Pulmonary arterial hypertension (PAH) is considered a rare disease, and is listed on the NIH Office of Rare Diseases Research website (http://rarediseases.info.nih.gov/). Whilst rare, PAH is a devastating disease of the small pulmonary arteries that rapidly leads to right heart failure and premature death. Its exact incidence is unknown but according to British,1 American,2 French,3 and Scottish4 registries the annual estimated incidence is 2-10 cases per million of population per year. The updated REVEAL registry in 2010 showed poorly understood female predominance with 4:1 female to male ratio.5 The estimated median survival of untreated PAH patients is between 2 to 3 years. The disease is insidious, and patients are generally not diagnosed until they begin to experience symptoms of right heart failure.
Most PAH patients are unresponsive to treatment with calcium channel blockers. A recent meta-analysis of 23 randomized controlled trials of three commonly used classes of drugs (prostanoids, endothelin-1 receptor blockers, or phosphodiesterase type-5 inhibitors) shows that while the treatment achieves moderate improvement in symptoms, hemodynamics, and survival, the patient morbidity and mortality rate remain unacceptably high.6 At present, lung transplantation is the only potential cure of PAH. However, these studies are performed mostly in developed countries. The clinical and pathological course of PAH in developing countries is still poorly understood and considered non-existent. In a recent paper by Idrees et al, the authors succinctly demonstrated clinical characteristics of PAH based on a single center experience in Saudi Arabia.7
PAH is a spectrum of diseases, a group of disorders characterized by drastic elevations of the pulmonary arterial pressure leading to right heart failure and death. Most interesting of all are pathologic features that are common to all PAH patients regardless of the presence or absence of associated conditions. The lack of definitive studies in the developing world makes it impossible to estimate the true burden of pulmonary hypertension and this study is a step forward in the fight against PAH.
Although a breakthrough in the field of pulmonary hypertension came along with cardiac catheterization in 1944,8 developing countries still only have very limited and rare access to this important procedure for diagnosis. In absence of hemodynamic parameters, the diagnosis of pulmonary hypertension is established via conventional clinical methodology. A compatible clinical picture (e.g. dyspnea with exertion, palpitation, chest pains, cyanosis), with signs of cardiomegaly on a chest radiograph, and right axis deviation and/or right ventricular hypertrophy on an electrocardiogram are all supportive of the diagnosis, although misdiagnosis is more common. Therefore, the inclusion of hemodynamic parameters by Idrees et al increases the strength of their study.7
This study highlights the demographic differences in PAH in different continents and suggests that PAH occurred earlier than previously assumed in Saudi Arabia. Additionally, the mean age of the PAH patient in this study was relatively younger than what had been previously established as the mean age of diagnosis. As shown by other registries, idiopathic PAH was the common subtype of PAH with female predominance. Consistent with the REVEAL registry,5 this study showed a long lag between onset of symptom and diagnosis. A lack of distinctive clinical features, poor index of suspicion and a shortage of readily available medical care may account for the delay in diagnosis. In addition, a major challenge in carefully dissecting the PAH characteristics in the developing world also lies in the prevalence of many infectious diseases that can lead to pulmonary hypertension. Further, factors such as high altitude and other conditions such as undiagnosed rheumatic and congenital heart diseases may contribute to the PAH pathogenesis in the developing world.
In summary, the authors elegantly outline the characteristics of Saudi PAH patients and this data is of high clinical significance. This study could encourage other centers in the world to publish their data defining disease characteristics in their region so as to increase our global understanding of pulmonary arterial hypertension. It is well understood that better understanding of disease characteristics translates into an improved diagnostic and therapeutic approach. Therefore it is necessary to spread the word about PAH and actively initiate and participate in such studies.
1. Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JS, Howard LS, Pepke-Zaba J, Sheares KK, Corris PA, Fisher AJ, Lordan JL, Gaine S, Coghlan JG, Wort SJ, Gatzoulis MA, Peacock AJ. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. American journal of respiratory and critical care medicine 2012; 186: 790-796.
2. Frost AE, Badesch DB, Barst RJ, Benza RL, Elliott CG, Farber HW, Krichman A, Liou TG, Raskob GE, Wason P, Feldkircher K, Turner M, McGoon MD. 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.
3. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Simonneau G. Pulmonary arterial hypertension in France: results from a national registry. American journal of respiratory and critical care medicine 2006; 173: 1023-1030.
4. Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. The European respiratory journal 2007; 30: 104-109.
5. Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Turner M, Giles S, Feldkircher K, Miller DP, McGoon MD. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010; 137: 376-387.
6. Galie N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 2009; 30: 394-403.
7. Idrees M. “Pulmonary hypertension in Saudi Arabia: A single center experience,” which was published in the previous issue of Annals of Thoracic Medicine. Annals of thoracic medicine 2014; 9: 49.
8. Cournand A, Riley RL, Breed ES, Baldwin ED, Richards DW, Lester MS, Jones M. Measurement of Cardiac Output in Man Using the Technique of Catheterization of the Right Auricle or Ventricle. The Journal of clinical investigation 1945; 24: 106-116.