Author + information
- Rogerio Souza, MD, PhD∗ ( and )
- Gerald Simonneau, MD
- ↵∗Pulmonary Department, Heart Institute, University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar 44 - 5 and Bl 2, Sao Paulo 05403-000, Brazil
The Second World Symposium on Pulmonary Hypertension, held in Evian, France, in 1998, settled the basis of the current classification system, representing a significant step forward as compared to the previous approach that separated pulmonary hypertension (PH) into primary or secondary forms (1).
Since then, PH has been classified into 5 different categories trying to group together patients sharing similar hemodynamic profile, pathological findings, and therapeutic approach/response.
Hemolytic anemia as an associated condition to the development of pre-capillary PH has been changed into group 5 not just because of the hemodynamic profile. Indeed, recent cohorts on PH associated to hemolytic anemias demonstrated a singular hemodynamic profile, as a consequence of high cardiac output, with elevated pulmonary pressures and low pulmonary vascular resistance (2–4). This fact was markedly relevant to support the decision of not including pulmonary vascular resistance as a mandatory part of the definition of PH, since different cardiac output states would demand different cutoffs of abnormality. Even more importantly, the available data on the pathological findings and treatment trials for patients with PH associated to hemolytic anemia have also been reviewed. As mentioned by Klings et al. (2), literature evaluating pulmonary arterial hypertension (PAH) therapy in sickle cell disease associated PH is limited. In fact, there is no consistent controlled data supporting the use of specific PAH therapy in this setting. Regarding pathology findings, differently from all other subforms of PAH included in group 1, many inconsistencies also exist regarding the pulmonary vascular findings in patients with sickle cell disease and PH. In the study from Haque et al. (5), 1 of the largest available series, most of the included patients present cirrhosis as a clear confounding factor for the interpretation of the data.
Based on these 3 different aspects, hemolytic anemia was changed into group 5 in the current classification, until new data support otherwise (6). It is undeniable that PH is a significant complication of hemolytic anemia, with strong prognostic implication and, as such, should be better understood in order to support the use of specific treatment strategies. Such a situation also occurs in other clinical conditions that may develop pre-capillary PH. Sarcoidosis is a clear example of a clinical condition in which a significant proportion of patients may develop PH. Nevertheless, the lack of appropriate pathological studies and treatment trials prevent its inclusion into group 1, even considering those presenting true pre-capillary PH.
The current classification system for PH has limitations. For instance, prevalence of each one of the forms of PH is not covered by the current classification system and this may overemphasize the importance of group 1 over the other groups, and should be considered in future reviews of the current classification.
Nevertheless, it is important to highlight that for any specific subform of PH, targeted therapies should be appropriately tested instead of extrapolating the results from studies enrolling potentially similar conditions. Also in this sense, hemolytic anemias, as other clinical conditions within group 5, represent an open and important field for PH research.
Finally, the change in clinical classification was proposed by 12 of the 13 members of the Task Force on Clinical Classification and approved by more than 85% of the attendees during the plenary session of the 5th World Symposium held in 2013, in Nice, France.
Please note: Dr. Simonneau has served on the advisory boards of Eli Lilly, Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline, and Novartis; received lecture fees from Eli Lilly, Pfizer, Bayer-Schering, GlaxoSmithKline; and received grant support from Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline, and Novartis. Dr. Souza has reported that he has no relationships relevant to the contents of this paper to disclose.
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