© 2015, Wiley Periodicals, Inc. DOI: 10.1111/echo.12925
Echocardiography
Carotid Arterial Stiffness in Patients with Congenital Heart Disease–Related Pulmonary Hypertension Assessed with Radio Frequency Data Technique Ying Hou, M.D.,* Li-Jun Yuan, M.D.,* Chang-Yang Xing, M.D.,* Fu-Jun Shang, M.D.,† and Yun-You Duan, M.D.* *Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; and †Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
Background: It has been well known that pulmonary hypertension (PH) caused by congenital heart disease (CHD) leads to reduced flexibility of the small pulmonary arteries, due to hemodynamic changes in the pulmonary circulation and alterations of the vasoactive profile. However, whether CHD-related PH affects the elasticity of the systemic arteries, such as the common carotid artery (CCA), has not been fully investigated. The purpose of this study was to explore the CCA stiffness in patients with CHDrelated PH using the radio frequency data technique. Methods: Forty patients with CHD were included. They were divided into PH and non-PH (NPH) groups by the right heart catheter-determined or regurgitation velocity-determined mean pulmonary arterial pressure (mPAP). MyLabTwice (Esaote, Genoa, Italy) ultrasound machine equipped with automatic quality intima–media thickness (QIMT) and quality arterial stiffness (QAS) capabilities was used to measure the left common carotid arterial (CCA) intima– media thickness and arterial stiffness parameters. Results: The results have shown that the left CCA internal diameter, pulse wave velocity, arterial wall tension, and local diastolic pressure were increased in the CHD-related PH group compared with the CHD-related NPH group (all P < 0.05). The left CCA internal diameter negatively and significantly correlated with the mean PAP. Conclusions: Common carotid artery diameter and stiffness increase in patients with CHD-related pulmonary hypertension. QIMT and QAS ultrasound techniques may provide a comprehensive assessment of the CCA remodeling. (Echocardiography 2015;32:1676–1680) Key words: pulmonary hypertension, arterial stiffness, vascular ultrasound, congenital heart disease As a pathophysiological syndrome with various underlying causes, pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular resistance. The 3-year survival rate in patients with PH is only about 67%.1 PH can be classified into five major categories according to its etiology. It can also be categorized as pre- or postcapillary PH.2 Regardless of the causes, vasoconstriction and vascular remodeling are fundamental changes related to PH, in which vascular remodeling mainly refers to the proliferation and remodeling of the small pulmonary vessels. PH due to congenital heart disease (CHD) Address for correspondence and reprint requests: Yun-You Duan, M.D., Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China. Fax: +86-29-83510181; E-mail: [email protected] and Li-Jun Yuan, M.D., Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China. Fax: +86-29-83510181; E-mail: [email protected]
1676
leads to reduced flexibility of the small pulmonary arteries, due to hemodynamic changes in the pulmonary circulation and alterations of the vasoactive profile.3 Recently, a new echocardiographic parameter, pulmonary pulse transit time, has been proposed that might be an interesting surrogate marker of pulmonary hemodynamic and vascular alterations in pulmonary hypertension.4 However, it is unknown whether CHDrelated PH affects the elasticity of the systemic arteries, such as the common carotid artery (CCA). Radio frequency signal-based quantitative technology for detecting the vascular intima– media thickness (IMT) and the arterial stiffness has recently become important methods for evaluating vascular function and morphology, which is now available in MyLabTwice ultrasound machine that are equipped with automatic quality intima–media thickness (QIMT) and quality arterial stiffness (QAS) capabilities. The QIMT calculation automatically measures the thickness between the intima and the media on the image
Carotid Arterial Stiffness in Pulmonary Hypertension
in real time using the radio frequency reception signal. The calculated value is compared with reference tables for the estimation of the expected age of the patient. The QAS calculation automatically measures the modification of the arterial diameter between the systolic and diastolic phases. The vessel stiffness is calculated starting from this value and from the brachial pressure values. These technologies surpass the spatial resolution limit of traditional ultrasound, offering good repeatability and accuracy for the obtained parameters.5–11 In this study, we employed this radio frequency data technology to evaluate the structural and elastic characteristics of the CCA in patients with CHD-related PH, as well as the relationship of these characteristics with the PAP. The findings could provide evidence for further understanding the pathophysiological changes of PH and for guiding clinical treatment of patients with PH. Materials and Methods: Subjects: Forty patients with congenital heart disease (CHD) were included and divided into PH (8 men, 13 women, age 32.33 15.62 years) and non-PH (NPH) groups (6 men, 13 women, age 27.6 7.1 years) by their right heart catheterdetermined and tricuspid regurgitation velocitybased mean pulmonary arterial pressure values (≥25 mmHg) according to the guidelines of the European Society of Cardiology and the European Respiratory Society.2 These patients were atrial septal defect (n = 18), ventricular septal
defect (n = 10), and patent ductus arteriosus (n = 12). All subjects were recruited from the routine In-Patient Department of Tangdu Hospital between November 2012 and July 2013. PH patients with severe shortness of breath and arrhythmia were excluded from the study. No subject had any other risk factors (e.g. diabetes) of artery stiffening. The study was approved by the Human Subjects Ethics Committee of the Fourth Military Medical University. Informed consent was obtained from every participant. CCA Measurements: We observed both the left and right CCAs but only demonstrated the data from the left CCA as the changes of the left CCA are relatively greater than the right CCA due to the anatomical different origin of the left CCA from that of the right CCA. The CCA morphology and stiffness measurements by radio frequency data technique were described in our previous study.12 Briefly, the internal diameter of the CCA was measured in a longitudinal section. The IMT and artery stiffness measurements were automatically performed on the same segment of the left CCA (Figs. 1 and 2). All measurements were performed by one investigator (HY), who was blinded to the group. The MyLabTwice ultrasound machine, equipped with a 12-MHz vascular probe (LA523) and with automatic quality IMT (QIMT) and quality arterial stiffness (QAS) capabilities, was employed. The following arterial stiffness indices were obtained: pulse wave velocity (m/s), distensibility coefficient (1/kPa), compliance coefficient (mm2/kPa), augmentation index
Figure 1. Measurement of the intima–media thickness (IMT) of the right carotid artery by radio frequency data technique.
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Hou, et al.
Figure 2. Measurement of the quality arterial stiffness (QAS) of the common carotid artery by radio frequency data technique.
(%), artery stiffness parameters a and b, and the local systolic and diastolic blood pressures (mmHg). The artery wall tension (T, mmHg/cm) was calculated as follows: T = P (mmHg/ cm2) 9 r (cm), where P is the pressure imposed on the artery wall and r is the radius of the CCA.13 The intra- and inter-observer variability of the CCA stiffness was previously reported. Good agreement was found between CCA parameter measurements taken by the same observer and by two independent observers with this method.11 Statistical Analysis: We used SPSS Version 20.0 software (SPSS, IBM, USA) for statistical analysis. Some data were presented as mean SD. Data were tested by homogeneity of variances. The independent samples t-test was used for comparisons between groups. Some data compared two population for proportion. Spearman’s linear correlation and linear regression analyses were used to analyze the correlation among indicators. A P-value < 0.05 was considered statistically significant. Results: Table I presents the demographic characteristics of the subjects. No significant difference was found between the groups in terms of age, sex, or body surface area. No significant difference was found in the cardiac or systemic artery blood pressures between the two groups. Mean PAP and systolic PAP were higher in the PH group compared with the NPH group (45.1 20.6 vs. 18.4 3.2 mmHg, P < 0.01; 65.0 23.8 vs. 28.6 5.3 mmHg, P < 0.0001). Table II compares the geometric (internal diameter and IMT) and mechanical (stiffness) CCA parameters between the PH and NPH groups. In the PH group, the internal diameter of the left CCA (7.6 0.9 mm vs. 6.7 0.4 mm, 1678
P = 0.002), pulse-wave velocity (6.7 1.7 m/s vs. 5.6 1.1 m/s, P = 0.021), artery wall tension (42.2 11.3 mmHg/cm vs. 34.1 4.0 mmHg/ cm, P = 0.006), and local diastolic blood pressure (76.0 13.2 mmHg vs. 66.1 8.5 mmHg, P = 0.01) were increased, compared with the NPH group. No significant difference was found in IMT between the two groups. The internal diameter of the left CCA correlated well with the PASP and pulmonary arterial mean pressure (PAMP) (r = 0.555, P = 0.001; r = 0.504, P = 0.004) (Fig. 3). Discussion: We employed ultrasonic QIMT and QAS capabilities to assess elastic arterial remodeling in
TABLE I General Characteristics of the Subjects Indicators Male (n, %) Female (n, %) Age (years) Etiology Atrial septal defect Ventricular septal defect Patent ductus arteriosus Clinical parameters Heart rate (beats/min) Systolic BP (mmHg) Diastolic BP (mmHg) Body surface area (m2) Pericardial effusion Mean PAP (mmHg) Systolic PAP (mmHg)
PH Group (n = 21)
NPH Group (n = 19)
8 (57) 13 (50) 32 16
6 (43) 13 (50) 28 7
9 5 7 83 120 75 1.61 6 45.1 65.0
9 5 5 14 22 11 0.29 20.6* 23.8*
78 111 72 1.53 2 18.4 28.6
10 7 6 0.21 3.2 5.3
PH = pulmonary hypertension; NPH = nonpulmonary hypertension; BP = blood pressure; PAP = pulmonary artery pressure. * P < 0.0001 versus NPH group.
Carotid Arterial Stiffness in Pulmonary Hypertension
TABLE II Comparison of Left CCA Elasticity between the PH and NPH Groups (x s). Indicators Mean IMT (lm) Distension (lm) Diastolic lumen diameter (mm) Pulse-wave velocity (m/s) Distensibility coefficient (1/kPa) Compliance coefficient (mm2/kPa) Artery stiffness coefficient a Artery stiffness coefficient b Local systolic BP (mmHg) Local diastolic BP (mmHg) Tension (mmHg/cm)
PH Group (n = 21)
NPH Group (n = 15)
516.3 133.5 365.8 128.5 7.6 0.9†
500.5 68.7 471.2 147.8 6.7 0.4
6.7 1.7* 0.02 0.01
5.6 1.1 0.03 0.01
1.1 0.6
1.1 0.5
4.1 1.8
3.2 1.1
8.4 3.7
6.5 2.2
110.0 19.6 76.0 13* 42.2 11.3†
101.0 12.5 66.1 8.5 34.1 4.0
PH = pulmonary hypertension; NPH = nonpulmonary hypertension; IMT = intima–media thickness; BP = blood pressure. * P < 0.05 versus NPH group. † P < 0.01 versus NPH group.
patients with CHD-related PH. The internal diameter of the left CCA and artery stiffness were significantly increased, and the internal diameter of the left CCA was closely correlated with the systolic PAP and pulmonary arterial mean pressure. These findings suggest that, in addition to vasoconstriction of the small pulmonary arteries, PH patients seemed to exhibit abnormal arterial remodeling and mechanics in the large extrapulmonary elastic systemic arteries. However, no significant difference in IMT was found between the two groups. This result might indicate that the change of IMT needs more time compared with the changes of the stiffness. Pulmonary hypertension due to any cause is associated with certain basic pathophysiological changes, which include the proliferation and remodeling of the small pulmonary vessels.14,15 These changes are related to the excessive contraction of the pulmonary vessels, the abnormal function or expression of potassium channels in the smooth muscle cells, and endothelial dysfunction. Some unusual factors (e.g., hypoxia, mechanical shearing force, inflammation, and drugs) can cause endothelial dysfunction, leading to the decreased production of vasodilators (e.g., NO, prostacyclin, and other substances) and the overexpression of vasoconstrictors (e.g. endothelia [ET-1], thromboxane A2, and 5-HT), thereby eliciting an increase in vascular tone and vascular
Figure 3. Correlation between the mean pulmonary artery pressure (mPAP) and the internal diameter of the left common carotid artery (L-Dia). The L-Dia was positively correlated with mPAP (r = 0.615, P < 0.0001). White circles = NPH group; Black dots = PH group.
reconstruction. Roles for angiopoietin-1, plasma 5-HT, transforming growth factor-b, extracellular matrix dysfunction, and other factors have also been implicated in PH development.3 Together, these factors may have an influence on other elastic arteries, such as the carotid artery. The changes of the carotid artery might represent the systemic vascular manifestation to the release of the endothelium-dependent vasoconstrictors and decreased vasodilators. In the current study, we employed the QIMT and QAS capabilities, which could be used to automatically get IMT and stiffness parameters. In this method, the original radio frequency signal is obtained, and thus, it is not related to the quality of the ultrasound images themselves.5,6,10,11 The resolution can reach the micron level, which makes the ultrasound measurements more accurate. The error between two successive measurements with QIMT and QAS is only about 3&. Thus, the technology has a good reproducibility. In conclusion, QIMT and QAS can be used to comprehensively and objectively evaluate the elastic systemic arterial remodeling from both the morphological and functional aspects.16 Limitations: There are several limitations to this study. The first is the small number of patients. This small number was owing to the specific disease state being studied (PH caused by CHD). The second limitation is that the stiffness changes of CCA after treatment were not provided. The last is the 1679
Hou, et al.
absence of the pulmonary vascular resistance parameters. Further studies including all above data and larger population should be performed to verify these results. Conclusions: Patients with CHD-related PH exhibited increased left CCA internal diameter, arterial stiffness, and wall tension. QIMT and QAS capabilities showed potential role in noninvasive and comprehensive assessment of the remodeling of the local elastic arteries in PH patients. The results of this study might contribute to a comprehensive understanding of the pathophysiological changes of CHD-related PH.
6.
7. 8. 9. 10. 11.
Acknowledgment: This work was supported by a grant from the National Natural Science Foundation of China (NSFC 81171349). 12.
References
N, Torbicki A, Barst R, et al: Guidelines on diagnosis 1. Galie and treatment of pulmonary arterial hypertension. Eur Heart J 2004;25:2243–2278. 2. Gali e N, Humbert MA, Vachiery T, et al: Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009;34:1219–1263. 3. Humbert M, Morrell NW, Archer SL, et al: Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll of Cardiol 2004;43:13S–24S. €diger S, Scharnbeck D, et al: Pulmonary 4. Wibmer T, Ru pulse transit time: A novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary Fibrosis. Echocardiography 2015;32:904–911. 5. Bots ML, Evans GW, Riley WA, et al: Carotid intimamedia thickness measurements in intervention studies:
1680
13. 14. 15. 16.
Design options, progression rates, and sample size considerations; a point of view. Stroke 2003;34:2985– 2994. Dan HJ, Wang Y, Zeng MX, et al: Evaluation of intimamedia thickness and vascular elasticity of the common carotid artery in patients with isolated systolic hypertension using ultrasound radiofrequency-data technology. Clin Physiol Funct Imaging 2011;31:315–319. Mitchell GF, Conlin PR, Dunlap ME, et al: Aortic diameter, wall stiffness, and wave reflection in systolic hypertension. Hypertension 2008;51:105–111. O’Rourke MF, Safar ME, Nichols WW: Proximal aortic diameter and aortic pressure-flow relationship in systolic hypertension. Circulation 2004;109:e227–e228. O’Rourke MF, Nichols WW: Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension 2005;45:652–658. Pannier BM, Avolio AP, Hocks A, et al: Methods and devices for measuring arterial compliance in humans. Am J Hypertens 2002;15:743–753. Reneman RS, Meinders JM, Hoeks AP: Non-invasive ultrasound in arterial wall dynamics in humans: what have we learned and what remains to be solved. Eur Heart J 2005;26:960–966. Yuan LJ, Xue D, Duan YY, et al: Carotid arterial intima– media thickness and arterial stiffness in pre-eclampsia: Analysis with a radiofrequency ultrasound technique. Ultrasound Obstet Gynecol 2013;42:644–652. Meinders JM, Hoeks AP: Simultaneous assessment of diameter and pressure waveforms in the carotid artery. Ultrasound Med Biol 2004;30:147–154. Ernande L, Cottin V, Leroux PY, et al: Right isovolumic contraction velocity predicts survival in pulmonary hypertension. J Am Soc Echocardiogr 2013;26:297–306. Gerald S, Galie N, Rubin LJ, et al: Clinical classification of pulmonary hypertension. J Am Coll of Cardiol 2004;43:5S–12S. Wang Y, Duan YY, Zhang L, et al: Evaluation of carotid artery elasticity in patients with coronary artery disease by ultrasound radio-frequency data technique. Chinese J Med Ultrasound 2012;9:34–38.
Echocardiography
Carotid Arterial Stiffness in Patients with Congenital Heart Disease–Related Pulmonary Hypertension Assessed with Radio Frequency Data Technique Ying Hou, M.D.,* Li-Jun Yuan, M.D.,* Chang-Yang Xing, M.D.,* Fu-Jun Shang, M.D.,† and Yun-You Duan, M.D.* *Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; and †Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
Background: It has been well known that pulmonary hypertension (PH) caused by congenital heart disease (CHD) leads to reduced flexibility of the small pulmonary arteries, due to hemodynamic changes in the pulmonary circulation and alterations of the vasoactive profile. However, whether CHD-related PH affects the elasticity of the systemic arteries, such as the common carotid artery (CCA), has not been fully investigated. The purpose of this study was to explore the CCA stiffness in patients with CHDrelated PH using the radio frequency data technique. Methods: Forty patients with CHD were included. They were divided into PH and non-PH (NPH) groups by the right heart catheter-determined or regurgitation velocity-determined mean pulmonary arterial pressure (mPAP). MyLabTwice (Esaote, Genoa, Italy) ultrasound machine equipped with automatic quality intima–media thickness (QIMT) and quality arterial stiffness (QAS) capabilities was used to measure the left common carotid arterial (CCA) intima– media thickness and arterial stiffness parameters. Results: The results have shown that the left CCA internal diameter, pulse wave velocity, arterial wall tension, and local diastolic pressure were increased in the CHD-related PH group compared with the CHD-related NPH group (all P < 0.05). The left CCA internal diameter negatively and significantly correlated with the mean PAP. Conclusions: Common carotid artery diameter and stiffness increase in patients with CHD-related pulmonary hypertension. QIMT and QAS ultrasound techniques may provide a comprehensive assessment of the CCA remodeling. (Echocardiography 2015;32:1676–1680) Key words: pulmonary hypertension, arterial stiffness, vascular ultrasound, congenital heart disease As a pathophysiological syndrome with various underlying causes, pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular resistance. The 3-year survival rate in patients with PH is only about 67%.1 PH can be classified into five major categories according to its etiology. It can also be categorized as pre- or postcapillary PH.2 Regardless of the causes, vasoconstriction and vascular remodeling are fundamental changes related to PH, in which vascular remodeling mainly refers to the proliferation and remodeling of the small pulmonary vessels. PH due to congenital heart disease (CHD) Address for correspondence and reprint requests: Yun-You Duan, M.D., Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China. Fax: +86-29-83510181; E-mail: [email protected] and Li-Jun Yuan, M.D., Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China. Fax: +86-29-83510181; E-mail: [email protected]
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leads to reduced flexibility of the small pulmonary arteries, due to hemodynamic changes in the pulmonary circulation and alterations of the vasoactive profile.3 Recently, a new echocardiographic parameter, pulmonary pulse transit time, has been proposed that might be an interesting surrogate marker of pulmonary hemodynamic and vascular alterations in pulmonary hypertension.4 However, it is unknown whether CHDrelated PH affects the elasticity of the systemic arteries, such as the common carotid artery (CCA). Radio frequency signal-based quantitative technology for detecting the vascular intima– media thickness (IMT) and the arterial stiffness has recently become important methods for evaluating vascular function and morphology, which is now available in MyLabTwice ultrasound machine that are equipped with automatic quality intima–media thickness (QIMT) and quality arterial stiffness (QAS) capabilities. The QIMT calculation automatically measures the thickness between the intima and the media on the image
Carotid Arterial Stiffness in Pulmonary Hypertension
in real time using the radio frequency reception signal. The calculated value is compared with reference tables for the estimation of the expected age of the patient. The QAS calculation automatically measures the modification of the arterial diameter between the systolic and diastolic phases. The vessel stiffness is calculated starting from this value and from the brachial pressure values. These technologies surpass the spatial resolution limit of traditional ultrasound, offering good repeatability and accuracy for the obtained parameters.5–11 In this study, we employed this radio frequency data technology to evaluate the structural and elastic characteristics of the CCA in patients with CHD-related PH, as well as the relationship of these characteristics with the PAP. The findings could provide evidence for further understanding the pathophysiological changes of PH and for guiding clinical treatment of patients with PH. Materials and Methods: Subjects: Forty patients with congenital heart disease (CHD) were included and divided into PH (8 men, 13 women, age 32.33 15.62 years) and non-PH (NPH) groups (6 men, 13 women, age 27.6 7.1 years) by their right heart catheterdetermined and tricuspid regurgitation velocitybased mean pulmonary arterial pressure values (≥25 mmHg) according to the guidelines of the European Society of Cardiology and the European Respiratory Society.2 These patients were atrial septal defect (n = 18), ventricular septal
defect (n = 10), and patent ductus arteriosus (n = 12). All subjects were recruited from the routine In-Patient Department of Tangdu Hospital between November 2012 and July 2013. PH patients with severe shortness of breath and arrhythmia were excluded from the study. No subject had any other risk factors (e.g. diabetes) of artery stiffening. The study was approved by the Human Subjects Ethics Committee of the Fourth Military Medical University. Informed consent was obtained from every participant. CCA Measurements: We observed both the left and right CCAs but only demonstrated the data from the left CCA as the changes of the left CCA are relatively greater than the right CCA due to the anatomical different origin of the left CCA from that of the right CCA. The CCA morphology and stiffness measurements by radio frequency data technique were described in our previous study.12 Briefly, the internal diameter of the CCA was measured in a longitudinal section. The IMT and artery stiffness measurements were automatically performed on the same segment of the left CCA (Figs. 1 and 2). All measurements were performed by one investigator (HY), who was blinded to the group. The MyLabTwice ultrasound machine, equipped with a 12-MHz vascular probe (LA523) and with automatic quality IMT (QIMT) and quality arterial stiffness (QAS) capabilities, was employed. The following arterial stiffness indices were obtained: pulse wave velocity (m/s), distensibility coefficient (1/kPa), compliance coefficient (mm2/kPa), augmentation index
Figure 1. Measurement of the intima–media thickness (IMT) of the right carotid artery by radio frequency data technique.
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Hou, et al.
Figure 2. Measurement of the quality arterial stiffness (QAS) of the common carotid artery by radio frequency data technique.
(%), artery stiffness parameters a and b, and the local systolic and diastolic blood pressures (mmHg). The artery wall tension (T, mmHg/cm) was calculated as follows: T = P (mmHg/ cm2) 9 r (cm), where P is the pressure imposed on the artery wall and r is the radius of the CCA.13 The intra- and inter-observer variability of the CCA stiffness was previously reported. Good agreement was found between CCA parameter measurements taken by the same observer and by two independent observers with this method.11 Statistical Analysis: We used SPSS Version 20.0 software (SPSS, IBM, USA) for statistical analysis. Some data were presented as mean SD. Data were tested by homogeneity of variances. The independent samples t-test was used for comparisons between groups. Some data compared two population for proportion. Spearman’s linear correlation and linear regression analyses were used to analyze the correlation among indicators. A P-value < 0.05 was considered statistically significant. Results: Table I presents the demographic characteristics of the subjects. No significant difference was found between the groups in terms of age, sex, or body surface area. No significant difference was found in the cardiac or systemic artery blood pressures between the two groups. Mean PAP and systolic PAP were higher in the PH group compared with the NPH group (45.1 20.6 vs. 18.4 3.2 mmHg, P < 0.01; 65.0 23.8 vs. 28.6 5.3 mmHg, P < 0.0001). Table II compares the geometric (internal diameter and IMT) and mechanical (stiffness) CCA parameters between the PH and NPH groups. In the PH group, the internal diameter of the left CCA (7.6 0.9 mm vs. 6.7 0.4 mm, 1678
P = 0.002), pulse-wave velocity (6.7 1.7 m/s vs. 5.6 1.1 m/s, P = 0.021), artery wall tension (42.2 11.3 mmHg/cm vs. 34.1 4.0 mmHg/ cm, P = 0.006), and local diastolic blood pressure (76.0 13.2 mmHg vs. 66.1 8.5 mmHg, P = 0.01) were increased, compared with the NPH group. No significant difference was found in IMT between the two groups. The internal diameter of the left CCA correlated well with the PASP and pulmonary arterial mean pressure (PAMP) (r = 0.555, P = 0.001; r = 0.504, P = 0.004) (Fig. 3). Discussion: We employed ultrasonic QIMT and QAS capabilities to assess elastic arterial remodeling in
TABLE I General Characteristics of the Subjects Indicators Male (n, %) Female (n, %) Age (years) Etiology Atrial septal defect Ventricular septal defect Patent ductus arteriosus Clinical parameters Heart rate (beats/min) Systolic BP (mmHg) Diastolic BP (mmHg) Body surface area (m2) Pericardial effusion Mean PAP (mmHg) Systolic PAP (mmHg)
PH Group (n = 21)
NPH Group (n = 19)
8 (57) 13 (50) 32 16
6 (43) 13 (50) 28 7
9 5 7 83 120 75 1.61 6 45.1 65.0
9 5 5 14 22 11 0.29 20.6* 23.8*
78 111 72 1.53 2 18.4 28.6
10 7 6 0.21 3.2 5.3
PH = pulmonary hypertension; NPH = nonpulmonary hypertension; BP = blood pressure; PAP = pulmonary artery pressure. * P < 0.0001 versus NPH group.
Carotid Arterial Stiffness in Pulmonary Hypertension
TABLE II Comparison of Left CCA Elasticity between the PH and NPH Groups (x s). Indicators Mean IMT (lm) Distension (lm) Diastolic lumen diameter (mm) Pulse-wave velocity (m/s) Distensibility coefficient (1/kPa) Compliance coefficient (mm2/kPa) Artery stiffness coefficient a Artery stiffness coefficient b Local systolic BP (mmHg) Local diastolic BP (mmHg) Tension (mmHg/cm)
PH Group (n = 21)
NPH Group (n = 15)
516.3 133.5 365.8 128.5 7.6 0.9†
500.5 68.7 471.2 147.8 6.7 0.4
6.7 1.7* 0.02 0.01
5.6 1.1 0.03 0.01
1.1 0.6
1.1 0.5
4.1 1.8
3.2 1.1
8.4 3.7
6.5 2.2
110.0 19.6 76.0 13* 42.2 11.3†
101.0 12.5 66.1 8.5 34.1 4.0
PH = pulmonary hypertension; NPH = nonpulmonary hypertension; IMT = intima–media thickness; BP = blood pressure. * P < 0.05 versus NPH group. † P < 0.01 versus NPH group.
patients with CHD-related PH. The internal diameter of the left CCA and artery stiffness were significantly increased, and the internal diameter of the left CCA was closely correlated with the systolic PAP and pulmonary arterial mean pressure. These findings suggest that, in addition to vasoconstriction of the small pulmonary arteries, PH patients seemed to exhibit abnormal arterial remodeling and mechanics in the large extrapulmonary elastic systemic arteries. However, no significant difference in IMT was found between the two groups. This result might indicate that the change of IMT needs more time compared with the changes of the stiffness. Pulmonary hypertension due to any cause is associated with certain basic pathophysiological changes, which include the proliferation and remodeling of the small pulmonary vessels.14,15 These changes are related to the excessive contraction of the pulmonary vessels, the abnormal function or expression of potassium channels in the smooth muscle cells, and endothelial dysfunction. Some unusual factors (e.g., hypoxia, mechanical shearing force, inflammation, and drugs) can cause endothelial dysfunction, leading to the decreased production of vasodilators (e.g., NO, prostacyclin, and other substances) and the overexpression of vasoconstrictors (e.g. endothelia [ET-1], thromboxane A2, and 5-HT), thereby eliciting an increase in vascular tone and vascular
Figure 3. Correlation between the mean pulmonary artery pressure (mPAP) and the internal diameter of the left common carotid artery (L-Dia). The L-Dia was positively correlated with mPAP (r = 0.615, P < 0.0001). White circles = NPH group; Black dots = PH group.
reconstruction. Roles for angiopoietin-1, plasma 5-HT, transforming growth factor-b, extracellular matrix dysfunction, and other factors have also been implicated in PH development.3 Together, these factors may have an influence on other elastic arteries, such as the carotid artery. The changes of the carotid artery might represent the systemic vascular manifestation to the release of the endothelium-dependent vasoconstrictors and decreased vasodilators. In the current study, we employed the QIMT and QAS capabilities, which could be used to automatically get IMT and stiffness parameters. In this method, the original radio frequency signal is obtained, and thus, it is not related to the quality of the ultrasound images themselves.5,6,10,11 The resolution can reach the micron level, which makes the ultrasound measurements more accurate. The error between two successive measurements with QIMT and QAS is only about 3&. Thus, the technology has a good reproducibility. In conclusion, QIMT and QAS can be used to comprehensively and objectively evaluate the elastic systemic arterial remodeling from both the morphological and functional aspects.16 Limitations: There are several limitations to this study. The first is the small number of patients. This small number was owing to the specific disease state being studied (PH caused by CHD). The second limitation is that the stiffness changes of CCA after treatment were not provided. The last is the 1679
Hou, et al.
absence of the pulmonary vascular resistance parameters. Further studies including all above data and larger population should be performed to verify these results. Conclusions: Patients with CHD-related PH exhibited increased left CCA internal diameter, arterial stiffness, and wall tension. QIMT and QAS capabilities showed potential role in noninvasive and comprehensive assessment of the remodeling of the local elastic arteries in PH patients. The results of this study might contribute to a comprehensive understanding of the pathophysiological changes of CHD-related PH.
6.
7. 8. 9. 10. 11.
Acknowledgment: This work was supported by a grant from the National Natural Science Foundation of China (NSFC 81171349). 12.
References
N, Torbicki A, Barst R, et al: Guidelines on diagnosis 1. Galie and treatment of pulmonary arterial hypertension. Eur Heart J 2004;25:2243–2278. 2. Gali e N, Humbert MA, Vachiery T, et al: Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009;34:1219–1263. 3. Humbert M, Morrell NW, Archer SL, et al: Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll of Cardiol 2004;43:13S–24S. €diger S, Scharnbeck D, et al: Pulmonary 4. Wibmer T, Ru pulse transit time: A novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary Fibrosis. Echocardiography 2015;32:904–911. 5. Bots ML, Evans GW, Riley WA, et al: Carotid intimamedia thickness measurements in intervention studies:
1680
13. 14. 15. 16.
Design options, progression rates, and sample size considerations; a point of view. Stroke 2003;34:2985– 2994. Dan HJ, Wang Y, Zeng MX, et al: Evaluation of intimamedia thickness and vascular elasticity of the common carotid artery in patients with isolated systolic hypertension using ultrasound radiofrequency-data technology. Clin Physiol Funct Imaging 2011;31:315–319. Mitchell GF, Conlin PR, Dunlap ME, et al: Aortic diameter, wall stiffness, and wave reflection in systolic hypertension. Hypertension 2008;51:105–111. O’Rourke MF, Safar ME, Nichols WW: Proximal aortic diameter and aortic pressure-flow relationship in systolic hypertension. Circulation 2004;109:e227–e228. O’Rourke MF, Nichols WW: Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension 2005;45:652–658. Pannier BM, Avolio AP, Hocks A, et al: Methods and devices for measuring arterial compliance in humans. Am J Hypertens 2002;15:743–753. Reneman RS, Meinders JM, Hoeks AP: Non-invasive ultrasound in arterial wall dynamics in humans: what have we learned and what remains to be solved. Eur Heart J 2005;26:960–966. Yuan LJ, Xue D, Duan YY, et al: Carotid arterial intima– media thickness and arterial stiffness in pre-eclampsia: Analysis with a radiofrequency ultrasound technique. Ultrasound Obstet Gynecol 2013;42:644–652. Meinders JM, Hoeks AP: Simultaneous assessment of diameter and pressure waveforms in the carotid artery. Ultrasound Med Biol 2004;30:147–154. Ernande L, Cottin V, Leroux PY, et al: Right isovolumic contraction velocity predicts survival in pulmonary hypertension. J Am Soc Echocardiogr 2013;26:297–306. Gerald S, Galie N, Rubin LJ, et al: Clinical classification of pulmonary hypertension. J Am Coll of Cardiol 2004;43:5S–12S. Wang Y, Duan YY, Zhang L, et al: Evaluation of carotid artery elasticity in patients with coronary artery disease by ultrasound radio-frequency data technique. Chinese J Med Ultrasound 2012;9:34–38.
