Quantification and Significance of Pulmonary Vascular Volume in Predicting Response to Ultrasound-Facilitated, Catheter-Directed Fibrinolysis in Acute Pulmonary Embolism (SEATTLE-3D)
2019; Lippincott Williams & Wilkins; Volume: 12; Issue: 12 Linguagem: Inglês
10.1161/circimaging.119.009903
ISSN1942-0080
AutoresFarbod N. Rahaghi, Raúl San Jośe Estépar, Samuel Z. Goldhaber, Jasleen Minhas, Pietro Nardelli, Gonzalo Vegas‐Sánchez‐Ferrero, Isaac de La Bruere, Syed Moin Hassan, Stefanie Mason, Samuel Y. Ash, Carolyn E. Come, George R. Washko, Gregory Piazza,
Tópico(s)Radiation Dose and Imaging
ResumoHomeCirculation: Cardiovascular ImagingVol. 12, No. 12Quantification and Significance of Pulmonary Vascular Volume in Predicting Response to Ultrasound-Facilitated, Catheter-Directed Fibrinolysis in Acute Pulmonary Embolism (SEATTLE-3D) Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBQuantification and Significance of Pulmonary Vascular Volume in Predicting Response to Ultrasound-Facilitated, Catheter-Directed Fibrinolysis in Acute Pulmonary Embolism (SEATTLE-3D) Farbod N. Rahaghi, MD, PhD, Raúl San José Estépar, PhD, Samuel Z. Goldhaber, MD, Jasleen K. Minhas, MD, Pietro Nardelli, PhD, Gonzalo Vegas Sanchez-Ferrero, PhD, Isaac De La Bruere, BS, Syed M. Hassan, MD, Stefanie Mason, MD, Samuel Y. Ash, MD, MPH, Carolyn E. Come, MD, MPH, George R. Washko, MD, MS and Gregory Piazza, MD, MS Farbod N. RahaghiFarbod N. Rahaghi Farbod N. Rahaghi, MD, PhD, Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Email E-mail Address: [email protected] Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Raúl San José EstéparRaúl San José Estépar Applied Chest Imaging Laboratory, Department of Radiology (R.S.J.E., P.N., G.V.S.F.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Samuel Z. GoldhaberSamuel Z. Goldhaber Division of Cardiovascular Medicine (S.Z.G., G.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Jasleen K. MinhasJasleen K. Minhas Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Pietro NardelliPietro Nardelli Applied Chest Imaging Laboratory, Department of Radiology (R.S.J.E., P.N., G.V.S.F.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Gonzalo Vegas Sanchez-FerreroGonzalo Vegas Sanchez-Ferrero Applied Chest Imaging Laboratory, Department of Radiology (R.S.J.E., P.N., G.V.S.F.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Isaac De La BruereIsaac De La Bruere Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Syed M. HassanSyed M. Hassan Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Stefanie MasonStefanie Mason Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Samuel Y. AshSamuel Y. Ash Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , Carolyn E. ComeCarolyn E. Come Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. , George R. WashkoGeorge R. Washko Pulmonary and Critical Care Medicine (F.N.R., J.K.M., I.D.L.B., S.M.H., S.M., S.Y.A., C.E.C., G.R.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. and Gregory PiazzaGregory Piazza Division of Cardiovascular Medicine (S.Z.G., G.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Originally published17 Dec 2019https://doi.org/10.1161/CIRCIMAGING.119.009903Circulation: Cardiovascular Imaging. 2019;12:e009903In acute pulmonary embolism (PE), chest computed tomography (CT) provides both diagnostic and prognostic information. CT measures of lung vessel volume loss have been associated with clinical and hemodynamic measures in pulmonary vascular disease.1 Parenchymal vascular volume has also been shown to increase in response to vasodilatory challenges and therapy.2 In the SEATTLE II study, 150 subjects with acute massive or submassive PE with evidence of right heart strain were treated with ultrasound-facilitated, catheter-directed fibrinolysis. CT imaging was obtained at the time of diagnosis and 48 hours post-initiation of treatment. The primary clinical outcome was a reduction in right ventricular/left ventricular diameter ratio (RV/LV).3 We sought to determine if objective assessment of the intraparenchymal vasculature could provide insight into the relationship of the vascular volume with RV dilation in SEATTLE II. Our primary hypothesis was that the loss of distal vascular volume was associated with RV dilation and would be predictive of treatment response.Subjects with thin-sliced (<1.25 mm) CT scans having matching pre- and post-acquisition protocols without significant pneumonia or motion artifact were selected for this analysis. RV volume to LV volume (VRV/VLV) ratio was measured using a CT-based reconstruction.4 Lung segmentation, vessel detection, and measurement of vascular volumes were performed using a fully automated system. Arteries and veins were labeled using a convolutional neural network algorithm.5 Distal arterial and venous vessel volumes (VDISTAL_ART and VDISTAL_VEN) were measured in vessels <20 mm2 in cross-section with the remainder of the volume labeled as proximal (VPROXIMAL_ART and VPROXIMAL_VEN). All vascular measures were then normalized by the volume of the lung (eg, VDISTAL_ART/VLUNG and VDISTAL_VEN/VLUNG) and represented as milliliters of vasculature per liters of lung. The distal arterial-venous difference (VDISTAL_ART-VEN/VLUNG) was defined as the difference between the VDISTAL_ART/VLUNG and VDISTAL_VEN/VLUNG. The Modified Miller Index, a measurement of angiographic clot obstruction, was measured as part of SEATTLE II. The SEATTLE II study (in which informed consent for imaging was obtained) and this analysis (SEATTLE-3D) were approved by the Brigham and Women's Hospital Institutional Review Board (Boston, MA). Because of the sensitive nature of the data collected for this study, requests to access the data set from qualified researchers trained in human subject confidentiality protocols may be sent to the corresponding author.Seventeen subjects were identified as having matching, thin-sliced CT imaging. Both the heart and pulmonary vasculature were successfully reconstructed for all cases (Figure). At baseline, both decreased distal venous volume and increased distal arterial-venous difference were associated with RV dilation (Figure, VDISTAL_VEN/VLUNG R=−0.55, P=0.02; VDISTAL_ART-VEN/VLUNG R=0.62; P=0.008). Neither VDISTAL_ART/VLUNG (R=0.09, P=0.74) nor the proximal volumes were related to baseline VRV/VLV (VPROXIMAL_ART/VLUNG: R=0.32, P=0.21; VPROXIMAL_VEN/VLUNG R=0.36, P=0.16; and VPROXIMAL_ART-VEN/VLUNG R=0.19, P=0.46). Baseline Modified Miller Index was not related to baseline VRV/VLV (R=0.01, P=0.97). In response to therapy, there was a decrease in VRV/VLV (1.30±0.34 to 0.95±0.21; P=0.003) and an increase in VDISTAL_VEN/VLUNG (14.4±3.4 to 15.9±2.6; P=0.02) but not in VDISTAL_ART/VLUNG (25.8±3.3 to 26.5±3.9, P=0.40).Download figureDownload PowerPointFigure. Sample Images and reconstructions prior to, and after treatment with Ultrasound-facilitated catheter directed fibrinolysis as well as the relationship between vascular reconstruction parameters with baseline and change in right ventricular size.A, Three-dimensional heart surface model generated from the computed tomography (CT) scan is used to compute the right ventricular volume (VRV) and left ventricular volume (VLV) and the corresponding ratio (VRV/VLV), pre (A) and post (B) treatment with ultrasound-facilitated,catheter-directed fibrinolysis. Axial slices from pre and post-treatment show increased distal vessel visibility (C and D). CT vascular reconstruction before (E) and after treatment (F) show increased distal vasculature, labeled as arterial (blue) and venous (red) by an automated convolutional neural network trained on previously manually labeled data sets. Decreased distal venous vascular volume density at baseline is associated with increased VRV/VLV ratio at baseline (G) without similar finding on the arterial phase (H). The density of distal arterial volume adjusted by the venous volume is associated with increased baseline VRV/VLV ratio (I) and with VRV/VLV response to treatment (J).Baseline distal arterial and venous volumes did not predict the percent change in VRV/VLV (VDISTAL_ART/VLUNG R=0.35, P=0.17; VDISTAL_VEN/VLUNG R=0.26, P=0.32). However, an increased baseline arterial-venous difference (VDISTAL_ART-VEN/VLUNG) predicted a larger decrease in VRV/VLV in response to intervention (R=−0.58, P=0.01; Figure). Baseline proximal volumes and baseline Modified Miller Index were not predictive of change in VRV/VLV (VPROXIMAL_ART/VLUNG R=0.09, P=0.72; VPROXIMAL_VEN/VLUNG R=0.18, P=0.48; VPROXIMAL_ART-VEN/VLUNG R=0.01, P=0.96; Modified Miller Index R=0.17, P=0.52).In this study, we found that the distal venous vascular volume and the degree of difference between distal arterial and venous volumes were related to baseline RV dilation, with the latter also predictive of the degree of RV decompression after therapy. One possible mechanism for this observation includes the loss of flow distal to clot leading to a greater collapse of the venous bed compared to the arterial bed. However, the role of RV dysfunction in limiting contrast from reaching distal vasculature cannot be ruled out using this data. Nonetheless, this observation suggests that distal vascular volumes can serve as a quantifiable biomarker with potential utility in phenotyping, prognostication, and predicting treatment response. These findings also suggest that in addition to proximal clot burden, processes involving the distal vasculature may play an important role in the impact of PE on the right heart. Aside from proximal clot reduction and vasodilatory effect of oxygen therapy, possible mechanisms for distal vascular reperfusion may include fibrinolysis of small vessel thromboembolic material or in this case ultrasound-triggered modulation of pulmonary vasodilators and vasoconstrictors.Limitations to this study include cohort size, retrospective design, heterogeneity of scan acquisition protocols, and use of non-ECG gated scans to estimate cardiac size. SEATTLE II focused on a specific range of disease severity appropriate for thrombolysis, and only one type of intervention was tested with no control arm. While investigators were not blinded to outcomes, all analyses were performed using an automated pipeline. These automated methods allow for integration into radiological work-flow, making future clinical applications possible. Studies are planned to further model the relationship between CT based arterial and venous morphology with clinical and hemodynamic outcomes in acute PE and in response to treatment.AcknowledgmentsDr Piazza, Dr Goldhaber, Dr Rahaghi, and G.R. Washko have been involved from the conceptualization throughout to the generation of this article. Dr Piazza, Dr Goldhaber, Dr Rahaghi, and G.R. Washko were responsible for the design of the study and final interpretation of the data. Drs Piazza and Goldhaber designed and executed the original clinical trial (SEATTLE II). Dr Rahaghi, Dr San José Estépar, Dr Minhas, Dr Nardelli, Dr Vegas Sanchez-Ferrero, I. De La Bruere, Dr Mason, Dr Hassan, and Dr Ash contributed to the implementation of the analysis and generation of derived data and development of analysis code. All authors were involved in generation of the article.Sources of FundingThis study was supported, in part, by a research grant from EKOS, a BTG International Company, and in part by NHLBI grants 1R01HL116931 (Dr San José Estépar and G.R. Washko), 1K23HL136905 (Dr Rahaghi).DisclosuresDr Piazza's financial disclosures are BMS- grant/research support; Daiichi-Sankyo- grant/research support; BTG- grant/research support; Janssen- grant/research support; Bayer- grant/research support, advisory panel; Portola- grant/research support, advisory panel; and Pfizer- advisory panel. Dr Washko reports grants from National Institutes of Health, grants and other from Boehringer Ingelheim, other from Quantitative Imaging Solutions, other from PulmonX, grants from BTG Interventional Medicine, grants and other from Janssen Pharmaceuticals, other from GlaxoSmithKline, outside the submitted work; and Dr Washko's spouse works for Biogen which is focused on developing therapies for fibrotic lung disease. Dr Goldhaber reports research support and consultant fees from Portola Pharmaceuticals Inc. The other authors report no conflicts.FootnotesFarbod N. Rahaghi, MD, PhD, Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Email [email protected]harvard.eduReferences1. Rahaghi FN, Argemi G, Nardelli P, Dominguez-Fandos D, Arguis P, Peinado VI, Ross JC, Ash SY, de La Bruere I, Come CE, et alPulmonary vascular density: comparison of findings on computed tomography imaging with histology.Eur Respir J. 2019; 54:1900370. doi: 10.1183/13993003.00370-2019CrossrefMedlineGoogle Scholar2. Rahaghi FN, Winkler T, Kohli P, Nardelli P, Martí-Fuster B, Ross JC, Radhakrishnan R, Blackwater T, Ash SY, de La Bruere I, et alQuantification of the pulmonary vascular response to inhaled nitric oxide using noncontrast computed tomography imaging.Circ Cardiovasc Imaging. 2019; 12:e008338. doi: 10.1161/CIRCIMAGING.118.008338LinkGoogle Scholar3. Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, Jones NJ, Gurley JC, Bhatheja R, Kennedy RJ, et al; SEATTLE II Investigators. A prospective, single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II study.JACC Cardiovasc Interv. 2015; 8:1382–1392. doi: 10.1016/j.jcin.2015.04.020CrossrefMedlineGoogle Scholar4. Rahaghi FN, Vegas-Sanchez-Ferrero G, Minhas JK, Come CE, De La Bruere I, Wells JM, González G, Bhatt SP, Fenster BE, Diaz AA, et al; COPDGene Investigators. Ventricular geometry from non-contrast non-ECG-gated CT scans: an imaging marker of cardiopulmonary disease in smokers.Acad Radiol. 2017; 24:594–602. doi: 10.1016/j.acra.2016.12.007CrossrefMedlineGoogle Scholar5. Nardelli P, Jimenez-Carretero D, Bermejo-Pelaez D, Washko GR, Rahaghi FN, Ledesma-Carbayo MJ, San Jose Estepar R. Pulmonary artery-vein classification in CT images using deep learning.IEEE Trans Med Imaging. 2018; 37:2428–2440. doi: 10.1109/TMI.2018.2833385CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Klok F, Piazza G, Sharp A, Ní Ainle F, Jaff M, Chauhan N, Patel B, Barco S, Goldhaber S, Kucher N, Lang I, Schmidtmann I, Sterling K, Becker D, Martin N, Rosenfield K and Konstantinides S (2022) Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study, American Heart Journal, 10.1016/j.ahj.2022.05.011, 251, (43-53), Online publication date: 1-Sep-2022. Alenezi F, Covington T, Mukherjee M, Mathai S, Yu P and Rajagopal S (2022) Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart, Circulation Research, 130:9, (1445-1465), Online publication date: 29-Apr-2022. Piazza G (2021) Off the beaten path: the need for innovation in medical therapy to improve outcomes in acute pulmonary embolism, European Heart Journal. Acute Cardiovascular Care, 10.1093/ehjacc/zuab100, 11:1, (10-12), Online publication date: 12-Jan-2022. Minhas J, Nardelli P, Hassan S, Al-Naamani N, Harder E, Ash S, Sánchez-Ferrero G, Mason S, Hunsaker A, Piazza G, Goldhaber S, Waxman A, Kawut S, Estépar R, Washko G and Rahaghi F (2021) Loss of Pulmonary Vascular Volume as a Predictor of Right Ventricular Dysfunction and Mortality in Acute Pulmonary Embolism, Circulation: Cardiovascular Imaging, 14:9, (e012347), Online publication date: 1-Sep-2021. Piazza G (2021) Trailblazing in pulmonary embolism research: the importance of extending beyond randomized controlled trials, European Heart Journal. Acute Cardiovascular Care, 10.1093/ehjacc/zuab002, 10:3, (237-239), Online publication date: 11-May-2021. Piazza G (2020) Advanced Management of Intermediate- and High-Risk Pulmonary Embolism, Journal of the American College of Cardiology, 10.1016/j.jacc.2020.05.028, 76:18, (2117-2127), Online publication date: 1-Nov-2020. Piazza G, Sterling K, Tapson V, Ouriel K, Sharp A, Liu P and Goldhaber S (2020) One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism, Circulation: Cardiovascular Interventions, 13:8, Online publication date: 1-Aug-2020. December 2019Vol 12, Issue 12 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.119.009903PMID: 31842589 Originally publishedDecember 17, 2019 Keywordsfibrinolysiscomputed tomography angiographypulmonary embolismventricular dysfunction, rightPDF download Advertisement SubjectsAngiographyComputerized Tomography (CT)EmbolismThrombosisTreatment
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