Not just CTEPH: a narrative review on the spectrum approach to post pulmonary embolism conditions

Three mutually exclusive entities can underlie a post-pulmonary-embolism-syndrome (PPES): not obstructed post-pulmonary embolism syndrome (NOPPES), chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlie respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the RV dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of NOPPES, which has been reported in a highly comorbid with lung and heart diseases, so that a “two hit” hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and/or respiratory diseases. More than one third of PE survivors develops PPES, with only a small, but widely varying fraction (0.1-11%) represented by CTEPH. A value of ≈3% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between NOPPES and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension (ExPH) and if it is a precursor of CTEPH. CTEPD and CTEPH can undergo effective surgical or interventional treatment, while no dedicated strategy exists for NOPPES. Further research is needed to improve the understanding and the management of CTEPD and NOPPES.