Multimodality RV Phenotyping for Risk Stratification and Short-Term Outcomes in Group 1 PAH

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.

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