TY - JOUR
T1 - Right Atrial Adaptation to Precapillary Pulmonary Hypertension
T2 - Pressure-Volume, Cardiomyocyte, and Histological Analysis
AU - Wessels, Jeroen N.
AU - van Wezenbeek, Jessie
AU - de Rover, Jari
AU - Smal, Rowan
AU - Llucià-Valldeperas, Aida
AU - Celant, Lucas R.
AU - Marcus, J. Tim
AU - Meijboom, Lilian J.
AU - Groeneveldt, Joanne A.
AU - Oosterveer, Frank P. T.
AU - Winkelman, Toon A.
AU - Niessen, Hans W. M.
AU - Goumans, Marie-José
AU - Bogaard, Harm Jan
AU - Noordegraaf, Anton Vonk
AU - Strijkers, Gustav J.
AU - Handoko, M. Louis
AU - Westerhof, Berend E.
AU - de Man, Frances S.
N1 - Funding Information: The authors thank prof.dr. Coen Ottenheijm and Stefan Conijn of the Department of Physiology, Amsterdam UMC for their introduction and support on the cardiomyocyte set-up. Publisher Copyright: © 2023 The Authors
PY - 2023/8/22
Y1 - 2023/8/22
N2 - Background: Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. Objectives: This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses. Methods: RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis. Results: RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm2 accompanied by interstitial and perivascular fibrosis. Conclusions: RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.
AB - Background: Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. Objectives: This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses. Methods: RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis. Results: RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm2 accompanied by interstitial and perivascular fibrosis. Conclusions: RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.
KW - pressure-volume loop
KW - pulmonary arterial hypertension
KW - right atrioventricular coupling
KW - right atrium
KW - right ventricle
UR - http://www.scopus.com/inward/record.url?scp=85166908051&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jacc.2023.05.063
DO - https://doi.org/10.1016/j.jacc.2023.05.063
M3 - Article
C2 - 37587582
SN - 0735-1097
VL - 82
SP - 704
EP - 717
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 8
ER -