Abstract
BACKGROUND
Pharmacologically induced pulmonary hypertension (PH) is infrequent nowadays and it is included in the type 1 of the classification of PH.
Tyrosine kinase inhibitors (TKI) are the cornerstone of the treatment of many haemotopoietic stem cell diseases. Dasatinib is a second-generation TKI used in chronic myeloid leukemia (CML) and as an infrequent cardiovascular side-effect (< 0,50%) could induce PH, usually reversible but life threatening. Only a few case series are published.
CASE DESCRIPTION: We present a 51-year-old woman who was diagnosed of a CML when she was 46. Initially, she underwent therapy with imatinib but after 5 years of treatment she developed resistance to this drug, and dasatinib was prescribed as a second line drug. After 3 months of continuous treatment, she started with dry cough and effort dyspnea. Blood analysis, EKG and Chest X-Ray were made but did not show outstanding findings. An unspecific viral infection was the final diagnosis. The patient clinical condition deteriorated with major dyspnea and edemas in the lower limbs. A TTE showed moderate tricuspid regurgitation and severe HP systolic pulmonary artery pressure (sPAP) of 80 mmHg. The pulmonary acceleration time was shortened and a mesosistolic knock was present. Systolic dysfunction of the right ventricle and pericardial effusion (image 1,2,3,4) were noted. The right atrium was not dilated. Cava vein was dilated but with inspiratory collapse >50%. The left ventricular function was preserved, but first degree diastolic dysfunction was found. Other causes of PH were excluded (types 2, 3, 4). A CT pulmonary angiogram did not show segmental perfusion defects. Finally, a right heart catheterization confirmed the TTE findings: severe precapillary PH without postcapillary component. After the diagnosis was confirmed, TKI was stopped and double targeted therapy with ambrisentan + tadalafil was started. After 6 months of treatment a new TTE was made with complete reversal of the secondary changes in the myocardium induced by the PH. No tricuspid regurgitation was detected nor any indirect sign of PH was found. (image 5,6).
CONCLUSIONS
Drug-induced PH is rare nowadays and most cases were described in the seventies in the USA related with the epidemic of anorexigenic drugs. Although the pathogenesis still remains unclear, treatment includes immediately stopping the offending agent.
Echocardiography due to its accessibility, reproducibility, consistence and low cost should be the first diagnostic tool to be considered, because as it is known, in the early stages of the disease, before developing right disfunction, clinical and conventional tests are non-specific.
Abstract P1721 Figure. Echo images: previous and afte treatment
Pulmonary hypertension with dasatinib and other tyrosine kinase inhibitors
