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1. Recovery of right ventricular function after intermediate-risk pulmonary embolism: results from the multicentre Pulmonary Embolism International Trial (PEITHO)-2

Author

Mavromanoli, A.C., Barco, S., Ageno, W., Bouvaist, H., Brodmann, M., Cuccia, C., Couturaud, F., Dellas, C., Dimopoulos, K., Duerschmied, D., Empen, K., Faggiano, P., Ferrari, E., Galie, N., Galvani, M., Ghuysen, A., Giannakoulas, G., Huisman, M.V., Jimenez, D., Kozak, M., Lang, I.M., Meneveau, N., Munzel, T., Palazzini, M., Petris, A.O., Piovaccari, G., Salvi, A., Schellong, S., Schmidt, K.H., Verschuren, F., Schmidtmann, I., Toenges, G., Klok, F.A., Konstantinides, S.V., and PEITHO-2 Investigators

Subjects
Science & Technology, Cardiac & Cardiovascular Systems, Pulmonary embolism, WORKING GROUP, General Medicine, ASSOCIATION, GUIDELINES, EUROPEAN-SOCIETY, DYSFUNCTION, Echocardiography, Dysfunction, Cardiovascular System & Cardiology, MANAGEMENT, HEART, Right ventricle, Intermediate-risk, Cardiology and Cardiovascular Medicine, FOLLOW-UP, Life Sciences & Biomedicine, CARDIOLOGY
Abstract

Background Right ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe. Methods Echocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure. Results RV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180. Conclusion In the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term. Graphical Abstract

Published
2022

2. ESC/ERS 2015 guidelines for the diagnosis and treatment of pulmonary hypertension

Author

Galie N., Humbert M., Vachiery J. -L., Gibbs S., Lang I., Torbicki A., Simonneau G., Peacock A., Noordegraaf A. V., Beghetti M., Ghofrani A., Sanchez M. A. G., Hansmann G., Klepetko W., Lancellotti P., Matucci M., McDonagh T., Pierard L. A., Trindade P. T., Zompatori M., Hoeper M., Aboyans V., Carneiro A. V., Achenbach S., Agewall S., Allanore Y., Asteggiano R., Badano L., Barbera J. A., Bouvaist H., Bueno H., Byrne R. A., Carerj S., Castro G., Erol C., Falk V., Funck-Brentano C., Gorenflo M., Grantonc J., Iung B., Kiely D. G., Kirchhof P., Kjellstrom B., Landmesser U., Lekakis J., Lionis C., Lip G. Y. H., Orfanos S. E., Park M. H., Piepoli M. F., Ponikowski P., Revel M. -P., Rigau D., Rosenkranz S., Voller H., Zamorano J. L., Galie, N, Humbert, M, Vachiery, J, Gibbs, S, Lang, I, Torbicki, A, Simonneau, G, Peacock, A, Noordegraaf, A, Beghetti, M, Ghofrani, A, Sanchez, M, Hansmann, G, Klepetko, W, Lancellotti, P, Matucci, M, Mcdonagh, T, Pierard, L, Trindade, P, Zompatori, M, Hoeper, M, Aboyans, V, Carneiro, A, Achenbach, S, Agewall, S, Allanore, Y, Asteggiano, R, Badano, L, Barbera, J, Bouvaist, H, Bueno, H, Byrne, R, Carerj, S, Castro, G, Erol, C, Falk, V, Funck-Brentano, C, Gorenflo, M, Grantonc, J, Iung, B, Kiely, D, Kirchhof, P, Kjellstrom, B, Landmesser, U, Lekakis, J, Lionis, C, Lip, G, Orfanos, S, Park, M, Piepoli, M, Ponikowski, P, Revel, M, Rigau, D, Rosenkranz, S, Voller, H, and Zamorano, J

Subjects
practice guideline, pulmonary hypertension, human, Review, medical society
Published
2016

3. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

Author

Galie N., Humbert M., Vachiery J. -L., Gibbs S., Lang I., Torbicki A., Simonneau G., Peacock A., Vonk Noordegraaf A., Beghetti M., Ghofrani A., Gomez Sanchez M. A., Hansmann G., Klepetko W., Lancellotti P., Matucci M., McDonagh T., Pierard L. A., Trindade P. T., Zompatori M., Hoeper M., Aboyans V., Vaz Carneiro A., Achenbach S., Agewall S., Allanore Y., Asteggiano R., Badano L., Albert Barbera J., Bouvaist H., Bueno H., Byrne R. A., Carerj S., Castro G., Erol C., Falk V., Funck-Brentano C., Gorenflo M., Granton J., Iung B., Kiely D. G., Kirchhof P., Kjellstrom B., Landmesser U., Lekakis J., Lionis C., Lip G. Y. H., Orfanos S. E., Park M. H., Piepoli M. F., Ponikowski P., Revel M. -P., Rigau D., Rosenkranz S., Voller H., Luis Zamorano J., Myftiu S., Bonderman D., Firdovsi I., Lazareva I., De Pauw M., Sokolovic S., Velchev V., Cikes M., Moutiris J. A., Jansa P., Nielsen-Kudsk J. E., Anton L., Jaaskelainen P., Bauer F., Chukhrukidze A., Opitz C., Giannakoulas G., Karlocai K., Oddsson O., Gaine S., Menachemi D., Emdin M., Sooronbaev T., Rudzitis A., Gumbiene L., Lebrun F., Micallef J., Botnaru V., Oukerraj L., Andreassen A. K., Kurzyna M., Leite Baptista M. J. R., Coman I. M., Moiseeva O., Stefanovic B. S., Simkova I., Wikstrom G., Schwerzmann M., Srbinovska-Kostovska E., van Dijk A. P. J., Mahdhaoui A., Kaymaz C., Coghlan G., Sirenko Y., Galie, N, Humbert, M, Vachiery, J, Gibbs, S, Lang, I, Torbicki, A, Simonneau, G, Peacock, A, Vonk Noordegraaf, A, Beghetti, M, Ghofrani, A, Gomez Sanchez, M, Hansmann, G, Klepetko, W, Lancellotti, P, Matucci, M, Mcdonagh, T, Pierard, L, Trindade, P, Zompatori, M, Hoeper, M, Aboyans, V, Vaz Carneiro, A, Achenbach, S, Agewall, S, Allanore, Y, Asteggiano, R, Badano, L, Albert Barbera, J, Bouvaist, H, Bueno, H, Byrne, R, Carerj, S, Castro, G, Erol, C, Falk, V, Funck-Brentano, C, Gorenflo, M, Granton, J, Iung, B, Kiely, D, Kirchhof, P, Kjellstrom, B, Landmesser, U, Lekakis, J, Lionis, C, Lip, G, Orfanos, S, Park, M, Piepoli, M, Ponikowski, P, Revel, M, Rigau, D, Rosenkranz, S, Voller, H, Luis Zamorano, J, Myftiu, S, Bonderman, D, Firdovsi, I, Lazareva, I, De Pauw, M, Sokolovic, S, Velchev, V, Cikes, M, Moutiris, J, Jansa, P, Nielsen-Kudsk, J, Anton, L, Jaaskelainen, P, Bauer, F, Chukhrukidze, A, Opitz, C, Giannakoulas, G, Karlocai, K, Oddsson, O, Gaine, S, Menachemi, D, Emdin, M, Sooronbaev, T, Rudzitis, A, Gumbiene, L, Lebrun, F, Micallef, J, Botnaru, V, Oukerraj, L, Andreassen, A, Kurzyna, M, Leite Baptista, M, Coman, I, Moiseeva, O, Stefanovic, B, Simkova, I, Wikstrom, G, Schwerzmann, M, Srbinovska-Kostovska, E, van Dijk, A, Mahdhaoui, A, Kaymaz, C, Coghlan, G, and Sirenko, Y

Subjects
Endothelin receptor antagonist, Chronic thromboembolic pulmonary hypertension, Heart failure, Guideline, Prostacyclin analogue, Respiratory failure, Pulmonary arterial hypertension, Chronic thromboembolic pulmonary hypertension, Congenital heart disease, Connective tissue disease, Endothelin receptor antagonists, Guidelines, Heart failure, Left heart disease, Lung disease, Phosphodiesterase type 5 inhibitors, Prostacyclin analogues, Pulmonary arterial hypertension, Pulmonary hypertension, Respiratory failure, Pulmonary hypertension, Phosphodiesterase type 5 inhibitor, Left heart disease, Lung disease, Connective tissue disease, Congenital heart disease
Abstract

Document Reviewers: Victor Aboyans (CPG Review Coordinator) (France), Antonio Vaz Carneiro (CPG Review Coordinator) (Portugal), Stephan Achenbach (Germany), Stefan Agewall (Norway), Yannick Allanore (France), Riccardo Asteggiano (Italy), Luigi Paolo Badano (Italy), Joan Albert Barbera (Spain), Helene Bouvaist (France), Hector Bueno (Spain), Robert A. Byrne (Germany), Scipione Carerj (Italy), Graca Castro (Portugal), Cetin Erol (Turkey), Volkmar Falk (Germany), Christian Funck-Brentano (France), Matthias Gorenflo (Germany), John Granton (Canada), Bernard Iung (France), David G. Kiely (UK), Paulus Kirchhof (Germany/UK), Barbro Kjellstrom (Sweden), Ulf Landmesser (Switzerland), John Lekakis (Greece), Christos Lionis (Greece), Gregory Y. H. Lip (UK), Stylianos E. Orfanos (Greece), Myung H. Park (USA), Massimo F. Piepoli (Italy), Piotr Ponikowski (Poland), Marie-Pierre Revel (France), David Rigau (ERS methodologist) (Switzerland), Stephan Rosenkranz (Germany), Heinz Voller (Germany), and Jose Luis Zamorano (Spain)

Published
2016

4. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial

Author

Konstantinides SV, Meyer G, Lang I, Verschuren F, Meneveau N, Charbonnier B, Bouvaist H, Geibel A, Beyer Westendorf J, Dellas C, Empen K, Kupatt C, Giancarlo, Becattini C, Salvi A, Pruszczyk P, Torbicki A, Franca A, Lohmann C, Kozak M, Jiménez D, Kucher N, Goldhaber SZ, Danays T, Bluhmki E, Gallula P., GALIE', NAZZARENO, Konstantinides SV, Meyer G, Lang I, Verschuren F, Meneveau N, Charbonnier B, Bouvaist H, Geibel A, Beyer-Westendorf J, Dellas C, Empen K, Kupatt C, Galiè N, Giancarlo, Becattini C, Salvi A, Pruszczyk P, Torbicki A, Franca A, Lohmann C, Kozak M, Jiménez D, Kucher N, Goldhaber SZ, Danays T, Bluhmki E, and Gallula P.

Subjects
Heparin, Patient Selection, Ventricular Dysfunction, Right, Myocardial Infarction, Blood Pressure, Pulmonary Embolism Thrombolysi, Treatment Outcome, Fibrinolytic Agents, Research Design, Tissue Plasminogen Activator, Injections, Intravenous, Tenecteplase, Humans, Cardiology and Cardiovascular Medicine, Pulmonary Embolism, CLINICAL TRIALS
Abstract

Background: In acute pulmonary embolism (PE), overt right ventricular (RV) failure with cardiogenic shock indicates a poor prognosis. However, normotensive patients with acute RV dysfunction on echocardiography or computed tomography and with myocardial troponin elevation may also have an adverse outcome. Thrombolysis rapidly reverses RV pressure overload in PE, but it remains unclear whether it may improve the early and long-term clinical outcome of selected normotensive patients. Design: The Pulmonary EmbolIsm THrOmbolysis (PEITHO) trial is a prospective, multicenter, international, randomized (1:1), double-blind comparison of thrombolysis with tenecteplase vs placebo in normotensive patients with confirmed PE, an abnormal right ventricle on echocardiography or computed tomography, and a positive troponin I or T test result. Both treatment groups receive standard anticoagulation. The primary efficacy outcome is the composite of death from any cause or hemodynamic collapse within 7 days of randomization. Safety outcomes include ischemic/hemorrhagic strokes and other major bleeding episodes. In addition, 180-day clinical and echocardiographic follow-up will be performed. The study is expected to enroll approximately 1,000 patients. Conclusions: By determining the benefits vs risks of thrombolysis in submassive or intermediate-risk PE, this trial is expected to answer a long-standing query on the management of this patient population

Published
2011

5. Incomplete echocardiographic recovery at 6months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial

Author

Jan Beyer-Westendorf, Cecilia Becattini, Stefano Barco, Nicolas Meneveau, Bożena Sobkowicz, Emile Ferrari, Guy Meyer, Stavros Konstantinides, Laurent Bertoletti, Thierry Danays, Maciej Kostrubiec, Matija Kozak, Sebastian Schellong, Nazzareno Galiè, Frederikus A. Klok, Francis Couturaud, Olivier Sanchez, Aldo Salvi, Piotr Pruszczyk, Christian Kupatt, Mareike Lankeit, Hélène Bouvaist, Klaus Empen, David Jiménez, Matteo Rugolotto, Massimiliano Palazzini, Mariaconcetta Russo, Daniel Duerschmied, Eric Vicaut, Irene M. Lang, Claudia Dellas, Barco S., Russo M., Vicaut E., Becattini C., Bertoletti L., Beyer-Westendorf J., Bouvaist H., Couturaud F., Danays T., Dellas C., Duerschmied D., Empen K., Ferrari E., Galie N., Jimenez D., Klok F.A., Kostrubiec M., Kozak M., Kupatt C., Lang I.M., Lankeit M., Meneveau N., Palazzini M., Pruszczyk P., Rugolotto M., Salvi A., Sanchez O., Schellong S., Sobkowicz B., Meyer G., and Konstantinides S.V.

Subjects
Male, Time Factors, medicine.medical_treatment, Chronic thromboembolic pulmonary hypertension, Post-PE impairment, Pulmonary embolism, Right ventricular dysfunction, Risk stratification, Acute Disease, Disease Progression, Echocardiography, Female, Fibrinolytic Agents, Follow-Up Studies, Heart Ventricles, Humans, Middle Aged, Pulmonary Embolism, Retrospective Studies, Risk Factors, Tenecteplase, Thrombolytic Therapy, Treatment Outcome, Ventricular Function, Right, Recovery of Function, 030204 cardiovascular system & hematology, New york heart association, 0302 clinical medicine, Ventricular Function, 030212 general & internal medicine, General Medicine, Thrombolysis, 3. Good health, ddc, Right, Cardiology, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, Original Paper, business.industry, medicine.disease, Pulmonary hypertension, Heart failure, business, Intermediate risk
Abstract

INTRODUCTION: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined. METHODS: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) 'post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV. RESULTS: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up. CONCLUSIONS: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae. peerReviewed

Published
2019

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