO functional class distribution and a 6-minute walk distance (6MWD). Hemodynamic parameters measured and calculated via RHC included mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance (PVR), and mixed venous oxygen saturation (SvO\u003csub\u003e2\u003c/sub\u003e).\u003c/p\u003e\n\u003ch3\u003ePhysiologic assessment\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePressure Wire Derived FFR\u003c/h2\u003e \u003cp\u003eA standard 0.014-inch pressure wire (Verrata, Philips Volcano, San Diego, California, USA) was calibrated according to previously reported procedures (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), equalized to the guiding catheter pressure, and advanced across the target lesion. FFR was calculated as the ratio of distal to proximal pressure (Pd/Pa).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePressure Microcatheter Derived FFR\u003c/h3\u003e\n\u003cp\u003e Following standard guidewire crossing, a pressure microcatheter (TruePhysio, Insight Lifetech, Shenzhen, China) was advanced over the guidewire to the distal segment of the target lesion (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Calibration and equalization were performed per manufacturer instructions. Microcatheter-based Pd/Pa measurements were recorded under the same state as the pressure-wire assessment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIf the pressure wire was used first, it was withdrawn while leaving the guidewire in place before advancing the microcatheter. If the microcatheter was used first, the guidewire remained unchanged to avoid bias from repeated crossing.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrimary and secondary endpoints\u003c/h2\u003e \u003cp\u003eThe primary endpoint for this study is the mean bias between FFR of MEMS-PMC and PW, as assessed by Bland\u0026ndash;Altman analysis. Using FFR (PW)\u0026thinsp;\u0026le;\u0026thinsp;0.80 as the dichotomous threshold for physiological significance. Other endpoints include the Pearson correlation coefficient, vessel diagnostic performance, the independent predictors for diagnostic agreement, Passing-Bablok regression, ROC analysis, device success and drift.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eAll statistical analyses were performed using R software. Continuous variables were assessed for normality using the Shapiro\u0026ndash;Wilk test. Normally distributed data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, and non-normally distributed variables as median (IQR). Categorical variables are presented as counts and percentages. Group comparisons were performed with the unpaired t-test or Mann\u0026ndash;Whitney U test, as appropriate. Changes in paired measurements were evaluated using the paired t-test or Wilcoxon signed-rank test. Categorical data were compared using the chi-square test or Fisher\u0026rsquo;s exact test, depending on expected frequencies. Correlation between FFR (PMC) and FFR (PW) was examined using Pearson correlation analysis. Agreement between the two measurements was assessed using Bland\u0026ndash;Altman analysis, including the mean bias and 95% limits of agreement. Diagnostic performance metrics\u0026mdash;sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy\u0026mdash;were calculated using FFR(PW)\u0026thinsp;\u0026le;\u0026thinsp;0.80 as the reference. The discriminatory ability of FFR (PMC) was evaluated using receiver operating characteristic (ROC) analysis, and the area under the curve (AUC) was reported with 95% confidence intervals. \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline clinical and lesion Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 31 patients with CTEPH were analyzed in this study\u0026nbsp;(Figure 2), with a mean age of 57.8\u0026plusmn;12.4 years. There were 17 male patients (54.8%). Medical history showed that 17 patients (54.8%) had pulmonary embolism, 18 patients (58.1%) had deep vein thrombosis, 5 patients (16.1%) had hypertension, and 3 patient each had coronary artery disease and diabetes mellitus (9.7% each). Oral anticoagulant medications included warfarin in 8 cases (25.8%) and rivaroxaban in 23 cases (74.2%). Other medications used were riociguat in 10 cases (32.3%), macitentan in 3 cases (9.7%), and sildenafil in 3 cases (9.7%).\u0026nbsp;Additionally, the hemodynamics, exercise capacity, NT-proBNP levels, World Health Organization functional class (WHO FC) and 6MWD, are detailed in Table 1.\u003c/p\u003e\n\u003cp\u003eTable 1 Baseline characteristics\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAll patients (n=31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57.8\u0026plusmn;12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17(54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistory of PE, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17(54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistory of DVT, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (58.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComorbidities, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCoronary heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnticoagulants, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWarfarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRivaroxaban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (74.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTargeted therapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePDE5i\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eERA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003esGC stimulator\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMean PAP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.41\u0026plusmn;11.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCardiac output (L/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.83\u0026plusmn;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePVR (Wood Unit）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.63\u0026plusmn;3.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSvO2\u0026nbsp;(%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e73.47\u0026plusmn;8.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNT-proBNP (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e245.50 (44.51, 291.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWHO-FC (n%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (51.60）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (48.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6MWD (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e440.15\u0026plusmn;92.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviation: PE, pulmonary embolism; DVT, deep vein thrombosis; PDE5i, phosphodiesterase 5 inhibitor; ERA, endothelin receptor antagonist; sGC, soluble guanylate cyclase;\u0026nbsp;PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance; SvO\u003csub\u003e2\u003c/sub\u003e, mixed venous oxygen saturation; NT-proBNP, N-terminal pro-B-type natriuretic peptide; WHO-FC, World Health Organization functional class; 6MWD, 6-minute walking distance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study included a total of 75 vessels with lesions. The mean FFR (PW) was 0.60\u0026plusmn;0.17; the mean FFR (PMC) was 0.59\u0026plusmn;0.18. The anatomical distribution of the lesioned vessels was as follows: 2 cases (2.7%) in the left upper lobe, 30 cases (40.0%) in the left lower lobe, 8 cases (10.7%) in the right upper lobe, 9 cases (12.0%) in the right middle lobe, and 26 cases (34.6%) in the right lower lobe. Selective pulmonary angiography (SPA) showed 29 cases (38.7%) of ring-like stenotic lesions, 44 cases (58.7%) of web lesions, and 2 cases (2.6%) of subtotal lesions. Detailed characteristics are summarized in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 2 Baseline characteristics of FFR,\u0026nbsp;Vessel number, vascular location and Pulmonary artery lesions\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVessel number (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFractional flow reserve (PW) (`x\u0026plusmn;s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.60\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFFR-Pa (PW) (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38.30\u0026plusmn;10.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFFR-Pd (PW) (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21.26\u0026plusmn;7.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFractional flow reserve (PMC) (`x\u0026plusmn;s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.59\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFFR-Pa (PMC) (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.12\u0026plusmn;10.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFFR-Pd (PMC) (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21.07\u0026plusmn;7.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVascular location, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft lung\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32 (42.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;left lung upper lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;left lung lower lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRight lung\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e43 (57.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eright lung upper lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;right lung middle lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9 (12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eright lung lower lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26 (34.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePulmonary artery lesions, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;ring-like stenosis lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29 (38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eweb lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e44 (58.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003esubtotal lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003etotal occlusion lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003etortuous lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: FFR, fractional flow reserve; PW, pressure wire; Pa, proximal pressure; Pd, distal pressure;PMC, pressure microcatheter.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary endpoints\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAgreement Between FFR (PW) and FFR (PMC)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 75 paired FFR measurements obtained using a pressure wire and a microcatheter were included in the analysis. Bland\u0026ndash;Altman analysis demonstrated a high level of agreement between the two measurement techniques. The mean difference (bias) between microcatheter FFR and pressure-wire FFR was \u0026minus;0.010, indicating a minimal systematic difference between the two methods. The standard deviation of the differences was 0.032. The 95% limits of agreement ranged from \u0026minus;0.071 to 0.052, with the vast majority of paired measurements lying within these limits (Figure 3). Bland\u0026ndash;Altman plot showed no apparent trend in the differences across the range of mean FFR values, suggesting the absence of proportional bias. Agreement was consistent across both lower and higher FFR values, indicating stable measurement performance of the microcatheter-based approach throughout the clinically relevant FFR spectrum.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary endpoints\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation, regression, diagnostic performance, and ROC analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing FFR (PW) \u0026le; 0.80 as the reference, FFR (PMC) demonstrated a sensitivity of 98.4% (95% CI: 91.7\u0026ndash;99.7%), specificity of 90.9% (95% CI: 62.3\u0026ndash;98.4%), positive predictive value of 98.4% (95% CI: 91.7\u0026ndash;99.7%), and negative predictive value of 90.9% (95% CI: 62.3\u0026ndash;98.4%). The diagnostic accuracy was 97.3% (95% CI: 90.8\u0026ndash;99.3%) (Figure 4). The McNemar test showed no statistically significant difference in the diagnostic distribution between the two methods (\u003cem\u003ep\u003c/em\u003e=1.000), further confirming the interchangeability of the microcatheter system with the conventional pressure wire.\u003c/p\u003e\n\u003cp\u003eThe overall diagnostic accuracy of FFR (PMC) was further evaluated using receiver operating characteristic (ROC) analysis. The ROC curve demonstrated an area under the curve (AUC) of 0.992 (95% CI: 0.976\u0026ndash;1.000, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), indicating excellent diagnostic performance and near-perfect agreement between the two measurement methods (Figure 5). In addition, a strong linear relationship was observed between FFR (PMC) and FFR (PW)values (r = 0.983, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001), suggesting a very high level of consistency between the two measurement methods (Figure 6).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis clinical study compared the performance of pressure wire-derived and pressure microcatheter-derived fractional flow reserve (FFR) in evaluating pulmonary arterial lesions in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The two techniques showed a high degree of agreement, as reflected by a strong correlation, minimal bias on Bland–Altman analysis, and consistently excellent diagnostic performance. Bland–Altman analysis shows the mean bias between the two systems is −0.010, with 95% limits of agreement (LoA) of 0.071 to 0.052. With respect to diagnostic agreement, using the cutoff FFR ≤ 0.80 as the reference, the FFR (PMC) demonstrated an accuracy of 97.3%, sensitivity of 98.4%, and specificity of 90.9%. These findings indicate that microcatheter-based FFR can reliably reflect physiological lesion severity in the pulmonary artery.\u003c/p\u003e\n\u003cp\u003eIn clinical practice, precise guidance and evaluation methods for BPA therapy in patients who were eligible for intervention remain lacking. Conventional approaches based on right heart catheterization (RHC) data and (PFG) (20, 21)\u0026nbsp;lack quantification and depend on operators’ judgement. Studies have shown pressure wires to evaluate pulmonary artery lesions, which showed an accurate assessment for clinical treatment effects\u0026nbsp;(22, 23). However, in complex pulmonary arterial lesions, advancing a pressure wire across the stenotic segment may carry risks such as vascular injury or wire deformation. In the coronary arteries field, pressure microcatheters have been widely adopted in clinical practice\u0026nbsp;(24-26).\u003c/p\u003e\n\u003cp\u003eCompared with pressure wires, pressure microcatheters provide several practical advantages. They are easier to handle, eliminate the need for wire exchanges, shorten procedural time, reduce radiation exposure, forward support force and streamline the workflow during BPA procedures in which multiple vessels are typically evaluated within a single session. Although concerns have been raised that the larger diameter of microcatheters may alter flow or artificially elevate pressure readings, the negligible average bias observed in this study suggests that such effects are minimal in the pulmonary arterial system. This may be attributable to the larger vessel caliber and lower baseline resistance of the pulmonary artery compared with coronary arteries.\u003c/p\u003e\n\u003cp\u003eThe consistency of FFR measurements across these lesion types further supports the robustness of the microcatheter method. These findings imply that physiological assessment using a microcatheter may enhance lesion selection, reduce unnecessary dilatation of hemodynamically insignificant segments, and potentially improve procedural efficiency and patient outcomes.\u003c/p\u003e\n\u003cp\u003eSeveral limitations warrant consideration. First, this was a single-center analysis with a relatively small number of patients, which may limit broader applicability. Second, all measurements were obtained at rest. The optimal physiological testing conditions for the pulmonary artery remain debated, and whether additional stimuli could refine assessment is yet to be determined. Third, this study did not include follow-up data on BPA response or long-term hemodynamic improvement, preventing direct evaluation of whether FFR-guided strategies translate into clinical benefit. Larger, multicenter studies with longitudinal follow-up will be important to verify these findings and clarify the role of microcatheter-derived FFR in procedural planning.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study demonstrates that microcatheter-derived FFR provides reliable and accurate physiological assessment of pulmonary arterial lesions in CTEPH, showing strong agreement with the pressure wire standard. Given its operational advantages and stable measurement characteristics, the pressure microcatheter represents a promising tool for more precise, physiology-based guidance during BPA.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJinzhi Wang and Ruzetuoheti Yiminniyaze collected the clinical information and completed the manuscript. Wanmu Xie, Qian Gao, Shuai Zhang, Yunxia Zhang, Dingyi Wang, Zhu Zhang, Yu Zhang, Jixiang Liu, Linfeng Xi, Yuzhi Tao and Yanhua Kong completed data analysis and revised manuscript. Xincheng Li, Lu Sun, Haobo Li and Hanyu Zheng completed data analysis, Peiran Yang, Qiang Huang and Zhenguo Zhai were conception and design of the study.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is supported by The National Key Research and Development Program of China (2023YFC2507200), CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-049). National High Level Hospital Clinical Research Funding（2022-NHLHCRF-LX-01-0203）.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of China-Japan Friendship Hospital (No. 2021-136-K94). All patients provided written informed consent to participate in the study, and the study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKhangoora VS, Shlobin OA. Evolving spectrum of treatment for CTEPH. Curr Opin Pulm Med. 2020;26(5):406\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang JZ, Poch DS, Ang L, Mahmud E, Kim NH. Balloon pulmonary angioplasty in the current era of CTEPH treatment: How did we get here? Pulm Circ. 2023;13(4):e12312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKataoka M, Inami T, Kawakami T, Fukuda K, Satoh T. Balloon Pulmonary Angioplasty (Percutaneous Transluminal Pulmonary Angioplasty) for Chronic Thromboembolic Pulmonary Hypertension: A Japanese Perspective. JACC Cardiovasc Interv. 2019;12(14):1382\u0026ndash;8.\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(38):3618\u0026ndash;731.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim NH, Channick R, Delcroix M, Madani M, Pepke-Zaba J, Borissoff JI, et al. Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial). Eur Respir J. 2024;64(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiedenroth CB, Steinhaus K, Rolf A, Breithecker A, Adameit MSD, Kriechbaum SD, et al. Patient-Reported Long-Term Outcome of Balloon Pulmonary Angioplasty for Inoperable CTEPH. Thorac Cardiovasc Surg. 2025;73(3):237\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuth S, Wilkens H, Halank M, Held M, Hobohm L, Konstantinides S, et al. [Chronic thromboembolic pulmonary hypertension]. Pneumologie. 2023;77(11):937\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelcroix M, Pepke-Zaba J, D'Armini AM, Fadel E, Guth S, Hoole SP, et al. Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy. Circulation. 2024;150(17):1354\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLang IM, Andreassen AK, Andersen A, Bouvaist H, Coghlan G, Escribano-Subias P, et al. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: a clinical consensus statement of the ESC working group on pulmonary circulation and right ventricular function. Eur Heart J. 2023;44(29):2659\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJa\u0026iuml;s X, Brenot P, Bouvaist H, Jevnikar M, Canuet M, Chabanne C, et al. Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study. Lancet Respir Med. 2022;10(10):961\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawakami T, Matsubara H, Shinke T, Abe K, Kohsaka S, Hosokawa K, et al. Balloon pulmonary angioplasty versus riociguat in inoperable chronic thromboembolic pulmonary hypertension (MR BPA): an open-label, randomised controlled trial. Lancet Respir Med. 2022;10(10):949\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCottin V, Bensimon L, Raguideau F, Chaize G, Hakm\u0026eacute; A, Levy-Bachelot L, et al. Hospital costs of Balloon Pulmonary Angioplasty (BPA) procedure and management for CTEPH patients: An observational study based on the French national hospital discharge database (PMSI). PLoS One. 2021;16(12):e0260483.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSatoh T, Yaoita N, Higuchi S, Nochioka K, Yamamoto S, Sato H, et al. Improving Balloon Pulmonary Angioplasty Through Target Endpoint Optimization With Pressure Catheter and Angiographic Lung Perfusion. JACC Cardiovasc Interv. 2024;17(20):2394\u0026ndash;407.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInami T, Kataoka M, Shimura N, Ishiguro H, Yanagisawa R, Fukuda K, et al. Pressure-wire-guided percutaneous transluminal pulmonary angioplasty: a breakthrough in catheter-interventional therapy for chronic thromboembolic pulmonary hypertension. JACC Cardiovasc Interv. 2014;7(11):1297\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIshiguro H, Kataoka M, Inami T, Shimura N, Yanagisawa R, Kawakami T, et al. Diversity of Lesion Morphology in CTEPH Analyzed by OCT, Pressure Wire, and Angiography. JACC Cardiovasc Imaging. 2016;9(3):324\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi C, Yang J, Dong S, Dong L, Chen J, Shen L, et al. Multicenter clinical evaluation of a piezoresistive-MEMS-sensor rapid-exchange pressure microcatheter system for fractional flow reserve measurement. Catheter Cardiovasc Interv. 2021;98(2):E243-e53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoutaleb AM, Scalia A, Ghafari C, Carlier S. Microcatheter-versus wire-based measurement of the fractional flow reserve. Acta Cardiol. 2023;78(9):1024\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDemir OM, Mitomo S, Mangieri A, Ancona MB, Regazzoli D, Lanzillo G, et al. Diagnostic Accuracy of Microcatheter Derived Fractional Flow Reserve. Am J Cardiol. 2019;124(2):183\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeligman H, Shun-Shin MJ, Vasireddy A, Cook C, Ahmad YY, Howard J, et al. Fractional flow reserve derived from microcatheters versus standard pressure wires: a stenosis-level meta-analysis. Open Heart. 2019;6(1):e000971.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFu Z, Xie W, Gao Q, Zhang S, Zhang Z, Zhang Y, et al. Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Disease: Success Rate and Complications among Different Patient Populations. Respiration. 2025;104(2):110\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInami T, Kataoka M, Shimura N, Ishiguro H, Yanagisawa R, Taguchi H, et al. Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty. JACC Cardiovasc Interv. 2013;6(7):725\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSu J, Manisty C, Parker KH, Simonsen U, Nielsen-Kudsk JE, Mellemkjaer S, et al. Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension. J Am Heart Assoc. 2017;6(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan JCY, Man HSJ, Asghar UM, McRae K, Zhao Y, Donahoe LL, et al. Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant. 2023;42(11):1578\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFearon WF, Chambers JW, Seto AH, Sarembock IJ, Raveendran G, Sakarovitch C, et al. ACIST-FFR Study (Assessment of Catheter-Based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement). Circ Cardiovasc Interv. 2017;10(12):e005905.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStables RH, Elguindy M, Kemp I, Nicholas Z, Mars C, Mullen L, et al. A randomised controlled trial to compare two coronary pressure wires using simultaneous measurements in human coronary arteries: the COMET trial. EuroIntervention. 2019;14(15):e1578-e84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWijntjens GW, van de Hoef TP, Kraak RP, Beijk MA, Sjauw KD, Vis MM, et al. The IMPACT Study (Influence of Sensor-Equipped Microcatheters on Coronary Hemodynamics and the Accuracy of Physiological Indices of Functional Stenosis Severity). Circ Cardiovasc Interv. 2016;9(12).\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Chronic thromboembolic pulmonary hypertension, Balloon pulmonary angioplasty, Fractional flow reserve, Pressure microcatheter, Physiologic assessment","lastPublishedDoi":"10.21203/rs.3.rs-8896926/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8896926/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study aimed to compare the efficacy and procedural performance of pressure microcatheters and pressure guidewires for fractional flow reserve (FFR) measurement in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis prospective observational study enrolled patients with CTEPH undergoing BPA between April 2022 and December 2025. FFR was sequentially measured using a pressure microcatheter (PMC) followed by a pressure guidewire (PW). Agreement between methods was evaluated using Bland\u0026ndash;Altman analysis. Diagnostic performance of FFR (PMC) was assessed using receiver operating characteristic analysis, with FFR(PW)\u0026thinsp;\u0026le;\u0026thinsp;0.80 as the reference standard.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSeventy-five vessels were included. The mean FFR (PW) was 0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17; the mean FFR (PMC) was 0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18. The mean bias between methods was \u0026minus;\u0026thinsp;0.010, with 95% limits of agreement from \u0026minus;\u0026thinsp;0.071 to 0.052. FFR (PMC) demonstrated a sensitivity of 98.4% and specificity of 90.9%, with an area under the curve of 0.992 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003e FFR (PMC) shows excellent agreement and diagnostic accuracy compared with FFR (PW), supporting its use as an alternative physiological assessment during BPA in CTEPH.\u003c/p\u003e","manuscriptTitle":"Evaluating the Efficacy of Pressure Microcatheters for Fractional Flow Reserve Measurement in Chronic Thromboembolic Pulmonary Hypertension: A Comparative Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-25 05:53:04","doi":"10.21203/rs.3.rs-8896926/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-19T14:28:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-19T11:13:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"22910025381670254623469002360617427170","date":"2026-04-19T10:53:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T05:07:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-04T13:27:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327241247453292355099996120050016015975","date":"2026-03-29T14:58:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264868685884695176010683327592850816088","date":"2026-03-19T21:08:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-19T20:45:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-20T10:09:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-20T06:05:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2026-02-19T15:22:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f85c4722-5774-450d-a63f-15d8343b7a86","owner":[],"postedDate":"March 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T07:08:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-25 05:53:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8896926","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8896926","identity":"rs-8896926","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}