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. 2023 Aug 22;82(8):704-717.
doi: 10.1016/j.jacc.2023.05.063.

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

Jeroen N Wessels  1 , Jessie van Wezenbeek  1 , Jari de Rover  2 , Rowan Smal  1 , Aida Llucià-Valldeperas  1 , Lucas R Celant  1 , J Tim Marcus  3 , Lilian J Meijboom  3 , Joanne A Groeneveldt  1 , Frank P T Oosterveer  1 , Toon A Winkelman  4 , Hans W M Niessen  5 , Marie-José Goumans  6 , Harm Jan Bogaard  1 , Anton Vonk Noordegraaf  1 , Gustav J Strijkers  7 , M Louis Handoko  8 , Berend E Westerhof  1 , Frances S de Man  9
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Free article

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

Jeroen N Wessels et al. J Am Coll Cardiol. .
Free article

Abstract

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.

Keywords: pressure-volume loop; pulmonary arterial hypertension; right atrioventricular coupling; right atrium; right ventricle.

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Conflict of interest statement

Funding Support and Author Disclosures Drs Bogaard, Vonk Noordegraaf, Goumans, and de Man were supported by the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences (CVON-2012-08 PHAEDRA, CVON-2018-29 PHAEDRA-IMPACT, and CVON-2017-10 Dolphin-Genesis). Drs Vonk Noordegraaf and de Man were further supported by the Netherlands Organization for Scientific Research (NWO-VICI: 918.16.610, NWO-VIDI: 917.18.338). Dr de Man was supported by a Dutch Heart Foundation Dekker senior postdoc grant (2018T059). Drs Bogaard and Vonk Noordegraaf have received research grant support from Actelion, GSK, and Ferrer (Therabel). Dr de Man has received research grant support from Janssen and BIAL. Dr Handoko has received consultancy/speaker fees from Novartis, Boehringer Ingelheim, AstraZeneca, Vifor, Bayer, MSD, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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