المؤلفون: Chantal Lokhorst, Sjoukje van der Werf, Rolf M. F. Berger, Johannes M. Douwes

المصدر: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 13, Iss 13 (2024)

مصطلحات موضوعية: outcome, pediatric pulmonary hypertension, pulmonary arterial hypertension, risk assessment, risk stratification, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Background In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of serial risk stratification in adult and pediatric pulmonary arterial hypertension and to explore the usability of serial risk stratification as treatment target. Methods and Results Electronic databases PubMed, Embase, and Web of Science were searched up to January 30, 2023, using terms associated with pulmonary arterial hypertension, pediatric pulmonary hypertension, and risk stratification. Observational studies and clinical trials describing risk stratification at both baseline and follow‐up were included. Sixty five studies were eligible for inclusion, including only 2 studies in a pediatric population. C‐statistic range at baseline was 0.31 to 0.77 and improved to 0.30 to 0.91 at follow‐up. In 53% of patients, risk status changed (42% improved, 12% worsened) over 168 days (interquartile range, 137–327 days; n=22 studies). The average proportion of low‐risk patients increased from 18% at baseline to 36% at a median follow‐up of 244 days (interquartile range, 140–365 days; n=40 studies). In placebo‐controlled drug studies, risk statuses of the intervention groups improved more and worsened less compared with the placebo groups. Furthermore, a low‐risk status, but also an improved risk status, at follow‐up was associated with a better outcome. Similar results were found in the 2 pediatric studies. Conclusions Follow‐up risk stratification has improved prognostic value compared with baseline risk stratification, and change in risk status between baseline and follow‐up corresponded to a change in survival. These data support the use of serial risk stratification as treatment target in pulmonary arterial hypertension.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2047-9980Test

الوصول الحر: https://doaj.org/article/392de329ebd24ee2a932852da3aa7067Test

المؤلفون: Chantal Lokhorst, Sjoukje van der Werf, Rolf M. F. Berger, Johannes M. Douwes

المصدر: Frontiers in Cardiovascular Medicine, Vol 9 (2022)

مصطلحات موضوعية: pulmonary arterial hypertension, pediatric pulmonary hypertension, risk stratification, risk assessment, survival, outcome, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: IntroductionCurrently, risk stratification is the cornerstone of determining treatment strategy for patients with pulmonary arterial hypertension (PAH). Since the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for the diagnosis and treatment of pulmonary hypertension recommended risk assessment, the number of studies reporting risk stratification has considerably increased. This systematic review aims to report and compare the variables and prognostic value of the various risk stratification models for outcome prediction in adult and pediatric PAH.MethodsA systematic search with terms related to PAH, pediatric pulmonary hypertension, and risk stratification was performed through databases PubMed, EMBASE, and Web of Science up to June 8, 2022. Observational studies and clinical trials on risk stratification in adult and pediatric PAH were included, excluding case reports/series, guidelines, and reviews. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. Data on the variables used in the models and the predictive strength of the models given by c-statistic were extracted from eligible studies.ResultsA total of 74 studies were eligible for inclusion, with this review focusing on model development (n = 21), model validation (n = 13), and model enhancement (n = 9). The variables used most often in current risk stratification models were the non-invasive WHO functional class, 6-minute walk distance and BNP/NT-proBNP, and the invasive mean right atrial pressure, cardiac index and mixed venous oxygen saturation. C-statistics of current risk stratification models range from 0.56 to 0.83 in adults and from 0.69 to 0.78 in children (only two studies available). Risk stratification models focusing solely on echocardiographic parameters or biomarkers have also been reported.ConclusionStudies reporting risk stratification in pediatric PAH are scarce. This systematic review provides an overview of current data on risk stratification models and its value for guiding treatment strategies in PAH.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316885Test], identifier [CRD42022316885].

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2022.1035453/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/2e5824a3136a460286d38a05451e2c23Test

المؤلفون: Emmanouil Mavrogiannis, Quint A. J. Hagdorn, Venetia Bazioti, Johannes M. Douwes, Diederik E. Van Der Feen, Silke U. Oberdorf‐Maass, Marit Westerterp, Rolf M. F. Berger

المصدر: Pulmonary Circulation, Vol 12, Iss 3, Pp n/a-n/a (2022)

مصطلحات موضوعية: caspase‐1, IL‐18, IL‐1β, vascular remodeling, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the respiratory system, RC705-779

الوصف: Abstract Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arterial pressure, inflammation, and neointimal remodeling of pulmonary arterioles. Serum levels of interleukin (IL)‐1β and IL‐18 are elevated in PAH patients and may enhance proinflammatory neointimal remodeling. NLRP3 inflammasome activation induces cleavage of the cytokines IL‐1β and IL‐18, required for their secretion. Pirfenidone (PFD), an antifibrotic and anti‐inflammatory drug, has been suggested to inhibit NLRP3 inflammasome activation. We hypothesized that PFD delays the progression of PAH by suppressing NLRP3 inflammasome activation. We assessed the effects of PFD treatment in a rat model for neointimal PAH induced by monocrotaline and aortocaval shunt using echocardiographic, hemodynamic, and vascular remodeling parameters. We measured inflammasome activation by NLRP3 immunostaining, Western blots for caspase‐1, IL‐1β, and IL‐18 cleavage, and macrophage IL‐1β secretion. PFD treatment ameliorated pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary vascular remodeling in PAH rats. In PAH rats, immunostaining of NLRP3 in pulmonary arterioles and caspase‐1, IL‐1β, and IL‐18 cleavage in lung homogenates were increased compared to controls, reflecting NLRP3 inflammasome activation in vivo. PFD decreased IL‐1β and IL‐18 cleavage, as well as macrophage IL‐1β secretion in vitro. Our studies show that PFD ameliorates pulmonary hemodynamics and vascular remodeling in experimental PAH. Although PFD did not affect all NLRP3 inflammasome parameters, it decreased IL‐1β and IL‐18 cleavage, the products of NLRP3 inflammasome activation that are key to its downstream effects. Our findings thus suggest a therapeutic benefit of PFD in PAH via suppression of NLRP3 inflammasome activation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-8940Test

الوصول الحر: https://doaj.org/article/00ca98c48dea427ca494de673259cd0eTest

المؤلفون: Meindina G. Haarman, Iris Coenraad, Quint A. J. Hagdorn, Hans L. Hillege, Tineke P. Willems, Rolf M. F. Berger, Johannes M. Douwes

المصدر: Children, Vol 10, Iss 4, p 756 (2023)

مصطلحات موضوعية: pediatric pulmonary hypertension, cardiac magnetic resonance, outcome, Pediatrics, RJ1-570

الوصف: Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, affecting RV remodeling and RV performance, a major determinant of outcome in PAH-patients. In children with PAH, treatment strategy is guided by risk stratification where noninvasive prognosticators are highly needed. The prognostic value of RV characteristics derived by cardiac magnetic resonance (CMR) has been scarcely studied in pediatric PAH. We aimed to identify CMR-derived morphometric and functional RV characteristics prognostic for outcome in children with PAH. From the Dutch National cohort, thirty-eight children with either idiopathic/heritable PAH (IPAH/HPAH) or PAH associated with congenital heart disease (PAH-CHD), who underwent CMR, were included (median (interquartile range) [IQR] age 13.0 years (10.8–15.0), 66% females). Patients had severe PAH, characterized by their World Health Organization Functional Class, increased N-terminal pro-B-type natriuretic peptide and high pulmonary arterial pressure and pulmonary vascular resistance index at time of CMR. RV-ejection fraction (RVEF), indexed RV-mass (RVMi), the ratio between RV and LV mass (RVM/LVM-ratio) and left ventricular eccentricity index (LVEI) all correlated with transplant-free survival from time of CMR. These correlations could not be confirmed in the PAH-CHD group. This study shows that CMR-derived measures reflecting RV function and remodeling (LVEI, RVMi, RVM/LVM-ratio, RVEF) predict transplant-free survival in children with IPAH/HPAH and may be included in risk stratification scores in pediatric PAH.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2227-9067/10/4/756Test; https://doaj.org/toc/2227-9067Test

الوصول الحر: https://doaj.org/article/c14e2cfabebe465aae159a3d3a8fd225Test

المؤلفون: Baukje M. Zaaijer, Nienke Duppen, Brigitte W.M. Willemse, Martijn V. Verhagen, Marcus T.R. Roofthooft, Wim Timens, Rolf M.F. Berger, Johannes M. Douwes

المصدر: Respiratory Medicine Case Reports, Vol 34, Iss , Pp 101564- (2021)

مصطلحات موضوعية: Outcome, Hereditary hemorrhagic telangiectasia, Pulmonary hypertension, Pulmonary veno-occlusive disease, Pediatrics, Cardiology, Diseases of the respiratory system, RC705-779

الوصف: We describe a case of an adolescent male with the rare combination of pulmonary arterial hypertension (PAH) and pulmonary arteriovenous malformations (PAVM's) without confirmed hereditary hemorrhagic telangiectasia (HHT). The patient showed clinical deterioration on standard vasodilator therapy, leading us to question our initial diagnosis. Post-mortem evaluation confirmed the presence of pulmonary veno-occlusive disease of which no conclusive signs were recognized at diagnostic work-up. This case demonstrates the heterogeneity in the diseases causing PAH and shows that an unexpected treatment response should alert the physician to question the original diagnosis.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2213007121002264Test; https://doaj.org/toc/2213-0071Test

الوصول الحر: https://doaj.org/article/327744aeaa434d3fb488df2a9fdfa8e9Test

المؤلفون: Rolf M F Berger, Dunbar Ivy, Johannes M Douwes, Melanie J Dufva, Kristen Campbell, Aimee Lam, Adam Rauff, Karel T N Breeman, Vitaly Oleg Kheyfets, Kendall Hunter

المصدر: Open Heart, Vol 8, Iss 2 (2021)

مصطلحات موضوعية: Diseases of the circulatory (Cardiovascular) system, RC666-701

العلاقة: https://openheart.bmj.com/content/8/2/e001611.fullTest; https://doaj.org/toc/2053-3624Test; https://doaj.org/article/7a7dbf6ac2f6446981106e6262279f74Test

الإتاحة: https://doi.org/10.1136/openhrt-2021-001611Test
https://doaj.org/article/7a7dbf6ac2f6446981106e6262279f74Test

المؤلفون: Johannes M. Douwes, Meindina G. Haarman, Mark-Jan Ploegstra, Rolf M. F. Berger, Marcus T. R. Roofthooft, Douwe Postmus, Erika B. Rosenzweig, Hans L. Hillege, D. Dunbar Ivy, Usha Krishnan, Willemijn M. H. Zijlstra

المساهمون: Life Course Epidemiology (LCE), Value, Affordability and Sustainability (VALUE), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC)

المصدر: Annals of the American Thoracic Society, 19(2), 227-237

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Pulmonary Arterial Hypertension, business.industry, Hypertension, Pulmonary, MEDLINE, Prostanoid, Epoprostenol, 03 medical and health sciences, chemistry.chemical_compound, Treatment Outcome, 0302 clinical medicine, 030228 respiratory system, chemistry, Anesthesia, Prostaglandins, Humans, Weaning, Medicine, lipids (amino acids, peptides, and proteins), 030212 general & internal medicine, Dosing, Child, business, Antihypertensive Agents, Retrospective Studies

الوصف: RATIONALE: There is currently no data supporting specific dosing and weaning strategies for parental prostanoid therapy in children with pulmonary arterial hypertension (PAH).OBJECTIVES: To describe the clinical practice of intravenous (IV) or subcutaneous (SC) prostanoid therapy in pediatric PAH and identify dosing strategies associated with favorable outcome.METHODS: From an international multicenter cohort of 275 children with PAH, 98 patients that received IV/SC prostanoid therapy were retrospectively analyzed.RESULTS: IV/SC prostanoids were given as monotherapy (20%), or combined with other PAH-targeted drugs as dual (46%) or triple therapy (34%). The median time-averaged dose was 37 ng/kg/min, ranging 2-136 ng/kg/min. During follow up, IV/SC prostanoids were discontinued and transitioned to oral or inhaled PAH-targeted therapies in 29 patients. Time-dependent ROC analyses showed specific hemodynamic criteria at discontinuation of IV/SC prostanoids (mean pulmonary arterial pressure (mPAP)25 ng/kg/min), early start after diagnosis and combination with other PAH-targeted drugs were associated with better transplant-free survival.CONCLUSIONS: Early initiation of IV/SC prostanoids, higher doses of IV/SC prostanoids and combination with additional PAH-targeted therapy were associated with favorable outcome. Transition from IV/SC prostanoid therapy to oral or inhaled therapies is safe on the long-term in selected children, identified by reaching hemodynamic criteria for durable IV/SC prostanoid discontinuation while on IV/SC prostanoid therapy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3668b7c7798b60ec7f0696c2c2ee4aa8Test
https://doi.org/10.1513/annalsats.202012-1563ocTest

المؤلفون: Uyen Truong, Gareth J. Morgan, Benjamin S. Frank, Michal Schäfer, Jesse A. Davidson, Lorna P. Browne, Johannes C. von Alvensleben, Alex J. Barker, Max B. Mitchell, Johannes M. Douwes, Sandra Burzlaff, Steven H. Abman, D. Dunbar Ivy

المصدر: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 318(2), H401-H412. AMER PHYSIOLOGICAL SOC
Am J Physiol Heart Circ Physiol

مصطلحات موضوعية: Male, medicine.medical_specialty, Adolescent, pediatrics, Physiology, IMPACT, Ventricular Dysfunction, Right, Blood Pressure, 030204 cardiovascular system & hematology, discoordination, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Physiology (medical), Internal medicine, pulmonary hypertension, medicine, Humans, Child, Mechanical Phenomena, Retrospective Studies, Pulmonary Arterial Hypertension, business.industry, DYSSYNCHRONY, Hemodynamics, medicine.disease, Pulmonary hypertension, Magnetic Resonance Imaging, Myocardial Contraction, Electrophysiological Phenomena, Treatment Outcome, Heart Function Tests, MECHANICS, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Research Article, electromechanics, MRI

الوصف: Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR ( n = 64) and healthy controls ( n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls ( P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit. NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f91537a373f4af644766cc4621aeb55Test
https://doi.org/10.1152/ajpheart.00355.2019Test

المؤلفون: Chantal Lokhorst, Sjoukje van der Werf, Rolf M. F. Berger, Johannes M. Douwes

مصطلحات موضوعية: Cardiology, Cardiology (incl. Cardiovascular Diseases), Cardiorespiratory Medicine and Haematology not elsewhere classified, pulmonary arterial hypertension, pediatric pulmonary hypertension, risk stratification, risk assessment, survival, outcome, prognosis, children

الوصف: Introduction Currently, risk stratification is the cornerstone of determining treatment strategy for patients with pulmonary arterial hypertension (PAH). Since the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for the diagnosis and treatment of pulmonary hypertension recommended risk assessment, the number of studies reporting risk stratification has considerably increased. This systematic review aims to report and compare the variables and prognostic value of the various risk stratification models for outcome prediction in adult and pediatric PAH. Methods A systematic search with terms related to PAH, pediatric pulmonary hypertension, and risk stratification was performed through databases PubMed, EMBASE, and Web of Science up to June 8, 2022. Observational studies and clinical trials on risk stratification in adult and pediatric PAH were included, excluding case reports/series, guidelines, and reviews. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. Data on the variables used in the models and the predictive strength of the models given by c-statistic were extracted from eligible studies. Results A total of 74 studies were eligible for inclusion, with this review focusing on model development (n = 21), model validation (n = 13), and model enhancement (n = 9). The variables used most often in current risk stratification models were the non-invasive WHO functional class, 6-minute walk distance and BNP/NT-proBNP, and the invasive mean right atrial pressure, cardiac index and mixed venous oxygen saturation. C-statistics of current risk stratification models range from 0.56 to 0.83 in adults and from 0.69 to 0.78 in children (only two studies available). Risk stratification models focusing solely on echocardiographic parameters or biomarkers have also been reported. Conclusion Studies reporting risk stratification in pediatric PAH are scarce. This systematic review provides an overview of current data on risk stratification models and its ...

العلاقة: https://figshare.com/articles/dataset/Table_3_Risk_stratification_in_adult_and_pediatric_pulmonary_arterial_hypertension_A_systematic_review_DOCX/21529821Test

الإتاحة: https://doi.org/10.3389/fcvm.2022.1035453.s003Test
https://figshare.com/articles/dataset/Table_3_Risk_stratification_in_adult_and_pediatric_pulmonary_arterial_hypertension_A_systematic_review_DOCX/21529821Test

المؤلفون: Melanie J Dufva, Rolf M. F. Berger, Adam Rauff, Karel T N Breeman, Kendall S. Hunter, Johannes M. Douwes, Aimee Lam, D. Dunbar Ivy, Kristen Campbell, Vitaly O. Kheyfets

المساهمون: Cardiovascular Centre (CVC)

المصدر: Open Heart
Open Heart, Vol 8, Iss 2 (2021)
Open Heart, 8(2), 1-10. BMJ PUBLISHING GROUP

مصطلحات موضوعية: Right heart catheterization, Male, medicine.medical_specialty, Cardiac Catheterization, hypertension, Adolescent, pulmonary, medicine.medical_treatment, Heart Ventricles, Hemodynamics, Blood Pressure, Pulmonary Artery, Afterload, Internal medicine, Medicine, Diseases of the circulatory (Cardiovascular) system, Humans, Atrial septostomy, Child, outcome assessment, Retrospective Studies, Pulmonary Arterial Hypertension, business.industry, healthcare, Infant, Stroke Volume, Transplantation, Special Populations, medicine.anatomical_structure, Ventricle, RC666-701, Cardiology, Vascular resistance, Ventricular Function, Right, Female, Cardiology and Cardiovascular Medicine, business, Ventricular vascular coupling, Follow-Up Studies, Forecasting

الوصف: AimsVentricular–vascular coupling, the ratio between the right ventricle’s contractile state (Ees) and its afterload (Ea), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular–vascular coupling ratio (Ees/Ea) derived using right ventricular (RV) pressure alone in children with PAH.MethodsOne hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period. Maximum RV isovolumic pressure and end-systolic pressure were estimated using two single-beat methods from Takeuchi et al (Ees/Ea_(Takeuchi)) and from Kind et al (Ees/Ea_(Kind)) and used with an estimate of end-systolic pressure to compute ventricular–vascular coupling from pressure alone. Patients were identified as either idiopathic/hereditary PAH or associated PAH (IPAH/HPAH and APAH, respectively). Haemodynamic data, clinical functional class and clinical worsening outcomes—separated into soft (mild) and hard (severe) event categories—were assessed. Adverse soft events included functional class worsening, syncopal event, hospitalisation due to a proportional hazard-related event and haemoptysis. Hard events included death, transplantation, initiation of prostanoid therapy and hospitalisation for atrial septostomy and Pott’s shunt. Cox proportional hazard modelling was used to assess whether Ees/Ea was predictive of time-to-event.ResultsIn patients with IPAH/HPAH, Ees/Ea_(Kind) and Ees/Ea_(Takeuchi) were both independently associated with time to hard event (p=0.003 and p=0.001, respectively) and when adjusted for indexed pulmonary vascular resistance (p=0.032 and p=0.013, respectively). Neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to soft event. In patients with APAH, neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to hard event or soft event.ConclusionsEes/Ea derived from pressure alone is a strong independent predictor of adverse outcome and could be a potential powerful prognostic tool for paediatric PAH.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96cb2144f2528253cc5f69901f35cd62Test
http://europepmc.org/articles/PMC8479945Test