Development of prognostic tools in pulmonary arterial hypertension: Lessons from modern day registries

Summary

Pulmonary arterial hypertension (PAH) is characterised by increased pressure in the pulmonary arteries leading to right-sided ventricular failure, and death. Identification of factors that affect patient survival is important to improve patient management and outcomes. The first registry to evaluate survival and develop a prognostic model was the National Institutes of Health (NIH) registry in 1981. Importantly this prognostic model is based on data collected prior to availability of PAH-targeted therapies and does not reflect survival rates for treated patients. Since the 1980s, however, four modern registries of PAH now exist which compensate for the NIH equations shortcomings and include the French National registry, Pulmonary Hypertension Connection registry, the Mayo registry, and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). The similarities and difference in these registries are highlighted in this review and although similar in many respects, the four registries vary in patient population, including the numbers of newly and previously diagnosed patients, as well as the era of observation, period of survival, and timing of assessment of potential predictive factors. Despite this, the predictive factors identified in each registry and described in detail within the body of this manuscript share surprising homology in that disease aetiology, patient gender and factors reflective of right heart failure are integral in depicting survival. Future modifications of modern prognostic equations should be an ongoing goal of the PAH community in order to provide increased accuracy with identification of novel risk factors and prediction of disease course.

Keywords

Prognosis - pulmonary arterial hypertension - REVEAL - risk calculator - survival prediction

• References

• 1 Galie N, Hoeper MM, Humbert M. et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the 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 the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009; 30: 2493-2537.
• 2 Benza RL, Miller DP, Barst RJ. et al. An Evaluation of Long-Term Survival From Time of Diagnosis in Pulmonary Arterial Hypertension From REVEAL. Chest. 2012 prepub online
• 3 Rich S, Dantzker DR, Ayres SM. et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987; 107: 216-223.
• 4 D’Alonzo GE, Barst RJ, Ayres SM. et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343-349.
• 5 Simonneau G, Robbins IM, Beghetti M. et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009; 54: S43-54.
• 6 Benza RL, Miller DP, Gomberg-Maitland M. et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010; 122: 164-172.
• 7 Jing ZC, Xu XQ, Han ZY. et al. Registry and survival study in chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest 2007; 132: 373-379.
• 8 Fasnacht MS, Tolsa JF, Beghetti M. The Swiss registry for pulmonary arterial hypertension: the paediatric experience. Swiss Med Wkly 2007; 137: 510-513.
• 9 Humbert M, Sitbon O, Chaouat A. et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173: 1023-1030.
• 10 Thenappan T, Shah SJ, Rich S. et al. A USA-based registry for pulmonary arterial hypertension 1982-2006. Eur Respir J 2007; 30: 1103-1110.
• 11 Mukerjee D, St George D, Coleiro B. et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 2003; 62: 1088-1093.
• 12 Peacock AJ, Murphy NF, McMurray JJ. et al. An epidemiological study of pulmonary arterial hypertension. Eur Respir J 2007; 30: 104-109.
• 13 McGoon MD, Krichman A, Farber HW. et al. Design of the REVEAL registry for US patients with pulmonary arterial hypertension. Mayo Clin Proc 2008; 83: 923-931.
• 14 Humbert M, Sitbon O, Chaouat A. et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156-163.
• 15 Humbert M, Sitbon O, Chaouat A. et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173: 1023-1030.
• 16 Humbert M, Sitbon O, Yaici A. et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J 2011; 36: 549-555.
• 17 Thenappan T, Shah SJ, Rich S. et al. A USA-based registry for pulmonary arterial hypertension:1982-2006. Eur Respir J 2007; 30: 1103-1110.
• 18 Thenappan T, Shah SJ, Rich S. et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J 2010; 35: 1079-1087.
• 19 Kane GC, Maradit-Kremers H, Slusser JP. et al. Integration of clinical and hemodynamic parameters in the prediction of long-term survival in patients with pulmonary arterial hypertension. Chest 2011; 139: 1285-1293.
• 20 Badesch DB, Raskob GE, Elliott CG. et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010; 137: 376-387.
• 21 Frost AE, Badesch DB, Barst RJ. et al. The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US contemporary registries. Chest 2011; 139: 128-137.
• 22 Carroll KJ. On the use and utility of the Weibull model in the analysis of survival data. Control Clin Trials 2003; 24: 682-701.
• 23 McLaughlin VV, Suissa S. Prognosis of pulmonary arterial hypertension: the power of clinical registries of rare diseases. Circulation 2010; 122: 106-108.
• 24 Pencina MJ, D’Agostino RB. Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med 2004; 23: 2109-2123.
• 25 Levy WC, Mozaffarian D, Linker DT. et al. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation 2006; 113: 1424-1433.
• 26 Aaronson KD, Schwartz JS, Chen TM. et al. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation 1997; 95: 2660-2667.
• 27 Suissa S. Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Saf 2007; 16: 241-249.
• 28 Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008; 167: 492-499.
• 29 Nickel N, Golpon H, Greer M. et al. The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2011; 34: 132-137.
• 30 Benza RL, Gomberg-Maitland M, Miller DP. et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 2012; 141: 354-362.
• 31 Thenappan T, Glassner C, Gomberg-Maitland M. Validation of the pulmonary hypertension connection for survival prediction in pulmonary arterial hypertension. Chest 2012; 141: 642-650.
• 32 Benza RL, Miller DP, Frantz RP. et al. Association between serial 6MWD assessments and the REVEAL PAH risk score calculator [abstract 123]. J Heart Lung Transplant 2010; 29: S46.
• 33 Benza RL, Gomberg-Maitland M, Naeije R. et al. Prognostic factors associated with increased survival in patients with pulmonary arterial hypertension treated with subcutaneous treprostinil in randomized, placebo-controlled trials. J Heart Lung Transplant 2011; 30: 982-989.
• 34 Sachdev A, Villarraga HR, Frantz RP. et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest 2011; 139: 1299-1309.