Systemic Abnormalities Derived From Chronic Thromboembolic Pulmonary Hypertension and Their Improvement by Balloon Pulmonary Angioplasty

The influence of chronic thromboembolic pulmonary hypertension (CTEPH) on systemic abnormalities and their improvement by balloon pulmonary angioplasty (BPA), the latest treatment option for CTEPH and mainly developed in Japan,^1–3 are evaluated by Dr Tatebe et al of Tohoku University School of Medicine.⁴ Whether these generalized abnormalities other than cardiorespiratory disorder result from CTEPH is difficult to assess either because these changes, such as hypertension, are prevalent in the general population or, on the contrary, they may be attributable to CTEPH. However, in this report, BPA improved the hemodynamics of CTEPH patients, and both alteration of generalized disorders and a relationship of hemodynamic to systemic changes were observed, meaning that if improvement in systemic abnormality correlates with hemodynamic improvement, the systemic abnormality derived from CTEPH.

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The study subjects were 58 patients with CTEPH treated with BPA. Before treatment, generalized complications such as hypertension, diabetes mellitus, dyslipidemia and advanced chronic kidney disease were noted in 58%, 7%, 33% and 36%, respectively. After treatment, these abnormalities improved after an average follow-up period of 474±245 days, with correlation with hemodynamic amelioration as follows. There was no reference to changes in blood pressure. Regarding diabetes mellitus, the percent change in 6-min walk distance (6MWD) correlated with that in hemoglobin A1c (HbA1c), suggesting that poor exercise capacity related to abnormal pulmonary hemodynamics may have caused glucose intolerance. Concerning lipid profile abnormality, there was a significant negative correlation between the percent change in B-type natriuretic peptide (BNP) and that in low-density lipoprotein cholesterol (LDL-C), and positive correlations between the percent change in BNP and those in eicosapentaenoic acid (EPA) and the EPA/AA (arachidonic acid ratio), although absolute values of EPA and EPA/AA increased after BPA, meaning that improvement in hemodynamics and right ventricle overload may have improved the poor nutritional state in patients with CTEPH. On the other hand, EPA and EPA/AA improved after BPA, suggesting that BPA had a direct effect on these lipid changes. As for renal dysfunction, there were significant decreases in serum creatinine (Cr) and uric acid (0.82±0.29–0.74±0.25, 5.9±1.7–5.2±1.6, respectively) and an increase in the glomerular filtration ratio (65.5±18.8–71.8±19.5), without significant correlation with improvement in hemodynamics (Figure). These results indicate that some of these apparent improvements in systemic abnormalities derive from indirect effects of hemodynamic amelioration but some are direct effects.

Figure.

Correlation between percent changes in hemodynamics with those in metabolic, renal and vascular functions after balloon pulmonary angioplasty (BPA). ∆, percent change in each clinical parameter after BPA; 6MWD, 6-min walk distance; BNP, B-type natriuretic peptide; CI, cardiac index; EPA, eicosapentaenoic acid; EPA/AA, eicosapentaenoic acid to arachidonic acid ratio; HbA1c, hemoglobin A1c; HOMA-IR, homeostasis model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol; mPAP, mean pulmonary artery pressure; mRAP, mean right atrial pressure; TC, total cholesterol. (Extracted from Tatebe S, et al.⁴)

To consider why these systematic abnormalities were improved by BPA, the mechanism of BPA’s effect on the whole body is also important because it will show how additional treatment to BPA should be contemplated to rapidly and sufficiently improve the condition of CTEPH patients.^5,6 Cardiac index and mean right atrial pressure did not improve, but mean pulmonary arterial pressure and BNP did improve after BPA. No data on blood oxygen concentration are presented, but it may have improved in view of the decrease in the number of patients receiving ambulatory oxygen therapy. These findings suggest that, according to the data demonstrated in this report, perfusion of the entire organ may not have changed but a reduction in venous congestion and perfusion of more oxygenated blood to systemic organs may have resulted. This suggests that sufficient oxygenation and control of venous congestion is also important in the treatment of CTEPH.

It is very meaningful that this report demonstrated that CTEPH causes generalized debilitation leading to a poor prognosis, and the mechanism by which CTEPH impairs other organs, with resultant systemic dysfunction. Further studies on the influence of CTEPH on the body as a whole are anticipated in the future.

Disclosure

Research funds from Actelion Pharmaceuticals.

References

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