Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry.
cohort studies
delayed diagnosis
mortality
pulmonary hypertension
survival analysis
Journal
Respirology (Carlton, Vic.)
ISSN: 1440-1843
Titre abrégé: Respirology
Pays: Australia
ID NLM: 9616368
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
26
06
2019
revised:
09
11
2019
accepted:
06
01
2020
pubmed:
31
1
2020
medline:
25
6
2021
entrez:
31
1
2020
Statut:
ppublish
Résumé
Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.
Sections du résumé
BACKGROUND AND OBJECTIVE
Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients.
METHODS
A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression.
RESULTS
A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival.
CONCLUSION
PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
863-871Subventions
Organisme : Actelion Pharmaceuticals
Organisme : Allied Healthcare
Organisme : Bayer
Organisme : GlaxoSmithKline Australia
Organisme : Novartis
Organisme : Pfizer
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Asian Pacific Society of Respirology.
Références
Humbert M, Lau EM, Montani D, Jais X, Sitbon O, Simonneau G. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation 2014; 130: 2189-208.
Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Herve P, Rainisio M, Simonneau G. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J. Am. Coll. Cardiol. 2002; 40: 780-8.
Provencher S, Sitbon O, Humbert M, Cabrol S, Jais X, Simonneau G. Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur. Heart J. 2006; 27: 589-95.
Humbert M, Ghofrani H-A. The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax 2016; 71: 73-83.
McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002; 106: 1477-82.
McGoon MD, Benza RL, Escribano-Subias P, Jiang X, Miller DP, Peacock AJ, Pepke-Zaba J, Pulido T, Rich S, Rosenkranz S et al. Pulmonary arterial hypertension: epidemiology and registries. J. Am. Coll. Cardiol. 2013; 62: D51-9.
Escribano-Subias P, Blanco I, López-Meseguer M, Lopez-Guarch CJ, Roman A, Morales P, Castillo-Palma MJ, Segovia J, Gómez-Sanchez MA, Barberà JA. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur. Respir. J. 2012; 40: 596-603.
Strange G, Lau EM, Giannoulatou E, Corrigan C, Kotlyar E, Kermeen F, Williams T, Celermajer DS, Dwyer N, Whitford H et al. Survival of idiopathic pulmonary arterial hypertension patients in the modern era in Australia and New Zealand. Heart Lung Circ. 2018; 27: 1368-75.
Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Turner M et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010; 137: 376-87.
Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156-63.
Thenappan T, Shah SJ, Rich S, Tian L, Archer SL, Gomberg-Maitland M. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur. Respir. J. 2010; 35: 1079-87.
Hoeper MM, Simon RGJ. The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur. Respir. Rev. 2014; 23: 450-7.
Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Koerner SK et al. Primary pulmonary hypertension. A national prospective study. Ann. Intern. Med. 1987; 107: 216-23.
Dunlap B, Weyer G. Pulmonary hypertension: diagnosis and treatment. Am. Fam. Physician 2016; 94: 463-9.
Condliffe R, Kiely DG, Peacock AJ, Corris PA, Gibbs JS, Vrapi F, Das C, Elliot CA, Johnson M, DeSoyza J et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am. J. Respir. Crit. Care Med. 2009; 179: 151-7.
D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann. Intern. Med. 1991; 115: 343-9.
Wilkens H, Grimminger F, Hoeper M, Stähler G, Ehlken B, Plesnila-Frank C, Berger K, Resch A, Ghofrani A. Burden of pulmonary arterial hypertension in Germany. Respir. Med. 2010; 104: 902-10.
Brown LM, Chen H, Halpern S, Taichman D, McGoon MD, Farber HW, Frost AE, Liou TG, Turner M, Feldkircher K et al. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest 2011; 140: 19-26.
Tueller C, Stricker H, Soccal P, Tamm M, Aubert JD, Maggiorini M, Zwahlen M, Nicod L. Epidemiology of pulmonary hypertension: new data from the Swiss registry. Swiss Med. Wkly 2008; 138: 379-84.
Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F et al. Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. 2006; 173: 1023-30.
Jing ZC, Xu XQ, Han ZY, Wu Y, Deng KW, Wang H, Wang ZW, Cheng XS, Xu B, Hu SS et al. Registry and survival study in Chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest 2007; 132: 373-9.
Strange G, Gabbay E, Kermeen F, Williams T, Carrington M, Stewart S, Keogh A. Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: the delay study. Pulm. Circ. 2013; 3: 89-94.
Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest 2012; 142: 448-56.
Royston P, Sauerbrei W. Building multivariable regression models with continuous covariates in clinical epidemiology - with an emphasis on fractional polynomials. Methods Inf. Med. 2005; 44: 561-71.
Strange G, Rose M, Kermeen F, O'Donnell C, Keogh A, Kotlyar E, Grigg L, Bullock A, Disney P, Dwyer N et al. A binational registry of adults with pulmonary arterial hypertension complicating congenital heart disease. Intern. Med. J. 2015; 45: 944-50.
Wray J, Frigiola A, Bull C. Loss to specialist follow-up in congenital heart disease; out of sight, out of mind. Heart 2013; 99: 485-90.
Armstrong I, Rochnia N, Harries C, Bundock S, Yorke J. The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study. BMJ Open 2012; 2: e000806.
Thenappan T, Glassner C, Gomberg-Maitland M. Validation of the pulmonary hypertension connection equation for survival prediction in pulmonary arterial hypertension. Chest 2012; 141: 642-50.
O'Callaghan DS, Humbert M. A critical analysis of survival in pulmonary arterial hypertension. Eur. Respir. Rev. 2012; 21: 218-22.