Author + information
- Zhehao Dai,
- Yoshihiro Fukumoto, MD, PhD∗ (, )
- Shunsuke Tatebe, MD, PhD,
- Koichiro Sugimura, MD, PhD,
- Yutaka Miura, MD, PhD,
- Kotaro Nochioka, MD, PhD,
- Tatsuo Aoki, MD, PhD,
- Saori Miyamichi-Yamamoto, MD, PhD,
- Nobuhiro Yaoita, MD,
- Kimio Satoh, MD, PhD and
- Hiroaki Shimokawa, MD, PhD
- ↵∗Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Significant progress has been made in intravascular imaging with optical coherence tomography (OCT), which has enabled us to precisely examine pulmonary artery (PA) morphology in pulmonary hypertension (PH) patients, as we recently demonstrated (1,2). In the present study, we aimed to examine with OCT whether PA remodeling precedes the development of PH and whether reverse remodeling of the PA could be induced in response to current treatments.
The ethical committees of Tohoku University Hospital approved the study protocol and all patients provided written informed consent. We prospectively enrolled 124 individuals who underwent both right heart catheterization and PA-OCT at our hospital from February 2009 to December 2012, including 79 PH patient (mean pulmonary artery pressure [PAP] ≥25 mm Hg at rest), 10 borderline PH patients (mean PAP between 21 and 24 mm Hg), and 35 non-PH subjects (mean PAP ≤20 mm Hg).
We performed OCT imaging of the PA by using the time domain M2 OCT system (LightLab Imaging Inc., Westford, Massachusetts). For morphometric assessment, we determined the PA wall thickness, the thickness-diameter ratio defined as the wall thickness divided by the outer diameter, and the wall-area ratio; with all of these 3 parameters averaged over 2 to 6 representative cross sections (mean ± SD, 2.65 ± 0.76 sections; diameter between 1 and 4 mm) at each OCT examination in each subject. The wall-area ratio was determined as follows: the wall area was calculated as the whole-vessel area encircled by the outside edge of the vessel subtracted from the luminal area. We defined the ratio of the wall area divided by the whole-vessel area as the wall-area ratio. All of these morphometric evaluations were performed on offline saved images by using LightLab Imaging M2 Office Review Workstation (LightLab Imaging Inc.). We defined reverse remodeling as improvement of >2 of the 3 morphometric PA parameters. Correlation tests were performed using Pearson’s correlation, except in those involving the brain natriuretic peptide (BNP) level, for which Spearman’s correlation was used.
Representative cross-sectional images of PA-OCT are shown in Figure 1A. The 3 morphometric parameters (wall-area ratio, thickness-diameter ratio, and thickness) were all significantly increased in borderline PH and PH compared with non-PH subjects (Figs. 1B to 1D). As continuous variables, the 3 morphometric parameters were highly and significantly correlated with the mean PAP (Figs. 1E to 1G) and pulmonary vascular resistance (PVR) (r2 = 0.2238, p < 0.0001; r2 = 0.1941, p < 0.0001; r2 = 0.2575, p < 0.0001, respectively) in all subjects (N = 124).
We also evaluated the correlation of the 3 morphometric parameters with established prognostic factors, including cardiac index (r2 = 0.0147, p < 0.05; r2 = 0.0378, p < 0.05; r2 = 0.0198, p = NS, respectively), plasma BNP level (ρ = 0.2970, p < 0.001; ρ = 0.2815, p < 0.005; ρ = 0.1233, p = NS, respectively), and serum uric acid level (r2 = 0.0502, p < 0.05; r2 = 0.0566, p < 0.01; r2 = 0.0632, p < 0.01, respectively) in all subjects (N = 124). In the 29 pulmonary arterial hypertension (PAH) patients who underwent the 6-min walk test, we evaluated its association with OCT-detected morphology (r2 = 0.1662, p < 0.05; r2 = 0.1414, p < 0.05; r2 < 0.0001, p = NS, respectively). All the 4 prognostic factors were significantly correlated with wall-area ratio and thickness-diameter ratio, but not thickness.
Of the 79 PH patients, 14 with PAH underwent follow-up PA-OCT and catheterization after the treatments. They underwent right heart catheterization and OCT ≥2 times (2.43 ± 0.73 times, 34 times in total, 20 serial changes analyzed). No correlation was observed between the serial changes in mean PAP or PVR and those in wall-area ratio, thickness-diameter ratio, or thickness, except a significant correlation between the serial change in PVR and that in thickness (r2 = 0.2462, p < 0.05). Among the 14 patients, 8 presented with morphological improvement in ≥2 parameters on the second examination compared with the first, defined as reverse remodeling. Compared with the remaining 6 patients without reverse remodeling, those with reverse remodeling were characterized with significantly less prevalence of PAH associated with connective tissue diseases, increased serum uric acid level, and more patients prescribed spironolactone (p < 0.05 each).
To the best of our knowledge, this is the first report that OCT can demonstrate the development of PA remodeling in the very early stages in PH, when the mean PAP is between 21 and 24 mm Hg, defined as borderline PH in the current criteria, as well as the occurrence of reverse remodeling in response to the treatment in PH patients.
Please note: This work was supported in part by the Grants-in-Aid (#13210312 and #13383052) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation