59 results on '"Vonk-Noordegraaf, Anton"'
Search Results
2. CTA-derived left to right atrial size ratio distinguishes between pulmonary hypertension due to heart failure and idiopathic pulmonary arterial hypertension
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Huis in 't Veld, Anna E., Van Vliet, Alexander G., Spruijt, Onno A., Handoko, M. Louis, Marcus, J. Tim, Vonk Noordegraaf, Anton, and Bogaard, Harm-Jan
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- 2016
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3. 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.
- Abstract
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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4. 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
- Abstract
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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5. Early changes of cardiac structure and function in COPD patients with mild hypoxemia *
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Vonk-Noordegraaf, Anton, Marcus, J. Tim, Holverda, Sebastiaan, Roseboom, Bea, and Postmus, Pieter E.
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Lung diseases, Obstructive -- Diagnosis -- Care and treatment ,Magnetic resonance imaging -- Usage ,Hypoxia -- Diagnosis -- Care and treatment ,Pulmonary hypertension -- Diagnosis -- Care and treatment ,Health ,Diagnosis ,Care and treatment ,Usage - Abstract
Background: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD [...]
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- 2005
6. Effects of epoprostenol on right ventricular hypertrophy and dilatation in pulmonary hypertension *
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Roeleveld, Roald J., Vonk-Noordegraaf, Anton, Marcus, J. Tim, Bronzwaer, Jean G.F., Marques, Koen M.J., Postmus, Pieter E., and Boonstra, Anco
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Health - Abstract
Objectives: To gain more knowledge of changes in main pulmonary artery flow and right ventricular mass and volumes in patients with pulmonary hypertension during epoprostenol therapy. Methods: Eleven patients (9 [...]
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- 2004
7. Pulmonary vascular responses to hypoxia and hyperoxia in healthy volunteers and COPD patients measured by electrical impedance tomography *. (clinical investigations)
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Smit, Henk J., Vonk-Noordegraaf, Anton, Marcus, J. Tim, van der Weijden, Saskia, Postmus, Pieter E., de Vries, Peter M.J.M., and Boonstra, Anco
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Lung diseases, Obstructive -- Physiological aspects -- Methods -- Analysis ,Impedance, Bioelectric -- Methods -- Analysis -- Physiological aspects ,Hypoxia -- Physiological aspects -- Analysis -- Methods ,Pulmonary function tests -- Analysis -- Methods -- Physiological aspects ,Tomography -- Methods -- Physiological aspects -- Analysis ,Health ,Analysis ,Physiological aspects ,Methods - Abstract
Background: Electrical impedance tomography (EIT) is a noninvasive imaging technique using impedance to visualize and measure blood volume changes. Study objective: To examine the validity of EIT in the measurement [...]
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- 2003
8. Tracheobronchial stenting in the terminal care of cancer patients with central airways obstruction *. (clinical investigations)
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Vonk-Noordegraaf, Anton, Postmus, Pieter E., and Sutedja, Tom G.
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Stent (Surgery) -- Usage ,Palliative treatment -- Usage ,Cancer -- Care and treatment ,Lung cancer, Non-small cell -- Complications and side effects ,Esophageal cancer -- Complications and side effects ,Health ,Complications and side effects ,Usage - Abstract
Study objectives: To evaluate the palliative benefit of stent insertion in a group of patients with central airways obstruction due to terminal cancer. Design: Retrospective analysis of the symptomatic score [...]
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- 2001
9. Noninvasive assessment of right ventricular diastolic function by electrical impedance tomography
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Vonk Noordegraaf, Anton, Faes, Theo J.C., Janse, Andre, Marcus, Johan T., Bronzwaer, Jean G.F., Postmus, Pieter E., and Vries, Peter M.J.M. de
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Diastole (Cardiac cycle) -- Analysis ,Heart ventricle, Right -- Analysis ,Impedance, Bioelectric -- Analysis ,Tomography -- Evaluation -- Analysis ,Health ,Evaluation ,Analysis - Abstract
Study objectives: Electrical impedance tomography (KIT) offers the possibility to study blood volume changes within the right atrium during the cardiac cycle. The aim of this study was to determine [...]
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- 1997
10. 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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11. Interventricular mechanical asynchrony due to right ventricular pressure overload in pulmonary hypertension plays an important role in impaired left ventricular filling
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Vonk-Noordegraaf, Anton, Marcus, Johan T., Gan, C. Tji, Boonstra, Anco, and Postmus, Pieter E.
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Pulmonary hypertension -- Risk factors -- Research ,Heart failure -- Causes of -- Risk factors -- Research ,Health ,Research ,Risk factors ,Causes of - Abstract
Key words: left ventricle; MRI; pulmonary arterial hypertension; right heart failure; right ventricle; ventricular asynchrony Abbreviations: EDV = end-diastolic volume; LV = left ventricle, ventricular; PAH = pulmonary arterial hypertension; [...]
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- 2005
12. Left ventricular encasement after pneumonectomy: Case report
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Smulders, Sietske A., Marcus, Johan T., Gan, C. Tji-Joong, Sutedja, Thomas G., Smeenk, Frank W.J.M., and Vonk-Noordegraaf, Anton
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Health - Abstract
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2006.04.014 Byline: Sietske A. Smulders (a), Johan T. Marcus (b), C. Tji-Joong Gan (c), Thomas G. Sutedja (c), Frank W.J.M. Smeenk (a), Anton Vonk-Noordegraaf (c) Author Affiliation: (a) Department of Pulmonology, Catharina Hospital, Eindhoven, The Netherlands (b) Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (c) Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands. Article History: Received 13 March 2006; Accepted 5 April 2006
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- 2006
13. Compliance of extremely dilated main pulmonary arteries in pulmonary arterial hypertension
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Groeneveldt, Joanne, van der Wel, Tijmen, Marcus, Tim, De Man, Frances, Vonk Noordegraaf, Anton, Westerhof, Nicolaas, and Westerhof, Berend
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- 2017
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14. TRACHEOBRONCHIAL STENT PLACEMENT IN 18 PATIENTS IN DANGER OF ASPHYXIATION
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Vonk-Noordegraaf, Anton, Postmus, Pieter E., and Sutedja, Thomas G.
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Asphyxia -- Prevention -- Care and treatment ,Stent (Surgery) -- Health aspects ,Airway obstruction (Medicine) -- Care and treatment -- Prevention ,Health ,Prevention ,Care and treatment ,Health aspects - Abstract
Anton Vonk-Noordegraaf, MD(*); Pieter E Postmus, MD and Thomas G Sutedja, MD. Departments of Pulmonary Medicine, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. PURPOSE: Central airway obstuction with danger of [...]
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- 2000
15. HYPOXEMIA PRODUCES RIGHT BUT NOT LEFT VENTRICULAR HYPERTROPHY IN COPD
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Vonk-Noordegraaf, Anton, Marcus, J Tim, Roseboom, Bea, and Postmus, Pieter E.
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Lung diseases, Obstructive -- Care and treatment ,Heart enlargement -- Causes of -- Care and treatment ,Health ,Care and treatment ,Causes of - Abstract
Anton Vonk-Noordegraaf, MD(*); J Tim Marcus, PhD; Bea Roseboom, MD and Pieter E Postmus, MD, FCCP. University Hospital Vrije Universiteit, Amsterdam, The Netherlands. PURPOSE: COPD is often associated with the [...]
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- 2000
16. The Relationship Between the Right Ventricle and its Load in Pulmonary Hypertension.
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Vonk Noordegraaf, Anton, Westerhof, Berend E., and Westerhof, Nico
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PULMONARY hypertension , *RIGHT heart ventricle , *PREHYPERTENSION , *PULMONARY circulation , *BLOOD pressure - Abstract
In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduction in stroke volume, with uncoupling and increased wall stress as a consequence. With pressure-volume analysis, we separately describe the changing properties of the pulmonary vascular system and the right ventricle, as well as their coupling, as important concepts for understanding the changes that occur in pulmonary hypertension. On the basis of the unique properties of the pulmonary circulation, we show how all relevant physiological parameters can be derived using an integrative approach. Because coupling is maintained by hypertrophy until the end stage of the disease, when progressive dilation begins, right ventricular volume is the essential parameter to measure in follow-up of patients with pulmonary hypertension. [ABSTRACT FROM AUTHOR]
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- 2017
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17. 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
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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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18. 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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19. 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]
- Published
- 2014
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20. 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.
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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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21. Right ventricular ejection fraction is better reflected by transverse rather than longitudinal wall motion in pulmonary hypertension.
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Kind, Taco, Mauritz, Gert-Jan, Marcus, J. Tim, van de Veerdonk, Mariëlle, Westerhof, Nico, and Vonk-Noordegraaf, Anton
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MEDICAL research ,PULMONARY hypertension ,PULMONARY circulation ,CARDIOVASCULAR diseases ,PATIENTS ,MAGNETIC resonance ,MAGNETIC fields ,BLOOD circulation disorders ,SHEAR waves ,BIOCHEMISTRY - Abstract
Background: Longitudinal wall motion of the right ventricle (RV), generally quantified as tricuspid annular systolic excursion (TAPSE), has been well studied in pulmonary hypertension (PH). In contrast, transverse wall motion has been examined less. Therefore, the aim of this study was to evaluate regional RV transverse wall motion in PH, and its relation to global RV pump function, quantified as RV ejection fraction (RVEF). Methods: In 101 PH patients and 29 control subjects cardiovascular magnetic resonance was performed. From fourchamber cine imaging, RV transverse motion was quantified as the change of the septum-free-wall (SF) distance between end-diastole and end-systole at seven levels along an apex-to-base axis. For each level, regional absolute and fractional transverse distance change (SFD and fractional-SFD) were computed and related to RVEF. Longitudinal measures, including TAPSE and fractional tricuspid-annulus-apex distance change (fractional-TAAD) were evaluated for comparison. Results: Transverse wall motion was significantly reduced at all levels compared to control subjects (p < 0.001). For all levels, fractional-SFD and SFD were related to RVEF, with the strongest relation at mid RV (R² = 0.70, p < 0.001 and R² = 0.62, p < 0.001). For TAPSE and fractional-TAAD, weaker relations with RVEF were found (R² = 0.21, p < 0.001 and R² = 0.27, p < 0.001). Conclusions: Regional transverse wall movements provide important information of RV function in PH. Compared to longitudinal motion, transverse motion at mid RV reveals a significantly stronger relationship with RVEF and thereby might be a better predictor for RV function. [ABSTRACT FROM AUTHOR]
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- 2010
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22. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: Does the beneficial effect persist?
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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.
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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
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23. Brain Natriuretic Peptide as Noninvasive Marker of the Severity of Right Ventricular Dysfunction in Chronic Thromboembolic Pulmonary Hypertension.
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Reesink, Herre J., Tulevski, Igor I., Marcus, J. Tim, Boomsma, Frans, Kloek, Jaap J., Vonk Noordegraaf, Anton, and Bresser, Paul
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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
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24. 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.
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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]
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- 2007
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25. Multiple suspicious lesions detected by autofluorescence bronchoscopy predict malignant development in the bronchial mucosa in high risk patients
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Pasic, Arifa, Vonk-Noordegraaf, Anton, Risse, Elle K.J., Postmus, Pieter E., and Sutedja, Tom G.
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BRONCHOSCOPY , *MUCOUS membranes , *BIOCHEMICAL genetics - Abstract
Autofluorescence bronchoscopy (AFB) has been shown to be sensitive to detect preneoplastic lesions in central airways. Apart from bronchial mucosa thickness, tissue autofluorescence is also related to the biochemical properties of the target cells. Genetic studies have shown molecular abnormalities to be present in histologically normal mucosal specimens. Forty-six high-risk individuals, free of micro-invasive cancer at the initiation of the study, were included in this analysis and have been subjected to repeat bronchoscopic examinations every 4–6 months. They had previous curatively treated lung cancer (n=18), ENT tumor (n=11) or were at risk to acquire lung cancer primaries (n=17). Baseline AFB is scored for each suspicious lesion, thus the total score represents the number of AFB suspicious lesions present in each individual at risk. Baseline AFB score was correlated to outcome, i.e. the development of squamous-cell cancer (SCC) in each individual. So far, 11/46 (24%) of the individuals acquired SCC. Follow up has been 12–80 months. All five individuals with ≥3 lesions (100%, 12–36 months), five of the ten (50%, 12–48 months) individuals who had two lesions and one among the 12 (8%, 36 months) individuals with one suspicious AFB lesion, developed SCC. Up till now (12–80 months), the remaining 19 individuals without any suspicious AFB lesion have not acquired SCC. The average AFB score for the group of individuals which developed SCC was significantly different (P<0.001) from the remaining individuals who did not acquire SCC (2.64±1.1 vs. 0.6±0.7 S.D.). The number of suspicious lesions at baseline AFB is a good predictor for the development of SCC in the individuals at risk in our study population. This finding is compatible with field carcinogenesis and warrants a more upfront use of AFB in a lung cancer screening to sift the different risk-cohorts in a population mainly at risk for developing metachronous lung cancer. [Copyright &y& Elsevier]
- Published
- 2003
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26. Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection: a follow-up study
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Vonk-Noordegraaf, Anton, Postmus, Pieter E., and Sutedja, Tom G.
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LUNG cancer treatment , *BRONCHOSCOPY - Abstract
Bronchoscopic treatment (BT) has a curative potential for patients with intraluminal microinvasive radiographically occult lung cancer (ROLC). We report the long-term follow-up in a group of 32 patients, ineligible for surgery, in whom ROLC was diagnosed and treated with BT. Tumors were strictly ⩽1 cm in size, intraluminally located in the central airways, with no bronchial wall invasion or extraluminal tumor growth on high resolution CT (HRCT), with visible distal margin under conventional and autofluorescence bronchoscopy (AFB). BT was given with curative intent and consecutive patients were treated with photodynamic therapy (five patients), Nd-YAG laser therapy (one patient), electrocautery (24 patients) and argon plasma coagulation (two patients). Follow-up evaluation at 3–4 months interval included HRCT scans, both conventional and AFB, including biopsies and brush cytology for histological evaluation. The average follow-up period was 5 years (range: 2–10 years). In three patients local recurrence was again successfully treated with electrocautery. Sixteen patients died during follow-up. Eight of the nine patients who died due to lung cancer had a previous resection of a more advanced stage lung cancer up to 5 years before BT of the ROLC. The remaining seven patients cause of death was not related to lung cancer. Sixteen patients are still alive without any tumor recurrence. These data showed that BT is an effective treatment modality for high-risk patients with ROLC, who are not eligible for surgical resection. [Copyright &y& Elsevier]
- Published
- 2003
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27. Right ventricular adaptation to pressure-overload: Differences between chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension.
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Braams, Natalia J., van Leeuwen, Joost W., Vonk Noordegraaf, Anton, Nossent, Esther J., Ruigrok, Dieuwertje, Marcus, J. Tim, Bogaard, Harm Jan, Meijboom, Lilian J., and de Man, Frances S.
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PULMONARY hypertension , *CARDIAC magnetic resonance imaging , *THROMBOEMBOLISM , *ETIOLOGY of diseases - Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) are both associated with right ventricular (RV) failure and mortality. However, CTEPH patients are older, more often male and usually have more co-morbidities than iPAH patients, including a history of venous thromboembolism. Therefore, RV adaptation to pressure-overload in CTEPH may be different than in iPAH. We included all treatment-naive CTEPH and iPAH patients diagnosed in the Amsterdam UMC between 2000 and 2019 if cardiac magnetic resonance imaging (CMR) and a right heart catheterization were performed at time of diagnosis. Load-dependent RV volumes and mass were assessed with CMR. Load-independent RV contractility, afterload and diastolic stiffness in relation to afterload were obtained using single beat pressure-volume loop analysis. Differences in RV characteristics between CTEPH and iPAH were analyzed using multiple linear regression with interaction testing after correcting for confounders. We included 235 patients in this study and performed pressure-volume loop analysis in 136 patients. In addition to being older and more often male, CTEPH patients had a lower pulmonary vascular resistance than iPAH patients at the time of diagnosis. After correcting for these confounders, CTEPH patients had a somewhat higher RV end-diastolic volume index (87 ± 27 ml vs 82 ± 25 ml; p <.01), and a lower RV relative wall thickness (0.6 ± 0,1 g/ml vs 0.7 ± 0,2 g/ml; p <.01). The correlation coefficient of RV diastolic stiffness to afterload was higher in CTEPH compared to iPAH (p <.05; independent of age and gender). Despite differences in patient characteristics, disease etiology and physiology, RV functional parameters in CTEPH and iPAH are mostly similar. The right ventricle in CTEPH is marginally more dilated, stiffer and less hypertrophic than in iPAH. [ABSTRACT FROM AUTHOR]
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- 2021
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28. Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension.
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Kianzad, Azar, Baccelli, Andrea, Braams, Natalia J., Andersen, Stine, van Wezenbeek, Jessie, Wessels, Jeroen N., Celant, Lucas R., Vos, Anna E., Davies, Rachel, Lo Giudice, Francesco, Haji, Gulammehdi, Rinaldo, Rocco F., Vigo, Beatrice, Gopalan, Deepa, Symersky, Petr, Winkelman, Jacobus A., Boonstra, Anco, Nossent, Esther J., Tim Marcus, J., and Vonk Noordegraaf, Anton
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ENDARTERECTOMY , *AEROBIC capacity , *PULMONARY hypertension , *CARDIAC magnetic resonance imaging , *HEMODYNAMICS , *THROMBOEMBOLISM - Abstract
Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO 2 max <80%) at 18 months were analyzed. A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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29. Interventricular asynchrony in Chronic Thrombo Embolic Pulmonary Hypertension recovers after pulmonary endarterectomy: role of right ventricular wall stress.
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Marcus, J. Tim, Mauritz, Gert Jan, Surie, Sulaiman, Bosboom, Joachim, Kloek, Jaap J., and Vonk-Noordegraaf, Anton
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ENDARTERECTOMY - Abstract
An abstract of the paper "Interventricular Asynchrony in Chronic Thrombo Embolic Pulmonary Hypertension Recovers After Pulmonary Endarterectomy: Role of Right Ventricular Wall Stress," by J. Tim Marcus and colleagues from the 2011 SCMR/Euro CMR Joint Scientific Sessions in Nice, France from February 3-6, 2011 is presented.
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- 2011
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30. The Authors Reply:.
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Haddad, Francois, Vonk-Noordegraaf, Anton, and Zamanian, Roham T.
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- 2016
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31. Where is the heart after left-sided pneumonectomy?
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Smulders, Sietske A., Van Den Bosch, Harrie C.m., Post, Johannes C., Noordegraaf, Anton Vonk, Postmus, Pieter E., and Vonk Noordegraaf, Anton
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- 2006
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32. Pneumomediastinum and Pneumopericardium Due to High-Speed Air Turbine Drill Used During a Dental Procedure.
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Johannesma, Paul Christiaan and Vonk Noordegraaf, Anton
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- 2014
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33. Right Heart Adaptation to Pulmonary Arterial Hypertension: Physiology and Pathobiology.
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Vonk-Noordegraaf, Anton, Haddad, François, Chin, Kelly M., Forfia, Paul R., Kawut, Steven M., Lumens, Joost, Naeije, Robert, Newman, John, Oudiz, Ronald J., Provencher, Steve, Torbicki, Adam, Voelkel, Norbert F., and Hassoun, Paul M.
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PULMONARY hypertension , *PULMONARY artery abnormalities , *PULMONARY artery physiology , *SYSTOLIC blood pressure , *GENE targeting , *PULMONARY hypertension treatment , *HEART failure , *PROGNOSIS - Abstract
Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. [ABSTRACT FROM AUTHOR]
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- 2013
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34. Cardiac Magnetic Resonance Imaging: What Can It Add to Our Knowledge of the Right Ventricle in Pulmonary Arterial Hypertension?
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Vonk-Noordegraaf, Anton and Souza, Rogério
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CARDIAC magnetic resonance imaging , *RIGHT heart ventricle , *PULMONARY hypertension , *PULMONARY blood vessels , *FOLLOW-up studies (Medicine) , *HEMODYNAMICS , *ECHOCARDIOGRAPHY , *VASOCONSTRICTION - Abstract
Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular remodeling leading to a progressive increase in pulmonary vascular resistance (PVR). It is becoming increasingly recognized that it is the response of the right ventricle (RV) to the increased afterload resulting from this increase in PVR that is the most important determinant of patient outcome. A range of hemodynamic, structural, and functional measures associated with the RV have been found to have prognostic importance in PAH and, therefore, have potential value as parameters for the evaluation and follow-up of patients. If such measures are to be used clinically, there is a need for simple, reproducible, accurate, easy-to-use, and noninvasive methods to assess them. Cardiac magnetic resonance imaging (CMRI) is regarded as the “gold standard” method for assessment of the RV, the complex structure of which makes accurate assessment by 2-dimensional methods, such as echocardiography, challenging. However, the majority of data concerning the use of CMRI in PAH have come from studies evaluating a variety of different measures and using different techniques and protocols, and there is a clear need for the development of standardized methodology if CMRI is to be established in the routine assessment of patients with PAH. Should such standards be developed, it seems likely that CMRI will become an important method for the noninvasive assessment and monitoring of patients with PAH. [Copyright &y& Elsevier]
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- 2012
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35. Improvement of cardial function in patients through reefing of an elevated diaphragm.
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Zengerink, Hans, Vonk-Noordegraaf, Anton, Oosterhuis, Wolter, and Paul, Rick
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- 2007
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36. Early detection and intervention for central airway cancers: 10 year experience.
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Lee, Pyng, Vonk-Noordegraaf, Anton, Van Den Berg, Remco, Brokx, Hes A., Postmus, Pieter E., and Sutedja, Tom G.
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- 2007
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37. Unusual Manifestation of Riedel’s Thyroiditis.
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Lee, Pyng, Vonk-Noordegraaf, Anton, Paul, Marinus A., and Sutedja, Tom G.
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- 2007
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38. Idiopathic pulmonary arterial hypertension patients with a high H2FPEF-score: Insights from the Amsterdam UMC PAH-cohort.
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Kianzad, Azar, van Wezenbeek, Jessie, Celant, Lucas R., Oosterveer, Frank P.T, Vonk Noordegraaf, Anton, Meijboom, Lilian J., de Man, Frances S., Bogaard, Harm Jan, and Handoko, M. Louis
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PULMONARY arterial hypertension , *LEFT ventricular dysfunction , *HYPERTENSION , *OLDER patients , *PULMONARY hypertension - Abstract
The idiopathic pulmonary arterial hypertension (iPAH) phenotype is changing from a predominantly young female patient to an older, frequently obese patient of either sex. Many newly diagnosed iPAH-patients have risk factors for left ventricular diastolic dysfunction (LVDD), possibly affecting management and treatment. To determine whether the H 2 FPEF-score identifies a subgroup of iPAH-patients with blunted response to PAH-targeted treatment. We performed a retrospective analysis of 253 treatment-naïve iPAH-patients (1989-2019) with a confirmed diagnosis after right heart catheterization by a multidisciplinary team. Follow-up RHC measurements were available in 150 iPAH-patients. iPAH-patients were stratified by the H 2 FPEF-score; a score ≥5 identified a higher possibility of (concealed) LVDD. The presence of a high H 2 FPEF-score in incident iPAH-patients rose 30% in thirty years. Patients with a H 2 FPEF-score ≥5 were older, more often male and/or obese, and had more comorbidities than patients with a H 2 FPEF-score ≤1. A high H 2 FPEF-score was associated with worse survival and poor functional capacity. Right ventricular function was equally depressed among iPAH-groups. Imaging and invasive hemodynamic measurements suggested concealed LVDD in iPAH patients with a high H 2 FPEF-score. At follow-up, hemodynamic and functional responses were similar in iPAH-patients with a high or low H 2 FPEF-score. While a high H 2 FPEF-score in iPAH is associated with a worse prognosis and signs of LVDD, hemodynamic and functional responses to PAH treatment are not predicted by the H 2 FPEF-score. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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39. Assessment of right ventricular responses to therapy in pulmonary hypertension.
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Spruijt, Onno A., Bogaard, Harm-Jan, and Vonk-Noordegraaf, Anton
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RIGHT heart ventricle , *PULMONARY hypertension treatment , *PULMONARY blood vessels , *PULMONARY hypertension , *CLINICAL trials , *PATIENTS , *PHYSIOLOGY - Abstract
Irrespective of its cause, pulmonary hypertension (PH) leads to an increase in pulmonary vascular resistance (PVR). Failing adaption of the right ventricle (RV) to the increased afterload is the main cause of death in PH patients and therefore monitoring RV function during treatment is essential. However, consensus on the optimal method for serial assessment of RV function is lacking and therefore the major clinical trials on PH-specific therapies have not provided clear answers with respect to the response of the RV to treatment. This short review will give an overview of the most important load-dependent and load-independent parameters for assessing RV response to therapy in PH patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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40. Pulmonary vascular imaging characteristics after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.
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Braams, Natalia J., Ruigrok, Dieuwertje, Schokker, Monique G.M., Padervinskiene, Lina, de Man, Frances S., Marcus, J. Tim, Lely, Rutger J., Beijk, Marcel A.M., Klok, Frederikus A., Huisman, Menno V., Nossent, Esther J., Vonk Noordegraaf, Anton, Symersky, Petr, Bogaard, Harm Jan, and Meijboom, Lilian J.
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PULMONARY hypertension , *ENDARTERECTOMY , *MAGNETIC resonance imaging , *PULMONARY artery , *PEAS - Abstract
Between 16% and 51% of patients with chronic thromboembolic pulmonary hypertension will have residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Whether residual PH is related to remaining (sub-)segmental macrovascular lesions or to microvascular disease is unknown. New imaging techniques can provide detailed information about (sub-)segmental pulmonary arteries and parenchymal perfusion. The aim of this study was to describe the prevalence after PEA of remaining (sub-)segmental vascular lesions on electrocardiogram-gated computed tomography pulmonary angiography (CTPA) and parenchymal hypoperfusion on magnetic resonance imaging (MRI) and to relate these imaging abnormalities to the presence or absence of residual PH after PEA. In a prospective cohort of patients with operable chronic thromboembolic pulmonary hypertension, hemodynamics, CTPA, and lung perfusion MRI were performed before and 6 months after PEA. The percentage of (sub-)segmental vascular lesions was calculated on CTPA and parenchymal hypoperfusion on lung perfusion MRI. PEA led to significant improvements in hemodynamics and a reduction of imaging abnormalities. Residual PH was present in 45% of patients after PEA, whereas remaining (sub-)segmental vascular lesions and parenchymal hypoperfusion were present in 20% and 21% of the pulmonary vasculature, respectively. Patients with and without residual PH after PEA had similar percentages of remaining (sub-)segmental vascular lesions (25% ± 14% vs 17% ± 15%; p = 0.16) and similar degrees of parenchymal hypoperfusion (20% ± 7% vs 19% ± 6%; p = 0.63). After successful PEA, advanced imaging shows that around 20% of the pulmonary vasculature remains abnormal, independent of the presence of residual PH. This may suggest that microvascular disease, rather than residual macrovascular lesions, plays a prominent role in residual PH after PEA. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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41. Pulmonary vascular remodeling patterns and expression of general control nonderepressible 2 (GCN2) in pulmonary veno-occlusive disease.
- Author
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Nossent, Esther J., Antigny, Fabrice, Montani, David, Bogaard, Harm Jan, Ghigna, Maria Rosa, Lambert, Mélanie, Thomas de Montpréville, Vincent, Girerd, Barbara, Jaïs, Xavier, Savale, Laurent, Mercier, Olaf, Fadel, Elie, Soubrier, Florent, Sitbon, Olivier, Simonneau, Gérald, Vonk Noordegraaf, Anton, Humbert, Marc, Perros, Frédéric, and Dorfmüller, Peter
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VASCULAR remodeling , *PULMONARY blood vessels , *OCCLUSIVE surgical dressings , *CELL proliferation , *IDIOPATHIC pulmonary fibrosis - Abstract
Background Heritable pulmonary veno-occlusive disease (PVOD) is linked to mutations in the eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4 ) gene, leading to a loss of general control nonderepressible 2 ( GCN2). The role of GCN2 expression in pulmonary vascular remodeling remains obscure. We sought to identify specific histologic and biologic features in heritable PVOD. Methods Clinical data and lung histology of 24 PVOD patients (12 EIF2AK4 mutation carriers, 12 non-carriers) were submitted to systematic histologic analysis and semiautomated morphometry. GCN2 expression was quantified by Western blotting in 24 PVOD patients, 44 patients with pulmonary arterial hypertension (PAH; 23 bone morphogenetic protein receptor type II [ BMPR2 ] mutation carriers, 21 non-carriers), and 3 experimental pulmonary hypertension models. Results PVOD patients showed a significant decrease of pulmonary arterial patency ( p < 0.0001) compared with healthy controls. Histology of EIF2AK4 mutation carriers was distinctive from non-carriers regarding (1) arterial remodeling, with significantly more severe intimal fibrosis ( p = 0.001), less severe medial hypertrophy ( p = 0.001), and (2) stronger muscular hyperplasia of interlobular septal veins ( p = 0.002). GCN2 expression was abolished in heritable PVOD ( p < 0.0001), but also importantly decreased in sporadic PVOD ( p = 0.03) as well as in heritable ( p = 0.002) and idiopathic PAH ( p = 0.003); moreover, GCN2 was abolished in 2 experimental pulmonary hypertension models and importantly decreased in 1 model ( p < 0.0001 for all models). Conclusions Pulmonary arterial remodeling in PVOD is present to an important extent. A significant decrease of GCN2 expression is a common denominator of all tested groups of PVOD and PAH, including their respective experimental models. Our results underline specific morphologic and biologic similarities between PAH and PVOD and let us consider both conditions rather in one large spectrum of disease than as two distinct and clear-cut entities. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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42. Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension.
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de Raaf, Michiel Alexander, Beekhuijzen, Manon, Guignabert, Christophe, Vonk Noordegraaf, Anton, and Bogaard, Harm Jan
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ENDOTHELIN receptors , *PULMONARY hypertension , *FETAL abnormalities , *FETAL development , *DRUG side effects , *VASCULAR resistance , *PREVENTION - Abstract
The Pregnancy Prevention Program (PPP) is in place to prevent drug-induced developmental malformations. Remarkably, among the ten PPP-enlisted drugs are three endothelin-1 (ET-1) receptor antagonists (ERA's: ambrisentan, bosentan and macitentan), which are approved for the treatment of Pulmonary Arterial Hypertension (PAH). This review describes the effects of ERA's in PAH pathobiology and cardiopulmonary fetal development. While ERA's hamper pathological remodeling of the pulmonary vasculature and as such exert beneficial effects in PAH, they disturb fetal development of cardiopulmonary tissues. By blocking ET-1-mediated positive inotropic effects and myocardial fetal gene induction, ERA's may affect right ventricular adaptation to the increased pulmonary vascular resistance in both the fetus and the adult PAH patient. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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43. Contractile Dysfunction of Left Ventricular Cardiomyocytes in Patients With Pulmonary Arterial Hypertension.
- Author
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Manders, Emmy, Bogaard, Harm-Jan, Handoko, M. Louis, de Veerdonk, Marielle C. van, Keogh, Anne, Westerhof, Nico, Stienen, Ger J. M., Remedios, Cristobal G. dos, Humbert, Marc, Dorfmüller, Peter, Fadel, Elie, Guignabert, Christophe, van der Velden, Jolanda, Vonk-Noordegraaf, Anton, de Man, Frances S., and Ottenheijm, Coen A. C.
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LEFT heart ventricle diseases , *PULMONARY hypertension treatment , *PULMONARY hypertension , *MORTALITY , *HEART cells , *LUNG transplantation , *PATIENTS , *PHYSIOLOGY ,SURGICAL complication risk factors - Abstract
Background After lung transplantation, increased left ventricular (LV) filling can lead to LV failure, increasing the risk of post-operative complications and mortality. LV dysfunction in pulmonary arterial hypertension (PAH) is characterized by a reduced LV ejection fraction and impaired diastolic function. Objectives The pathophysiology of LV dysfunction in PAH is incompletely understood. This study sought to assess the contribution of atrophy and contractility of cardiomyocytes to LV dysfunction in PAH patients. Methods LV function was assessed by cardiac magnetic resonance imaging. In addition, LV biopsies were obtained in 9 PAH patients and 10 donors. The cross-sectional area (CSA) and force-generating capacity of isolated single cardiomyocytes was investigated. Results Magnetic resonance imaging analysis revealed a significant reduction in LV ejection fraction in PAH patients, indicating a reduction in LV contractility. The CSA of LV cardiomyocytes of PAH patients was significantly reduced (~30%), indicating LV cardiomyocyte atrophy. The maximal force-generating capacity, normalized to cardiomyocyte CSA, was significantly reduced (~25%). Also, a reduction in the number of available myosin-based cross-bridges was found to cause the contractile weakness of cardiomyocytes. This finding was supported by protein analyses, which showed an ~30% reduction in the myosin/actin ratio in cardiomyocytes from PAH patients. Finally, the phosphorylation level of sarcomeric proteins was reduced in PAH patients, which was accompanied by increased calcium sensitivity of force generation. Conclusions The contractile function and the CSA of LV cardiomyocytes is substantially reduced in PAH patients. We propose that these changes contribute to the reduced in vivo contractility of the LV in PAH patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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44. Effect of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension on Stroke Volume Response to Exercise.
- Author
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Surie, Sulaiman, van der Plas, Mart N., Marcus, J. Tim, Kind, Taco, Kloek, Jaap J., Vonk-Noordegraaf, Anton, and Bresser, Paul
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ENDARTERECTOMY , *PULMONARY hypertension , *STROKE volume (Cardiac output) , *EXERCISE , *CARDIAC magnetic resonance imaging - Abstract
In pulmonary hypertension, exercise is limited by an impaired right ventricular (RV) stroke volume response. We hypothesized that improvement in exercise capacity after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is paralleled by an improved RV stroke volume response. We studied the extent of PEA-induced restoration of RV stroke volume index (SVI) response to exercise using cardiac magnetic resonance imaging (cMRI). Patients with CTEPH (n = 18) and 7 healthy volunteers were included. Cardiopulmonary exercise testing and cMRI were performed before and 1 year after PEA. For cMRI studies, pre- and post-operatively, all patients exercised at 40% of their preoperative cardiopulmonary exercise testingeassessed maximal workload. Post-PEA patients (n = 13) also exercised at 40% of their postoperative maximal workload. Control subjects exercised at 40%of their predicted maximal workload. Preoperatively, SVI (n[18) decreased during exercise from 35.9 ± 7.4 to 33.0 ± 9.0 ml.m² (p = 0.023); in the control subjects, SVI increased (46.6 ± 7.6 vs 57.9 ± 11.8 ml.mL², p[0.001). After PEA, the SVI response (DSVI) improved from L2.8 ± 4.6 to 4.0 ± 4.6 ml.m² (p <0.001; n = 17). On exercise at 40% of the postoperativemaximal workload, SVI did not increase further and was still significantly lower compared with controls. Moreover, 4 patients retained a negative SVI response, despite (near) normalization of their pulmonary hemodynamics. The improvement in SVI response was accompanied by an increased exercise tolerance and restoration of RV remodeling. In conclusion, in CTEPH, exercise is limited by an impaired stroke volume response. PEAinduces a restoration ofSVI response to exercise that appears, however, incomplete and not evident in all patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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45. The interventricular septum in pulmonary hypertension does not show features of right ventricular failure.
- Author
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Ruiter, Gerrina, van de Veerdonk, Mariëlle C., Bogaard, Harm-Jan, Wong, Yeun Ying, Marcus, J. Tim, Lammertsma, Adriaan A., Westerhof, Nico, van der Laarse, Willem J., de Man, Frances S., and Vonk-Noordegraaf, Anton
- Published
- 2014
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46. Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension
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Ruiter, Gerrina, Ying Wong, Yeun, de Man, Frances S., Louis Handoko, M., Jaspers, Richard T., Postmus, Pieter E., Westerhof, Nico, Niessen, Hans W.M., van der Laarse, Willem J., and Vonk-Noordegraaf, Anton
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RIGHT heart ventricle , *PULMONARY hypertension , *OXYGEN consumption , *HEART cells , *GENETIC transcription , *MESSENGER RNA - Abstract
Background: In pulmonary arterial hypertension (PAH), high right ventricular (RV) power output requires increased myocardial oxygen consumption. Oxygen supply, however, does not increase in proportion. It is unknown what cellular mechanisms underlie this lack of adaptation. We therefore determined oxygen supply parameters in RV tissue slices of deceased PAH patients and compared them with RV tissue of patients who died from left ventricular myocardial infarction (MI). Because autopsy tissue only reflects end-stage disease, rat models with stable and progressive pulmonary hypertension (PH) were studied as well. Methods: Myocardial tissue of 10 PAH and 10 MI patients was collected at autopsy. In rats, stable PH (n = 6) and progressive PH (n = 6) was induced by 40 or 60 mg/kg monocrotaline, respectively. Six rats were used as controls. Results: RV cardiomyocyte cross-sectional area was strongly increased in PAH compared with MI patients (p < 0.001), whereas capillary density decreased (p < 0.01). Rat data showed similar RV hypertrophy in stable and progressive PH, and RV capillary density was decreased in both (p < 0.01 and p < 0.0001 vs control rats, respectively). RV myoglobin protein content and functional concentration were reduced in both human and rat PH RVs. In rats, this results from a lack of increase in myoglobin mRNA transcription per cardiomyocyte nucleus. Conclusions: All measured cellular oxygen supply parameters are decreased in the failing human and rat pulmonary hypertensive RV. In contrast to stable PH rats, compensatory adaptations do not occur in end-stage PAH, despite higher myocardial oxygen consumption. [ABSTRACT FROM AUTHOR]
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- 2013
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47. Accurate assessment of load-independent right ventricular systolic function in patients with pulmonary hypertension
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Trip, Pia, Kind, Taco, van de Veerdonk, Marielle C., Marcus, Johannes T., de Man, Frances S., Westerhof, Nico, and Vonk-Noordegraaf, Anton
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PULMONARY hypertension , *SYSTOLIC blood pressure , *CARDIAC magnetic resonance imaging , *PULMONARY circulation , *COMPARATIVE studies , *MEDICAL imaging systems , *PATIENTS - Abstract
Background: End-systolic elastance (Ees), a load-independent measure of ventricular function, is of clinical interest for studies of the right ventricle (RV) in patients with pulmonary arterial hypertension (PAH). The objective of this study was to determine whether, in PAH patients, Ees can be estimated from mean pulmonary artery pressure (mPAP) and end-systolic volume (ESV) only. Methods: Right heart catheterization was used to measure mPAP. Maximal isovolumic pressure (Piso) was estimated from RV pressure curves with the so-called single-beat method. Cardiac magnetic resonance imaging (MRI) was used to assess RV end-diastolic and end-systolic volumes (EDV and ESV). Ees was then calculated as: Ees = (Piso−mPAP) / (EDV−ESV), and as Ees,V0 = 0 = mPAP/ESV (simplified method, with V0 = 0, is negligible volume at zero pressure). Right ventricular volume at zero pressure (V0) was then defined as the intercept of the end-systolic pressure–volume relation (single-beat method) with the horizontal axis. Results: Ees,V0 = 0 was significantly lower compared with Ees (0.61 vs 1.34 mm Hg/ml, respectively, p<0.01). A modified Bland–Altman analysis showed a contractility-dependent difference between Ees,V0 = 0 and Ees. Moreover, V0 ranged from−8 up to 171 ml, and a moderate and good correlation was found between V0 and EDV, and V0 and ESV, respectively (r = 0.65 and r = 0.87, p< 0.01). Conclusions: These findings show that V0 is dependent on RV dilation. Therefore, the assumption that V0 is negligible in PAH is incorrect. Consequently, for an accurate assessment of load-independent RV systolic function, RV volumes and pressure curves are required. [ABSTRACT FROM AUTHOR]
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- 2013
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48. Progressive Right Ventricular Dysfunction in Patients With Pulmonary Arterial Hypertension Responding to Therapy
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van de Veerdonk, Mariëlle C., Kind, Taco, Marcus, J. Tim, Mauritz, Gert-Jan, Heymans, Martijn W., Bogaard, Harm-Jan, Boonstra, Anco, Marques, Koen M.J., Westerhof, Nico, and Vonk-Noordegraaf, Anton
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RIGHT heart ventricle diseases , *HYPERTENSION , *VASCULAR resistance , *CARDIAC catheterization , *CARDIAC magnetic resonance imaging , *FOLLOW-up studies (Medicine) - Abstract
Objectives: The purpose of this study was to examine the relationship between changes in pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) and survival in patients with pulmonary arterial hypertension (PAH) under PAH-targeted therapies. Background: Despite the fact that medical therapies reduce PVR, the prognosis of patients with PAH is still poor. The primary cause of death is right ventricular (RV) failure. One possible explanation for this apparent paradox is the fact that a reduction in PVR is not automatically followed by an improvement in RV function. Methods: A cohort of 110 patients with incident PAH underwent baseline right heart catheterization, cardiac magnetic resonance imaging, and 6-min walk testing. These measurements were repeated in 76 patients after 12 months of therapy. Results: Two patients underwent lung transplantation, 13 patients died during the first year, and 17 patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard ratio [HR]: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of mortality. During the first 12 months, changes in PVR were moderately correlated with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p = 0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820) were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five percent of those patients with decreased PVR showed a deterioration of RV function and had a poor prognosis. Conclusions: After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR. [Copyright &y& Elsevier]
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- 2011
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49. Usefulness of Serial N-Terminal Pro–B-Type Natriuretic Peptide Measurements for Determining Prognosis in Patients With Pulmonary Arterial Hypertension
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Mauritz, Gert-Jan, Rizopoulos, Dimitris, Groepenhoff, Herman, Tiede, Henning, Felix, Janine, Eilers, Paul, Bosboom, Joachim, Postmus, Pieter E., Westerhof, Nico, and Vonk-Noordegraaf, Anton
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PULMONARY hypertension , *PROGNOSIS , *ATRIAL natriuretic peptides , *HEALTH outcome assessment , *BLOOD plasma , *HEART atrium , *PATIENTS - Abstract
Previous studies have shown the prognostic benefit of N-terminal pro–brain natriuretic peptide (NT–pro-BNP) in pulmonary arterial hypertension (PAH) at time of diagnosis. However, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT–pro-BNP in PAH. This study examined the value of serial NT–pro-BNP measurements in predicting prognosis PAH. We retrospectively analyzed all available NT–pro-BNP plasma samples in 198 patients who were diagnosed with World Health Organization group I PAH from January 2002 through January 2009. At time of diagnosis median NT–pro-BNP levels were significantly different between survivors (610 pg/ml, range 6 to 8,714) and nonsurvivors (2,609 pg/ml, range 28 to 9,828, p <0.001). In addition, NT–pro-BNP was significantly associated (p <0.001) with other parameters of disease severity (6-minute walking distance, functional class). Receiver operating curve analysis identified ≥1,256 pg/ml as the optimal NT–pro-BNP cutoff for predicting mortality at time of diagnosis. Serial measurements allowed calculation of baseline NT–pro-BNP (i.e., intercept obtained by back-extrapolation of concentration–time graph), providing a better discrimination between survivors and nonsurvivors than NT–pro-BNP at time of diagnosis alone (p = 0.010). Furthermore, a decrease of NT–pro-BNP of >15%/year was associated with survival. In conclusion, a serum NT–pro-BNP level ≥1,256 pg/ml at time of diagnosis identifies poor outcome in patients with PAH. In addition, a decrease in NT–pro-BNP of >15%/year is associated with survival in PAH. [ABSTRACT FROM AUTHOR]
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- 2011
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50. Long-term outcomes in pulmonary arterial hypertension in the first-line epoprostenol or first-line bosentan era
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Jacobs, Wouter, Boonstra, Anco, Brand, Monika, Rosenberg, Daniel M., Schaaf, Berthold, Postmus, Pieter E., and Vonk Noordegraaf, Anton
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PROSTACYCLIN , *PULMONARY hypertension treatment , *ENDOTHELINS , *TREATMENT effectiveness , *RETROSPECTIVE studies , *CARDIAC catheterization , *CARDIAC output , *MEDICAL statistics - Abstract
Background: The aim of this study was to describe the long-term outcomes in idiopathic pulmonary arterial hypertension (IPAH) treated with first-line bosentan or intravenous (IV) epoprostenol, and additional therapy as needed. Methods: In a single-center, retrospective, longitudinal cohort, data on right heart catheterization, 6-minute walk distance (6MWD), disease progression and mortality were collected. Outcomes were assessed in first-line bosentan and first-line epoprostenol patients. To reduce selection bias due to differences between groups, two independent analyses were performed. First, a comparison was made of World Health Organization (WHO) Functional Class (FC) III patients. Second, to control for disease severity, a matched-pairs analysis was performed, with matching according to baseline cardiac output and exercise capacity and irrespective of FC at baseline. Results: Thirty-seven IPAH patients initiated first-line bosentan treatment and 37 first-line IV epoprostenol. Twenty-nine of the bosentan patients and 16 of the IV epoprostenol patients were in WHO FC III; demographic profiles were similar, although hemodynamic measurements and 6MWD suggested more severe disease in the IV epoprostenol group at treatment initiation. At 1 and 3 years, median change in 6MWD for patients initiating bosentan was +54 m (95% confidence interval: −3 to 76) and +71 m (−123 to 116), respectively, and +92 m (17 to 128) and +142 m (−6 to 242) for those on IV epoprostenol. Absence of disease progression of WHO FC III at 1 and 3 years was 72% and 45% with bosentan and 75% and 44% with IV epoprostenol, respectively. Survival at 1 and 3 years was 93% and 89% with bosentan and 94% and 75% with IV epoprostenol, respectively. Results were confirmed in matched-pairs analysis of 16 bosentan and 16 IV epoprostenol patients with similar disease severity. Conclusions: First-line epoprostenol treatment may lead to greater improvement in exercise capacity than first-line bosentan. However, these greater exercise improvements did not translate into longer time to disease progression or survival. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
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