Nitric Oxide Attenuates Arterial Pulse Wave Reflection in a Vasodilator Responding Pulmonary Arterial Hypertension Patient

HomeCirculation: Cardiovascular InterventionsVol. 11, No. 3Nitric Oxide Attenuates Arterial Pulse Wave Reflection in a Vasodilator Responding Pulmonary Arterial Hypertension Patient Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCase ReportPDF/EPUBNitric Oxide Attenuates Arterial Pulse Wave Reflection in a Vasodilator Responding Pulmonary Arterial Hypertension Patient Junjing Su, PhD, Alun D. Hughes, PhD, Ulf Simonsen, PhD and Luke S. Howard, DPhil Junjing SuJunjing Su From the Department of Biomedicine, Aarhus University, Denmark (J.S., U.S.); National Heart and Lung Institute, Imperial College London, United Kingdom (J.S., A.D.H., L.S.H.); and Institute of Cardiovascular Science, University College London, United Kingdom (A.D.H.). , Alun D. HughesAlun D. Hughes From the Department of Biomedicine, Aarhus University, Denmark (J.S., U.S.); National Heart and Lung Institute, Imperial College London, United Kingdom (J.S., A.D.H., L.S.H.); and Institute of Cardiovascular Science, University College London, United Kingdom (A.D.H.). , Ulf SimonsenUlf Simonsen From the Department of Biomedicine, Aarhus University, Denmark (J.S., U.S.); National Heart and Lung Institute, Imperial College London, United Kingdom (J.S., A.D.H., L.S.H.); and Institute of Cardiovascular Science, University College London, United Kingdom (A.D.H.). and Luke S. HowardLuke S. Howard From the Department of Biomedicine, Aarhus University, Denmark (J.S., U.S.); National Heart and Lung Institute, Imperial College London, United Kingdom (J.S., A.D.H., L.S.H.); and Institute of Cardiovascular Science, University College London, United Kingdom (A.D.H.). Originally published16 Mar 2018https://doi.org/10.1161/CIRCINTERVENTIONS.117.006242Circulation: Cardiovascular Interventions. 2018;11:e006242IntroductionPulmonary arterial hypertension (PAH) is characterized by distal vasoconstriction, vascular remodeling, microvascular injury, and thrombosis leading to increased pulmonary vascular resistance (PVR) and elevated mean pulmonary arterial pressure (PAPm). A small subset (<10%) of patients with idiopathic PAH (IPAH) respond profoundly (≥10 mm Hg drop in PAPm to ≤40 mm Hg with stable or increased cardiac output) to acute vasodilators, such as inhaled nitric oxide (NO).1 These patients have an excellent prognosis when treated with high-dose calcium channel blockers.1 The principal disease mechanism in this rare subtype of IPAH may be vasoconstriction with limited vascular remodeling. Here, we describe for the first time how inhaled NO influences arterial pulse wave propagation in such a vasoreactive IPAH patient.The patient was a 33-year-old woman undergoing right heart catheterization, which was performed using a dual-tipped pressure and Doppler flow sensor wire to acquire simultaneous pressure and flow velocity measurements in the right pulmonary artery at rest and during NO inhalation (20 PPM). Wave intensity analysis (with and without subtraction of reservoir pressure) and pressure separation were performed.2,3During vasoreactivity testing, PAPm and PVR decreased (31→17 mm Hg and 4.1→1.0 Wood U, respectively), whereas arterial compliance and cardiac output increased (3.1→6.5 mm Hg·mL and 5.6→6.6 L/min, respectively). Arterial pulse wave velocity decreased (5.1→3.1 m/s) indicative of decreased vessel stiffness. The energy the pulse wave (forward compression wave in the Figure) generated by right ventricular ejection increased consistent with improved cardiac performance, whereas wave reflection index, defined as the ratio of the reflected wave energy (backward compression wave in the Figure) to forward compression wave energy, decreased (54%→13%). The reflection time (Δt in the Figure) lengthened, and the apparent reflective site, calculated by multiplying pulse wave velocity by Δt/2, was 15 to 17 cm downstream of the measurement site. Forward (Pf) and backward (Pb) pressures and the Pb/Pf ratio decreased (66%→39%) in response to NO. Qualitatively similar results were observed when analysis was performed using excess pressure (after subtracting reservoir pressure from the measured pressure).Download figureDownload PowerPointFigure. Analyses of pulmonary arterial wave propagation. By analyzing the incremental changes in pressure and flow velocity (A and B), wave intensity analysis (WIA; C and D) determines the origin (forward vs backward), type (compression vs decompression), and timing of the arterial pulse waves and the energy carried by the waves per cross-sectional area of the artery. Forward compression wave (FCW, dark blue) was observed in early systole; it increased the pressure and flow and was related to right ventricular ejection. Backward compression wave (BCW, dark green) was observed in midsystole; it decreased the flow while increasing the pressure and can be ascribed to reflection of the preceding FCW caused by impaired energy transmission between the proximal and distal vasculature. In late systole, forward decompression wave (light blue) was observed; it decreased the pressure and flow and corresponded to right ventricular relaxation. The observed backward decompression wave (light green) in late systole was most likely related to velocity signal artifact attributed to axial movement of the catheter. A potential limitation of separating wave intensity into their forward and backward components is that it depends on the estimated pulse wave velocity, which may be inaccurate if the reflection site is close to the site of measurement. Conversely, net wave intensity is not subjected to this problem, and therefore, the contour of the net wave intensity profile is highlighted in red. When performing WIA using the excess pressure (E and F, after subtracting the reservoir pressure from the measured pressure), similar wave intensity patterns were observed. Pressure separation (G and H) deconstructs the measured pressure (Pm) waveform into forward (Pf) and backward (Pb) pressures. Note that the ratio of the magnitude of BCW/FCW and the ratio of peak Pb/Pf reduced substantially during nitric oxide vasoreactivity testing, whereas the reflection time (Δt) increased.Vasoconstriction and arterial stiffening compromise wave transmission between the proximal and distal vasculature leading to increased reflection. Reflected waves arriving during systole augment pressure and impede flow and therefore impose an additional load on the contracting ventricle. During NO challenge, wave reflection reduced indicative of improved energy transmission properties. Reflections also arrived later, probably because of the lower pulse wave velocity. The estimated apparent reflective site likely corresponds to the level of pulmonary small arteries or arterioles, where NO exerts its dominant effect suggesting that improved pulse wave transmission results from vascular smooth muscle relaxation. Wave reflection index is minimal (<5%) in individuals without pulmonary vascular disease.2 It is noteworthy that, despite normalization of PAPm and PVR during NO challenge, there was some residual wave reflection index (13%). This may be attributable to underlying vascular remodeling and incomplete vasodilatation.This extent of attenuation in arterial pulse wave reflection in response to an intervention has not been witnessed previously in man. In another study, wave reflection remained unchanged despite of a mild decrease in PVR during NO challenge, it may be relevant that this study cohort had severely elevated pulmonary pressures (PAPm: ≈63 mm Hg).4 Large wave reflection was present in untreated and chronically treated PAH patients, even in patients with mild PAH2; substantial wave reflection persisted in patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy despite decreased PAPm and PVR (J. Su, et al, unpublished data, 2018). Therefore, the pronounced reduction in wave reflection during NO inhalation may suggest near-normal pulmonary vascular structure in vasoreactive IPAH with the predominant abnormality being vasoconstriction of the pulmonary arterioles.In conclusion, in response to NO, arterial pulse wave energy increased, pulse wave velocity decreased, and reflection decreased. Clearly, the results from this single case study cannot be extrapolated to other vasoreactivity testing agents or to all NO responders. Nevertheless, it provided a unique insight into arterial wave behavior in vasoreactive IPAH.DisclosuresNone.FootnotesCorrespondence to Junjing Su, PhD, Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Denmark. E-mail [email protected]References1. 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Feasibility of routine pulmonary arterial impedance measurements in pulmonary hypertension.Chest. 2004; 125:2121–2128.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Umemoto S, Abe K, Hosokawa K, Horimoto K, Saku K, Sakamoto T and Tsutsui H (2022) Increased Pulmonary Arterial Compliance after Balloon Pulmonary Angioplasty Predicts Exercise Tolerance Improvement in Inoperable CTEPH Patients with Lower Pulmonary Arterial Pressure, Heart & Lung, 10.1016/j.hrtlng.2021.11.003, 52, (8-15), Online publication date: 1-Mar-2022. Nakano Y and Adachi S (2022) Implications of Pulmonary Artery Wave Reflection in Patients With Pulmonary Hypertension, Circulation Journal, 10.1253/circj.CJ-21-0981, 86:6, (956-957), Online publication date: 25-May-2022. Hayama H, Moroi M, Adachi-Akahane S, Uejima T, Hara H and Hiroi Y (2022) A Novel Non-Invasive Method for Estimating Elevated Pulmonary Vascular Resistance Based on Echocardiographic Assessment of Pulmonary Artery Wave Reflection, Circulation Journal, 10.1253/circj.CJ-21-0646, 86:6, (947-955), Online publication date: 25-May-2022. Yoshida T, Mandour A, Matsuura K, Shimada K, El-Husseiny H, Hamabe L, Yilmaz Z, Uemura A and Tanaka R (2021) Changes in the Pulmonary Artery Wave Reflection in Dogs with Experimentally-Induced Acute Pulmonary Embolism and the Effect of Vasodilator, Animals, 10.3390/ani11071977, 11:7, (1977) Yoshida T, Shimada K, Hamabe L, Uchide T, Tanaka R and Matsuura K (2021) Measurement of Pulmonary Artery Wave Reflection Before and After Mitral Valvuloplasty in Canine Patients With Pulmonary Hypertension Caused by Myxomatous Mitral Valve Disease, Frontiers in Veterinary Science, 10.3389/fvets.2021.773035, 8 Yoshida T, Matsuura K, Seijirow G, Uemura A, Yilmaz Z and Tanaka R (2021) Non-invasive Assessment of Pulmonary Artery Wave Reflection in Dogs With Suspected Pulmonary Hypertension, Frontiers in Veterinary Science, 10.3389/fvets.2021.659194, 8 Yoshida T, Uejima T, Komeda S, Matsuura K, Uemura A, Hayama H, Yamashita T, Yilmaz Z and Tanaka R (2021) Estimation of Pulmonary Arterial Wave Reflection by Echo-Doppler: A Preliminary Study in Dogs With Experimentally-Induced Acute Pulmonary Embolism, Frontiers in Physiology, 10.3389/fphys.2021.752550, 12 March 2018Vol 11, Issue 3 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.117.006242PMID: 29870387 Originally publishedMarch 16, 2018 Keywordsnitric oxidepulse wave analysishemodynamicspulmonary hypertensionarterial pressurePDF download Advertisement SubjectsHemodynamicsPathophysiologyPharmacologyPulmonary Hypertension