Assessment of Right Ventricular Hemodynamic Force in Pediatric Pulmonary Hypertension Patients Following Initiation of Oral Treprostinil Therapy (RF_SA_466)

Presenting Author(s)

• SK

  Sarah E. Kollar, DO

  Advanced Imaging Cardiologist
  Children's National Hospital

Primary Author(s)

• SK

  Sarah E. Kollar, DO

  Advanced Imaging Cardiologist
  Children's National Hospital

Co-Author(s)

• FC

  Francesco Capuano, PhD

  Assistant Professor
  Universitat Politecnica deCatalunya Barcelona Tech, Spain
• SG

  Susana Gaviria, MD

  Pediatric Resident
  MedStar Georgetown
• 

  Yue-Hin Loke, MD

  Associate Professor
  Children's National Medical Center
• 

  Uyen Truong, MD

  Associate Professor
  Children's National Hospital
• SI

  Seiji Ito, MD

  Children's National Medical Center
• RV

  Ravi Vamsee Vegulla, MD

  Assistant Professor of Pediatrics
  Children's National Medical Center
• MU

  Michelle Udine, MD

  Advanced Imaging Cardiologist
  Children's National Medical Center

Background: Pulmonary hypertension (PH) is an incurable, progressive disease that contributes to significant morbidity and mortality. Cardiac catheterization is standard of care for diagnosis and serial monitoring of PH patients; however, it comes with significant risk of morbidity and mortality in pediatric PH patients.  Cardiac magnetic resonance (CMR) imaging provides critical information about the right ventricle (RV) and left ventricle (LV), and may have prognostic power over cardiac catheterization. Novel techniques such as hemodynamic force (HDF) can amplify minor mechanical adaptations and may be an early indicator of worsening disease severity. We aim to use CMR to assess for hemodynamic changes in pediatric PH patients who were initiated on oral treprostinil and compare these PH patients to healthy controls.

Methods: This is a retrospective analysis of a prospective multi-center study including 9 PH patients and 20 healthy pediatric controls. Patients with PH underwent a baseline CMR study, as well as a follow up study 24 weeks following initiation of oral treprostinil therapy. Amongst the PH patients, treprostinil was a new therapeutic agent for 3 of them, while the other 6 were transitioned from inhaled/intravenous treprostinil to oral treprostinil.  The CMR studies are from TDE-PH-206, a pediatric oral treprostinil study to investigate CMR parameters.  Feature-tracking (Qstrain, Medis) was performed on short/long-axis cine to capture RV and LV wall motion. Novel diffeomorphic mapping was used to generate kinematic models and calculate HDF vectors in the RV (apical-basal, septal-free wall, diaphragm-RVOT) throughout the cardiac cycle (Figure 1). HDF was correlated with RV and LV strain, volumetric data, and conventional functional parameters both pre and post initiation of oral treprostinil therapy. 

Results: Eighteen CMR studies from 9 patients were compared against 20 controls. Average baseline RV ejection fraction (EF) was 48±6% compared to post oral treprostinil initiation RV EF 52±6% (p = 0.188). Average baseline RV global longitudinal strain (GLS) was -20.5±3% compared to post oral treprostinil initiation RV GLS -23.3±2% (p = 0.025). PH patients had decreased RV apical-basal, septal-free wall, and diaphragm-RVOT HDF across multiple points in the cardiac cycle compared to controls (Figure 2). Patients who were transitioned from intravenous/inhaled treprostinil to oral treprostinil maintained the same HDF throughout the cardiac cycle (Figure 2). There was significant difference in RV whole cycle RMS HDF, RV systolic RMS HDF, and RV diastolic RMS HDF between patients with PH and healthy controls (p < 0.0001).  Increase in LV end systolic volume index correlated with increased systolic RMS HDF, while improved RV EF correlated with increased diastolic RMS HDF (Figure 3).

Conclusion: Cine-derive HDF is significantly altered in PH.  Decreased systolic HDF may be a novel indicator of subclinical myocardial dysfunction in conjunction with conventional CMR testing in pediatric PH patients.  Future studies will investigate HDF as a biomarker of disease progression and therapeutic response.

Figure 1: (A) MRI-based reference frame in the RV demonstrating apical-to-basal (red), diaphragm-to-RVOT (blue), and septal-to-free wall (green) coordinate axes of HDF. (B) Methodology of using 3D modeling and feature tracking of cine imaging to derive HDF.

Figure 2: Mean HDF over the entire cardiac cycle, phases #1-30, for the RV in the apical-basal, septal-free wall, and diaphragm-RVOT axes. Statistically significant difference between PH and control patients for each phase in the cardiac cycle are denoted by * p < 0.05, ** p < 0.01, *** p < 0.001. There was no significant difference in HDF following transition from intravenous/inhaled treprostinil to oral treprostinil.

Figure 3: (A) Increase in LV end systolic volume index (LV ESVi) correlated with increased systolic HDF RMS (r = 0.598, p = 0.009). (B) Increased RV ejection fraction (EF) correlated with increased diastolic HDF RMS (r = 0.666, p = 0.003).