106 results on '"Vonk-Noordegraaf, Anton"'
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2. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study
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Ghofrani, Hossein-Ardeschir, Simonneau, Gérald, D'Armini, Andrea M, Fedullo, Peter, Howard, Luke S, Jaïs, Xavier, Jenkins, David P, Jing, Zhi-Cheng, Madani, Michael M, Martin, Nicolas, Mayer, Eckhard, Papadakis, Kelly, Richard, Dominik, Kim, Nick H, Lang, Irene, Kähler, Christian, Delcroix, Marion, Bshouty, Zoheir, Sepulveda Varela, Pablo, Jing, Zhi-Cheng, Yang, Yuanhua, Liu, Jinming, Zhang, Gangcheng, Zhang, Nuofu, Mi, Yuhong, Zhu, Xianyang, Jansa, Pavel, Jaïs, Xavier, Prévot, Grégoire, Bouvaist, Hélène, Sanchez, Olivier, Grimminger, Friedrich, Held, Matthias, Wilkens, Heinrike, Rosenkranz, Stephan, Grünig, Ekkehard, Karlócai, Kristóf, Temesvári, András, Edes, Istvan, Aidietienė, Sigita, Miliauskas, Skaidrius, Pulido Zamudio, Tomas Rene, Jerjes Sanchez, Carlos, Vonk Noordegraaf, Anton, Lewczuk, Jerzy, Podolec, Piotr, Kasprzak, Jarosław, Mularek-Kubzdela, Tatiana, Grzywna, Ryszard, Dheda, Keertan, Moiseeva, Olga, Chernyavskiy, Alexander, Shipulin, Vladimir, Barbarash, Olga, Martynyuk, Tamila, Kim, Hyung-Kwan, Park, Jun-Bean, Lee, Jae Seung, Speich, Rudolf, Ulrich, Silvia, Aubert, John-David, Phrommintikul, Arintaya, Jaimchariyatam, Nattapong, Sompradeekul, Suree, Onen, Zeynep Pinar, Okumus, Gulfer, Solovey, Lyubomyr, Gavrysyuk, Volodymyr, Howard, Luke, Pepke-Zaba, Joanna, Condliffe, Robin, McConnell, John, Kerr, Kim, Nguyen, Lan Hieu, and Pham, Nguyen Vinh
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Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar.
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- 2024
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3. Toward the Implementation of Optimal Cardiac Magnetic Resonance Risk Stratification in Pulmonary Arterial Hypertension
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Celant, Lucas R., Wessels, Jeroen N., Marcus, J.Tim, Meijboom, Lilian J., Bogaard, Harm Jan, de Man, Frances S., and Vonk Noordegraaf, Anton
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The 2022 European Society of Cardiology/European Respiratory Society pulmonary hypertension (PH) guidelines incorporate cardiac magnetic resonance (CMR) imaging metrics in the risk stratification of patients with pulmonary arterial hypertension (PAH). Thresholds to identify patients at estimated 1-year mortality risks of < 5%, 5% to 20%, and > 20% are introduced. However, these cutoff values are mostly single center-based and require external validation.
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- 2024
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4. Effect of Macitentan in Pulmonary Arterial Hypertension and the Relationship Between Echocardiography and cMRI Variables: REPAIR Echocardiography Sub-study Results
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Torbicki, Adam, Channick, Richard, Galiè, Nazzareno, Kiely, David G., Moceri, Pamela, Peacock, Andrew, Swift, Andrew J., Tawakol, Ahmed, Vonk Noordegraaf, Anton, Flores, Dayana, Martin, Nicolas, and Rosenkranz, Stephan
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Introduction: The aim of this sub-study was to evaluate the relationship between echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) variables and to utilize echo to assess the effect of macitentan on right ventricle (RV) structure and function. Methods: REPAIR (NCT02310672) was a prospective, multicenter, single-arm, open-label, 52-week, phase 4 study in pulmonary arterial hypertension (PAH) patients, which investigated the effect of macitentan 10 mg as monotherapy, or in combination with a phosphodiesterase 5 inhibitor, on RV structure, function, and hemodynamics using cMRI and right heart catheterization. In this sub-study, patients were also assessed by echo at screening and at weeks 26 and/or 52. Post hoc correlation analyses between echo and cMRI variables were performed using Pearson’s correlation coefficient, Spearman's correlation coefficient, and Bland–Altman analyses. Results: The Echo sub-study included 45 patients. Improvements in echo-assessed RV stroke volume (RVSV), left ventricular SV (LVSV), LV end-diastolic volume (LVEDV), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and in 2D global longitudinal RV strain (2D GLRVS) were observed at weeks 26 and 52 compared to baseline. There was a strong correlation between echo (LVSV, 2D GLRVS, and LVEDV) and cMRI variables, with a moderate correlation for RVSV. Bland–Altman analyses showed a good agreement for LVSV measured by echo versus cMRI, whereas an overestimation in echo-assessed RVSV was observed compared to cMRI (bias of − 15 mL). Hemodynamic and functional variables, as well as safety, were comparable between the Echo sub-study and REPAIR. Conclusions: A good relationship between relevant echo and cMRI parameters was shown. Improvements in RV structure and function with macitentan treatment was observed by echo, consistent with results observed by cMRI in the primary analysis of the REPAIR study. Echo is a valuable complementary method to cMRI, with the potential to non-invasively monitor treatment response at follow-up. Trial registration number: REPAIR NCT02310672. Graphical Abstract:
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- 2024
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5. Diagnostic efficacy of ECG-derived ventricular gradient for the detection of chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism.
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Luijten, Dieuwke, Meijer, Fleur M.M., Boon, Gudula J.A.M., Ende-Verhaar, Yvonne M., Bavalia, Roisin, El Bouazzaoui, Lahassan H., Delcroix, Marion, Huisman, Menno V., Mairuhu, Albert T.A., Middeldorp, Saskia, Pruszcyk, Piotr, Ruigrok, Dieuwertje, Verhamme, Peter, Vonk Noordegraaf, Anton, Vriend, Joris W.J., Vliegen, Hubert W., and Klok, Frederikus A.
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Application of the chronic thromboembolic pulmonary hypertension (CTEPH) rule out criteria (manual electrocardiogram [ECG] reading and N-terminal pro-brain natriuretic peptide [NTproBNP] test) can rule out CTEPH in pulmonary embolism (PE) patients with persistent dyspnea (InShape II algorithm). Increased pulmonary pressure may also be identified using automated ECG-derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO). A predefined analysis of the InShape II study was performed. The diagnostic performance of the VG-RVPO for the detection of CTEPH and the incremental diagnostic value of the VG-RVPO as new rule-out criteria in the InShape II algorithm were evaluated. 60 patients were included; 5 (8.3%) were ultimately diagnosed with CTEPH. The mean baseline VG-RVPO (at time of PE diagnosis) was −18.12 mV·ms for CTEPH patients and − 21.57 mV·ms for non-CTEPH patients (mean difference 3.46 mV·ms [95%CI −29.03 to 35.94]). The VG-RVPO (after 3–6 months follow-up) normalized in patients with and without CTEPH, without a clear between-group difference (mean Δ VG-RVPO of −8.68 and − 8.42 mV·ms respectively; mean difference of −0.25 mV·ms, [95%CI −12.94 to 12.44]). The overall predictive accuracy of baseline VG-RVPO, follow-up RVPO and Δ VG-RVPO for CTEPH was moderate to poor (ROC AUC 0.611, 0.514 and 0.539, respectively). Up to 76% of the required echocardiograms could have been avoided with VG-RVPO criteria replacing the InShape II rule-out criteria, however at cost of missing up to 80% of the CTEPH diagnoses. We could not demonstrate (additional) diagnostic value of VG-RVPO as standalone test or as on top of the InShape II algorithm. • The VG-RVPO improved over time after acute PE for CTEPH and non-CTEPH patients. • The VG-RVPO as a standalone test does not accurately discriminate CTEPH from non-CTEPH patients. • Additional diagnostic value of VG-RVPO on top of the InShape II algorithm could not be shown. • Our findings should be regarded as hypothesis generating due to low sample size. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Restoration of right ventricular function in the treatment of pulmonary arterial hypertension
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Celant, Lucas R, Wessels, Jeroen N, Kianzad, Azar, Marcus, J Tim, Meijboom, Lilian J, Bogaard, Harm Jan, de Man, Frances S, and Vonk Noordegraaf, Anton
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ObjectiveA 45% threshold of right ventricular ejection fraction (RVEF) is proposed clinically relevant in patients with pulmonary arterial hypertension (PAH). We aim to determine treatment response, long-term right ventricular (RV) functional stability and prognosis of patients with PAH reaching or maintaining the RVEF 45% threshold.MethodsIncident, treatment-naive, adult PAH patients with cardiac magnetic resonance imaging at baseline and first follow-up were included (total N=127) and followed until date of censoring or death/lung transplantation. Patients were categorised into two groups based on 45% RVEF. Baseline predictors, treatment response and prognosis were assessed with logistic regression analyses, two-way analysis of variance and log-rank tests.ResultsPatients were 50±17 years old, 73% female, of which N=75 reached or maintained the 45% RVEF threshold at follow-up (RVEF≥45%@FU), while N=52 patients did not (RVEF<45%@FU). RV end-diastolic volume and N-terminal pro-B-type natriuretic peptide at baseline were multivariable predictors of an RVEF ≥45% at follow-up. A 40% pulmonary vascular resistance (PVR) reduction resulted in greater improvement in RV function (ΔRVEF 17±11 vs. 5±8; pinteraction<0.001) compared to a PVR reduction <40%, but did not guarantee an RVEF ≥45%. Finally, the 45% RVEF threshold was associated with stable RV function during long-term follow-up and better survival (HR: 1.91 (95% CI: 1.11 to 3.27)). Patients failing to reach or maintain the 45% RVEF threshold at first follow-up mostly stayed below this threshold over the next consecutive visits.ConclusionAfter treatment initiation, 60% of patients with PAH reach or maintain the 45% RVEF threshold, which is associated with a long-term stable RV function and favourable prognosis.
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- 2023
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7. Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis
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Hoeper, Marius M, Dwivedi, Krit, Pausch, Christine, Lewis, Robert A, Olsson, Karen M, Huscher, Doerte, Pittrow, David, Grünig, Ekkehard, Staehler, Gerd, Vizza, Carmine Dario, Gall, Henning, Distler, Oliver, Opitz, Christian, Gibbs, John Simon R, Delcroix, Marion, Park, Da-Hee, Ghofrani, Hossein Ardeschir, Ewert, Ralf, Kaemmerer, Harald, Kabitz, Hans-Joachim, Skowasch, Dirk, Behr, Juergen, Milger, Katrin, Lange, Tobias J, Wilkens, Heinrike, Seyfarth, Hans-Jürgen, Held, Matthias, Dumitrescu, Daniel, Tsangaris, Iraklis, Vonk-Noordegraaf, Anton, Ulrich, Silvia, Klose, Hans, Claussen, Martin, Eisenmann, Stephan, Schmidt, Kai-Helge, Swift, Andrew J, Thompson, Alfred A Roger, Elliot, Charlie A, Rosenkranz, Stephan, Condliffe, Robin, Kiely, David G, and Halank, Michael
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Among patients meeting diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH), there is an emerging lung phenotype characterised by a low diffusion capacity for carbon monoxide (DLCO) and a smoking history. The present study aimed at a detailed characterisation of these patients.
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- 2022
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8. The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension.
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Vonk Noordegraaf, Anton, Channick, Richard, Cottreel, Emmanuelle, Kiely, David G., Marcus, J. Tim, Martin, Nicolas, Moiseeva, Olga, Peacock, Andrew, Swift, Andrew J., Tawakol, Ahmed, Torbicki, Adam, Rosenkranz, Stephan, and Galiè, Nazzareno
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The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC). RV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials. REPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints. At a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials. In the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672) [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2022
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9. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial.
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Hoeper, Marius M, Al-Hiti, Hikmet, Benza, Raymond L, Chang, Sung-A, Corris, Paul A, Gibbs, J Simon R, Grünig, Ekkehard, Jansa, Pavel, Klinger, James R, Langleben, David, McLaughlin, Vallerie V, Meyer, Gisela M B, Ota-Arakaki, Jaquelina, Peacock, Andrew J, Pulido, Tomás, Rosenkranz, Stephan, Vizza, Carmine Dario, Vonk-Noordegraaf, Anton, White, R James, and Chang, Mikyung
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PULMONARY hypertension ,PHOSPHODIESTERASE-5 inhibitors ,INTERACTIVE voice response (Telecommunication) ,RESPIRATORY infections ,BRAIN natriuretic factor ,ENDOTHELIN receptors ,OBSTRUCTIVE lung diseases - Abstract
Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality. Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) was an open-label, randomised controlled trial in 81 hospital-based pulmonary hypertension centres in 22 countries. The study enrolled patients aged 18–75 years with symptomatic PAH at intermediate risk of 1-year mortality (based on the European Society for Cardiology–European Respiratory Society guideline thresholds for WHO functional class and 6-min walk distance [6MWD]) who were receiving treatment with a PDE5i with or without an endothelin receptor antagonist for at least 6 weeks before randomisation. Patients were excluded if they had been previously treated with riociguat, had used prostacyclin analogues or prostacyclin receptor agonists within 30 days before randomisation, had clinically significant restrictive or obstructive parenchymal lung disease, or had left heart disease. Patients were randomly assigned (1:1) to remain on PDE5i treatment (oral sildenafil [≥60 mg per day] or oral tadalafil [20–40 mg per day]; the PDE5i group) or to switch to oral riociguat (up to 2·5 mg three times per day; the riociguat group), using an interactive voice and web response system, stratified by cause of PAH. The primary endpoint was clinical improvement by week 24, defined as an absence of clinical worsening and prespecified improvements in at least two of three variables (6MWD, WHO functional class, and N -terminal prohormone of brain natriuretic peptide), analysed using last observation carried forward in all randomly assigned patients with observed values at baseline and week 24 who received at least one dose of study medication (the full analysis set). Secondary endpoints included clinical worsening events. The trial has been completed and is registered with ClinicalTrials.gov , NCT02891850. Between Jan 11, 2017, and July 31, 2019, 293 patients were screened, of which 226 patients were randomly assigned to the riociguat group (n=111) or to the PDE5i group (n=115). 211 patients completed the study and 14 patients discontinued (seven in each group). One patient assigned to the PDE5i group did not receive treatment, so 225 patients were included in the safety analysis, and one further patient in the PDE5i group had missing components of the composite primary endpoint at baseline, so 224 patients were included in the full analysis set. The primary endpoint was met by 45 (41%) of 111 patients in the riociguat group and 23 (20%) of 113 patients in the PDE5i group; odds ratio [OR] 2·78 (95% CI 1·53–5·06; p=0·0007). Clinical worsening events occurred in one (1%) of 111 patients in the riociguat group (hospitalisation due to worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0·10 [0·01–0·73]; p=0·0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period. Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality. Bayer AG, Merck Sharp & Dohme. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial
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Aman, Jurjan, Duijvelaar, Erik, Botros, Liza, Kianzad, Azar, Schippers, Job R, Smeele, Patrick J, Azhang, Sara, Bartelink, Imke H, Bayoumy, Ahmed A, Bet, Pierre M, Boersma, Wim, Bonta, Peter I, Boomars, Karin A T, Bos, Lieuwe D J, van Bragt, Job J M H, Braunstahl, Gert-Jan, Celant, Lucas R, Eger, Katrien A B, Geelhoed, J J Miranda, van Glabbeek, Yurika L E, Grotjohan, Hans P, Hagens, Laura A, Happe, Chris M, Hazes, Boaz D, Heunks, Leo M A, van den Heuvel, Michel, Hoefsloot, Wouter, Hoek, Rianne J A, Hoekstra, Romke, Hofstee, Herman M A, Juffermans, Nicole P, Kemper, E Marleen, Kos, Renate, Kunst, Peter W A, Lammers, Ariana, van der Lee, Ivo, van der Lee, E Laurien, Maitland-van der Zee, Anke-Hilse, Mau Asam, Pearl F M, Mieras, Adinda, Muller, Mirte, Neefjes, Elisabeth C W, Nossent, Esther J, Oswald, Laurien M A, Overbeek, Maria J, Pamplona, Carolina C, Paternotte, Nienke, Pronk, Niels, de Raaf, Michiel A, van Raaij, Bas F M, Reijrink, Merlijn, Schultz, Marcus J, Serpa Neto, Ary, Slob, Elise M A, Smeenk, Frank W J M, Smit, Marry R, Smits, A Josien, Stalenhoef, Janneke E, Tuinman, Pieter R, Vanhove, Arthur L E M, Wessels, Jeroen N, van Wezenbeek, Jessie C C, Vonk Noordegraaf, Anton, de Man, Frances S, and Bogaard, Harm J
- Abstract
The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.
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- 2021
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11. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial
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Hoeper, Marius M, Al-Hiti, Hikmet, Benza, Raymond L, Chang, Sung-A, Corris, Paul A, Gibbs, J Simon R, Grünig, Ekkehard, Jansa, Pavel, Klinger, James R, Langleben, David, McLaughlin, Vallerie V, Meyer, Gisela M B, Ota-Arakaki, Jaquelina, Peacock, Andrew J, Pulido, Tomás, Rosenkranz, Stephan, Vizza, Carmine Dario, Vonk-Noordegraaf, Anton, White, R James, Chang, Mikyung, Kleinjung, Frank, Meier, Christian, Paraschin, Karen, Ghofrani, Hossein Ardeschir, Simonneau, Gérald, Olschewski, H, Delcroix, M, Andrade-Lima, M, de Amorim Corrêac, R, Figueiredo Campos, F, Ota Arakaki, J, Meyer, G, De Souza, R, Langleben, D, Al-Hiti, H, Jansa, P, Mellemkjær, S, Bauer, F, Montani, D, Simonneau, G, Drömann, D, Ghofrani, H-A, Grünig, E, Halank, M, Held, M, Hoeper, MM, Klose, H, Kneidinger, N, Leuchte, H, Opitz, C, Rosenkranz, S, Wilkens, H, Wirtz, H, Karvounis, H, Pitsiou, G, Orfanos, S, D'Alto, M, Ghio, S, Vizza, CD, Vitulo, P, Nakayama, T, Maki, H, Tatebe, S, de los Rios Ibarra, M, Pulido, T, Van Dijk, A, Vonk-Noordegraaf, A, Roleder, T, Castro, G, Loureiro, MJ, Robalo-Martins, S, Barberá, JA, Lázaro, M, Perez-Penate, GM, Román, A, Cheng, C-C, Hsu, C-H, Hsu, H-H, Atahan, E, Mogulkoc Bishop, N, Okumus, NG, Onen, Z, Chang, H-J, Chang, S-A, Lee, J-S, Kim, H-K, Coghlan, JG, Corris, PA, Church, AC, Condliffe, R, Gibbs, JSR, Peacock, AJ, Wort, S, Allen, R, Allen, S, Awdish, R, Benza, RL, DeSouza, S, Feldman, J, Johri, S, Klinger, JR, Layish, D, McConnell, J, McLaughlin, VV, Migliore, C, Rahaghi, F, Rischard, F, Robbins, I, Satterwhite, L, Shah, T, Sulica, R, and White, RJ
- Abstract
Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.
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- 2021
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12. Hemodynamic Effects of Pulmonary Arterial Hypertension-Specific Therapy in Patients With Heart Failure With Preserved Ejection Fraction and With Combined Post- and Precapillay Pulmonary Hypertension.
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Huis in't Veld, Anna E., Oosterveer, Frank P.T., De man, Frances S., Marcus, J. TIM, Nossent, Esther J., Boonstra, Anco, Van rossum, A.C. (Bert), Vonk Noordegraaf, Anton, Bogaard, Harm jan, and Handoko, M. Louis
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Background: Drugs approved for pulmonary arterial hypertension have been considered for patients with heart failure with preserved ejection fraction and combined post- and precapillary pulmonary hypertension (Cpc-PH). We aimed to study changes in cardiac volumes, cardiac load and left ventricular (LV) filling pressures in patients with heart failure with preserved ejection fraction and Cpc-PH in response to pulmonary arterial hypertension-specific treatment.Methods and Results: In this prospective study, 23 patients with heart failure with preserved ejection fraction and Cpc-PH underwent right-heart catheterization, including acute provocation testing (fluid loading and inhaled nitric oxide) and cardiac MRI at baseline. Right-heart catheterization and cardiac MRI were repeated after 4 months of treatment. At baseline, acutely increasing preload by fluid loading resulted in a significant increase in pulmonary arterial wedge pressure (PAWP), whereas reducing right ventricular (RV) afterload and increasing LV distensability by acute administration of inhaled nitric oxide had no effect on PAWP. After 4 months of treatment, we observed a significant reduction in RV and LV afterload and increased RV and LV stroke volume, but PAWP significantly increased.Conclusions: In patients with heart failure with preserved ejection fraction and Cpc-PH, 4 months of pulmonary arterial hypertension-specific treatment increased RV and LV stroke volume at the expense of increased PAWP. This increase in PAWP was similarly observed acutely after fluid loading. [ABSTRACT FROM AUTHOR]- Published
- 2020
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13. Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study
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Boon, Gudula J A M, Ende-Verhaar, Yvonne M, Bavalia, Roisin, El Bouazzaoui, Lahassan H, Delcroix, Marion, Dzikowska-Diduch, Olga, Huisman, Menno V, Kurnicka, Katarzyna, Mairuhu, Albert T A, Middeldorp, Saskia, Pruszczyk, Piotr, Ruigrok, Dieuwertje, Verhamme, Peter, Vliegen, Hubert W, Vonk Noordegraaf, Anton, Vriend, Joris W J, and Klok, Frederikus A
- Abstract
BackgroundThe current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms.MethodsIn this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the ‘CTEPH prediction score’ indicated high pretest probability or matching symptoms were present, the ‘CTEPH rule-out criteria’ were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography.Results424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation.ConclusionsThe InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.
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- 2021
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14. Incidence and clinical course of chronic thromboembolic pulmonary hypertension with or without a history of venous thromboembolism in Denmark
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Klok, Frederikus A., Vágó, Emese, Horváth-Puhó, Erzsébet, Barco, Stefano, Andersen, Asger, Bonnesen, Kasper, Vonk-Noordegraaf, Anton, Delcroix, Marion, Konstantinides, Stavros V., Luijten, Dieuwke, Cannegieter, Suzanne C., and Toft Sørensen, Henrik
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A considerable number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) lack a history of venous thromboembolism (VTE). We examined the annual incidence and prevalence of CTEPH in Denmark and compared the rate of VTE, bleeding and mortality in patients with CTEPH with versus without a history of VTE.
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- 2024
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15. Clinical correlates of a non-plexiform vasculopathy in patients diagnosed with idiopathic pulmonary arterial hypertension.
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Nossent, Esther J., Smits, Josien, Seegers, Celine, Meijboom, Lilian J., Boonstra, Anco, Aman, J., De Man, F.S., Bogaard, Harm Jan, Radonic, Teodora, Dorfmüller, Peter, and Vonk Noordegraaf, Anton
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The clinical phenotype of idiopathic pulmonary arterial hypertension (IPAH) patients has changed. . Whether or not subgroups of IPAH patients have different vascular phenotypes is a subject of debate.
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- 2024
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16. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis
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Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stéphanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe G N, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, J Simon R, Harley, John, He, Hua, Hill, Nicholas S, Hirsch, Russel, Houweling, Arjan C, Howard, Luke S, Ivy, Dunbar, Kiely, David G, Klinger, James, Kovacs, Gabor, Lahm, Tim, Laudes, Matthias, Machado, Rajiv D, MacKenzie Ross, Robert V, Marsolo, Keith, Martin, Lisa J, Moledina, Shahin, Montani, David, Nathan, Steven D, Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Oudiz, Ronald J, Ouwehand, Willem H, Peacock, Andrew J, Pepke-Zaba, Joanna, Rehman, Zia, Robbins, Ivan, Roden, Dan M, Rosenzweig, Erika B, Saydain, Ghulam, Scelsi, Laura, Schilz, Robert, Seeger, Werner, Shaffer, Christian M, Simms, Robert W, Simon, Marc, Sitbon, Olivier, Suntharalingam, Jay, Tang, Haiyang, Tchourbanov, Alexander Y, Thenappan, Thenappan, Torres, Fernando, Toshner, Mark R, Treacy, Carmen M, Vonk Noordegraaf, Anton, Waisfisz, Quinten, Walsworth, Anna K, Walter, Robert E, Wharton, John, White, R James, Wilt, Jeffrey, Wort, Stephen J, Yung, Delphine, Lawrie, Allan, Humbert, Marc, Soubrier, Florent, Trégouët, David-Alexandre, Prokopenko, Inga, Kittles, Richard, Gräf, Stefan, Nichols, William C, Trembath, Richard C, Desai, Ankit A, Morrell, Nicholas W, and Wilkins, Martin R
- Abstract
Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.
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- 2019
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17. Phenotypes of idiopathic pulmonary arterial hypertension – Authors' reply.
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Hoeper, Marius M, Vonk-Noordegraaf, Anton, and Kiely, David G
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PULMONARY arterial hypertension ,PHENOTYPES - Published
- 2022
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18. Serial assessment of right ventricular systolic function in patients with precapillary pulmonary hypertension using simple echocardiographic parameters: A comparison with cardiac magnetic resonance imaging.
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Spruijt, Onno A., Di Pasqua, Maria C., Bogaard, H.J., van der Bruggen, C.E.E., Oosterveer, Frank, Marcus, J. Tim, Vonk-Noordegraaf, Anton, and Handoko, M. Louis
- Abstract
Background Although cardiac magnetic resonance imaging (CMRI) is the gold standard for the (serial) assessment of right ventricular (RV) function, the technique has several drawbacks: CMRI is relatively expensive, has a limited availability, and the analyses are time consuming. Echocardiography (echo) can overcome several of these issues. The aim of this study was to compare simple echo-derived parameters of RV systolic function with CMRI-derived RV ejection fraction (RVEF) in patients with precapillary pulmonary hypertension (PH) and to determine which echo parameters best followed the change in CMRI-derived-RVEF during follow-up. Methods CMRI and echo were performed in 96 precapillary PH patients. In 38 patients a second set of a CMRI and echo were available. Retrospectively, echo-derived right ventricular fractional area change (RVFAC), tricuspid annulus plane systolic excursion (TAPSE), fractional transversal (FTWM), and longitudinal wall motion (FLWM) were assessed and compared with CMRI-derived-RVEF. Furthermore, the changes in RVFAC, TAPSE, FTWM, and FLWM during follow-up were compared with the change in CMRI-derived-RVEF. Results All four echo parameters were significantly correlated to CMRI-derived-RVEF. The strongest relationship was seen between CMRI-derived-RVEF and RVFAC ( r 2 = 0.567). However, sensitivity for predicting a deterioration in CMRI-derived RVEF was poor for all four echo-derived parameters (ranging from 33% to 56%). Conclusions Although RVFAC, TAPSE, FTWM, and FLWM were significantly correlated to CMRI-derived-RVEF, all four echo parameters showed a low sensitivity for predicting a deterioration in CMRI-derived RVEF during follow-up. Therefore, RVFAC, TAPSE, FTWM, and FLWM are not suitable parameters for the serial assessment of RV systolic function in patients with precapillary PH. [ABSTRACT FROM AUTHOR]
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- 2017
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19. Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension
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da Silva Gonçalves Bós, Denielli, Van Der Bruggen, Cathelijne E. E., Kurakula, Kondababu, Sun, Xiao-Qing, Casali, Karina R., Casali, Adenauer G., Rol, Nina, Szulcek, Robert, dos Remedios, Cris, Guignabert, Christophe, Tu, Ly, Dorfmüller, Peter, Humbert, Marc, Wijnker, Paul J.M., Kuster, Diederik W.D., van der Velden, Jolanda, Goumans, Marie-José, Bogaard, Harm-Jan, Vonk-Noordegraaf, Anton, de Man, Frances S., and Handoko, M. Louis
- Abstract
Supplemental Digital Content is available in the text.
- Published
- 2018
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20. Sensitivity of a Simple Noninvasive Screening Algorithm for Chronic Thromboembolic Pulmonary Hypertension after Acute Pulmonary Embolism
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Ende-Verhaar, Yvonne M., Ruigrok, Dieuwertje, Bogaard, Harm Jan, Huisman, Menno V., Meijboom, Lilian J., Vonk Noordegraaf, Anton, and Klok, Frederikus A.
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- 2018
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21. Phenotypes of idiopathic pulmonary arterial hypertension – Authors' reply
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Hoeper, Marius M, Vonk-Noordegraaf, Anton, and Kiely, David G
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- 2022
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22. Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension Relative Contribution of Fibrosis and Myofibril Stiffness.
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Rain, Silvia, Andersen, Stine, Najafi, Aref, Schultz, Jacob Gammelgaard, da Silva Gonçalves Bós, Denielli, Handoko, M. Louis, Bogaard, Harm-Jan, Vonk-Noordegraaf, Anton, Andersen, Asger, van der Velden, Jolanda, Ottenheijm, Coen A. C., and de Man, Frances S.
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Background--The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibrilmediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results--By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membranepermeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions--RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosismediated stiffness contribute to increased RV myocardial stiffness. [ABSTRACT FROM AUTHOR]
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- 2016
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23. Right Heart Score for Predicting Outcome in Idiopathic, Familial, or Drug- and Toxin-Associated Pulmonary Arterial Hypertension.
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Haddad, François, Spruijt, Onno A., Denault, Andre Y., Mercier, Olaf, Brunner, Nathan, Furman, David, Fadel, Elie, Bogaard, Harm J., Schnittger, Ingela, Vrtovec, Bojan, Wu, Joseph C., de Jesus Perez, Vinicio, Vonk-Noordegraaf, Anton, and Zamanian, Roham T.
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Objectives This study sought to determine whether a simple score combining indexes of right ventricular (RV) function and right atrial (RA) size would offer good discrimination of outcome in patients with pulmonary arterial hypertension (PAH). Background Identifying a simple score of outcome could simplify risk stratification of patients with PAH and potentially lead to improved tailored monitoring or therapy. Methods We recruited patients from both Stanford University (derivation cohort) and VU University Medical Center (validation cohort). The composite endpoint for the study was death or lung transplantation. A Cox proportional hazard with bootstrap CI adjustment model was used to determine independent correlates of death or transplantation. A predictive score was developed using the beta coefficients of the multivariable models. Results For the derivation cohort (n = 95), the majority of patients were female (79%), average age was 43 ± 11 years, mean pulmonary arterial pressure was 54 ± 14 mm Hg, and pulmonary vascular resistance index was 25 ± 12 Wood units × m 2 . Over an average follow-up of 5 years, the composite endpoint occurred in 34 patients, including 26 deaths and 8 patients requiring lung transplant. On multivariable analysis, RV systolic dysfunction grade (hazard ratio [HR]: 3.4 per grade; 95% confidence interval [CI]: 2.0 to 7.8; p < 0.001), severe RA enlargement (HR: 3.0; 95% CI: 1.3 to 8.1; p = 0.009), and systemic blood pressure <110 mm Hg (HR: 3.3; 95% CI: 1.5 to 9.4; p < 0.001) were independently associated with outcome. A right heart (RH) score constructed on the basis of these 3 parameters compared favorably with the National Institutes of Health survival equation (0.88; 95% CI: 0.79 to 0.94 vs. 0.60; 95% CI: 0.49 to 0.71; p < 0.001) but was not statistically different than the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) score c-statistic of 0.80 (95% CI: 0.69 to 0.88) with p = 0.097. In the validation cohort (n = 87), the RH score remained the strongest independent correlate of outcome. Conclusions In patients with prevalent PAH, a simple RH score may offer good discrimination of long-term outcome. [ABSTRACT FROM AUTHOR]
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- 2015
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24. Effects of Bisoprolol and Losartan Treatment in the Hypertrophic and Failing Right Heart.
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Andersen, Stine, Schultz, Jacob Gammelgaard, Andersen, Asger, Ringgaard, Steffen, Nielsen, Jan M., Holmboe, Sarah, Vildbrad, Mads D., de Man, Frances S., Bogaard, Harm J., Vonk-Noordegraaf, Anton, and Nielsen-Kudsk, Jens Erik
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Background Sympathetic adrenergic stimulation and the renin-angiotensin-aldosterone system are highly elevated in right heart failure. We evaluated if treatment with the adrenergic receptor blocker bisoprolol or the angiotensin II receptor blocker losartan could prevent the progression of right ventricular (RV) hypertrophy and failure in rats after pulmonary trunk banding (PTB). Methods and Results Male Wistar rats were randomized to severe PTB with a 0.5-mm banding clip (PTB0.5, n = 29), moderate PTB with a 0.6-mm banding clip (PTB0.6, n = 28), or sham operation (SHAM, n = 13). The PTB0.5 and PTB0.6 rats were randomized to 6 weeks of 10 mg/kg/d bisoprolol treatment, 20 mg/kg/d losartan treatment, or vehicle treatment. The PTB caused hypertrophy, dilation, and reduced function of the RV in all rats subjected to the procedure. Rats subjected to the more severe banding developed decompensated RV failure with extracardiac manifestations. Treatment with bisoprolol slowed the heart rate, and treatment with losartan lowered mean arterial pressure, confirming adequate dosing, but none of the treatments improved RV function or arrested the progression of RV hypertrophy and failure compared with vehicle. Conclusions In our PTB model of pressure overload–induced RV hypertrophy and failure, treatment with bisoprolol and losartan did not demonstrate any beneficial effects in compensated or decompensated RV failure. [ABSTRACT FROM AUTHOR]
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- 2014
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25. Abstract 13105: The Effect of Mechanical Stress on Cardiac Fibroblasts in Pulmonary Arterial Hypertension
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Bekedam, Fjodor T, Smit, Marisa C, Vonk Noordegraaf, Anton, Bogaard, Harm J, Goumans, Marie Jose, De Man, Frances S, and Llucia-Valldeperas, Aida
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Introduction:Pulmonary arterial hypertension (PAH) is a rare fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. To study PAH-induced cardiac fibrosis we develop an in vitromodel of the failing right ventricle, for which cardiac fibroblasts (cFBs) were generated from healthy subjects’ and PAH patients’ induced pluripotent stem cells (iPSC).Methods:Confluent iPSC were induced to differentiate by adding 12 μM CHIR99021 for 24h to RPMI supplemented with B27 without insulin. Next, cells recovered for 24 h in RPMI supplemented with B27 without insulin, followed by stimulation with 75 ng/ml FGF2 up to day 20. Finally, the differentiated cells were reseeded and submitted to 10% cyclic stretch at 1 Hz for 4 days using the Flexcell FX-6000 system. Control and PAH cFBs were characterized at gene and protein levels.Results:The differentiated cells had a spindle morphology typical of FBs. Furthermore, the presence of cardiac (GATA4, TCF21) and fibroblast (VIM, PDGFRα, COL1A1) markers at gene and protein levels confirmed the cFB identity. Comparable expression of fibroblast related genes was observed in PAH cFBs as well as controls. Over 4 weeks of culture, iPSC-cFBs increasingly expressed markers of activated FBs (ACTA2and POSTN)over time, similar to in vitro adult cFBs. When exposed to mechanical stretch, cell aligned to the stretch direction. Surprisingly, no increase in gene expression of extracellular matrix (COL1A1, COL3A1) or activated fibroblasts (ACTA2, POSTN) markers was observed.Interestingly, under static and stretch conditions expression of these genes was increased in PAH cFBs compared to healthy cells.Conclusion:The cellular morphology after differentiation as well as the gene and protein analyses indicate that cFBs were successfully generated. Furthermore, cyclic stretch induced alignment of the cells but was not sufficient to stimulate fibroblast activation in either PAH or healthy cFBs.
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- 2022
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26. Abstract 14691: Sex Differences in the Prognostic Value of N-Terminal Brain Natriuretic Peptide in Pulmonary Arterial Hypertension
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Van Wezenbeek, Jessie, Llucia-Valldeperas, Aida, Smal, rowan, Bekedam, Fjodor T, Vonk Noordegraaf, Anton, Goumans, Marie Jose, Bogaard, Harm J, and De Man, Frances S
- Abstract
Introduction:Pulmonary arterial hypertension (PAH) causes right heart failure (HF) and mainly affects females, but males have worse survival. Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), along with N-terminal BNP (NTproBNP), are secreted from cardiomyocytes upon stretch and are important biomarkers in HF. Sex differences are observed in NTproBNP levels and prognostic value in left HF, but unknown in right HF. The aim was to assess sex differences in NTproBNP levels and prognostic value in PAH from a translational perspective.Methods:We screened patients with baseline NTproBNP measurements and right heart catheterization between 2002 and 2020. Induced pluripotent stem cells (iPSCs) from 1 male and 1 female PAH-patients were differentiated into cardiomyocytes (iPSC-CMs), and stretched for 24h at 1Hz and 10% on the Flexcell FX-6000 system (N=2). Gene expression analyses were performed on static and stretched samples.Results:266 patients (N=106 male, N=166 female) were included. Median baseline NTproBNP levels were similar in male and female patients (1118 vs832 ng/ml, P=0.58). We risk stratified patients on NTproBNP according to the guidelines and assessed differences in 1-year survival. In males highest 1-year mortality was observed in low and low-intermediate risk groups (16,4% and 7.7%, respectively) vsfemales (4.7% and 4.2%, respectively) (Figure1 A,B). Preliminary results indicate ~2x higher BNP mRNA expressions on male vsfemale patients (0.80 vs0.37, N=3 male and N=3 female, P=0.018), after mechanical stretch (Figure1 C).Conclusions:Although no sex differences were observed in NTproBNP plasma levels, it had different prognostic value in male and female patients. Furthermore, in vitromale iPSC-CMs had higher BNP levels after stretch compared to female iPSC-CMs.
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- 2022
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27. Abstract 13936: Increased Bone Morphogenetic Protein 10 in Pulmonary Hypertension
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Llucia-Valldeperas, Aida, Van Wezenbeek, Jessie, Groeneveldt, Joanne, Smal, rowan, Sanchez-Duffhues, Gonzalo, Becher, Clarissa, Vonk Noordegraaf, Anton, Bogaard, Harm J, Goumans, Marie Jose, and De Man, Frances S
- Abstract
Introduction:Pulmonary Hypertension (PH) is characterized by increased right atrial (RA) stretch and pressure. The major genetic predisposing risk factor for PH involves mutations in the bone morphogenetic protein (BMP) receptor 2 (BMPR2), for which BMP9 and BMP10 are ligands. Although BMP9 is mostly produced by hepatocytes, BMP10 is predominantly produced by adult RA cardiomyocytes. Therefore, its role is of interest in PH despite an elusive BMP10 release mechanism.Hypothesis:Increased RA wall stress in PH may be a trigger for BMP10 secretion.Methods:We first investigated BMP10 gene and protein expressions, as well as BMP activity, in RA tissue samples from control (N=5) and PH-patients (N=4). We also quantified BMP10, BMP9, IL-6 and active TGF-β plasma levels in controls (N=16) and PH-patients (N=48) by ELISA. We studied BMP10 and BMP9 activities, using a BMP-inducible reporter assay. Last, we established correlations between BMP10 activity and PH clinical parameters.Results:BMP10 mRNA, protein and activity (pSMAD1/5/8 and ID3) were increased in RA tissue of PH-patients compared to controls (Figure1 A-E). BMP10, BMP9 and IL-6 plasma levels were also augmented (Figure1 F-H); while TGF-β plasma levels, and BMP10 and BMP9 activities between PH-patients and controls were preserved. Finally, we divided the PH cohort on median BMP10-activity (0.33 AU). Higher BMP10 activity in PH-patients was associated with diminished RA compliance, reduced right ventricular function, lower stroke volume and elevated NT-proBNP (Figure1 I).Conclusions:Although BMP10 plasma levels were increased, BMP10 activity was preserved in PH-patients, probably because of high inflammatory cytokines, such as IL-6. High BMP10 activity was associated with increased RA pressure and worse disease severity in PH-patients.
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- 2022
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28. Abstract 13087: Right Atrial Adaptation in Pulmonary Hypertension: Pressure-Volume and Histological Analysis
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Wessels, Jeroen N, Van Wezenbeek, Jessie, de Rover, Jari, Smal, rowan, Llucia-Valldeperas, Aida, Celant, Lucas, Marcus, J. Tim, meiboom, lilian, Groeneveldt, Joanne, Niessen, Hans, Goumans, Marie Jose J, Bogaard, Harm J, Vonk Noordegraaf, Anton, Strijkers, Gustav, Westerhof, Berend, and De Man, Frances S
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Introduction:Pulmonary arterial hypertension (PAH) is associated with increased right atrial (RA) pressure and volume. We hypothesized that these patients have RA hypertrophy, increased stroke work, fibrosis and stiffness and that RA adaptation falls short in severe right ventricular (RV) diastolic stiffness (end-diastolic elastance; Eed).Methods:RA pressure-volume loops were created through a novel method in controls (N=9) and patients (N=27). RA volume was measured on a magnetic resonance transverse stack of slices and pressure with catheterization. In a larger cohort of controls (N=20) and PAH patients with low (N=39) or high Eed(N=41), RA volume was measured on a 4-chamber view and stroke work estimated through multiplying active emptying by A-wave pressure. Atriovenous stiffness was measured as the slope from minimal pressure and volume and V-wave. In PAH-patients (N=4) and controls (N=5) that died or underwent heart- and lung-transplantation, we collected RA tissue to study hypertrophy and capillarization (CD31 and wheat germ agglutinin staining) and fibrosis (Masson’s trichrome staining).Results:Averaged pressure-volume loops show RA dilatation in patients and elevated pressure, especially during atrial contraction. Atriovenous stiffness was similar in PAH and controls, but higher in high Eedwhen compared to low Eedpatients. RA stroke work and pressure rise during atrial contraction were higher in PAH. However, when corrected for Eed, these parameters were decreased in high Eedpatients, indicating RA-RV uncoupling. Histological analysis showed increased RA hypertrophy, number of capillaries per cardiomyocyte and perivascular/interstitial fibrosis in PAH patients.Conclusions:In PAH patients there is RA hypertrophy and increased stroke work. In severe RV diastolic stiffness, RA adaptation falls short and RA-RV uncoupling occurs. Although there is increased fibrosis, atriovenous stiffness is not different between PAH and controls.
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- 2022
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29. Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension
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van der Bruggen, Cathelijne E., Happé, Chris M., Dorfmüller, Peter, Trip, Pia, Spruijt, Onno A., Rol, Nina, Hoevenaars, Femke P., Houweling, Arjan C., Girerd, Barbara, Marcus, Johannes T., Mercier, Olaf, Humbert, Marc, Handoko, M. Louis, van der Velden, Jolanda, Vonk Noordegraaf, Anton, Bogaard, Harm Jan, Goumans, Marie-José, and de Man, Frances S.
- Abstract
Supplemental Digital Content is available in the text.
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- 2016
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30. Is there a vanishing pulmonary capillary syndrome?
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Hoeper, Marius M and Vonk-Noordegraaf, Anton
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PULMONARY hypertension diagnosis ,PULMONARY hypertension treatment ,PULMONARY function tests ,PULMONARY gas exchange ,PHENOTYPES - Published
- 2017
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31. Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension-Targeted Therapy.
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Peacock, Andrew J., Crawley, Stephen, McLure, Lindsey, Blyth, Kevin, Vizza, Carmine Dario, Poscia, Roberto, Francone, Marco, Iacucci, Ilaria, Olschewski, Horst, Kovacs, Gabor, vonk Noordegraaf, Anton, Marcus, J. Tim, van de Veerdonk, Marielle C., and Oosterveer, Frank P.T.
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Most measures that predict survival in pulmonary hypertension (PH) relate directly to, or correlate with, right ventricular (RV) function. Direct assessment of RV function using noninvasive techniques such as cardiac MRI may therefore be an appropriate way of determining response to therapy and monitoring disease progression in PH.In this pan-European study, 91 patients with PH (mean pulmonary arterial pressure 46±15 mm Hg) underwent clinical and cardiac MRI assessments at baseline and after 12 months of disease-targeted therapy (predominantly endothelin receptor antagonists [47.3%] or phosphodiesterase type-5 inhibitors [25.3%]). At month 12, functional class had improved in 21 patients, was unchanged in 63 patients, and had deteriorated in 7 patients. Significant improvements were achieved in RV and left ventricular ejection fraction (P<0.001 and P=0.0007, respectively), RV stroke volume index (P<0.0001), and left ventricular end-diastolic volume index (P=0.0015). Increases in 6-minute walk distance were significant (P<0.0001) and correlated with change in RV ejection fraction and left ventricular end-diastolic volume, although correlation coefficients were low (r=0.28, P=0.01 and r=0.26, P=0.02, respectively).On-treatment changes in cardiac MRI-derived variables from left and right sides of the heart reflected changes in functional class and survival in patients with PH. Direct measurement of RV function using cardiac MRI can fully assess potential benefits of treatment in PH. [ABSTRACT FROM AUTHOR]
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- 2014
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32. The Value of Passive Leg Raise During Right Heart Catheterization in Diagnosing Heart Failure With Preserved Ejection Fraction.
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van de Bovenkamp, Arno A., Wijkstra, Niels, Oosterveer, Frank P.T. c, Vonk Noordegraaf, Anton, Bogaard, Harm Jan, van Rossum, Albert C., de Man, Frances S., Borlaug, Barry A., and Handoko, M. Louis
- Abstract
Background: Because of limited accuracy of noninvasive tests, diastolic stress testing plays an important role in the diagnostic work-up of patients with heart failure with preserved ejection fraction (HFpEF). Exercise right heart catheterization is considered the gold standard and indicated when HFpEF is suspected but left ventricular filling pressures at rest are normal. However, performing exercise during right heart catheterization is not universally available. Here, we examined whether pulmonary capillary wedge pressure (PCWP) during a passive leg raise (PLR) could be used as simple and accurate method to diagnose or rule out occult-HFpEF. Methods: In our tertiary center for pulmonary hypertension and HFpEF, all patients who received a diagnostic right heart catheterization with PCWP-measurements at rest, PLR, and exercise were evaluated (2014-2020). The diagnostic value of PCWP
PLR was compared with the gold standard (PCWPEXERCISE ). Cut-offs derived from our cohort were subsequently validated in an external cohort (N=74). Results: Thirty-nine non-HFpEF, 33 occult-HFpEF, and 37 manifest-HFpEF patients were included (N=109). In patients with normal PCWPREST (<15 mmHg), PCWPPLR significantly improved diagnostic accuracy compared with PCWPREST (AUC=0.82 versus 0.69, P =0.03). PCWPPLR >=19 mmHg (24% of cases) had a specificity of 100% for diagnosing occult-HFpEF, irrespective of diuretic use. PCWPPLR >=11 mmHg had a 100% sensitivity and negative predictive value for diagnosing occult-HFpEF. Both cut-offs retained a 100% specificity and 100% sensitivity in the external cohort. Absolute change in PCWPPLR or V-wave derived parameters had no incremental value in diagnosing occult-HFpEF. Conclusions: PCWPPLR is a simple and powerful tool that can help to diagnose or rule out occult-HFpEF. * Passive leg raise (PLR) during right heart catheterization can be used as an extra simple maneuver to diagnose or rule out occult heart failure with preserved ejection fraction. * Pulmonary capillary wedge pressure (PCWP) during PLR (PCWPPLR ) of below 11 mm Hg could be used to rule out occult heart failure with preserved ejection fraction, and PCWPPLR of 19 mm Hg and above could be used to diagnose occult heart failure with preserved ejection fraction with 100% accuracy. * Using the above described cut-offs of PCWPPLR to diagnose or rule out heart failure with preserved ejection fraction would allow for omission of exercise testing in approximately one-third of the patients with normal left ventricular filling pressures at rest. * PCWPPLR is especially of value in centers where exercise during a right heart catheterization is difficult to perform. [ABSTRACT FROM AUTHOR]- Published
- 2022
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33. Right Ventricular and Right Atrial Function Are Less Compromised in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension With Similar Pressure Overload.
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van Wezenbeek, Jessie, Kianzad, Azar, van de Bovenkamp, Arno, Wessels, Jeroen, Mouratoglou, Sophia A., Braams, Natalia J., Jansen, Samara M.A., Meulblok, Eva c, Meijboom, Lilian J., Marcus, J. Tim, Vonk Noordegraaf, Anton, Jose Goumans, Marie, Jan Bogaard, Harm, Handoko, M. Louis, and de Man, Frances S.
- Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and ventricular (RV) dysfunction are frequently observed. The question remains whether the PH with the associated RV/RA dysfunction in HFpEF are markers of disease severity. Methods: To obtain insight in the relative importance of pressure-overload and left-to-right interaction, we compared RA and RV function in 3 groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (PH limited to mPAP >=30 and <=50 mmHg) (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. /p> Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH. In addition, RV ejection fraction was more preserved (HFpEF-PH: 52+/-11 versus PAH: 36+/-12%). RV filling patterns differed: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10 [8-14] versus PAH: 7 [5-10] mm Hg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14 [0.10-0.17] versus PAH: 0.08 [0.06-0.11] mm Hg/mL). RA stiffness was associated with an increased eccentricity index (HFpEF-PH: 1.3+/-0.2 versus PAH: 1.2+/-0.1) and interatrial pressure gradient (9 [5 to 12] versus 2 [-2 to 5] mm Hg). Conclusions: RV/RA function was less compromised in HFpEF-PH than in PAH, despite similar pressure-overload. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Therefore, our results indicate that increased RA pressure is not a sign of overt RV failure but rather a reflection of HFpEF-severity. [ABSTRACT FROM AUTHOR]
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- 2022
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34. Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency
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Ruiter, Gerrina, Manders, Emmy, Happé, Chris M., Schalij, Ingrid, Groepenhoff, Herman, Howard, Luke S., Wilkins, Martin R., Bogaard, Harm J., Westerhof, Nico, van der Laarse, Willem J., de Man, Frances S., and Vonk-Noordegraaf, Anton
- Abstract
AbstractIn patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P= 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P< 0.001) and aerobic capacity (P< 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal were unchanged. Furthermore, iron treatment was associated with improved quality of life (P< 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. (Trial registration: ClinicalTrials.gov identifier NCT01288651)
- Published
- 2015
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35. Characteristics of Pulmonary Arterial Hypertension in Affected Carriers of a Mutation Located in the Cytoplasmic Tail of Bone Morphogenetic Protein Receptor Type 2
- Author
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Girerd, Barbara, Coulet, Florence, Jaïs, Xavier, Eyries, Mélanie, Van Der Bruggen, Cathelijne, De Man, Frances, Houweling, Arjan, Dorfmüller, Peter, Savale, Laurent, Sitbon, Olivier, Vonk-Noordegraaf, Anton, Soubrier, Florent, Simonneau, Gérald, Humbert, Marc, and Montani, David
- Abstract
Mutations in BMPR2encoding bone morphogenetic protein receptor type 2 (BMPRII) is the main genetic risk factor for heritable pulmonary arterial hypertension (PAH). The suspected mechanism is considered to be a defect of BMP signaling. The BMPRII receptor exists in a short isoform without a cytoplasmic tail, which has preserved BMP signaling.
- Published
- 2015
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- View/download PDF
36. Signs of Right Ventricular Deterioration in Clinically Stable Patients With Pulmonary Arterial Hypertension
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van de Veerdonk, Mariëlle C., Marcus, J. Tim, Westerhof, Nico, de Man, Frances S., Boonstra, Anco, Heymans, Martijn W., Bogaard, Harm-Jan, and Vonk Noordegraaf, Anton
- Abstract
BACKGROUND: Even after years of stable response to therapy, patients with idiopathic pulmonary arterial hypertension (IPAH) may show an unexpected clinical deterioration due to progressive right ventricular (RV) failure. Therefore, the aim of this study was to assess in 5-year clinically stable patients with IPAH whether initial differences or subsequent changes in RV volumes precede late clinical progression.
- Published
- 2015
- Full Text
- View/download PDF
37. Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit
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Vonk Noordegraaf, Anton, Haddad, Francois, Bogaard, Harm J., and Hassoun, Paul M.
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- 2015
- Full Text
- View/download PDF
38. Bisoprolol Delays Progression Towards Right Heart Failure in Experimental Pulmonary Hypertension.
- Author
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De Man, Frances S., Handoko, M. Louis, Van Ballegoij, Joris J.M., Schalij, Ingrid, Bogaards, Sylvia J.P., Postmus, Pieter E., Van der Velden, Jolanda, Westerhof, Nico, Paulus, Walter J., and Vonk-Noordegraaf, Anton
- Subjects
PULMONARY hypertension ,BISOPROLOL ,HEART failure ,RIGHT heart ventricle ,CARDIAC contraction ,DIASTOLE (Cardiac cycle) ,EARLY death - Abstract
The article discusses a study that showed bisoprolol delays right heart failure ( RHF) progression and preserves right ventricular (RV) systolic and diastolic function in experimental pulmonary hypertension (PH). It is stated that PH is characterized by progressive vascular remodeling and increased RV afterload leading to RHF and premature death. The study revealed that bisoprolol increased Ees, a measure of contractility, resulting in partial normalization of ventriculo-arterial coupling.
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- 2012
- Full Text
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39. Right Ventricular Failure in Idiopathic Pulmonary Arterial Hypertension Is Associated With Inefficient Myocardial Oxygen Utilization.
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Yeun Ying Wong, Ruiter, Gerrina, Lubberink, Mark, Raijmakers, Pieter G., Knaapen, Paul, Marcus, J. Tim, Boonstra, Anco, Lammertsma, Adriaan A., Westerhof, Nico, van der Laarse, Willem J., and Vonk-Noordegraaf, Anton
- Subjects
VENTRICULAR outflow obstruction ,PULMONARY hypertension diagnosis ,CARDIAC catheterization complications ,POSITRON emission tomography ,EDUCATION - Abstract
The article discusses a study on the association between right ventricular (RV) failure in idiopathic pulmonary arterial hypertension (IPAH) and reduced efficiency of myocardial oxygen utilization. The study involved patients in the New York Heart Association (NYHA) class II and class III. The patients underwent right heart catheterization and positron emission tomography (PET). Both groups had similar RV power and oxygen supply. Class II had lower RV oxygen extraction compared with class III.
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- 2011
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40. Right Ventricular Energetics in Patients With Hypertrophic Cardiomyopathy and the Effect of Alcohol Septal Ablation.
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Timmer, S.A.J., Knaapen, P., Germans, Tjeerd, Lubberink, Mark, Dijkmans, Pieter A., Vonk-Noordegraaf, Anton, ten Berg, Jurrien M., ten Cate, Folkert J., Lammertsma, Adriaan A., and van Rossum, Albert C.
- Abstract
Abstract: Background: Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is accompanied by augmented left ventricular (LV) end-diastolic pressure, above all in the presence of LV outflow tract (LVOT) obstruction. Increased back-pressure may augment right ventricular (RV) afterload and induce an oxidative metabolic imbalance between the 2 ventricles. The aim was to study right-to-left ventricular oxidative metabolism in HCM and the effects of alcohol septal ablation (ASA). Methods and Results: Twenty-one HCM patients were enrolled. Eleven healthy subjects served as a control group. Subjects underwent 2-dimensional echocardiography to assess LVOT gradient, left atrial size, and diastolic function. [
11 C]Acetate positron-emission tomography (PET) was performed to determine RVk2 and LVk2 , as a noninvasive index of oxidative metabolism. Seven HCM patients with LVOT obstruction, scheduled to undergo ASA, were also studied 6 months after the procedure. RVk2 was higher in HCM patients than i control subjects (0.081 ± 0.021 min−1 vs. 0.061 ± 0.017 min−1 ; P = .05), whereas LVk2 was similar between groups. Consequently, RVk2 /LVk2 was increased in the patients (0.85 ± 0.19 vs 0.59 ± 0.13; P = .004). In patients with obstructive HCM, ASA reduced RVk2 (0.085 ± 0.021 min−1 to 0.072 ± 0.022 min−1 ; P = .001). Inasmuch as LVk2 remained unaffected by the procedure, RVk2 /LVk2 was decreased after ASA (0.66 ± 0.18; P = .03). The absolute change in LVOT gradient was related to the absolute change in RVk2 (r = 0.77; P = .044). Conclusions: In HCM patients, RV oxygen consumption is increased in relation to the LV. ASA reduces RV oxygen consumption in HCM patients with LVOT obstruction, suggesting that increased LV loading conditions and diastolic dysfunction play a predominant role in augmenting RV workload in these patients. [Copyright &y& Elsevier]- Published
- 2011
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41. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: Does the beneficial effect persist?
- Author
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van Loon, Rosa Laura E., Hoendermis, Elke S., Duffels, Marielle G.J., Vonk-Noordegraaf, Anton, Mulder, Barbara J.M., Hillege, Hans L., and Berger, Rolf M.F.
- Subjects
PULMONARY artery diseases ,PULMONARY surfactant ,PATIENTS - Abstract
Background: Data on long-term response to bosentan in adults and especially children with pulmonary arterial hypertension (PAH) associated with systemic-to-pulmonary shunt are scarce. Methods: We studied bosentan efficacy in 30 patients (20 adults, 10 children) with the disease at short- (4 months), and long-term follow-up (through 2.7 years). World Health Organization functional class (WHO class), transcutaneous oxygen saturation, and 6-minute walk distance were assessed at baseline, 4 months, 1 year, 1.5 years, and at latest follow-up (median 2.7 years). Results: At baseline, children tended to have more severe disease compared with adults with regard to WHO class and congenital heart defects. At 4 months'' follow-up, WHO class and 6-minute walk distance significantly improved in both adults and children. During long-term follow-up, this improvement persisted through 1 year but declined thereafter in the total group. In the children, a progressive decline in exercise capacity was observed from 1-year follow-up, whereas in the adults, improvement lasted longer. No change from baseline was seen in transcutaneous oxygen saturation. Three (10%) patients died, 2 (7%) discontinued bosentan, and 5 (17%) required additional PAH therapy (of whom 1 eventually died). One- and 2-year persistence of beneficial bosentan effect was 68% and 43% (total group), 78% and 57% (adults), and 50% and 20% (children), respectively. Conclusions: Our experience with bosentan suggests short-term improvement in both adults and children with PAH associated with systemic-to-pulmonary shunt. At long-term follow-up, a progressive decline in beneficial bosentan effect was observed. The decline appeared most pronounced in the pediatric patients, who, in this study, tended to have more severe disease at baseline. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
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42. Brain Natriuretic Peptide as Noninvasive Marker of the Severity of Right Ventricular Dysfunction in Chronic Thromboembolic Pulmonary Hypertension.
- Author
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Reesink, Herre J., Tulevski, Igor I., Marcus, J. Tim, Boomsma, Frans, Kloek, Jaap J., Vonk Noordegraaf, Anton, and Bresser, Paul
- Subjects
ATRIAL natriuretic peptides ,RIGHT heart ventricle ,THROMBOEMBOLISM ,PULMONARY hypertension - Abstract
Background: Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to identify RV dysfunction in CTEPH patients. Therefore, plasma BNP levels were studied in relation to cardiac remodeling and function as determined by cardiac magnetic resonance imaging (MRI). Methods: Thirty-eight patients with CTEPH (55 ± 15 years), and ten healthy controls (46 ± 15 years) were studied. The BNP was determined by an immunoradiometric assay. Results: The CTEPH patients had a mean pulmonary artery pressure of 49 ± 13 mm Hg, cardiac index 2.1 ± 0.7 l · min
−1 · m−2 , and pulmonary vascular resistance of 867 ± 432 dynes · s · cm−5 . In CTEPH patients, compared with controls, right ventricular (RV) remodeling was demonstrated. In the patients, BNP was increased and correlated (all p < 0.0001; Spearman rank test) with MRI parameters of RV remodeling and function: end diastolic (r = 0.71) and end systolic (r = 0.74) volumes, RV mass (r = 0.68), leftward ventricular septal bowing (r = −0.80) and ejection fraction (EF; r = −0.81). By receiver operating curve analysis, BNP levels of 11.5 picomole (pmol)/L and 48.5 pmol/L, respectively, detected RV dysfunction as defined by RVEF less than 0.45 and less than 0.30, respectively, with high sensitivity and specificity. Hemodynamically, BNP levels greater than 48.5 pmol/L identified the most severely affected patients. Conclusions: In CTEPH patients, BNP levels correlate with RV remodeling and can be used to identify RV dysfunction. Future studies are warranted on the role of BNP to identify “high risk” CTEPH patients and its relation to postoperative hemodynamic outcome, RV failure, and mortality. [Copyright &y& Elsevier]- Published
- 2007
- Full Text
- View/download PDF
43. Cardiac Function and Position More Than 5 Years After Pneumonectomy.
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Smulders, Sietske A., Holverda, Sebastiaan, Vonk-Noordegraaf, Anton, van den Bosch, Harrie C.M., Post, Johannes C., Marcus, J. Tim, Smeenk, Frank W.J.M., and Postmus, Pieter E.
- Subjects
CARDIAC imaging ,PNEUMONECTOMY ,CARDIAC magnetic resonance imaging ,DIAGNOSTIC imaging - Abstract
Background: Pneumonectomy not only reduces the pulmonary vascular bed but also changes the position of the heart and large vessels, which may affect the function of the heart. We investigated long-term effects of pneumonectomy on right ventricular (RV) and left ventricular (LV) function and whether this function is influenced by the side of pneumonectomy or the migration of the heart to its new position. Methods: In 15 patients who underwent pneumonectomy and survived for more than 5 years, we evaluated by dynamic magnetic resonance imaging the function of the RV and LV and the position of the heart within the thorax. Results: Long-term effect of pneumonectomy on the position of the heart is characterized by a lateral shift after right-sided pneumonectomy and rotation of the heart after left-sided pneumonectomy. Postoperatively, heart rate was high (p = 0.006) and stroke volume was low (p = 0.001), compared with the reference values, indicating impaired cardiac function. Patients after right-sided pneumonectomy had an abnormal low RV end-diastolic volume of 99 ± 29 mL together with a normal LV function. No signs of RV hypertrophy were found. In left-sided pneumonectomy patients, RV volumes were normal whereas LV ejection fraction was abnormally low. Conclusions: The long-term effects of pneumonectomy on the position of the heart are characterized by a lateral shift in patients after right-sided pneumonectomy and rotation of the heart in patients after left-sided pneumonectomy. Overall, cardiac function in long-term survivors after pneumonectomy is compromised, and might be explained by the altered position of the heart. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
44. Is there a vanishing pulmonary capillary syndrome?
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Hoeper, Marius M and Vonk-Noordegraaf, Anton
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- 2017
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- View/download PDF
45. Pulmonary hypertension with warm hands
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Botros, Liza, Aman, Jurjan, Bogaard, Harm Jan, and Vonk Noordegraaf, Anton
- Published
- 2017
- Full Text
- View/download PDF
46. The Right Ventricle Explains Sex Differences in Survival in Idiopathic Pulmonary Arterial Hypertension
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Jacobs, Wouter, van de Veerdonk, Mariëlle C., Trip, Pia, de Man, Frances, Heymans, Martijn W., Marcus, Johannes T., Kawut, Steven M., Bogaard, Harm-Jan, Boonstra, Anco, and Vonk Noordegraaf, Anton
- Abstract
Male sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This finding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate the underlying cause of sex differences in survival in patients treated for PAH.
- Published
- 2014
- Full Text
- View/download PDF
47. Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension–Targeted Therapy
- Author
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Peacock, Andrew J., Crawley, Stephen, McLure, Lindsey, Blyth, Kevin, Vizza, Carmine Dario, Poscia, Roberto, Francone, Marco, Iacucci, Ilaria, Olschewski, Horst, Kovacs, Gabor, vonk Noordegraaf, Anton, Marcus, J. Tim, Veerdonk, Marielle C. van de, and Oosterveer, Frank P.T.
- Abstract
Most measures that predict survival in pulmonary hypertension (PH) relate directly to, or correlate with, right ventricular (RV) function. Direct assessment of RV function using noninvasive techniques such as cardiac MRI may therefore be an appropriate way of determining response to therapy and monitoring disease progression in PH.
- Published
- 2014
- Full Text
- View/download PDF
48. The Value of Passive Leg Raise During Right Heart Catheterization in Diagnosing Heart Failure With Preserved Ejection Fraction
- Author
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van de Bovenkamp, Arno A., Wijkstra, Niels, Oosterveer, Frank P.T., Vonk Noordegraaf, Anton, Bogaard, Harm Jan, van Rossum, Albert C., de Man, Frances S., Borlaug, Barry A., and Handoko, M. Louis
- Published
- 2022
- Full Text
- View/download PDF
49. Right Ventricular and Right Atrial Function Are Less Compromised in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension With Similar Pressure Overload
- Author
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van Wezenbeek, Jessie, Kianzad, Azar, van de Bovenkamp, Arno, Wessels, Jeroen, Mouratoglou, Sophia A., Braams, Natalia J., Jansen, Samara M.A., Meulblok, Eva, Meijboom, Lilian J., Marcus, J. Tim, Vonk Noordegraaf, Anton, José Goumans, Marie, Jan Bogaard, Harm, Handoko, M. Louis, and de Man, Frances S.
- Abstract
Supplemental Digital Content is available in the text.
- Published
- 2022
- Full Text
- View/download PDF
50. Pulmonary 2-deoxy-2-[18F]-fluoro-d-glucose uptake is low in treated patients with idiopathic pulmonary arterial hypertension
- Author
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Ruiter, Gerrina, Wong, Yeun Ying, Raijmakers, Pieter, Huisman, Marc C., Lammertsma, Adriaan A., Knaapen, Paul, Man, Frances S. de, Westerhof, Nico, Laarse, Willem J. van der, and Vonk-Noordegraaf, Anton
- Abstract
Abstract Glucose metabolism measurement using 2-deoxy-2-[18F]-fluoro-d-glucose (18FDG) positron emission tomography (PET) could provide in vivo information about pulmonary vascular remodeling. The purpose of this study was to assess whether pulmonary 18FDG uptake in idiopathic pulmonary arterial hypertension (IPAH) patients changes and, if so, to determine whether the change is related to disease severity and survival. Sixteen IPAH patients who were treated with IPAH-specific therapy and 7 patients who had a myocardial infarction (MI) without pulmonary hypertension were included. IPAH disease severity was determined using the 6-minute walk test and right heart catheterization 2 days before 18FDG PET. Regions of interest were defined for left and right lungs, and standardized uptake values (SUVs), normalized to body weight, injected dose, and plasma glucose level, were derived. Mean SUVs for IPAH left and right lungs were and , respectively. In MI patients, SUVs were and in left and right lungs, respectively. Total lung SUVs were similar in IPAH and MI patients ( vs. ; ). There was no correlation between SUV and IPAH disease severity parameters. In addition, lung SUV did not predict survival in IPAH patients (hazard ratio, 1.155; 95% confidence interval, 0.16–8.26; ). In conclusion, pulmonary 18FDG uptake in treated IPAH patients is low and is not associated with disease severity and survival, thereby limiting its clinical use in patient care.
- Published
- 2013
- Full Text
- View/download PDF
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