Right Atrial Fibrosis in Pulmonary Hypertension (RAFE-PH)

The study aim to assess right atrial (RA) remodeling, in terms of RA fibrosis, in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients. This will be investigated in detail with in-depth cardiac magnet resonance imaging (CMRI). A cohort with exclusion of pulmonary hypertension which underwent CMRI due to dyspnoe of unkown reason will be the control group.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension; Pulmonary Hypertension; Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Diagnostic test: cardiac magnetic resonance imaging

Detailed Description

Right atrial (RA) function consists of a reservoir, conduit, and active contractile function and can serve as a tool for the evaluation of the severity of RV dysfunction and prognosis in pulmonary hypertension according to recent data. In-depth evaluation of phasic RA function was previously undertaken either by echocardiographic speckle tracking or by cardiac magnetic resonance (CMR) imaging-derived feature tracking. However, it is currently unknown if right atrial remodeling is present.

As described for left atrial fibrosis, the presence and extent of atrial fibrosis can be quantified using CMR late gadolinium enhancement. The protocol for the assessment of left atrial fibrosis will be used and adapted to the RA. Patients will undergo 3-dimensional late gadolinium enhancement CMRI along with a contrast-enhanced magnetic resonance angiography and cine imaging in order to define the anatomy of the RA and the superior and inferior vein. High-resolution late gadolinium enhancement images of the RA will be acquired 15 to 30 min after gadolinium-based contrast agents administration using a 3-dimensional inversion-recovery prepared, respiration navigated, and electrocardiogram triggered gradient-echo pulse sequence with fat saturation. Following acquisition of the scans, the endocardial borders of the RA will be defined in each slice by manual tracing. After manual adjustment of the epicardial RA surface, the quantification of fibrosis based on the relative intensity (signal intensity) of late gadolinium enhancement will be performed. Finally, a 3-dimensional model of the RA will be rendered with the maximum enhancement intensities being projected on the model surface.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Germany
  • Hesse
    • Bad Nauheim, Hesse, Germany
      • Kerckhoff-Klinik
    • Gießen, Hesse, Germany, 35390
      • University of Gießen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

40 subjects with pulmonary arterial hypertension, group 1 and chronic thromboembolic pulmonary hypertension, group 4; Patients with invasive exclusion of pulmonary hypertension undergoing diagnostic right heart catheterisation due to dyspnoe will serve as control

Description

Inclusion Criteria:

• Confirmed diagnosis of pulmonary arterial hypertension, WHO group 1 or chronic thromboembolic pulmonary hypertension, group 4
• Invasive exclusion of pulmonary hypertension
• Age ≥ 18 years
• Signed informed consent
• planned right heart catheterization based on clinical grounds

Exclusion Criteria:

• Other etiologic groups of pulmonary hypertension (WHO group 2, 3, 5)
• Patients with congenital heart disease
• Atrial septal defects
• Clinical relevant left heart disease
• Atrial fibrillation / Atrial flutter
• Ablations of the right atrium
• History of major cardiac surgery
• Atrial occlude
• Metallic implants
• Pacemakers
• Severe renal impairment (eGFR < 30 ml/min)
• Other severe disease with a life expectancy below 12 month
• Pregnancy
• Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results
• Intolerance to a contrast agent containing gadolinium
• Inability to perform a cardiac magnetic resonance imaging (claustrophobia or similar)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulmonary arterial hypertension; Patients with mean pulmonary arterial pressure above 25 mmHg, and a pulmonary capillary wedge pressure below 15 mmHg classified into group 1 of the clinical classification of pulmonary hypertension.	Diagnostic test: cardiac magnetic resonance imaging; right atrial late gadolinium enhancement in % and cm2
Chronic thromboembolic pulmonary hypertension; Patients with mean pulmonary arterial pressure above 25 mmHg, and a pulmonary capillary wedge pressure below 15 mmHg with a history of pulmonary embolism, classified into group 4 of the clinical classification of pulmonary hypertension.	Diagnostic test: cardiac magnetic resonance imaging; right atrial late gadolinium enhancement in % and cm2
Control; Patients with invasive exclusion of pulmonary hypertension (mean pulmonary arterial pressure below 25 mmHg) undergoing diagnostic CMRI due to the evaluation of dyspnoea.	Diagnostic test: cardiac magnetic resonance imaging; right atrial late gadolinium enhancement in % and cm2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
atrial fibrosis	right atrial late gadolinium enhancement in % and cm2	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of right atrial fibrosis with functional and exercise capacity	right atrial late gadolinium enhancement in % and cm2 correlated with 6minute walking distance in m or peak oxygen uptake in ml/min/kg	1 day
Correlation of right atrial fibrosis with remodeling of the right atrium, backflow and systemic congestion	right atrial late gadolinium enhancement in % and cm2 correlated with right atrial size (volume and cm2) and inferior vena cava diameter in cm2	1 day
Correlation of right atrial fibrosis with pulmonary hemodynamics	right atrial late gadolinium enhancement in % and cm2 correlated with mean right atrial pressure	1 day
Correlation of right atrial fibrosis with load-independent right ventricular function assessed by pressure-volume loop catheterization	right atrial late gadolinium enhancement in % and cm2 correlated with end-systolic to arterial elastance	1 day
Correlation of right atrial fibrosis with biomarkers	right atrial late gadolinium enhancement in % and cm2 correlated with B-type natriuretic peptide in pg/ml	1 day
Prognostic relevance of right atrial fibrosis	right atrial late gadolinium enhancement in % and cm2 as a predictor of clinical worsening or death	1 day

Collaborators and Investigators

• Sponsor: University of Giessen
• Investigators: Principal Investigator: Richter Manuel, MD, UKGM Giessen

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: AZ 12320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No