Multimodality RV Phenotyping for Risk Stratification and Short-Term Outcomes in Group 1 PAH (MIRROR-PAH)
Multimodality Imaging-Based Right Ventricular Phenotyping for Risk Stratification and Short-Term Outcomes in Group 1 Pulmonary Arterial Hypertension: The MIRROR-PAH Study
The MIRROR-PAH is a single-center, prospective, observational cohort study evaluating the incremental value of multimodality imaging-derived right ventricular characteristics for risk stratification in patients with Group 1 pulmonary arterial hypertension (PAH). The study aims to determine whether incorporation of echocardiographic and cardiac magnetic resonance (CMR)-derived right ventricular parameters into established non-invasive risk assessment models results in risk reclassification and improves identification of patients at risk for short-term clinical worsening.
Adult patients with established Group 1 PAH undergoing routine follow-up and with available right heart catheterization (RHC) and CMR data will be consecutively enrolled. Clinical, laboratory, echocardiographic, and follow-up data will be prospectively collected over a 6-month period. Associations between multimodality imaging findings, invasive hemodynamic measurements, risk classification, and short-term clinical outcomes will be evaluated.
Study Overview
Status
Detailed Description
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling, increased pulmonary vascular resistance, and progressive right ventricular (RV) pressure overload. Despite substantial advances in targeted therapies, morbidity and mortality remain high, and patient prognosis is largely determined by the ability of the right ventricle to adapt to the increased afterload imposed by the pulmonary circulation.
Current clinical practice guidelines recommend periodic risk assessment to guide treatment decisions and monitor disease progression. Contemporary non-invasive risk stratification models incorporate clinical, functional, and biochemical parameters, including World Health Organization (WHO) functional class, exercise capacity, and natriuretic peptide levels. Although cardiac imaging provides important information regarding right ventricular structure and function and is widely used during the evaluation and follow-up of patients with PAH, imaging parameters are not routinely incorporated into simplified follow-up risk assessment models. Consequently, a considerable proportion of patients remain classified within intermediate-risk categories, representing a heterogeneous population with variable clinical trajectories and therapeutic needs.
Multimodality cardiac imaging provides comprehensive assessment of right ventricular structure, function, and remodeling. Echocardiography remains the cornerstone imaging modality for routine evaluation and longitudinal follow-up of PAH patients, while cardiac magnetic resonance (CMR) offers highly accurate and reproducible quantification of right ventricular volumes and function. Several imaging-derived parameters have been associated with disease severity and adverse outcomes in PAH. In addition, invasive hemodynamic assessment obtained by right heart catheterization (RHC) provides important prognostic information regarding pulmonary vascular disease and right ventricular adaptation. The integration of imaging and hemodynamic information may therefore provide incremental value beyond conventional non-invasive risk assessment strategies.
The MIRROR-PAH Study (Multimodality Imaging-Based Right Ventricular Phenotyping for Risk Stratification and Short-Term Outcomes in Group 1 Pulmonary Arterial Hypertension) is a single-center, prospective, observational cohort study designed to evaluate the relationship between multimodality imaging-derived right ventricular characteristics, invasive hemodynamic measurements, established risk assessment models, and short-term clinical outcomes in patients with Group 1 PAH.
Adult patients with established Group 1 PAH who are undergoing routine follow-up and have available RHC and CMR examinations will be consecutively enrolled. Baseline clinical, laboratory, echocardiographic, hemodynamic, and CMR data will be collected. Follow-up clinical assessment and transthoracic echocardiography will be performed at 6 months.
The primary objective of the study is to determine whether incorporation of multimodality imaging-derived right ventricular (RV) characteristics into established non-invasive PAH risk assessment models results in risk reclassification at baseline and at 6-month follow-up.
Secondary objectives are to:
- Evaluate the predictive value of imaging-augmented risk reclassification for composite clinical worsening during follow-up;
- Assess the incidence of composite clinical worsening, defined as PAH treatment escalation, PAH-related hospitalization, worsening WHO functional class, decline in 6-minute walk distance, or death;
- Identify multimodality imaging-derived RV characteristics associated with an increased risk of short-term clinical worsening;
- Evaluate the relationship between multimodality imaging-derived RV characteristics and invasive hemodynamic measurements obtained by right heart catheterization (RHC);
- Identify multimodality imaging-derived RV characteristics associated with high-risk classification according to established PAH risk stratification models;
- Evaluate changes in echocardiographic RV characteristics between baseline and 6-month follow-up;
- Assess the incremental prognostic value of multimodality imaging-derived RV characteristics beyond established non-invasive PAH risk assessment models for predicting clinical worsening.
The study is based on the hypothesis that multimodality assessment of right ventricular structure and function provides clinically relevant information beyond conventional non-invasive risk stratification models and may improve identification of patients at increased risk of disease progression and short-term adverse outcomes. By integrating echocardiographic, CMR, and invasive hemodynamic information, the MIRROR-PAH Study aims to explore the potential role of imaging-enhanced risk assessment in refining prognostic evaluation and supporting clinical decision-making during follow-up of patients with PAH.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Aybüke Geylan, MD
- Phone Number: +905061258579
- Email: aybukegeylan@gmail.com
Study Contact Backup
- Name: Barış Güven, MD
- Phone Number: +905321137507
- Email: guvenbariss@gmail.com
Study Locations
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Istanbul, Turkey (Türkiye)
- Recruiting
- Istanbul University Cerrahpasa Institute of Cardiology
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Contact:
- Aybüke Geylan, MD
- Phone Number: +905061258579
- Email: aybukegeylan@gmail.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adults aged 18 years or older
- Diagnosis of Group 1 pulmonary arterial hypertension (PAH) according to ESC/ERS guidelines
- Followed at the study center with a diagnosis of PAH
- Availability of right heart catheterization (RHC) and cardiac magnetic resonance (CMR) imaging data obtained within a clinically relevant time interval
- Availability of analyzable clinical, imaging, and hemodynamic data
- Willingness to participate in the study and provision of written informed consent
Exclusion Criteria:
- Age younger than 18 years
- Pulmonary hypertension groups other than Group 1 PAH (Groups 2-5 PH)
- Absence of either right heart catheterization or cardiac magnetic resonance imaging data within a clinically relevant time interval
- Incomplete clinical or imaging data preventing analysis
- Unavailable follow-up data
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Patients with Group 1 Pulmonary Arterial Hypertension
Participants are adult patients with established Group 1 pulmonary arterial hypertension (PAH) undergoing follow-up at a specialized pulmonary hypertension center.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Risk reclassification rate after incorporation of multimodality imaging-derived RV characteristics into established non-invasive PAH risk models
Time Frame: Baseline and 6-month follow-up
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The proportion of patients undergoing risk reclassification after incorporation of multimodality imaging-derived right ventricular (RV) characteristics obtained from echocardiography and cardiac magnetic resonance imaging into established non-invasive PAH risk assessment models will be evaluated.
Changes in risk category assignment compared with conventional non-invasive risk stratification will be assessed.
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Baseline and 6-month follow-up
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of Participants Experiencing Composite Clinical Worsening
Time Frame: 6 months
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Composite clinical worsening is defined as the occurrence of at least one of the following events during the 6-month follow-up period: pulmonary arterial hypertension (PAH) treatment escalation, PAH-related hospitalization, worsening World Health Organization (WHO) functional class, decline in 6-minute walk distance, or death.
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6 months
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Change in Predictive Performance for Composite Clinical Worsening After Addition of RV Imaging Characteristics to Conventional PAH Risk Classification
Time Frame: 6 months
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The predictive performance of conventional three-strata pulmonary arterial hypertension risk classification for 6-month composite clinical worsening will be compared with the predictive performance of an imaging-augmented risk classification incorporating predefined right ventricular imaging characteristics.
Predictive performance will be assessed using the area under the receiver operating characteristic curve.
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6 months
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RV imaging characteristics associated with clinical worsening
Time Frame: 6 months
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Multimodality imaging-derived RV characteristics associated with an increased risk of composite clinical worsening will be identified.
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6 months
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Agreement Between Cardiovascular Magnetic Resonance-Derived Stroke Volume Index and Right Heart Catheterization-Derived Stroke Volume Index
Time Frame: Baseline
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Agreement between stroke volume index (mL/m²) measured by cardiovascular magnetic resonance imaging using ventricular volumetric analysis and stroke volume index (mL/m²) calculated from cardiac output obtained during right heart catheterization will be assessed at baseline using Bland-Altman analysis.
The mean difference in stroke volume index (mL/m²) between the two methods will be reported.
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Baseline
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RV imaging characteristics associated with high-risk status
Time Frame: Baseline and 6-month follow-up
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Multimodality imaging-derived RV characteristics associated with high-risk classification according to established PAH risk assessment models will be identified.
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Baseline and 6-month follow-up
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Change in Right Ventricular Free-Wall Longitudinal Strain From Baseline to 6 Months
Time Frame: Baseline to 6 months
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Change in right ventricular free-wall longitudinal strain (%) measured by two-dimensional speckle-tracking echocardiography will be assessed between baseline and the 6-month follow-up.
The mean change in right ventricular free-wall longitudinal strain (%) from baseline to 6 months will be reported.
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Baseline to 6 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Aybüke Geylan, MD, Istanbul University Cerrahpasa Institute of Cardiology
- Study Chair: Umit Yasar Sinan, Professor, Istanbul University Cerrahpasa Institute of Cardiology
Publications and helpful links
General Publications
- Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Radegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023 Jan 6;61(1):2200879. doi: 10.1183/13993003.00879-2022. Print 2023 Jan. No abstract available.
- Lewis RA, Johns CS, Cogliano M, Capener D, Tubman E, Elliot CA, Charalampopoulos A, Sabroe I, Thompson AAR, Billings CG, Hamilton N, Baster K, Laud PJ, Hickey PM, Middleton J, Armstrong IJ, Hurdman JA, Lawrie A, Rothman AMK, Wild JM, Condliffe R, Swift AJ, Kiely DG. Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2020 Feb 15;201(4):458-468. doi: 10.1164/rccm.201909-1771OC.
- Dardi F, Boucly A, Benza R, Frantz R, Mercurio V, Olschewski H, Radegran G, Rubin LJ, Hoeper MM. Risk stratification and treatment goals in pulmonary arterial hypertension. Eur Respir J. 2024 Oct 31;64(4):2401323. doi: 10.1183/13993003.01323-2024. Print 2024 Oct.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2026/171
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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