TY - JOUR
T1 - When right ventricular pressure meets volume
T2 - The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension
AU - Fukumitsu, Masafumi
AU - Groeneveldt, Joanne A.
AU - Braams, Natalia J.
AU - Bayoumy, Ahmed A.
AU - Marcus, J. Tim
AU - Meijboom, Lilian J.
AU - de Man, Frances S.
AU - Bogaard, Harm-Jan
AU - Noordegraaf, Anton Vonk
AU - Westerhof, Berend E.
N1 - Funding Information: Dr M. Fukumitsu was supported by European Respiratory Society Short-Term Research Fellowship 2019 (STRF201904-00595) and Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad. Drs B. E. Westerhof and J. A. Groeneveldt were supported by NWO-VICI (918.16.610). Dr A. Bayoumy was supported by the Egyptian ministry of Higher education. Dr H-J Bogaard was supported by The Netherlands CardioVascular Research Initiative (CVON-2012-08 PHAEDRA, CVON-2017-10 DOLPHIN-GENESIS). Drs A. Vonk Noordegraaf and F. S. de Man were supported by The Netherlands CardioVascular Research Initiative (CVON-2012-08 PHAEDRA, CVON-2017-10 DOLPHIN-GENESIS) and The Netherlands Organization for Scientific Research (NWO-VIDI: 917.18.338, NWO-VICI: 918.16.610). Funding Information: Dr M. Fukumitsu was supported by European Respiratory Society Short‐Term Research Fellowship 2019 (STRF201904‐00595) and Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad. Drs B. E. Westerhof and J. A. Groeneveldt were supported by NWO‐VICI (918.16.610). Dr A. Bayoumy was supported by the Egyptian ministry of Higher education. Dr H‐J Bogaard was supported by The Netherlands CardioVascular Research Initiative (CVON‐2012‐08 PHAEDRA, CVON‐2017‐10 DOLPHIN‐GENESIS). Drs A. Vonk Noordegraaf and F. S. de Man were supported by The Netherlands CardioVascular Research Initiative (CVON‐2012‐08 PHAEDRA, CVON‐2017‐10 DOLPHIN‐GENESIS) and The Netherlands Organization for Scientific Research (NWO‐VIDI: 917.18.338, NWO‐VICI: 918.16.610). Funding Information: Dr N. J. Braams received a research grant from Actelion Pharmaceuticals. Dr J. T. Marcus received fees as a consultant for Actelion Pharmaceuticals. The remaining authors declare that they have no competing interests. Publisher Copyright: © 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
PY - 2022/5/15
Y1 - 2022/5/15
N2 - Abstract: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34–66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m–2, late-systolic return 44.4 ± 10.1 g m–2, diastolic return 42.8 ± 13.1 g m–2). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL–1. Wave speed was attenuated from 13.3 to 9.1 m s–1, and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. Key points: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.
AB - Abstract: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34–66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m–2, late-systolic return 44.4 ± 10.1 g m–2, diastolic return 42.8 ± 13.1 g m–2). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL–1. Wave speed was attenuated from 13.3 to 9.1 m s–1, and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. Key points: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.
KW - pulmonary artery–right ventricle coupling
KW - pulmonary hypertension
KW - right ventricle failure
KW - ventricular afterload
KW - wave reflection
UR - http://www.scopus.com/inward/record.url?scp=85128809015&partnerID=8YFLogxK
U2 - https://doi.org/10.1113/JP282422
DO - https://doi.org/10.1113/JP282422
M3 - Article
C2 - 35421903
SN - 0022-3751
VL - 600
SP - 2327
EP - 2344
JO - Journal of physiology
JF - Journal of physiology
IS - 10
ER -