Introduction: Right Ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) is the major cause of mortality. Myocardial architecture determines the basis of heart function and can be assessed by generalized Q-space imaging by MRI (GQI), yet remains understudied in the RV. Therefore, we assessed myocardial fiber architecture patterns and correlated them with disease severity in two models of PAH.
Methods: PAH was induced in Sprague-Dawley (SD) and Fischer (CDF) male rats by SU5416 (20 mg/kg; s.c.) followed by 3 wks of hypoxia (10% FiO2). Controls received vehicle and were kept at normoxia. After 4 wks, echocardiography and hemodynamics were performed. Whole hearts were resected in some animals (SD n=9, CDF n=8) and imaged via high-angular resolution GQI using a 7T magnet (512 directions, b=750 s/mm2). Patterns of inter-voxel coherence (tractography) were reconstructed, and transmural helix angle distribution (HAD) were assessed at 3 points across the LV and RV (Panel A) and normalized to a common vector. Finite-element models were developed via registering myofiber direction to anatomical mesh.
Results: Both animal strains developed PAH, however CDF rats had lower pulmonary artery acceleration time (140.6 vs. 191.3 ms, p<0.05) and TAPSE (1.50.06 vs. 1.90.09 mm, p<0.05) and higher RV afterload (1023167 vs. 28517, mmHg/mL p<0.05) compared to SD. PAH was associated with steeper slope of the RV transmural HAD in both SD and CDF vs. controls and slightly higher in CDF-PAH compared to SD-PAH (Panel B). No significant changes were noted in the LV (Panel C). Moreover, the RV HAD slope significantly correlated to RV functional parameters (TAPSE r= 0.58, RV global longitudinal strain r= -0.49) and RA area (r= -0.58). Transmural and regional variation in fiber direction was also observed (Panel D).
Conclusion: Myoarchitectural analysis of the RV in the setting of PAH reveals that myocardial HAD relates to functional parameters and may be a marker of maladaptation.