The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Impact of Sex on Outcome After Pulmonary Endarterectomy (PEA) for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)


      The impact of sex on long term outcomes after PEA for CTEPH remains unclear. We therefore examined phenotypical and genotypical differences between males and females to determine whether sex had an impact on outcomes after PEA.


      A retrospective study of 401 consecutive patients undergoing PEA at our institution between 08/2005 and 03/2020 was performed. Outcomes included survival, functional class and need for postoperative targeted PH therapy. PEA specimens were analyzed in 3 males and 2 females using single cell RNA sequencing.


      Females (n=203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p<0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p<0.01). Despite similar preoperative values, females had less improvement in postoperative total pulmonary vascular resistance (final TPR after PEA, 437 Dynes•s•cm−5 vs 324 Dynes•s•cm−5 in males, p<0.01). Survival at 10 years reached 73% in females and 84% in males, but females had worse functional class and higher requirement for PH therapy (Figure). Female sex remained an independent factor affecting the need for targeted PH therapy after PEA in a multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p=0.04). Both sexes expressed TGF-β1 in endothelial cells from the PEA specimen, but the receptor TGFβR1 was predominantly expressed in females (Figure).


      In our cohort, we found significant differences between males and females undergoing PEA. Although outcomes are excellent for both sexes, females had greater need for targeted PH therapy in the long term. Greater TGFβR1 expression in females PEA specimen suggests biological differences in CTEPH pathology.