Right Atrial Adaptation to Precapillary Pulmonary Hypertension: Pressure-Volume, Cardiomyocyte, and Histological...

Area of Science:

• Cardiovascular Physiology
• Pulmonary Hypertension Pathophysiology
• Cardiac Mechanics

Background:

• Precapillary pulmonary hypertension (precPH) is associated with impaired right atrial (RA) function.
• Right ventricular (RV) diastolic stiffness is a key characteristic in precPH patients.
• Understanding RA mechanics is crucial for managing precPH.

Purpose of the Study:

• To investigate right atrial (RA) function in precPH using pressure-volume (PV) loops.
• To analyze isolated cardiomyocyte function and histological changes in the RA.
• To correlate RA function with RV diastolic stiffness.

Main Methods:

• Constructed RA PV loops from magnetic resonance and catheterization data in controls and precPH patients.
• Assessed RA stiffness and right atrioventricular coupling index in a larger cohort.
• Isolated cardiomyocytes from RA tissue and analyzed autopsy samples for histology (hypertrophy, capillarization, fibrosis).

Main Results:

• RA PV loops revealed dilatation and elevated pressure in precPH, with three distinct cardiac phases.
• Severe RV diastolic stiffness correlated with increased RA stiffness and poorer atrioventricular coupling.
• RA cardiomyocytes showed significant hypertrophy, but unaltered active tension; advanced precPH exhibited reduced capillary density and fibrosis.

Conclusions:

• RA PV loops indicate increased RA stiffness and potential atrioventricular uncoupling in severe RV diastolic stiffness.
• Isolated RA cardiomyocytes in precPH are hypertrophied but lack intrinsic sarcomeric alterations.
• End-stage precPH is characterized by reduced capillary density and interstitial/perivascular fibrosis.