EXPRESS: Pulmonary vasodilator treatment in pulmonary hypertension due to left heart or lung disease: time for a high-definition picture?

Dear Editor, We read with great interest the article “Outcomes of pulmonary vasodilator use in Veterans with pulmonary hypertension associated with left heart disease and lung disease” by Gillmeyer et al. The study findings of increased risk of death or organ failure in patients exposed to pulmonary vasodilators, are consistent with findings from randomised clinical trials and other cohort studies and “real-world scenarios”, as quoted by the authors. However, a very important lesson from over two decades of studies is that proper phenotyping of pulmonary vascular disease is key to assess risk of progression of disease. As we progress in the study of these phenotypes, both in Group 2 and Group 3 PH, we might understand which mechanisms produce these subtle but clear differences in response to vasodilator treatment. We fully agree with the authors of the paper that the use of pulmonary vasodilators in Group 2 and Group 3 PH should be confined to randomised-controlled trials, not only in order to gather data on the numerous safety concerns, but also in order to generate new, reliable evidence. We also think that the use of registries will help garner more information on “real-world” scenarios and confirm on retrospective cohorts the results obtained in randomised-controlled trials, provided we are careful to study disease groups and subgroups appropriately, avoiding the temptation of lumping them together in a bigger cohort which will inevitably mixed pears with apples. Furthermore, in full agreement with the recommendations for future directions in research on Group 3 PH, we call for studies that delve deeper into these heterogeneous groups of diseases. After the low-definition group photos, we believe it is time to zoom in the picture to gather a better understanding of what exactly is killing the different subgroups within Group 2 and Group 3 PH patients.