A new era of therapeutic strategies for chronic thromboembolic pulmonary hypertension by two different interventional therapies; pulmonary endarterectomy and percutaneous transluminal pulmonary angioplasty

Abstract

Background: Pulmonary endarterectomy (PEA) is established for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary arteries. A shift in clinical practice of interventional therapies occurred in 2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of patients with CTEPH.

Methods and results: This study retrospectively included 136 patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and the other 107 underwent interventional therapies (Interventions-group) (39 underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis, 5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline hemodynamic parameters were significantly more severe in the Interventions-group, the outcome after the diagnosis was much better in the Interventions-group than in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic improvement in the PEA-group was a 46% decrease in mean pulmonary arterial pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up period; 74.7 ± 32.3 months), while those in the PTPA-group were a 40% decrease in mean PAP and a 49% decrease in TPR (follow-up period; 17.4 ± 9.3 months). The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival rate, occurrence of right heart failure, and re-vascularization rate in the PEA-group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%, and 2.9%, respectively.

Conclusion: The patients who underwent interventional therapies had better results than those treated only with drugs. The availability of both of these operative and catheter-based interventional therapies leads us to expect the dawn of a new era of therapeutic strategies for CTEPH.

Figure 1. Kaplan-Meier curves showing outcome from diagnosis.

Curves show outcome in patients treated with medical therapy alone (Drug-group) (green line) and patients treated with interventional therapy (Interventions-group) (orange line). Patients in the Interventions-group were treated with pulmonary endarterectomy (PEA) and/or percutaneous transluminal pulmonary angioplasty (PTPA). This analysis shows a significantly better outcome in the Interventions-group than in the Drug-group (log-rank test, p<0.01).

Figure 2. Hemodynamic changes in patients treated with PTPA (PTPA-group) (red boxes) and in patients with PEA (PEA-group) (blue boxes).

Open boxes indicate data before each therapy and solid boxes indicate data at follow-up. Data are shown as boxplot distributions. *: statistically significant (p<0.05) difference between before and after each therapy; †: statistically significant (p<0.05) difference between changes of variables in the two groups; RAP: right atrial pressure; PAP: pulmonary arterial pressure; TPR: total pulmonary resistance.

Figure 3. Changes of distribution of New York Heart Association functional class in PTPA-group and PEA-group.

*: statistically significant (p<0.05) difference between before and after each therapy; NS, not significant (p>0.05).

Figure 4. Changes in 6-minute-walk distance (6MWD) and plasma B-type natriuretic peptide (BNP) level in PTPA-group (red boxes) and PEA-group (blue boxes).

Open boxes indicate data before each therapy and solid boxes at follow-up. Data are shown as boxplot distributions. *: statistically significant (p<0.05) difference between before and after each therapy.

Figure 5. Kaplan-Meier curves to evaluate outcomes of two interventional therapies.

Curves show survival rate (A), rate of exacerbation of right heart failure (B), rate of additional re-vascularization (C), and these composite endpoints (D) from the time when each interventional therapy (PTPA or PEA) was performed in patients in PTPA-group (red line) and PEA-group (blue line).