Long-Term Effects of Pulmonary Endarterectomy on Right Ventricular Stiffness and Fibrosis in Chronic Thromboembolic Pulmonary Hypertension.

Autor:	Braams NJ; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Kianzad A; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., van Wezenbeek J; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Wessels JN; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Jansen SMA; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Andersen S; Department of Cardiology, Aarhus University Hospital, Denmark (S.A., A.A.)., Boonstra A; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.)., Nossent EJ; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Marcus JT; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.).; Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, the Netherlands (J.T.M., L.J.M.)., Bayoumy AA; Department of Internal Medicine, Chest Unit, Suez Canal University, School of Medicine, Ismailia, Egypt (A.A.B.)., Becher C; Department of Molecular Cell Biology, Leiden University Medical Centre, the Netherlands (C.B., M.-J.G.)., Goumans MJ; Department of Molecular Cell Biology, Leiden University Medical Centre, the Netherlands (C.B., M.-J.G.)., Andersen A; Department of Cardiology, Aarhus University Hospital, Denmark (S.A., A.A.)., Vonk Noordegraaf A; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., de Man FS; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Bogaard HJ; Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory, Department of Pulmonary Medicine, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., A.B., E.J.N., A.V.N., F.S.d.M., H.J.B.).; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.)., Meijboom LJ; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (N.J.B., A.K., J.v.W., J.N.W., S.M.A.J., E.J.N., J.T.M., A.V.N., F.S.d.M., H.J.B., L.J.M.).; Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, the Netherlands (J.T.M., L.J.M.).
Jazyk:	angličtina
Zdroj:	Circulation. Heart failure [Circ Heart Fail] 2023 Oct; Vol. 16 (10), pp. e010336. Date of Electronic Publication: 2023 Sep 07.
DOI:	10.1161/CIRCHEARTFAILURE.122.010336
Abstrakt:	Background: Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to the improvement of right ventricular (RV) function in the majority of patients with chronic thromboembolic pulmonary hypertension. However, RV mass does not always normalize. It is unknown whether incomplete reversal of RV remodeling results from extracellular matrix expansion (diffuse interstitial fibrosis) or cellular hypertrophy, and whether residual RV remodeling relates to altered diastolic function. Methods: We prospectively included 25 patients with chronic thromboembolic pulmonary hypertension treated with PEA. Structured follow-up measurements were performed before, and 6 and 18 months after PEA. With single beat pressure-volume loop analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV-arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed). The extracellular volume fraction of the RV free wall was measured by cardiac magnetic resonance imaging and used to separate the myocardium into cellular and matrix volume. Circulating collagen biomarkers were analyzed to determine the contribution of collagen metabolism. Results: RV mass significantly decreased from 43±15 to 27±11g/m 2 (-15.9 g/m 2 [95% CI, -21.4 to -10.5]; P <0.0001) 6 months after PEA but did not normalize (28±9 versus 22±6 g/m 2 in healthy controls [95% CI, 2.1 to 9.8]; P <0.01). On the contrary, Eed normalized after PEA. Extracellular volume fraction in the right ventricular free wall increased after PEA from 31.0±3.8 to 33.6±3.5% (3.6% [95% CI, 1.2-6.1]; P =0.013) as a result of a larger reduction in cellular volume than in matrix volume ( P interaction =0.0013). Levels of MMP-1 (matrix metalloproteinase-1), TIMP-1 (tissue inhibitor of metalloproteinase-1), and TGF-β (transforming growth factor-β) were elevated at baseline and remained elevated post-PEA. Conclusions: Although cellular hypertrophy regresses and diastolic stiffness normalizes after PEA, a relative increase in extracellular volume remains. Incomplete regression of diffuse RV interstitial fibrosis after PEA is accompanied by elevated levels of circulating collagen biomarkers, suggestive of active collagen turnover. Competing Interests: Disclosures All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this article.
Databáze:	MEDLINE
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