2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT
2019; Elsevier BV; Volume: 38; Issue: 9 Linguagem: Inglês
10.1016/j.healun.2019.06.022
ISSN1557-3117
AutoresGeorg Hansmann, Martin Köestenberger, Tero-Pekka Alastalo, Christian Apitz, Eric D. Austin, Damien Bonnet, Werner Budts, Michele D’Alto, Michael Α. Gatzoulis, Babar Hasan, Rainer Kozlik‐Feldmann, Raman Kumar, Astrid E. Lammers, Heiner Latus, Ina Michel‐Behnke, Oliver Miera, Nicholas W. Morrell, Guido Pieles, Daniel Quandt, Hannes Sallmon, Dietmar Schranz, Karin Tran‐Lundmark, Robert Tulloh, G. Warnecke, Håkan Wåhlander, Sven C. Weber, Peter Zartner,
Tópico(s)Congenital Heart Disease Studies
ResumoThe European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990–2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term “pulmonary hypertension” and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH. The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990–2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term “pulmonary hypertension” and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH. Pulmonary hypertension (PH) and associated pulmonary vascular disease (PVD) are characterized by pulmonary vascular remodeling leading to elevated pulmonary arterial pressure and, over time, right ventricular (RV) dysfunction, underfilling/compression of the left ventricle, and terminal heart failure.1Humbert M Guignabert C Bonnet S et al.Pathology and pathobiology of pulmonary hypertension: State of the art and research perspectives.Eur Respir J. 2019; 53Crossref Scopus (548) Google Scholar, 2Vonk Noordegraaf A Chin KM Haddad F et al.Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: An update.Eur Respir J. 2019; 53Crossref Scopus (221) Google Scholar, 3Hansmann G. Pulmonary hypertension in infants, children, and young adults.J Am Coll Cardiol. 2017; 69: 2551-2569Crossref PubMed Scopus (98) Google Scholar PH-associated mortality has been decreasing over the last 2 decades in children4Frank BS Ivy DD Diagnosis, evaluation and treatment of pulmonary arterial hypertension in children.Children (Basel). 2018; 5PubMed Google Scholar and adults,5Galiè N Channick RN Frantz RP et al.Risk stratification and medical therapy of pulmonary arterial hypertension.Eur Respir J. 2019; 53Crossref Scopus (466) Google Scholar likely because of increased awareness of this condition and its multiple etiologies, more accurate diagnosis, better risk stratification, and early initiation of combination pharmacotherapy.3Hansmann G. Pulmonary hypertension in infants, children, and young adults.J Am Coll Cardiol. 2017; 69: 2551-2569Crossref PubMed Scopus (98) Google Scholar,5Galiè N Channick RN Frantz RP et al.Risk stratification and medical therapy of pulmonary arterial hypertension.Eur Respir J. 2019; 53Crossref Scopus (466) Google Scholar, 6Lammers AE Apitz C Zartner P et al.Diagnostics, monitoring and outpatient care in children with suspected pulmonary hypertension/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii1-i13Crossref PubMed Scopus (45) Google Scholar, 7Hansmann G Apitz C. Treatment of children with pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii67-ii85Crossref PubMed Scopus (56) Google Scholar Nevertheless, transplant-free survival of children and adults with idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), and other forms of World Health Organization (WHO) Group 1 PH, such as Eisenmenger syndrome and persistent pulmonary arterial hypertension (PAH) after repair of congenital heart disease (CHD) (PAH-CHD) remains poor.3Hansmann G. Pulmonary hypertension in infants, children, and young adults.J Am Coll Cardiol. 2017; 69: 2551-2569Crossref PubMed Scopus (98) Google Scholar, 4Frank BS Ivy DD Diagnosis, evaluation and treatment of pulmonary arterial hypertension in children.Children (Basel). 2018; 5PubMed Google Scholar, 8Barst RJ McGoon MD Elliott CG et al.Survival in childhood pulmonary arterial hypertension: Insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management.Circulation. 2012; 125: 113-122Crossref PubMed Scopus (270) Google Scholar, 9Maxwell BG Nies MK Ajuba-Iwuji CC Coulson JD Romer LH Trends in hospitalization for pediatric pulmonary hypertension.Pediatrics. 2015; 136: 241-250Crossref PubMed Scopus (37) Google Scholar Although there is currently no cure for PAH, both the established and experimental therapies aim to stop or even reverse disease progression, thereby relieving the significant morbidity and mortality and improving the patients’ quality of life. The 2015 European Society of Cardiology (ESC) and European Respiratory Society guidelines on the diagnosis and treatment of PH includes comprehensive recommendations on the diagnosis and treatment of PH but mainly focuses on clinical care in adults.10Galiè N Humbert M Vachiery JL et al.2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Heart J. 2016; 37: 67-119Crossref PubMed Scopus (4071) Google Scholar Both a new definition and an expanded classification of PH were developed at the World Symposium on PH (WSPH, Nice, 2018)11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar, 12Rosenzweig EB Abman SH Adatia I et al.Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management.Eur Respir J. 2019; 53Crossref Scopus (274) Google Scholar (Box 1 and 2; Supplementary Tables S1, S2, and S3, available online at www.jhltonline.org). The unique features of pediatric PH were recognized for the first time at the 2013 WSPH, resulting in a dedicated short document on pediatric PH13Ivy DD Abman SH Barst RJ et al.Pediatric pulmonary hypertension.J Am Coll Cardiol. 2013; 62: D117-D126Crossref PubMed Scopus (325) Google Scholar that was recently updated.12Rosenzweig EB Abman SH Adatia I et al.Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management.Eur Respir J. 2019; 53Crossref Scopus (274) Google Scholar Based on our previous expert consensus recommendations in 2016,14Hansmann G Apitz C Abdul-Khaliq H et al.Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii86-i100Crossref PubMed Scopus (80) Google Scholar we deliver updated, comprehensive, practical guidelines for healthcare providers addressing the specifics of PH and PVD in children and young adults. In 2016, the EPPVDN published a multipaper consensus statement that contains practical recommendations for health care providers treating children and adolescents with different forms of PH.14Hansmann G Apitz C Abdul-Khaliq H et al.Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii86-i100Crossref PubMed Scopus (80) Google Scholar The objectives of our 2019 guidelines on pediatric PH are the following:1.To briefly discuss the most recent changes to the classification and definition of PH and its subtypes (World Symposium on PH in Nice 2018);11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar, 12Rosenzweig EB Abman SH Adatia I et al.Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management.Eur Respir J. 2019; 53Crossref Scopus (274) Google Scholar2.To outline clinical study results and their limitations;3.To provide graded, evidence-based, and expert-based recommendations for optimal diagnosis and treatment of infants, children, and young adults with PH (including CHD/Eisenmenger and single ventricle physiology/Fontan), according to the grading system provided by the American Heart Association and ESC;4.To address features of the disease and its management that are specific to pediatric PH;5.To define the multiple gaps in our knowledge on pediatric PH; and6.To briefly discuss emerging PH therapies (safety and efficacy). The EPPVDN is a registered non-profit organization. The network strives to define and develop effective, innovative diagnostic methods and treatment options for all forms of pediatric PH and associated heart failure. The EWG members were recruited from Austria, Belgium, Germany, Finland, France, India, Italy, Pakistan, Sweden, Switzerland, the United Kingdom, and the United States of America. The EWG consisted of 22 pediatricians (with expertise and board certifications in pediatric cardiology, critical care, pulmonology, neonatology, sports medicine, and/or genetics), 7 doctors with sub-specialty certifications for adults with CHD (3 adult cardiology, 4 pediatric cardiology), 1 adult pulmonologist, and 1 thoracic transplant surgeon. Previously, we followed a novel approach to develop 10 individual papers sorted by clinical topic, including “diagnosis/monitoring”6Lammers AE Apitz C Zartner P et al.Diagnostics, monitoring and outpatient care in children with suspected pulmonary hypertension/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii1-i13Crossref PubMed Scopus (45) Google Scholar, “treatment”7Hansmann G Apitz C. Treatment of children with pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii67-ii85Crossref PubMed Scopus (56) Google Scholar, and an “executive summary”14Hansmann G Apitz C Abdul-Khaliq H et al.Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii86-i100Crossref PubMed Scopus (80) Google Scholar, in a special issue on pediatric pulmonary hypertension (https://heart.bmj.com/content/102/Suppl_2). In these guidelines, status after the WSPH 2018 meeting, we updated and expanded the 2016 executive summary to develop the 2019 EPPVDN guidelines. The following disease-specific, complex, and common patient groups are addressed separately: (1) PH associated with CHD, including recommendations for both children and young adults with PAH-CHD; and (2) persistent PH of the newborn (PPHN) and PH associated with bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) in infancy. The 2019 updated EPPVDN guidelines also give detailed recommendations on the treatment of acute PH in the intensive care unit, including extracorporeal membrane oxygenation and lung transplantation, and comprehensive recommendations on mid- to long-term treatment of PH in inpatient and outpatient settings, including pharmacotherapy, catheter interventions, and surgery. Moreover, for the first time, we highlight the challenges and special aspects of diagnostics and treatment of PH in middle to low income regions (MLIRs). This consensus document has been endorsed by the Association for European Pediatric and Congenital Cardiology (AEPC), the European Society for Pediatric Research (ESPR), and the International Society of Heart and Lung Transplantation (ISHLT). Searches of the PubMed/MEDLINE bibliographic database were conducted for the time period 1990–2018. Clinical studies/trials, guidelines, consensus statements, and reviews including pediatric data and/or adults with CHD were searched using the terms “pulmonary hypertension” and up to 10 other keywords. The primary focus of this manuscript is on group 1 PH, according to the WSPH in Nice, 2018.11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar The COR and LOE grading was based on pediatric PH study data, adult PAH studies enrolling >10% children, or studies on children and adults with PAH-CHD. Details on the ESC/American Heart Association grading system for COR (Table 1) and LOE (Table 2), as well as the voting, peer review, and endorsement process, can be found in the Supplementary Material online. The supplement also includes additional text, figures, tables, and the supplementary references per section (ref. S3-1 to S12-26), as listed in numerical order in the graded recommendations (Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12). Importantly, healthcare providers must adhere to the medication labeling and follow future drug recommendations/warnings potentially published by the European Medicines Agency and the US Food and Drug Administration when applying these recommendations in clinical practice.Table 1COR as Currently Proposed by the ESC and the AHAClass of recommendationDefinitionSuggested wording to useClass IEvidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective.Is recommended/is indicatedClass IIConflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure.Class IIaWeight of evidence/opinion is in favor of usefulness/efficacy.Should be consideredClass IIbUsefulness/efficacy is less wellEstablished by evidence/opinion.May be consideredClass IIIEvidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful.Is not recommendedAHA, American Heart Association; COR, class of recommendation; ESC European Society of Cardiology.The color coding was used throughout the 2019 Updated Guidelines on the Diagnosis and Treatment of Pediatric Pulmonary Hypertension—The European Pediatric Pulmonary Vascular Disease Network. Open table in a new tab Table 2LOE as Currently Proposed by the ESC and the AHALevel of evidenceLevel of evidence AData derived from multiple randomized clinical trials or meta-analyses.Level of evidence BData derived from a single randomized clinical trial or large non-randomized studies.Level of evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, registries.AHA, American Heart Association; ESC European Society of Cardiology; LOE, level of evidence.The color coding was used throughout the 2019 Updated Guidelines on the Diagnosis and Treatment of Pediatric Pulmonary Hypertension—The European Pediatric Pulmonary Vascular Disease Network. Open table in a new tab AHA, American Heart Association; COR, class of recommendation; ESC European Society of Cardiology. The color coding was used throughout the 2019 Updated Guidelines on the Diagnosis and Treatment of Pediatric Pulmonary Hypertension—The European Pediatric Pulmonary Vascular Disease Network. AHA, American Heart Association; ESC European Society of Cardiology; LOE, level of evidence. The color coding was used throughout the 2019 Updated Guidelines on the Diagnosis and Treatment of Pediatric Pulmonary Hypertension—The European Pediatric Pulmonary Vascular Disease Network. Box 1DefinitionsPulmonary Hypertension (PH), according to the recent WSPH (Nice, 2018) mPAP > 20 mm Hg in children >3 months of age at sea levelPre-capillary PH (e.g., PAH) mPAP > 20 mm HgPAWP or LVEDP ≤ 15 mm HgaPVR index ≥ 3 WU × m2 (PVR ≥ 3 WU in adults)Diastolic TPG (DPG) ≥ 7 mm Hg (adjunct criterion)Isolated post-capillary PH (Ipc-PH) in adults (e.g., predominantly diastolic LV dysfunction [HFpEF]a) mPAP > 20 mm HgPAWP or LVEDP > 15 mm HgPVR index < 3 WU × m2 (PVR <3 WU in adults)Diastolic TPG (DPG) < 7 mm Hg (adjunct criterion)Combination of pre-capillary and post-capillary PH (Cpc-PH) in adultsa mPAP > 20 mm HgPAWP or LVEDP > 15 mm HgPVR ≥3 WU (PVR index ≥ 3 WU × m2 in children)Pulmonary Arterial Hypertension (PAH) mPAP > 20 mm HgPAWP or LVEDP ≤ 15 mm HgaPVR index ≥ 3 WU × m2, plus criteria for group 1 PHIdiopathic PAH (IPAH)PAH with no underlying disease known to be associated with PAHHeritable PAH (HPAH)PAH with no known underlying disease but with positive family history or positive genetic testing of the index patientEisenmenger syndrome (ES)Patient with longstanding pulmonary hypertension, suprasystemic PVR and PAP, and accordingly, right-to-left cardiovascular shunting with systemic hypoxemia (e.g., unrepaired VSD or PDA).Pulmonary Hypertensive Vascular Disease (PHVD)#bFor biventricular circulations: mPAP > 20 mm Hg and PVR index ≥ 3 WU × m2For circulations with cavopulmonary anastomosis (e.g., Fontan physiology):Mean TPG > 6 mm Hg (calculate mPAP minus mLAP or PAWP) or PVR index > 3 WU × m2Box 1. The classification of PH according to the WSPH (Nice, 2018)11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar and the classification of pediatric PHVD15Cerro MJ Abman S Diaz G et al.A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric TaskForce, Panama 2011.Pulm Circ. 2011; 1: 286-298Crossref PubMed Scopus (190) Google Scholar can be found in Supplementary Tables S1 and S2, respectively (available online). Details on hemodynamic definitions, invasive measures, and clinical implications are given in Supplementary Table S3 online. Detailed hemodynamic definitions of PH (e.g., value of the diastolic TPG) can be found in the 2015 ESC/ERS guidelines,10Galiè N Humbert M Vachiery JL et al.2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Heart J. 2016; 37: 67-119Crossref PubMed Scopus (4071) Google Scholar Hansmann (2017)3Hansmann G. Pulmonary hypertension in infants, children, and young adults.J Am Coll Cardiol. 2017; 69: 2551-2569Crossref PubMed Scopus (98) Google Scholar and Apitz et al. (2016)16Apitz C Hansmann G Schranz D Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.Heart. 2016; 102: ii23-ii29Google Scholar It should be noted that even mildly elevated mPAP values (20–24 mm Hg, prognostic threshold 17 mm Hg) are independent predictors of poor survival in adults with PH (Douschan et al., 2018).17Douschan P Kovacs G Avian A et al.Mild elevation of pulmonary arterial pressure as a predictor of mortality.Am J Respir Crit Care Med. 2018; 197: 509-516Crossref PubMed Scopus (106) Google Scholar In adults, PVR is usually not indexed to BSA.aIn many instances, it is useful to measure the PAWP simultaneously with LVEDP.bPVRI-Panama classification of pediatric PHVD, 2011 mPAP ≥ 25mm Hg used to define PHBSA, body surface area; Cpc-PH, combination of pre-capillary and post-capillary pulmonary hypertension; DPG, diastolic pulmonary gradient; ERS, European Respiratory Society ESC, European Society of Cardiology; HFpEF, heart failure with preserved ejection fraction; HPAH, heritable pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; Ipc-PH, isolated post-capillary pulmonary hypertension; LV, left ventricle; LVEDP, left ventricular end-diastolic pressure; mLAP, mean left atrial pressure; mPAP, mean pulmonary artery pressure; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PDA, patent ductus arteriosus; PH, pulmonary hypertension; PHVD, pulmonary hypertensive vascular disease; PVR, pulmonary vascular resistance; TPG, transpulmonary pressure gradient; VSD, ventricular septal defect; WSPH, World Symposium on Pulmonary Hypertension; WU, Wood units.Box 2What is new in the 2019 Updated EPPVDN Consensus Statement on Pediatric PH?1. The WSPH 2018 modified the definition and classification of PH presented in the 2015 ESC/ERS Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension.10Galiè N Humbert M Vachiery JL et al.2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Heart J. 2016; 37: 67-119Crossref PubMed Scopus (4071) Google Scholar In particular, the lower limit of normal mPAP was decreased from 24 to 20 mm Hg.11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar Even mildly elevated mPAP values (20–24 mm Hg, prognostic threshold 17 mm Hg) were recently found to be independent predictors of poor survival in adults with PH.17Douschan P Kovacs G Avian A et al.Mild elevation of pulmonary arterial pressure as a predictor of mortality.Am J Respir Crit Care Med. 2018; 197: 509-516Crossref PubMed Scopus (106) Google Scholar For consistency, this new definition of PH was also used in the pediatric WSPH 2018 document12Rosenzweig EB Abman SH Adatia I et al.Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management.Eur Respir J. 2019; 53Crossref Scopus (274) Google Scholar and our 2019 EPPVDN consensus statement, although the cut-off mPAP > 20 mm Hg remains arbitrary because no according prognostic pediatric data are available.2. As in adults, a sub-group of children with IPAH can be identified who are positive responders to AVT and would now be classified as “PAH long-term responders to CCBs” according to the WSPH 2018 (Group 1.5 PH).11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar AVT is estimated to be positive in approximately 15–30% of children with IPAH, depending on the AVT criteria applied (Sitbon, 15%; modified Barst/pediatric REVEAL, 30%). Because only half of the adult responders have a long-term hemodynamic and clinical improvement on CCB therapy, close long-term follow-up is required, and combination therapy may be warranted once CCB monotherapy becomes partly inefficient.3. PAH and PVOD/PCH are now considered a spectrum of PVDs rather than two clearly distinct entities.11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar According to the WSPH 2018, Group 1.6 PH is now called PAH with overt features of venous/capillary involvement (PVOD/PCH).11Simonneau G Montani D Celermajer DS et al.Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (1871) Google Scholar The prevalence for IPAH is 2.1–4.4 cases per million children,12Rosenzweig EB Abman SH Adatia I et al.Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management.Eur Respir J. 2019; 53Crossref Scopus (274) Google Scholar but several-fold higher for PAH-CHD. PVOD/PCH was diagnosed in only 0.7%–2% of PAH cases in European pediatric registries,12Rosenzweig EB Abman SH Adatia I et al.Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management.Eur Respir J. 2019; 53Crossref Scopus (274) Google Scholar and thus appears to be very rare.4. Diagnostic methods and variables and their application in pediatric PH have been updated. In particular, the EPPVDN evaluated new echocardiographic surrogate variables for its use in pediatric PH (normal reference values by age and gender available). The diagnostic algorithm is shown in Figure 1.5. The EPPVDN updated the table on pediatric determinants of risk according to new clinical pediatric PH data (Figure 2). A new Risk Score Sheet for Pediatric PH (Hansmann G et al., EPPVDN, 2019) has also been developed and may be used for risk stratification (Supplementary Figure S1 online).Figure 2Determinants of risk in pediatric PH and suspected PHVD. Variables are listed that distinguish between lower risk and higher risk, while the intermediate risk group is broad and not specifically defined. Overall, these determinants have only level of evidence C because of sparse or lacking pediatric data. Healthcare providers may include here PVR/SVR ratio, the 6 minute walk distance, and VO2max obtained during cardiopulmonary exercise testing as risk variables; however, it is unclear where exactly the cut-off values should be set. One must also note that most of these variables have been validated mostly for IPAH, and the cut-off levels used above may not necessarily apply to other forms of PAH. Furthermore, the use of approved therapies and their influence on the variables should be considered in the evaluation of the risk. See also supplementary Figure S1 for the EPPVDN risk score sheet (PH risk stratification). BMI, body mass index; BNP, brain natriuretic peptide; CI, cardiac index; CMR, cardiovascular magnetic resonance imaging; e.s., end-systolic; IPAH, idiopathic pulmonary arterial hypertension; mPAP, mean pulmonary artery pressure; mRAP, mean right atrial pressure; mSAP, mean systemic artery pressure; NT-proBNP, N terminal pro BNP; PAAT, pulmonary artery acceleration time by transthoracic Doppler echocardiography; PAH, pulmonary arterial hypertension; PH, p
Referência(s)