NCT07522203

Arterial Wave Energy Flux and Multidimensional Recovery in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Balloon Pulmonary Angioplasty

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 70 (estimated)
• Sponsor: Istanbul Mehmet Akif Ersoy Educational and Training Hospital · Other Government
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The goal of this observational study is to learn if advanced heart pressure wave analysis (called WIA and REPA) can help track and predict clinical improvement in adults (aged 18-85) with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) who are undergoing Balloon Pulmonary Angioplasty (BPA). The main questions it aims to answer are: Do changes in these advanced heart pressure wave patterns relate to improvements in a patient's walking distance, heart function, and overall quality of life after BPA treatment? Are these new measurements more effective than standard heart pressure tests at showing how much a patient has truly improved? Participants will: Undergo standard Balloon Pulmonary Angioplasty (BPA) sessions as part of their regular medical care for CTEPH. Have their heart pressure waves recorded through a catheter during the routine BPA procedure (this does not require any extra surgical steps). Complete walking tests (6-minute walk test), blood tests, and heart ultrasounds (echocardiography) before starting the treatment and after it is completed. Fill out short surveys regarding their daily physical activity and quality of life.

Detailed description

This prospective observational study aims to investigate the relationship between pulsatile wave-based hemodynamic metrics (WIA and REPA) derived from pulmonary artery pressure waveforms and multidimensional clinical improvement (RV strain, 6MWT, NT-proBNP, and quality of life) in CTEPH patients undergoing BPA. The study will be conducted within standard clinical care without additional invasive interventions. 2\. BACKGROUND AND RATIONALE 2.1 Definition and Importance CTEPH (Group 4 PH) results from organized thromboembolic material in the pulmonary arteries causing obstruction and microvascular disease. Diagnosis requires imaging (V/Q, CTPA) and confirmation via RHC. 2.2 Role of BPA BPA is indicated for patients who are technically inoperable or have persistent PH after PEA. Current guidelines support BPA for improving hemodynamics and functional capacity. 2.3 Limitations of Standard Parameters Traditional metrics (mPAP, PVR) represent steady-flow relationships. RV afterload is also dictated by pulsatile load (compliance and reflections). In CTEPH, proximal obstructions and distal disease timing significantly influence RV remodeling and clinical response. 2.4 Modern Hemodynamic Methods: WIA and REPA WIA identifies forward and backward compression waves (FCW, BCW) and expansion waves (FEW) within the cardiac cycle. REPA decomposes the pressure waveform into reservoir pressure (Pr), representing arterial storage, and excess pressure (Pxs), representing the dynamic wave component. 2.5 Study Rationale Clinical responses to BPA are heterogeneous and not always fully explained by mPAP or PVR. This study explores whether pulsatile metrics (WIA/REPA) provide earlier or more sensitive markers of clinical recovery or predict procedural success. 3\. OBJECTIVES AND HYPOTHESES 3.1 Primary Objective To evaluate the relationship between changes in WIA/REPA parameters (delta-WIA, delta-REPA) and multidimensional clinical improvement following sequential BPA sessions. 3.2 Secondary Objectives * Compare the strength of wave-based metrics versus traditional metrics (mPAP etc.) in predicting clinical outcomes. * Define temporal patterns of wave metrics intra-session (pre-post) and inter-session. * Explore the relationship between baseline wave metrics and safety outcomes (e.g., lung injury, hemoptysis). * Evaluate the discriminatory power (ROC-AUC) of WIA/REPA for responders versus non-responders. 3.3 Hypothesis Improvements in WIA and REPA parameters derived from PA pressure waveforms significantly correlate with multidimensional clinical improvement after BPA. 4\. STUDY DESIGN 4.1 Summary A prospective, single-center, observational cohort study. Consecutive patients scheduled for BPA for CTEPH will be enrolled. Measurements occur during routine clinical procedures. Data analysis is performed offline. 4.2 Timeline * T0 (Baseline): Clinical assessment, NT-proBNP, Echo (TAPSE), 6MWT, and EQ-5D-5L before the first BPA session. * During BPA: PA pressure waveform recording before and after each session. * Post-Session: Clinical and functional assessments repeated as per the evaluation schedule. * Final Follow-up: Final assessment 1 month after the last BPA session. 5. ETHICAL CONSIDERATIONS The study complies with the Declaration of Helsinki. Ethical Committee approval was obtained. Written informed consent will be obtained from all participants. Personal data will be pseudonymized. 6\. STUDY POPULATION 6.1 Inclusion Criteria * Age 18-85 years. * Confirmed CTEPH diagnosis eligible for BPA. * Hemodynamics: mPAP \>20 mmHg, PAWP \<=15 mmHg, and PVR \>2 WU. * Technically inoperable or persistent/recurrent PH post-PEA. 6.2 Exclusion Criteria * Predominant PH diagnosis other than CTEPH or severe parenchymal lung disease. * Active infection, uncontrolled systemic disease, malignancy, or life expectancy \<12 months. * Pregnancy or lactation. * Advanced renal failure (eGFR \<30 mL/min/1.73 m2) or contrast contraindication. * Inadequate Echo quality for strain analysis. * Significant artifacts in pressure tracings or uncontrolled arrhythmias (e.g., rapid AF). 7\. DATA COLLECTION AND MEASUREMENTS 7.1 RHC Hemodynamics Routine parameters (RA, sPAP/dPAP/mPAP, CO/CI, PVR, PAC) will be recorded. 7.2 PA Pressure Waveform Acquisition • Sampling rate: \>=100 Hz. • Recording: Minimum 8-10 consecutive artifact-free beats after stabilization. * Timing: Pre-intervention and post-intervention at each BPA session. 7.3 WIA and REPA Methodology A pressure-only approach will be utilized. WIA will quantify FCW, BCW, FEW, and the Wave Reflection Index (WRI). REPA will estimate reservoir pressure, excess pressure, the diastolic time constant (tau), and asymptotic pressure (Pinf). 7.4 Multidimensional Outcome Measures * RV Function: TAPSE * Functional Capacity: 6-minute walk distance (6MWD). * Biomarkers: NT-proBNP. * Quality of Life: EQ-5D-5L index and VAS. 8. ENDPOINTS 8.1 Primary Endpoint The continuous correlation/association between delta-WIA/REPA and changes in the four clinical domains (RV strain, 6MWD, NT-proBNP, and EQ-5D-5L). 8.2 Secondary Endpoints * Composite Clinical Response Score (Z-score based). * Intra-session vs. inter-session hemodynamic trends. * Predictive value for procedural complications. 9. STATISTICAL ANALYSIS PLAN Analyses will be performed using R and Python (alpha=0.05). * Descriptive Statistics: Mean +/- SD or Median (IQR). * Primary Analysis: Correlation (Pearson/Spearman) and linear regression between delta-metrics and clinical endpoints. * Modeling: Generalized Linear Mixed Models (GLMM) with patient ID as a random intercept to account for repeated BPA sessions. * Non-linear modeling: Restricted Cubic Splines (RCS) to assess non-linear relationships. * Added Value: Net Reclassification Improvement (NRI) for wave metrics over standard hemodynamics. 10\. SAMPLE SIZE AND POWER For a primary correlation analysis with two-sided alpha=0.05 and 80% power to detect a conservative effect size of r=0.33, approximately 70 evaluable patients are required. To account for technical dropouts and loss-to-follow-up, a target enrollment of \>=80 patients is planned. For pilot analysis, 40 patients will be enrolled. 11\. SAFETY AND MONITORING As an observational study, BPA complications (Reperfusion Lung Injury, hemoptysis, vessel injury) will be managed according to institutional protocols and recorded using standardized definitions. Serious Adverse Events (SAEs) will be reported to the Ethical Committee.

Conditions

• CTEPH
• Pulmonary Hypertension (PH)

Interventions

Type	Name	Description
PROCEDURE	Balloon Pulmonary Angioplasty	Balloon Pulmonary Angioplasty as per procedural standards

Timeline

• Start date: 2026-03-10
• Primary completion: 2028-04-01
• Completion: 2028-05-01
• First posted: 2026-04-13
• Last updated: 2026-04-13

Locations

1 site across 1 country: Turkey (Türkiye)