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Detection of right ventricle wall motion asynergy in pulmonary hypertension subjects without left-sided heart disease
International Journal of Cardiology 222 (2016) 375–378
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Detection of right ventricle wall motion asynergy in pulmonary hypertension subjects without left-sided heart disease Koya Ozawa a,1, Nobusada Funabashi a,⁎,1, Hiroyuki Takaoka a, Nobuhiro Tanabe b, Koichiro Tatsumi b, Yoshio Kobayashi a a b
Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan Department of Respirology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
a r t i c l e
i n f o
Article history: Received 18 July 2016 Accepted 24 July 2016 Available online 27 July 2016 Keywords: Right ventricle wall motion asynergy Pulmonary hypertension Left-sided heart disease CT
Right ventricular (RV) wall motion asynergy occurs in subjects with arrhythmogenic RV cardiomyopathy [1]. Pulmonary hypertension (PH) subjects frequently have an enlarged RV and right atria (RA), but they also may have RV wall motion asynergy [2]. Structures of the RV and RA are complex, especially when the RV and RA are enlarged, and it is often difficult to visualize accurately the configuration of the entire RV by transthoracic echocardiogram (TTE). Furthermore, it is difficult to evaluate accurately RV wall motion asynergy on TTE. Computed tomography (CT) is essential in assessing subjects with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) for the presence of thrombi in the pulmonary artery (PA) and for the presence of an enlarged PA. Furthermore, the quantitative evaluation of RV function by retrospective electrocardiogram (ECG)gated CT is defined as appropriate in the ACCF/SCCT/ACR/AHA/ASE/ ASNC/NASCI/SCAI/SCMR 2010 criteria for cardiac CT [3]. Previously, we reported the frequency of RV wall motion asynergy, as confirmed by four-dimensional (4D) 320-slice CT, in a total of 24 PH subjects (73% of the PH subjects demonstrated CTEPH and 44% demonstrated PAH). Our results showed that the presence of RV wall motion asynergy can be predicted by two-dimensional (2D) global longitudinal RV strain on TTE [2]. However, the relationship between RV wall motion
⁎ Corresponding author at: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan. E-mail address: [email protected] (N. Funabashi). 1 These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ijcard.2016.07.152 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
asynergy on CT and simple parameters such as RV size on TTE or serum brain natriuretic peptide (BNP) levels, in particular, in a large population of PH subjects without left-sided heart disease, is unclear. In this study, we used 4D CT images to detect RV wall motion asynergy in a large population of PH subjects with no significant leftsided heart disease. We attempted to predict the presence of RV wall motion asynergy using simple parameters such as RV size on TTE and serum BNP levels. This is a retrospective analysis of 62 PH subjects, confirmed by right heart catheterization (16 males, mean age of 55 ± 16 years; 45 CTEPH subjects who underwent conventional non-surgical medical therapy; and 17 PAH subjects) who underwent retrospective ECG-gated 320slice CT (Aquilion one; Toshiba Medical) and TTE (Vivid E9; GE Healthcare, iE33; Philips, or Aplio; Toshiba Medical) within 7 months without any clinical incidents and who revealed no significant leftsided heart disease, including coronary heart disease, on both CT and TTE. 2D TTE was performed to evaluate tricuspid regurgitation, the morphology of the RV, and RA size, in addition to ordinary leftsided heart evaluation. Parameters included a measure of RV end diastolic and systolic diameter on apical 4 chamber views (Fig. 1), RA major and minor diameter, and estimated systolic PA pressure established by guidelines of the American Society of Echocardiography [4]. To obtain images of the whole heart, including the RV and coronary arteries, and the PA, all CT scans were performed using a double volume conventional scan with retrospective ECG gating using 320-slice CT with a 0.5 mm slice thickness and 0.35 s/rotation with a downward direction [2,5,6]. Tube voltage was set at 120 kV and tube current was set at 580 mA with tube current dose modulation. Contrast material (350 mgI/ml, 60 ml) was injected at 3.5 ml/s, followed by injection of a saline-to-contrast material mixture (40 ml contrast material at 2.0 ml/s and 30 ml saline at 1.5 ml/s). Finally, pure saline (20 ml) was injected at 1.5 ml/s. All enhanced CT examinations in the early phase were performed for a normal workup to diagnose or evaluate PH, RV function, and coronary arteries, with a scanning delay of 20–30 s for optimal PA and coronary arterial visualization. At 6 min after injection of the contrast material, late phase acquisition was added to detect myocardial fibrosis or edema using a single volume conventional scan with prospective ECG gating at end diastole for the reduction of radiation exposure [7–13].
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K. Ozawa et al. / International Journal of Cardiology 222 (2016) 375–378
Fig. 1. Actual measurement of RV end diastolic (A) and systolic diameter (B) in an apical 4 chamber view on TTE.
Table 1 Comparison of patient characteristics and general hemodynamic state parameters between subjects with and without RV wall motion asynergy on CT. Serum brain natriuretic peptide (BNP) levels were significantly greater in subjects with RV wall asynergy than in subjects without RV wall motion asynergy.
Age (years) Males (%) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Serum BNP (pg/ml) Six minute walk test (m)
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
56 ± 16 11 (33.3%) 113 ± 16 72 ± 11 229 ± 290 354 ± 84
53 ± 16 5 (17.2%) 120 ± 21 71 ± 12 77 ± 103 388 ± 122
0.446 0.149 0.242 0.803 0.001 0.201
Bold numbers indicate significance at P b 0.05.
After acquisition, CT images in the early phase were reconstructed at every 5% of the R–R interval from 0 to 95% (total, 20 phases). We defined RV wall motion asynergy as RV focal abnormal wall motion on 4D CT images at the workstation (Virtual Place, Aze). We quantified RV free wall thickness at both end systole and end diastole and CT attenuation in RV myocardium at end diastole both in the early and late phase. We calculated the ratio of systolic/diastolic RV wall thickness (calculated as end systolic RV wall thickness per end diastolic RV wall thickness), which is considered an indicator of RV wall viability [14]. We also calculated the ratio of late/early CT attenuation in the RV myocardium (calculated as late phase CT attenuation per early phase CT attenuation in the RV myocardium), which is considered an indicator of the presence of RV myocardial fibrosis [7–13]. All right heart catheterizations were performed by respiratory physicians with more than 5 years of experience managing PH subjects. A Swan-Ganz thermodilution catheter was used and a jugular approach was preferred. Systolic, diastolic, and mean PA pressure, as well as cardiac output and cardiac index were measured by thermodilution method. Pulmonary vascular resistance was also measured. Our results demonstrated RV wall motion asynergy in 33 subjects (53%) on CT (CTEPH, 58%; PAH, 41%; P = 0.24). Serum BNP levels (Table 1), RV end diastolic and systolic diameter, RA minor diameter, and estimated systolic PA pressure on TTE (Table 2) were greater in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (all differences were significant at P b 0.05). There was a significant independence of the degree of tricuspid regurgitation between subjects with and without RV wall motion asynergy. However, there were no significant differences in any CT parameters, including RV wall thickness of both end systole
and end diastole, the ratio of systolic/diastolic RV wall thickness, CT attenuation in the RV myocardium both in the early and late phase, and ratio of late/early CT attenuation in the RV myocardium, between subjects with and without RV wall motion asynergy on CT (Table 3). Right heart catheterization findings showed that systolic, diastolic, and mean PA pressure and pulmonary vascular resistance were greater in subjects with RV wall motion asynergy than in subjects without RV
Table 2 Comparison of TTE findings between subjects with and without RV wall motion asynergy on CT. On TTE, RV end diastolic and end systolic diameters, right atrial minor diameter, and estimated systolic pulmonary arterial pressure were significantly greater in subjects with RV wall motion asynergy than in those without (all P b 0.05). There was a significant independence of degree of tricuspid regurgitation between subjects with and without RV wall motion asynergy on computed tomography. TTE Findings
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
RV end diastolic diameter (mm) RV end systolic diameter (mm) Right atrial major diameter (mm) Right atrial minor diameter (mm) Estimated systolic pulmonary arterial pressure (mmHg) Tricuspid regurgitation None Trivial Mild Moderate Severe
46.0 ± 7.9 38.5 ± 7.9 51.4 ± 10.7 43.4 ± 9.6 81.4 ± 18.5
35.7 ± 5.8 26.5 ± 6.6 47.5 ± 7.4 38.2 ± 7.6 61.4 ± 21.9
b0.001 b0.001 0.162 0.029 b0.001
1 (3%) 2 (6.1%) 22 (66.7%) 8 (24.2%) 0 (0%)
0 (0%) 10 (34.5%) 12 (41.4%) 6 (20.7%) 1 (3.4%)
0.035
K. Ozawa et al. / International Journal of Cardiology 222 (2016) 375–378
377
Table 3 Comparison of ECG-gated CT findings between subjects with and without RV wall motion asynergy on CT. On CT, there were no significant differences in all of these parameters between subjects with and without RV wall motion asnergy. ECG Gated CT Findings
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
RV free wall thickness (diastolic) (mm) RV free wall thickness (systolic) (mm) Ratio of RV free wall thickness systolic/diastolic CT attenuation in RV myocardium in early phase (HU) CT attenuation in RV myocardium in late phase (HU) Ratio of late/early CT attenuation in RV myocardium
3.97 ± 1.40
3.55 ± 1.15
0.280
6.17 ± 2.03 1.59 ± 0.37
5.95 ± 2.02 1.70 ± 0.37
0.688 0.242
96.8 ± 29.3
91.1 ± 28.8
0.454
85.2 ± 17.5 0.953 ± 0.350
86.9 ± 16.6 1.019 ± 0.270
0.916 0.280
wall motion asynergy (all differences were significant at P b 0.05). In addition, the cardiac index was significantly smaller in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (P b 0.05) (Table 4). Receiver operating characteristic (ROC) curves of the RV end diastolic and systolic diameter, and serum BNP for detection of subjects with RV wall motion asynergy on CT showed an area under the curve (AUC) of 0.85, 0.89, and 0.75, respectively. Best cutoff points were 37.5 mm (sensitivity of 91% and specificity of 66%) for RV end diastolic diameter (P b 0.001), 32.5 mm (sensitivity of 82% and specificity of 83%) for RV end diastolic diameter (P b 0.001), and 73 pg/ml (sensitivity of 70% and specificity of 76%) for BNP (P = 0.001), respectively (Figs. 2-4). In this study, we examined proven PH subjects without significant left-sided heart disease, and observed significant differences in RV and RA size and PA pressure on TTE; in PA pressure, cardiac index and pulmonary vascular resistance on right heart catheterization; and in serum BNP between subjects with or without RV wall motion asynergy on CT. However, no significant differences were observed in RV viability parameters, such as the ratio of systolic/diastolic RV wall thickness, or RV myocardial fibrosis parameters, such as the ratio of late/early CT attenuation in the RV myocardium, between subjects with or without RV wall motion asynergy on CT. Together, these results suggest that simple parameters such as RV size on TTE and serum BNP have a significant correlation with the presence of RV wall motion asynergy on 4D CT images in PH subjects without significant left-sided heart disease. Table 4 Comparison of right heart catheterization findings between subjects with and without RV wall motion asynergy on CT. Right heart catheterization findings show that systolic, diastolic, and mean pulmonary artery (PA) pressure and pulmonary vascular resistance were significantly greater in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (all comparisons at P b 0.05). The cardiac index was significantly smaller in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (P b 0.05). Right heart catheterization findings
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
Systolic PA pressure (mmHg) Diastolic PA pressure (mmHg) Mean PA pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Cardiac output (l/min) Cardiac index (l/min/m2) Pulmonary vascular resistance (dyne・sec・cm-5) Right atrial pressure (mmHg)
81.9 ± 16.9 26.6 ± 8.4 47.1 ± 8.7 8.9 ± 3.0
67.7 ± 22.9 21.6 ± 8.5 40.8 ± 13.5 8.6 ± 2.6
0.002 0.014 0.019 0.668
4.18 ± 0.86 2.70 ± 0.63 805 ± 224
4.69 ± 1.18 3.04 ± 0.81 595 ± 304
0.053 0.045 0.001
5.7 ± 3.5
5.1 ± 3.1
0.099
Fig. 2. ROC curves for the presence of RV wall motion asynergy on CT using RV end diastolic diameter on TTE. An ROC curve of RV end diastolic diameter to detect subjects with RV wall motion asynergy on CT shows an AUC of 0.85 (P b 0.001) with a best cutoff point of 37.5 mm (sensitivity of 91% and specificity of 66%).
Previously, we reported that RV wall motion asynergy on 4D CT images can be predicted by 2D global longitudinal RV strain on TTE in PH subjects [2]. The aims of the present study were to identify more convenient and simple parameters to predict the presence of RV wall motion asynergy on 4D CT images in a large population of subjects with PH and without left-sided heart disease. Our ROC analysis data suggest that RV wall motion asynergy on 4D CT images can be predicted by an enlarged RV size on TTE and an increase of serum BNP in PH subjects without leftsided heart disease. There are several limitations of this study. First, our study population was relatively small (N = 62), retrospective, non-randomized, and located in a single center. Second, 4D CT images require retrospective ECG gating, which produces more radiation exposure than conventional helical scans. Performing retrospective ECG-gated CT acquisition in subjects with an enlarged RV should be considered carefully because it is difficult to visualize the entire RV accurately on TTE. Third, the evaluation of RV wall motion asynergy on CT was qualitative and subjective, and, thus, intra and inter-observer reliability should be evaluated. Fourth, the clinical significant of the presence of RV wall motion asynergy on CT is unclear. However, in particular for patient prognosis, the presence of RV wall motion asynergy on CT may worsen patient prognosis, as demonstrated by our TTE and right heart catheterization results. Finally, even though there was no significant left-sided heart disease, including coronary heart disease, in all of our PH subjects on both CT and TTE, we did not consider the LV size and functional parameters, which may influence serum BNP, in this study. In conclusion, our results demonstrate that RV size on TTE and serum BNP levels are related significantly to the presence of RV wall motion asynergy on 4 D CT images in PH subjects without left-sided disease. Enlargement of RV size on TTE and elevated serum BNP levels may be simple, but useful candidates to detect the presence of RV wall motion asynergy on 4D CT images using retrospective ECG-gated CT acquisition in PH subjects without significant left-sided disease.
Fig. 3. ROC curves for the presence of RV wall motion asynergy on CT using RV end systolic diameter on TTE. An ROC curve of RV end systolic diameter to detect subjects with RV wall motion asynergy on CT shows an AUC of 0.89 (P b 0.001) with a best cutoff point of 32.5 mm (sensitivity of 82% and specificity of 83%).
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[4]
Fig. 4. ROC curves for the presence of RV wall motion asynergy on CT using serum brain natriuretic peptide (BNP) levels. An ROC curve of serum BNP levels to detect subjects with RV wall motion asynergy on CT shows an AUC of 0.75 (P = 0.001) with a best cutoff point of 73 pg/ml (sensitivity of 70% and specificity of 76%).
[5]
[6]
Disclosures None.
[7]
Conflict of interest
[8]
The authors report no relationships that could be construed as a conflict of interest.
[9]
Acknowledgement This work is supported by a Grant from Japan Heart Foundation Research Grant (no grant numbers). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
[10]
[11]
[12]
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Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Detection of right ventricle wall motion asynergy in pulmonary hypertension subjects without left-sided heart disease Koya Ozawa a,1, Nobusada Funabashi a,⁎,1, Hiroyuki Takaoka a, Nobuhiro Tanabe b, Koichiro Tatsumi b, Yoshio Kobayashi a a b
Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan Department of Respirology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
a r t i c l e
i n f o
Article history: Received 18 July 2016 Accepted 24 July 2016 Available online 27 July 2016 Keywords: Right ventricle wall motion asynergy Pulmonary hypertension Left-sided heart disease CT
Right ventricular (RV) wall motion asynergy occurs in subjects with arrhythmogenic RV cardiomyopathy [1]. Pulmonary hypertension (PH) subjects frequently have an enlarged RV and right atria (RA), but they also may have RV wall motion asynergy [2]. Structures of the RV and RA are complex, especially when the RV and RA are enlarged, and it is often difficult to visualize accurately the configuration of the entire RV by transthoracic echocardiogram (TTE). Furthermore, it is difficult to evaluate accurately RV wall motion asynergy on TTE. Computed tomography (CT) is essential in assessing subjects with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) for the presence of thrombi in the pulmonary artery (PA) and for the presence of an enlarged PA. Furthermore, the quantitative evaluation of RV function by retrospective electrocardiogram (ECG)gated CT is defined as appropriate in the ACCF/SCCT/ACR/AHA/ASE/ ASNC/NASCI/SCAI/SCMR 2010 criteria for cardiac CT [3]. Previously, we reported the frequency of RV wall motion asynergy, as confirmed by four-dimensional (4D) 320-slice CT, in a total of 24 PH subjects (73% of the PH subjects demonstrated CTEPH and 44% demonstrated PAH). Our results showed that the presence of RV wall motion asynergy can be predicted by two-dimensional (2D) global longitudinal RV strain on TTE [2]. However, the relationship between RV wall motion
⁎ Corresponding author at: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan. E-mail address: [email protected] (N. Funabashi). 1 These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ijcard.2016.07.152 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
asynergy on CT and simple parameters such as RV size on TTE or serum brain natriuretic peptide (BNP) levels, in particular, in a large population of PH subjects without left-sided heart disease, is unclear. In this study, we used 4D CT images to detect RV wall motion asynergy in a large population of PH subjects with no significant leftsided heart disease. We attempted to predict the presence of RV wall motion asynergy using simple parameters such as RV size on TTE and serum BNP levels. This is a retrospective analysis of 62 PH subjects, confirmed by right heart catheterization (16 males, mean age of 55 ± 16 years; 45 CTEPH subjects who underwent conventional non-surgical medical therapy; and 17 PAH subjects) who underwent retrospective ECG-gated 320slice CT (Aquilion one; Toshiba Medical) and TTE (Vivid E9; GE Healthcare, iE33; Philips, or Aplio; Toshiba Medical) within 7 months without any clinical incidents and who revealed no significant leftsided heart disease, including coronary heart disease, on both CT and TTE. 2D TTE was performed to evaluate tricuspid regurgitation, the morphology of the RV, and RA size, in addition to ordinary leftsided heart evaluation. Parameters included a measure of RV end diastolic and systolic diameter on apical 4 chamber views (Fig. 1), RA major and minor diameter, and estimated systolic PA pressure established by guidelines of the American Society of Echocardiography [4]. To obtain images of the whole heart, including the RV and coronary arteries, and the PA, all CT scans were performed using a double volume conventional scan with retrospective ECG gating using 320-slice CT with a 0.5 mm slice thickness and 0.35 s/rotation with a downward direction [2,5,6]. Tube voltage was set at 120 kV and tube current was set at 580 mA with tube current dose modulation. Contrast material (350 mgI/ml, 60 ml) was injected at 3.5 ml/s, followed by injection of a saline-to-contrast material mixture (40 ml contrast material at 2.0 ml/s and 30 ml saline at 1.5 ml/s). Finally, pure saline (20 ml) was injected at 1.5 ml/s. All enhanced CT examinations in the early phase were performed for a normal workup to diagnose or evaluate PH, RV function, and coronary arteries, with a scanning delay of 20–30 s for optimal PA and coronary arterial visualization. At 6 min after injection of the contrast material, late phase acquisition was added to detect myocardial fibrosis or edema using a single volume conventional scan with prospective ECG gating at end diastole for the reduction of radiation exposure [7–13].
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K. Ozawa et al. / International Journal of Cardiology 222 (2016) 375–378
Fig. 1. Actual measurement of RV end diastolic (A) and systolic diameter (B) in an apical 4 chamber view on TTE.
Table 1 Comparison of patient characteristics and general hemodynamic state parameters between subjects with and without RV wall motion asynergy on CT. Serum brain natriuretic peptide (BNP) levels were significantly greater in subjects with RV wall asynergy than in subjects without RV wall motion asynergy.
Age (years) Males (%) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Serum BNP (pg/ml) Six minute walk test (m)
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
56 ± 16 11 (33.3%) 113 ± 16 72 ± 11 229 ± 290 354 ± 84
53 ± 16 5 (17.2%) 120 ± 21 71 ± 12 77 ± 103 388 ± 122
0.446 0.149 0.242 0.803 0.001 0.201
Bold numbers indicate significance at P b 0.05.
After acquisition, CT images in the early phase were reconstructed at every 5% of the R–R interval from 0 to 95% (total, 20 phases). We defined RV wall motion asynergy as RV focal abnormal wall motion on 4D CT images at the workstation (Virtual Place, Aze). We quantified RV free wall thickness at both end systole and end diastole and CT attenuation in RV myocardium at end diastole both in the early and late phase. We calculated the ratio of systolic/diastolic RV wall thickness (calculated as end systolic RV wall thickness per end diastolic RV wall thickness), which is considered an indicator of RV wall viability [14]. We also calculated the ratio of late/early CT attenuation in the RV myocardium (calculated as late phase CT attenuation per early phase CT attenuation in the RV myocardium), which is considered an indicator of the presence of RV myocardial fibrosis [7–13]. All right heart catheterizations were performed by respiratory physicians with more than 5 years of experience managing PH subjects. A Swan-Ganz thermodilution catheter was used and a jugular approach was preferred. Systolic, diastolic, and mean PA pressure, as well as cardiac output and cardiac index were measured by thermodilution method. Pulmonary vascular resistance was also measured. Our results demonstrated RV wall motion asynergy in 33 subjects (53%) on CT (CTEPH, 58%; PAH, 41%; P = 0.24). Serum BNP levels (Table 1), RV end diastolic and systolic diameter, RA minor diameter, and estimated systolic PA pressure on TTE (Table 2) were greater in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (all differences were significant at P b 0.05). There was a significant independence of the degree of tricuspid regurgitation between subjects with and without RV wall motion asynergy. However, there were no significant differences in any CT parameters, including RV wall thickness of both end systole
and end diastole, the ratio of systolic/diastolic RV wall thickness, CT attenuation in the RV myocardium both in the early and late phase, and ratio of late/early CT attenuation in the RV myocardium, between subjects with and without RV wall motion asynergy on CT (Table 3). Right heart catheterization findings showed that systolic, diastolic, and mean PA pressure and pulmonary vascular resistance were greater in subjects with RV wall motion asynergy than in subjects without RV
Table 2 Comparison of TTE findings between subjects with and without RV wall motion asynergy on CT. On TTE, RV end diastolic and end systolic diameters, right atrial minor diameter, and estimated systolic pulmonary arterial pressure were significantly greater in subjects with RV wall motion asynergy than in those without (all P b 0.05). There was a significant independence of degree of tricuspid regurgitation between subjects with and without RV wall motion asynergy on computed tomography. TTE Findings
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
RV end diastolic diameter (mm) RV end systolic diameter (mm) Right atrial major diameter (mm) Right atrial minor diameter (mm) Estimated systolic pulmonary arterial pressure (mmHg) Tricuspid regurgitation None Trivial Mild Moderate Severe
46.0 ± 7.9 38.5 ± 7.9 51.4 ± 10.7 43.4 ± 9.6 81.4 ± 18.5
35.7 ± 5.8 26.5 ± 6.6 47.5 ± 7.4 38.2 ± 7.6 61.4 ± 21.9
b0.001 b0.001 0.162 0.029 b0.001
1 (3%) 2 (6.1%) 22 (66.7%) 8 (24.2%) 0 (0%)
0 (0%) 10 (34.5%) 12 (41.4%) 6 (20.7%) 1 (3.4%)
0.035
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Table 3 Comparison of ECG-gated CT findings between subjects with and without RV wall motion asynergy on CT. On CT, there were no significant differences in all of these parameters between subjects with and without RV wall motion asnergy. ECG Gated CT Findings
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
RV free wall thickness (diastolic) (mm) RV free wall thickness (systolic) (mm) Ratio of RV free wall thickness systolic/diastolic CT attenuation in RV myocardium in early phase (HU) CT attenuation in RV myocardium in late phase (HU) Ratio of late/early CT attenuation in RV myocardium
3.97 ± 1.40
3.55 ± 1.15
0.280
6.17 ± 2.03 1.59 ± 0.37
5.95 ± 2.02 1.70 ± 0.37
0.688 0.242
96.8 ± 29.3
91.1 ± 28.8
0.454
85.2 ± 17.5 0.953 ± 0.350
86.9 ± 16.6 1.019 ± 0.270
0.916 0.280
wall motion asynergy (all differences were significant at P b 0.05). In addition, the cardiac index was significantly smaller in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (P b 0.05) (Table 4). Receiver operating characteristic (ROC) curves of the RV end diastolic and systolic diameter, and serum BNP for detection of subjects with RV wall motion asynergy on CT showed an area under the curve (AUC) of 0.85, 0.89, and 0.75, respectively. Best cutoff points were 37.5 mm (sensitivity of 91% and specificity of 66%) for RV end diastolic diameter (P b 0.001), 32.5 mm (sensitivity of 82% and specificity of 83%) for RV end diastolic diameter (P b 0.001), and 73 pg/ml (sensitivity of 70% and specificity of 76%) for BNP (P = 0.001), respectively (Figs. 2-4). In this study, we examined proven PH subjects without significant left-sided heart disease, and observed significant differences in RV and RA size and PA pressure on TTE; in PA pressure, cardiac index and pulmonary vascular resistance on right heart catheterization; and in serum BNP between subjects with or without RV wall motion asynergy on CT. However, no significant differences were observed in RV viability parameters, such as the ratio of systolic/diastolic RV wall thickness, or RV myocardial fibrosis parameters, such as the ratio of late/early CT attenuation in the RV myocardium, between subjects with or without RV wall motion asynergy on CT. Together, these results suggest that simple parameters such as RV size on TTE and serum BNP have a significant correlation with the presence of RV wall motion asynergy on 4D CT images in PH subjects without significant left-sided heart disease. Table 4 Comparison of right heart catheterization findings between subjects with and without RV wall motion asynergy on CT. Right heart catheterization findings show that systolic, diastolic, and mean pulmonary artery (PA) pressure and pulmonary vascular resistance were significantly greater in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (all comparisons at P b 0.05). The cardiac index was significantly smaller in subjects with RV wall motion asynergy than in subjects without RV wall motion asynergy (P b 0.05). Right heart catheterization findings
With RV asynergy (N = 33)
Without RV asynergy (N = 29)
P value
Systolic PA pressure (mmHg) Diastolic PA pressure (mmHg) Mean PA pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Cardiac output (l/min) Cardiac index (l/min/m2) Pulmonary vascular resistance (dyne・sec・cm-5) Right atrial pressure (mmHg)
81.9 ± 16.9 26.6 ± 8.4 47.1 ± 8.7 8.9 ± 3.0
67.7 ± 22.9 21.6 ± 8.5 40.8 ± 13.5 8.6 ± 2.6
0.002 0.014 0.019 0.668
4.18 ± 0.86 2.70 ± 0.63 805 ± 224
4.69 ± 1.18 3.04 ± 0.81 595 ± 304
0.053 0.045 0.001
5.7 ± 3.5
5.1 ± 3.1
0.099
Fig. 2. ROC curves for the presence of RV wall motion asynergy on CT using RV end diastolic diameter on TTE. An ROC curve of RV end diastolic diameter to detect subjects with RV wall motion asynergy on CT shows an AUC of 0.85 (P b 0.001) with a best cutoff point of 37.5 mm (sensitivity of 91% and specificity of 66%).
Previously, we reported that RV wall motion asynergy on 4D CT images can be predicted by 2D global longitudinal RV strain on TTE in PH subjects [2]. The aims of the present study were to identify more convenient and simple parameters to predict the presence of RV wall motion asynergy on 4D CT images in a large population of subjects with PH and without left-sided heart disease. Our ROC analysis data suggest that RV wall motion asynergy on 4D CT images can be predicted by an enlarged RV size on TTE and an increase of serum BNP in PH subjects without leftsided heart disease. There are several limitations of this study. First, our study population was relatively small (N = 62), retrospective, non-randomized, and located in a single center. Second, 4D CT images require retrospective ECG gating, which produces more radiation exposure than conventional helical scans. Performing retrospective ECG-gated CT acquisition in subjects with an enlarged RV should be considered carefully because it is difficult to visualize the entire RV accurately on TTE. Third, the evaluation of RV wall motion asynergy on CT was qualitative and subjective, and, thus, intra and inter-observer reliability should be evaluated. Fourth, the clinical significant of the presence of RV wall motion asynergy on CT is unclear. However, in particular for patient prognosis, the presence of RV wall motion asynergy on CT may worsen patient prognosis, as demonstrated by our TTE and right heart catheterization results. Finally, even though there was no significant left-sided heart disease, including coronary heart disease, in all of our PH subjects on both CT and TTE, we did not consider the LV size and functional parameters, which may influence serum BNP, in this study. In conclusion, our results demonstrate that RV size on TTE and serum BNP levels are related significantly to the presence of RV wall motion asynergy on 4 D CT images in PH subjects without left-sided disease. Enlargement of RV size on TTE and elevated serum BNP levels may be simple, but useful candidates to detect the presence of RV wall motion asynergy on 4D CT images using retrospective ECG-gated CT acquisition in PH subjects without significant left-sided disease.
Fig. 3. ROC curves for the presence of RV wall motion asynergy on CT using RV end systolic diameter on TTE. An ROC curve of RV end systolic diameter to detect subjects with RV wall motion asynergy on CT shows an AUC of 0.89 (P b 0.001) with a best cutoff point of 32.5 mm (sensitivity of 82% and specificity of 83%).
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Fig. 4. ROC curves for the presence of RV wall motion asynergy on CT using serum brain natriuretic peptide (BNP) levels. An ROC curve of serum BNP levels to detect subjects with RV wall motion asynergy on CT shows an AUC of 0.75 (P = 0.001) with a best cutoff point of 73 pg/ml (sensitivity of 70% and specificity of 76%).
[5]
[6]
Disclosures None.
[7]
Conflict of interest
[8]
The authors report no relationships that could be construed as a conflict of interest.
[9]
Acknowledgement This work is supported by a Grant from Japan Heart Foundation Research Grant (no grant numbers). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
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[11]
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