Original Research Received: February 6, 2015 Accepted after revision: March 4, 2015 Published online: May 12, 2015
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
Measurements in Pediatric Patients with Cardiomyopathies: Comparison of Cardiac Magnetic Resonance Imaging and Echocardiography Yuting Zhang a Ling He a Jinhua Cai a Tiewei Lv b Qijian Yi b Yang Xu b Lingjuan Liu b Jing Zhu c Jie Tian b
Departments of a Radiology and b Cardiology, Children’s Hospital, Chongqing Medical University, and c Ministry of Education Key Laboratory of Child Development and Disorders, and Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, PR China
Key Words Cardiac function · Cardiac magnetic resonance imaging · Cardiomyopathy · Echocardiography
Abstract Aims: Cardiomyopathies are common cardiovascular diseases in children. Cardiac magnetic resonance imaging (cMRI) and echocardiography (Echo) are routinely applied in the detection and diagnosis of pediatric cardiomyopathies. In this study, we compared and explored the correlation between these two measurements in pediatric patients with various cardiomyopathies. Methods and Results: A total of 53 pediatric patients with cardiomyopathy hospitalized during the recent 3 years in our hospital were analyzed. All of them and 22 normal controls were assessed by both cMRI and Echo. Cardiac function of the patients was graded according to the New York Heart Association functional classification. The cardiac function indexes measured with both cMRI and Echo included left-ventricular (LV) end-diastolic volume (EDV), endsystolic volume, ejection fraction and fractional shortening. These parameters were somehow lower in cMRI measurements than in Echo measurements. The index of diastolic function, such as peak filling rate (PFR) measured with cMRI, had a good correlation with the clinical cardiac functional score, while the index of the diastolic function (early/atrial
© 2015 S. Karger AG, Basel 0008–6312/15/1314–0245$39.50/0 E-Mail [email protected] www.karger.com/crd
filling ratio and isovolumic relaxation time) measured with Echo was not well correlated with the clinical cardiac function score. Significant systolic dysfunction was detected by cMRI in 34 patients with dilated cardiomyopathy, LV noncompaction or endocardial fibroelastosis. Significant diastolic dysfunction was detected by cMRI in 19 patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy showing an alteration in PFR and EDV. Conclusion: Both cMRI and Echo are of great value in the diagnosis and assessment of cardiac function in pediatric patients with cardiomyopathy. cMRI could accurately display the characteristic morphological changes in the hearts affected with cardiomyopathies, and late gadolinium enhancement on cMRI may reveal myocardial fibrosis, which has obvious advantages over Echo measurements in diagnosis. Furthermore, cMRI can quantitatively determine ventricular function because it does not make invalid geometrical assumptions. © 2015 S. Karger AG, Basel
Introduction
Cardiomyopathies have been considered to represent diseases that primarily affect cardiac muscles. On the ground of their morphology and pathophysiology, cardiomyopathy may be classified into three major types: hyJie Tian, MD Department of Cardiology Children’s Hospital, Chongqing Medical University 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (PR China) E-Mail jietian @ cqmu.edu.cn
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pertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM). HCM and DCM are characterized, as their name implies, by a hypertrophic heart and a dilated ventricle, respectively, whereas RCM manifests itself as the restricted amount of blood that can fill the heart because the heart is abnormally stiffened due to unknown etiology. Cardiomyopathies are common cardiac disorders seen in pediatric patients with a poor prognosis. In survivors, persistent myocardial injury and myocardial dysfunction are common complications. Clinically, cardiac function can be evaluated and cardiomyopathies can be diagnosed using a variety of imaging techniques. Recently, with the development of highfield-strength magnetic resonance imaging (MRI) and the use of cardiac coils, MRI is able to confirm the cardiomyopathy by identifying the characteristic morphological changes and by evaluating noninvasively cardiac function. Furthermore, MRI with cardiac perfusion and delayed enhancement plays an important role in the diagnosis of cardiomyopathy with ischemic heart disease. In the present study, we have diagnosed 53 cases of pediatric cardiomyopathies using cardiac MRI (cMRI) and evaluated the value of cMRI compared to echocardiography (Echo) technology in the determination of cardiac function. The imaging data obtained from MRI or Echo are correlated with the clinical cardiac function classification.
was classified according to the New York Heart Association functional classification: class I, 5 cases; II, 21 cases; III, 19 cases, and IV, 8 cases. cMRI Protocols and Image Analysis cMRI was performed using a 1.5-tesla MR scanner (Signa EXCITE HD; GE Healthcare, USA) with a special 8-channel cardiac phased-array coil. All images were acquired using an electrocardiography-gated technique in real time in instances where breath-holding or a rhythm precluded imaging. First, fast-imaging employing steady-state acquisition (FIESTA) and fast spin Echo with double inversion recovery preparatory pulse [double IR FSE (D-IR FSE)] cine images were obtained in 3 long-axis (2-, 3- and 4-chamber) and 1 short-axis view covering the LV from base to apex. Subsequently, myocardial delayed enhancement (MDE) was typically performed 10 min after intravenous administration of 0.2 mmol/kg gadolinium-based contrast agent using a T1-weighted inversion recovery gradient Echo sequence, optimizing the inversion time for maximal contrast between nonenhancing and hyperenhancing myocardium. Experienced radiology technicians performed LV function analysis with dedicated software (ReportCARD 3.0; GE Healthcare). Epicardial and endocardial borders of the LV myocardium were manually traced during the whole cardiac phase on each cine short-axis image to obtain LV end-diastolic volume (EDV), LV end-systolic volume (ESV), LV ejection fraction (EF; EF = EDV – ESV/EDV), LV fractional shortening (FS; FS = EDD – ESD/EDD) and the diastolic function index, peak filling rate (PFR). Echocardiography was performed using an ultrasound instrument (Vivid 7; GE Healthcare) with a probe frequency of 2.5 MHz. All data obtained by echocardiography were analyzed with an EchoPAC workstation (GE Vingmed Ultrasound AS, Norway). Simpson’s rule algorithm for monoplane two-dimensional echocardiography was used to calculate LV EDV, ESV, EF and FS, the blood ratio of the mitral valve in the period of rapid early/atrial systolic filling and isovolumic relaxation time.
Patients and Methods
246
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
Statistical Analysis Data are given as means ± SD for continuous variables and as frequencies with percentages for categorical data. Differences between means were tested using the t test. Frequencies were compared using the χ2 test or Fisher’s exact test, as appropriate. Comparisons of clinical and MRI/Echo characteristics in patients were carried out using Spearman’s rank correlation analysis. p < 0.05 was considered to be statistically significant. Statistical analysis was performed using SPSS version 12.0.
Results
Comparison of the Two Imaging Methods in Patients with Cardiomyopathy Several morphological characteristics of the various cardiomyopathies were observed with cMRI. In HCM patients (fig. 1), cMRI showed diffuse LV myocardial wall thickening, mainly involving the interventricular septum and LV anterior wall at central and base parts, which was often accompanied by a significant LV cavity narrowing, Zhang/He/Cai/Lv/Yi/Xu/Liu/Zhu/Tian
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Patient Selection We conducted a retrospective study on 53 children with cardiomyopathy and 22 normal children who were treated in our hospital between November 2010 and June 2014. The patient group consisted of 34 males and 19 females aged 0.2–14 years (average age: 5.53 ± 4.29). In all cases, the diagnosis of cardiomyopathy was confirmed by chest X-ray, Echo and cMRI according to the diagnostic criteria set by the World Health Organization/International Society and Federation of Cardiology Task Force [1]. Echo and MRI data were analyzed by two experts (one in Echo and one in MRI) who were blinded to the case status. The control group, agematched normal volunteers, who were selected based on their physical examination, had no past or current history of cardiovascular disease. The control group consisted of 14 males and 8 females aged 0.5–14 years (average age: 5.88 ± 4.17). There was no statistically significant difference in gender or age between the two groups (χ2 = –0.440, p = 0.661; t = 0.002, p = 0.966). The study was approved by an institutional review committee of our hospital, and the subjects gave informed consent. Among the 53 pediatric patients with cardiomyopathies, there were 8 cases of HCM, 17 cases of DCM, 11 cases of RCM, 10 cases of endocardial fibroelastosis and 7 cases of left-ventricular (LV) noncompaction (LVNC). Among these patients, cardiac function
a
c
b
tum (VS) and LV anterior wall thickening. c Echo reveals ventricular wall thickening, but could not clearly display the apex and the free wall of the LV. RV = Right ventricle.
Color version available online
Fig. 1. Representative Echo and MRI scans of a 11-year-old male HCM patient with exertional palpitation for >1 year. a, b Fourchamber and short-axis D-IR FSE scans show interventricular sep-
b
Fig. 2. Representative Echo and MRI scans of a 10-year-old female DCM patient with chest congestion for >1 month. a, b Four-cham-
ber FIESTA cine and short-axis D-IR FSE show LV enlargement, diffuse myocardial wall thinning and abnormal ventricular move-
c
ments. c Echo reveals diffuse myocardial wall thinning, but the spatial resolution was lower than with MRI. LA = Left atrium; RA = right atrium; RV = right ventricle.
LV outflow tract stenosis and deficiency in ventricular diastolic function and mitral insufficiency (fig. 1a, b). In the same patient, Echo examination also showed ventricular wall thickening. However, Echo could not clearly display the apex and the LV free wall (fig. 1c). In patients with DCM, cMRI showed LV or doubleventricle dilatation, normal or thin myocardial wall thickness, and reduced EF and stroke volume (fig. 2a, b), and segmental or whole abnormal ventricular movement was observed. Echo could show a diffuse myocardial wall thinning, but the spatial resolution was lower compared to cMRI (fig. 2c). In patients with RCM, cMRI showed atrial enlargement, vena cava and portal vein expansion, and single- or double-ventricle diastolic dysfunction (fig. 3a, b). The ventricular cavity was normal or slightly narrowed, and
ventricular wall thickness was normal with normal or slightly decreased ventricular systolic function. In the same patient, Echo showed a similar atrial enlargement and diastolic dysfunction (fig. 3c). In patients with LVNC, MRI may reveal prominent multiple trabecular subendocardial and deep trabecular fossae communicating within the LV cavity (fig. 4a, b). Subepicardial densification in the myocardium was significantly thinner and the systolic LVNC myocardium and densification myocardium thickness ratio was >2. Compared to cMRI, Echo of the same patient could not show the whole heart (fig. 4c). In previous studies, MDE identified fibrous scars of the myocardium. In our study, there were only 3 cases of MDE. Diffuse subendocardial MDE was noted in 2 patients with RCM, suggesting the fibrosis formation (fig. 5).
MRI versus Echocardiography in Pediatric Cardiomyopathy
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
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a
Color version available online
a
b
Fig. 3. Representative Echo and MRI scans of a 11-year-old female
RCM patient with abdominal distension and weakness for 1 year. a, b Four-chamber D-IR FSE and FIESTA show double atrial en-
a
b
Fig. 4. Representative Echo and MRI of a 9-year-old male LVNC patient with coughing and limb weakness for 5 days. a, b Four-
chamber and short-axis FIESTA show subepicardial densification myocardium obviously thinning; arrows indicate subendocardial
c
largement, a normal ventricular cavity and ventricular diastolic dysfunction. c Echo reveals atrial enlargement. LA = Left atrium; RA = right atrium; RV = right ventricle.
c
multiple prominent trabeculae and deep trabecular fossae. c Echo reveals subendocardial multiple prominent trabeculae, but could not provide a complete overview of the whole heart. RV = Right ventricle.
Fig. 5. Representative MRI of MDE. a Short-axis view reveals diffuse abnormal
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a
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
b
Zhang/He/Cai/Lv/Yi/Xu/Liu/Zhu/Tian
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contrast enhancement of subendocardial myocardium of the left and right ventricle from a 1-year-old male patient with RCM. b Two-chamber view shows patchy MDE in the hypertrophic myocardium from an 11-year-old male patient with HCM. LA = Left atrium.
Table 1. Determination of LV function with cMRI and Echo in pediatric patients with cardiomyopathy and normal controls
Parameter
EF, % FS, % EDV, ml ESV, ml
Patients (n = 53)
Controls (n = 22)
cMRI
Echo
cMRI
Echo
31.35±22.13 17.30±8.27 90.18±69.27 66.66±59.44
49.51±14.75* 25.30±8.92* 148.33±127.83* 78.34±74.06*
53.24±10.37 23.18±10.13 66.91±34.91 28.94±14.27
61.91±6.89* 32.36±7.20* 83.51±50.63* 33.09±13.95*
Comparison of the Two Methods in the Detection of Cardiac Function in Patients with Cardiomyopathy LV function indexes, such as EDV, ESV, EF and FS, were assessed in these patients using both cMRI and Echo. In general, the values of these indexes were lower in cMRI than in Echo. The difference was statistically significant (p < 0.05; table 1). In both methods, systolic function indexes, such as EF and FS, had a good correlation with the clinical cardiac function grade (r = 0.577 and r = 0.583, respectively). PFR, a diastolic function index which was determined using cMRI, was correlated with clinical cardiac function classes (r = 0.477), while other diastolic function indexes, such as early/atrial systolic filling and isovolumic relaxation time, which were assessed using Echo, did correlate with clinical cardiac function classes (r = 0.086 and r = 0.057, respectively). cMRI-determined cardiac function indexes were significantly different between the patient group and the control group (p < 0.05). In 34 patients with DCM, LVNC and endocardial fibroelastosis, ESV, EF and FS were assessed using cMRI, and all parameters were significantly different compared to the normal control group (p < 0.05), indicating a systolic dysfunction. In 19 patients with HCM and RCM, cMRI-determined PFR and EDV were also significantly different compared to the normal control group (p < 0.05), indicating a diastolic dysfunction.
Cardiomyopathy is a common cardiac disease during childhood with a poor prognosis. The establishment of an early diagnosis and early treatment initiation are critical. Our data demonstrate that cMRI can accurately visualize morphological changes as well as functional alterations in pediatric patients with cardiomyopathy.
cMRI uses a variety of contrast options to reveal changes in the myocardial anatomy, function and organization. In recent years, the development of novel imaging technologies, such as FIESTA and fast-spin Echo with D-IR FSE, and the application of gadolinium-based contrast agent for MDE play an important role in the accurate diagnosis of cardiomyopathy and detection of fibrosis in the heart. Diagnosis is based on a comprehensive data set obtained from imaging of cardiac function and flow as well as characteristic changes in cardiac morphology [2]. The basis of the MDE technique is that the gadolinium-based contrast agent is delayed during wash-in and wash-out stages in fibrotic myocardial tissue compared to normal myocardial tissue. Most studies have shown that MDE indicates irreversible myocardial cell necrosis and fibrosis [3]. Depending on the different myocardial disease types and locations, MDE has unique value in the differential diagnosis of cardiomyopathy. Furthermore, another advantage for the application of MDE is that less ionizing radiation is used. It now becomes a new standard for showing fibrosis or myocardial infarction in the heart [4]. In our study, only 3 cases of MDE were observed, which is much lower than the proportion of adult patients reported in the literature. We think that the reason might be the age of the patients examined. In pediatric patients, due to the short course of the disease, significant changes in myocardial fibrosis have not yet occurred. Due to the noninvasive technology, lack of radiation and relatively low costs, Echo is currently the most commonly used method in the clinical diagnosis of cardiomyopathy in our country. However, the sensitivity and accuracy of the diagnosis of cardiomyopathy based on Echo only is limited because of its small field of vision, low spatial resolution and strong dependence on the experience of the person who performs Echo. By contrast, cMRI can provide a comprehensive overview on cardiac anomalies, especially on the LV apex and LV free wall. Furthermore,
MRI versus Echocardiography in Pediatric Cardiomyopathy
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
Discussion
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Means ± SD. * p < 0.01 compared between the cMRI and Echo in the patients and the controls, respectively.
cMRI provides more accurate information on regional heart motion abnormalities [5, 6]. In our study, cMRI has shown to be advantageous in the detection of characteristic morphological changes in various cases of different cardiomyopathies (fig. 1–4). The three-dimensional volume measured with cMRI shows good repeatability, which is not affected by heart cavity shape or heart size. Our study has shown that the cardiac function indexes of the LV (such as EDV, ESV, EF and FS) are significantly lower by cMRI than Echo in both study groups (p < 0.05). Indexes of systolic function (EF and FS) determined with the two different methods correlated well with clinical cardiac function classes (r = –0.577 and r = –0.596 in Echo, and r = –0.583 and r = –0.503 in cMRI). PFR, an index of diastolic function which was assessed by cMRI, also correlated with clinical cardiac function classes (r = –0.477), while early/atrial systolic filling and isovolumic relaxation time, indexes of diastolic function measured with Echo, did not (r = 0.086 and r = –0.057), which suggests that cardiac function is significantly overestimated using Echo, mainly because Echo measurements of LV function are based on the LV geometry and the selection of the appropriate formula to calculate LV volume. If the lateral resolution is poor and signal intensity of the endocardium low or missing, it will cause a tracing error. Moreover, because of the limited Echo window, Echo probes cannot clearly visualize the anatomical apex resulting in a low volume value [7]. By contrast, cMRI, which uses a step-by-step sketching method and directly calculates the ventricular volume without any geometric hypothetical construct, is much more sophisticated in the analysis of ventricular
gradients in the study models [8, 9]. Via sketching of about 9–12 levels of end-diastolic and end-systolic endocardium and epicardium from the apex to the bottom, cMRI can calculate the volume and show a clear distinction between the boundary of the endocardium and epicardium, which is helpful to reduce measurement errors. Therefore, application of cMRI for the detection of cardiac function is more accurate and reliable [10, 11]. Study Limitations This study has several limitations. First, the study is a retrospective, single-center study. Second, MDE evaluation is conducted visually and is semiquantitative. A prospective follow-up study recruiting a larger number of patients is planned using a protocol involving both cMRI and Echo for the diagnosis, evaluation and comparison of patients.
Conclusions
cMRI and Echo are of great value in the diagnosis and assessment of cardiac function in pediatric patients with cardiomyopathy. cMRI is more advantageous in displaying characteristic morphological changes of cardiomyopathy, and it is superior to Echo in the quantitative determination of ventricular function. In the quantitative analysis of cardiac function, cMRI has a high clinical value, and it is more accurate and reliable than Echo. However, cMRI examination takes longer and is more expensive. Further improvement is needed in the future.
References
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8 Anand IS, Florea VG, Solomon SD, et al: Noninvasive assessment of left ventricular remodeling: concepts, techniques, and implication for clinical trials. J Card Fail 2002;8(6 suppl): 452–464. 9 Chuang ML, Hibberd MG, Salton CJ, et al: Importance of imaging method over imaging modality in noninvasive determination of left ventricular volumes and ejection fraction: assessment by two- and three-dimensional echocardiography and magnetic resonance imaging. J Am Coll Cardiol 2002;35:477–484. 10 Mahnken AH, Spuntrup E, Wildberger JE, et al: Quantification of cardiac function with multiple spiral CT using retrospective ECG gating: comparison with MRI (in German). Rofo 2003;175:83–88. 11 Li KC, Liu YQ, Liu HY, et al: The MRI measurement of normal heart of Chinese people (in Chinese). Chin Circ J 1991;6:24–26.
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1 Richardson P, Mekenna W, Bristow M, et al: Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyophathies. Circulation 1996;93:841–842. 2 Zhang Z: Cardiovascular Magnetic Resonance Imaging. Beijing, People’s Medical Publishing House, 2006. 3 Tunstall Pedoe H, Kuulasmaa K, Amouyel P, et al: Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Circulation 1994; 90: 583– 612. 4 The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. The GUSTO Angiographic Investigators. N Engl J Med 1993; 329:1615–1622.
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
Measurements in Pediatric Patients with Cardiomyopathies: Comparison of Cardiac Magnetic Resonance Imaging and Echocardiography Yuting Zhang a Ling He a Jinhua Cai a Tiewei Lv b Qijian Yi b Yang Xu b Lingjuan Liu b Jing Zhu c Jie Tian b
Departments of a Radiology and b Cardiology, Children’s Hospital, Chongqing Medical University, and c Ministry of Education Key Laboratory of Child Development and Disorders, and Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, PR China
Key Words Cardiac function · Cardiac magnetic resonance imaging · Cardiomyopathy · Echocardiography
Abstract Aims: Cardiomyopathies are common cardiovascular diseases in children. Cardiac magnetic resonance imaging (cMRI) and echocardiography (Echo) are routinely applied in the detection and diagnosis of pediatric cardiomyopathies. In this study, we compared and explored the correlation between these two measurements in pediatric patients with various cardiomyopathies. Methods and Results: A total of 53 pediatric patients with cardiomyopathy hospitalized during the recent 3 years in our hospital were analyzed. All of them and 22 normal controls were assessed by both cMRI and Echo. Cardiac function of the patients was graded according to the New York Heart Association functional classification. The cardiac function indexes measured with both cMRI and Echo included left-ventricular (LV) end-diastolic volume (EDV), endsystolic volume, ejection fraction and fractional shortening. These parameters were somehow lower in cMRI measurements than in Echo measurements. The index of diastolic function, such as peak filling rate (PFR) measured with cMRI, had a good correlation with the clinical cardiac functional score, while the index of the diastolic function (early/atrial
© 2015 S. Karger AG, Basel 0008–6312/15/1314–0245$39.50/0 E-Mail [email protected] www.karger.com/crd
filling ratio and isovolumic relaxation time) measured with Echo was not well correlated with the clinical cardiac function score. Significant systolic dysfunction was detected by cMRI in 34 patients with dilated cardiomyopathy, LV noncompaction or endocardial fibroelastosis. Significant diastolic dysfunction was detected by cMRI in 19 patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy showing an alteration in PFR and EDV. Conclusion: Both cMRI and Echo are of great value in the diagnosis and assessment of cardiac function in pediatric patients with cardiomyopathy. cMRI could accurately display the characteristic morphological changes in the hearts affected with cardiomyopathies, and late gadolinium enhancement on cMRI may reveal myocardial fibrosis, which has obvious advantages over Echo measurements in diagnosis. Furthermore, cMRI can quantitatively determine ventricular function because it does not make invalid geometrical assumptions. © 2015 S. Karger AG, Basel
Introduction
Cardiomyopathies have been considered to represent diseases that primarily affect cardiac muscles. On the ground of their morphology and pathophysiology, cardiomyopathy may be classified into three major types: hyJie Tian, MD Department of Cardiology Children’s Hospital, Chongqing Medical University 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (PR China) E-Mail jietian @ cqmu.edu.cn
Downloaded by: UCONN Storrs 137.99.31.134 - 6/8/2015 8:34:45 PM
pertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM). HCM and DCM are characterized, as their name implies, by a hypertrophic heart and a dilated ventricle, respectively, whereas RCM manifests itself as the restricted amount of blood that can fill the heart because the heart is abnormally stiffened due to unknown etiology. Cardiomyopathies are common cardiac disorders seen in pediatric patients with a poor prognosis. In survivors, persistent myocardial injury and myocardial dysfunction are common complications. Clinically, cardiac function can be evaluated and cardiomyopathies can be diagnosed using a variety of imaging techniques. Recently, with the development of highfield-strength magnetic resonance imaging (MRI) and the use of cardiac coils, MRI is able to confirm the cardiomyopathy by identifying the characteristic morphological changes and by evaluating noninvasively cardiac function. Furthermore, MRI with cardiac perfusion and delayed enhancement plays an important role in the diagnosis of cardiomyopathy with ischemic heart disease. In the present study, we have diagnosed 53 cases of pediatric cardiomyopathies using cardiac MRI (cMRI) and evaluated the value of cMRI compared to echocardiography (Echo) technology in the determination of cardiac function. The imaging data obtained from MRI or Echo are correlated with the clinical cardiac function classification.
was classified according to the New York Heart Association functional classification: class I, 5 cases; II, 21 cases; III, 19 cases, and IV, 8 cases. cMRI Protocols and Image Analysis cMRI was performed using a 1.5-tesla MR scanner (Signa EXCITE HD; GE Healthcare, USA) with a special 8-channel cardiac phased-array coil. All images were acquired using an electrocardiography-gated technique in real time in instances where breath-holding or a rhythm precluded imaging. First, fast-imaging employing steady-state acquisition (FIESTA) and fast spin Echo with double inversion recovery preparatory pulse [double IR FSE (D-IR FSE)] cine images were obtained in 3 long-axis (2-, 3- and 4-chamber) and 1 short-axis view covering the LV from base to apex. Subsequently, myocardial delayed enhancement (MDE) was typically performed 10 min after intravenous administration of 0.2 mmol/kg gadolinium-based contrast agent using a T1-weighted inversion recovery gradient Echo sequence, optimizing the inversion time for maximal contrast between nonenhancing and hyperenhancing myocardium. Experienced radiology technicians performed LV function analysis with dedicated software (ReportCARD 3.0; GE Healthcare). Epicardial and endocardial borders of the LV myocardium were manually traced during the whole cardiac phase on each cine short-axis image to obtain LV end-diastolic volume (EDV), LV end-systolic volume (ESV), LV ejection fraction (EF; EF = EDV – ESV/EDV), LV fractional shortening (FS; FS = EDD – ESD/EDD) and the diastolic function index, peak filling rate (PFR). Echocardiography was performed using an ultrasound instrument (Vivid 7; GE Healthcare) with a probe frequency of 2.5 MHz. All data obtained by echocardiography were analyzed with an EchoPAC workstation (GE Vingmed Ultrasound AS, Norway). Simpson’s rule algorithm for monoplane two-dimensional echocardiography was used to calculate LV EDV, ESV, EF and FS, the blood ratio of the mitral valve in the period of rapid early/atrial systolic filling and isovolumic relaxation time.
Patients and Methods
246
Cardiology 2015;131:245–250 DOI: 10.1159/000381418
Statistical Analysis Data are given as means ± SD for continuous variables and as frequencies with percentages for categorical data. Differences between means were tested using the t test. Frequencies were compared using the χ2 test or Fisher’s exact test, as appropriate. Comparisons of clinical and MRI/Echo characteristics in patients were carried out using Spearman’s rank correlation analysis. p < 0.05 was considered to be statistically significant. Statistical analysis was performed using SPSS version 12.0.
Results
Comparison of the Two Imaging Methods in Patients with Cardiomyopathy Several morphological characteristics of the various cardiomyopathies were observed with cMRI. In HCM patients (fig. 1), cMRI showed diffuse LV myocardial wall thickening, mainly involving the interventricular septum and LV anterior wall at central and base parts, which was often accompanied by a significant LV cavity narrowing, Zhang/He/Cai/Lv/Yi/Xu/Liu/Zhu/Tian
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Patient Selection We conducted a retrospective study on 53 children with cardiomyopathy and 22 normal children who were treated in our hospital between November 2010 and June 2014. The patient group consisted of 34 males and 19 females aged 0.2–14 years (average age: 5.53 ± 4.29). In all cases, the diagnosis of cardiomyopathy was confirmed by chest X-ray, Echo and cMRI according to the diagnostic criteria set by the World Health Organization/International Society and Federation of Cardiology Task Force [1]. Echo and MRI data were analyzed by two experts (one in Echo and one in MRI) who were blinded to the case status. The control group, agematched normal volunteers, who were selected based on their physical examination, had no past or current history of cardiovascular disease. The control group consisted of 14 males and 8 females aged 0.5–14 years (average age: 5.88 ± 4.17). There was no statistically significant difference in gender or age between the two groups (χ2 = –0.440, p = 0.661; t = 0.002, p = 0.966). The study was approved by an institutional review committee of our hospital, and the subjects gave informed consent. Among the 53 pediatric patients with cardiomyopathies, there were 8 cases of HCM, 17 cases of DCM, 11 cases of RCM, 10 cases of endocardial fibroelastosis and 7 cases of left-ventricular (LV) noncompaction (LVNC). Among these patients, cardiac function
a
c
b
tum (VS) and LV anterior wall thickening. c Echo reveals ventricular wall thickening, but could not clearly display the apex and the free wall of the LV. RV = Right ventricle.
Color version available online
Fig. 1. Representative Echo and MRI scans of a 11-year-old male HCM patient with exertional palpitation for >1 year. a, b Fourchamber and short-axis D-IR FSE scans show interventricular sep-
b
Fig. 2. Representative Echo and MRI scans of a 10-year-old female DCM patient with chest congestion for >1 month. a, b Four-cham-
ber FIESTA cine and short-axis D-IR FSE show LV enlargement, diffuse myocardial wall thinning and abnormal ventricular move-
c
ments. c Echo reveals diffuse myocardial wall thinning, but the spatial resolution was lower than with MRI. LA = Left atrium; RA = right atrium; RV = right ventricle.
LV outflow tract stenosis and deficiency in ventricular diastolic function and mitral insufficiency (fig. 1a, b). In the same patient, Echo examination also showed ventricular wall thickening. However, Echo could not clearly display the apex and the LV free wall (fig. 1c). In patients with DCM, cMRI showed LV or doubleventricle dilatation, normal or thin myocardial wall thickness, and reduced EF and stroke volume (fig. 2a, b), and segmental or whole abnormal ventricular movement was observed. Echo could show a diffuse myocardial wall thinning, but the spatial resolution was lower compared to cMRI (fig. 2c). In patients with RCM, cMRI showed atrial enlargement, vena cava and portal vein expansion, and single- or double-ventricle diastolic dysfunction (fig. 3a, b). The ventricular cavity was normal or slightly narrowed, and
ventricular wall thickness was normal with normal or slightly decreased ventricular systolic function. In the same patient, Echo showed a similar atrial enlargement and diastolic dysfunction (fig. 3c). In patients with LVNC, MRI may reveal prominent multiple trabecular subendocardial and deep trabecular fossae communicating within the LV cavity (fig. 4a, b). Subepicardial densification in the myocardium was significantly thinner and the systolic LVNC myocardium and densification myocardium thickness ratio was >2. Compared to cMRI, Echo of the same patient could not show the whole heart (fig. 4c). In previous studies, MDE identified fibrous scars of the myocardium. In our study, there were only 3 cases of MDE. Diffuse subendocardial MDE was noted in 2 patients with RCM, suggesting the fibrosis formation (fig. 5).
MRI versus Echocardiography in Pediatric Cardiomyopathy
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a
Color version available online
a
b
Fig. 3. Representative Echo and MRI scans of a 11-year-old female
RCM patient with abdominal distension and weakness for 1 year. a, b Four-chamber D-IR FSE and FIESTA show double atrial en-
a
b
Fig. 4. Representative Echo and MRI of a 9-year-old male LVNC patient with coughing and limb weakness for 5 days. a, b Four-
chamber and short-axis FIESTA show subepicardial densification myocardium obviously thinning; arrows indicate subendocardial
c
largement, a normal ventricular cavity and ventricular diastolic dysfunction. c Echo reveals atrial enlargement. LA = Left atrium; RA = right atrium; RV = right ventricle.
c
multiple prominent trabeculae and deep trabecular fossae. c Echo reveals subendocardial multiple prominent trabeculae, but could not provide a complete overview of the whole heart. RV = Right ventricle.
Fig. 5. Representative MRI of MDE. a Short-axis view reveals diffuse abnormal
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contrast enhancement of subendocardial myocardium of the left and right ventricle from a 1-year-old male patient with RCM. b Two-chamber view shows patchy MDE in the hypertrophic myocardium from an 11-year-old male patient with HCM. LA = Left atrium.
Table 1. Determination of LV function with cMRI and Echo in pediatric patients with cardiomyopathy and normal controls
Parameter
EF, % FS, % EDV, ml ESV, ml
Patients (n = 53)
Controls (n = 22)
cMRI
Echo
cMRI
Echo
31.35±22.13 17.30±8.27 90.18±69.27 66.66±59.44
49.51±14.75* 25.30±8.92* 148.33±127.83* 78.34±74.06*
53.24±10.37 23.18±10.13 66.91±34.91 28.94±14.27
61.91±6.89* 32.36±7.20* 83.51±50.63* 33.09±13.95*
Comparison of the Two Methods in the Detection of Cardiac Function in Patients with Cardiomyopathy LV function indexes, such as EDV, ESV, EF and FS, were assessed in these patients using both cMRI and Echo. In general, the values of these indexes were lower in cMRI than in Echo. The difference was statistically significant (p < 0.05; table 1). In both methods, systolic function indexes, such as EF and FS, had a good correlation with the clinical cardiac function grade (r = 0.577 and r = 0.583, respectively). PFR, a diastolic function index which was determined using cMRI, was correlated with clinical cardiac function classes (r = 0.477), while other diastolic function indexes, such as early/atrial systolic filling and isovolumic relaxation time, which were assessed using Echo, did correlate with clinical cardiac function classes (r = 0.086 and r = 0.057, respectively). cMRI-determined cardiac function indexes were significantly different between the patient group and the control group (p < 0.05). In 34 patients with DCM, LVNC and endocardial fibroelastosis, ESV, EF and FS were assessed using cMRI, and all parameters were significantly different compared to the normal control group (p < 0.05), indicating a systolic dysfunction. In 19 patients with HCM and RCM, cMRI-determined PFR and EDV were also significantly different compared to the normal control group (p < 0.05), indicating a diastolic dysfunction.
Cardiomyopathy is a common cardiac disease during childhood with a poor prognosis. The establishment of an early diagnosis and early treatment initiation are critical. Our data demonstrate that cMRI can accurately visualize morphological changes as well as functional alterations in pediatric patients with cardiomyopathy.
cMRI uses a variety of contrast options to reveal changes in the myocardial anatomy, function and organization. In recent years, the development of novel imaging technologies, such as FIESTA and fast-spin Echo with D-IR FSE, and the application of gadolinium-based contrast agent for MDE play an important role in the accurate diagnosis of cardiomyopathy and detection of fibrosis in the heart. Diagnosis is based on a comprehensive data set obtained from imaging of cardiac function and flow as well as characteristic changes in cardiac morphology [2]. The basis of the MDE technique is that the gadolinium-based contrast agent is delayed during wash-in and wash-out stages in fibrotic myocardial tissue compared to normal myocardial tissue. Most studies have shown that MDE indicates irreversible myocardial cell necrosis and fibrosis [3]. Depending on the different myocardial disease types and locations, MDE has unique value in the differential diagnosis of cardiomyopathy. Furthermore, another advantage for the application of MDE is that less ionizing radiation is used. It now becomes a new standard for showing fibrosis or myocardial infarction in the heart [4]. In our study, only 3 cases of MDE were observed, which is much lower than the proportion of adult patients reported in the literature. We think that the reason might be the age of the patients examined. In pediatric patients, due to the short course of the disease, significant changes in myocardial fibrosis have not yet occurred. Due to the noninvasive technology, lack of radiation and relatively low costs, Echo is currently the most commonly used method in the clinical diagnosis of cardiomyopathy in our country. However, the sensitivity and accuracy of the diagnosis of cardiomyopathy based on Echo only is limited because of its small field of vision, low spatial resolution and strong dependence on the experience of the person who performs Echo. By contrast, cMRI can provide a comprehensive overview on cardiac anomalies, especially on the LV apex and LV free wall. Furthermore,
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Discussion
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Means ± SD. * p < 0.01 compared between the cMRI and Echo in the patients and the controls, respectively.
cMRI provides more accurate information on regional heart motion abnormalities [5, 6]. In our study, cMRI has shown to be advantageous in the detection of characteristic morphological changes in various cases of different cardiomyopathies (fig. 1–4). The three-dimensional volume measured with cMRI shows good repeatability, which is not affected by heart cavity shape or heart size. Our study has shown that the cardiac function indexes of the LV (such as EDV, ESV, EF and FS) are significantly lower by cMRI than Echo in both study groups (p < 0.05). Indexes of systolic function (EF and FS) determined with the two different methods correlated well with clinical cardiac function classes (r = –0.577 and r = –0.596 in Echo, and r = –0.583 and r = –0.503 in cMRI). PFR, an index of diastolic function which was assessed by cMRI, also correlated with clinical cardiac function classes (r = –0.477), while early/atrial systolic filling and isovolumic relaxation time, indexes of diastolic function measured with Echo, did not (r = 0.086 and r = –0.057), which suggests that cardiac function is significantly overestimated using Echo, mainly because Echo measurements of LV function are based on the LV geometry and the selection of the appropriate formula to calculate LV volume. If the lateral resolution is poor and signal intensity of the endocardium low or missing, it will cause a tracing error. Moreover, because of the limited Echo window, Echo probes cannot clearly visualize the anatomical apex resulting in a low volume value [7]. By contrast, cMRI, which uses a step-by-step sketching method and directly calculates the ventricular volume without any geometric hypothetical construct, is much more sophisticated in the analysis of ventricular
gradients in the study models [8, 9]. Via sketching of about 9–12 levels of end-diastolic and end-systolic endocardium and epicardium from the apex to the bottom, cMRI can calculate the volume and show a clear distinction between the boundary of the endocardium and epicardium, which is helpful to reduce measurement errors. Therefore, application of cMRI for the detection of cardiac function is more accurate and reliable [10, 11]. Study Limitations This study has several limitations. First, the study is a retrospective, single-center study. Second, MDE evaluation is conducted visually and is semiquantitative. A prospective follow-up study recruiting a larger number of patients is planned using a protocol involving both cMRI and Echo for the diagnosis, evaluation and comparison of patients.
Conclusions
cMRI and Echo are of great value in the diagnosis and assessment of cardiac function in pediatric patients with cardiomyopathy. cMRI is more advantageous in displaying characteristic morphological changes of cardiomyopathy, and it is superior to Echo in the quantitative determination of ventricular function. In the quantitative analysis of cardiac function, cMRI has a high clinical value, and it is more accurate and reliable than Echo. However, cMRI examination takes longer and is more expensive. Further improvement is needed in the future.
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