Next Article in Journal / Special Issue
Respiratory Dysfunction in Children and Adolescents with Mucopolysaccharidosis Types I, II, IVA, and VI
Previous Article in Journal
Active MMP-8 (aMMP-8) as a Grading and Staging Biomarker in the Periodontitis Classification
Previous Article in Special Issue
Molecular Characterization of a Novel Splicing Mutation Underlying Mucopolysaccharidosis (MPS) Type VI—Indirect Proof of Principle on Its Pathogenicity
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Diagnostics
Volume 10
Issue 2
10.3390/diagnostics10020062
diagnostics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses

by
Hsiang-Yu Lin
1,2,3,4,5,6,
Chih-Kuang Chuang
3,7,
Chung-Lin Lee
8,9,
Ming-Ren Chen
1,2,4,
Kuo-Tzu Sung
1,10,
Shan-Miao Lin
1,2,4,
Charles Jia-Yin Hou
10,
Dau-Ming Niu
9,11,
Tung-Ming Chang
12,13,
Chung-Lieh Hung
1,3,10,* and
Shuan-Pei Lin
1,2,3,14,*
1
Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan
2
Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan
3
Department of Medical Research, MacKay Memorial Hospital, New Taipei City 25160, Taiwan
4
MacKay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan
5
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
6
Institute of Biomedical Sciences, MacKay Medical College, New Taipei City 25245, Taiwan
7
College of Medicine, Fu-Jen Catholic University, Taipei 24205, Taiwan
8
Department of Pediatrics, MacKay Memorial Hospital, Hsinchu 30071, Taiwan
9
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
10
Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
11
Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan
12
Department of Pediatric Neurology, Changhua Christian Children’s Hospital, Changhua 500, Taiwan
13
School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
14
Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan
 
add Show full affiliation list
 
remove Hide full affiliation list
*
Authors to whom correspondence should be addressed.
Diagnostics 2020, 10(2), 62; https://doi.org/10.3390/diagnostics10020062
Submission received: 29 November 2019 / Revised: 12 January 2020 / Accepted: 21 January 2020 / Published: 23 January 2020
(This article belongs to the Special Issue Mucopolysaccharidoses: Diagnosis, Treatment, and Management)
Browse Figures
Versions Notes

Abstract

:
Background: Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders that can damage various organs, including the heart. Cardiac abnormalities have been observed in patients with all MPS types, with the most documented abnormalities being cardiac valvular regurgitation and stenosis, valvular thickening, and hypertrophic cardiomyopathy. Methods: Cardiac features of 53 Taiwanese patients with MPS (31 men and 22 women; age range 1.1–34.9 years; seven with MPS I, 16 with MPS II, nine with MPS III, 14 with MPS IVA, and seven with MPS VI) were evaluated using two-dimensional speckle-tracking echocardiography and conventional echocardiography. Results: The mean z scores of the global longitudinal strain (GLS), left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter of the 53 patients with MPS were 1.71, 0.35, 1.66, 1.03, and 3.15, respectively. Furthermore, z scores >2 were identified in 45%, 13%, 40%, 13%, and 70% of the GLS, LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most severe GLS was observed in those with MPS VI, followed by in those with MPS II and MPS I. The GLS z score was positively correlated with the LVMI z score (p < 0.01). Moreover, diastolic dysfunction (reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio < 1)) was identified in 12 patients (23%). Ejection and shortening fractions were abnormal in four (8%) and seven (13%) patients, respectively. Mitral regurgitation (MR) (92%) was the most common valvular heart disease, followed by aortic regurgitation (AR) (57%), mitral stenosis (MS) (21%), and aortic stenosis (AS) (15%). The z scores of the GLS and LVMI and severity scores of the MS, MR, AS, and AR were all positively correlated with increasing age (p < 0.05). Twenty patients (38%) had a left ventricular remodeling pattern. Conclusions: The most significant left ventricular myocardial deformation, hypertrophy and valvular heart disease were observed in the patients with MPS VI, II, and I, followed by those with MPS IV; in contrast, patients with MPS III had the mildest manifestations. Cardiac abnormalities in patients with MPS worsened with increasing age in accordance with the progressive nature of this disease.

1. Introduction

Mucopolysaccharidoses (MPS; OMIM 252700) are a group of rare inherited metabolic disorders resulting from a specific lysosomal enzyme deficiency associated with glycosaminoglycan (GAG) accumulation in various cells and tissues, leading to a progressive multiple organ dysfunction. The development of patients with MPS is usually unaffected at birth; however, multiple clinical manifestations may subsequently appear including coarse facial features, corneal clouding, hearing impairment, skeletal abnormalities, profound growth retardation, poor joint range of motion, hepatosplenomegaly, cardiac hypertrophy, and valvular heart disease. Seven major types of MPS disorders (I, II, III, IV, VI, VII, and IX) consisting of 11 diverse enzyme deficiencies have been identified. All MPS disorders are inherited with an autosomal recessive pattern, except for MPS II, which is an X-linked trait that mainly affects men. Patients with various types of MPS generally have a wide clinical heterogeneity, ranging from attenuated to severe forms in MPS I (Hurler, Hurler-Scheie (H/S), and Scheie syndromes), MPS II, and MPS VI [1,2]. The incidence of MPS in different populations ranges from 1.9 to 4.5 per 100,000 live births. In Taiwan, the collective birth incidence of all MPS types is estimated to be 2.04 per 100,000 live births [3].
Patients with all MPS types suffer from cardiac abnormalities, including cardiac hypertrophy, cardiac valve thickening, and valvular regurgitation and stenosis. The deformed valves with mitral or aortic leaflet thickening and calcification may lead to valvular stenosis or regurgitation [4,5,6,7,8,9,10,11,12,13,14,15]. GAG accumulation in the spongiosa of cardiac valves, myointima of coronary arteries, and myocardium has been associated with cardiomyopathy and valve defects [16]. The onset and extent of cardiovascular involvement is different in each MPS type, and defects in the cardiac structures in association with cardiac dysfunction meaningfully increase morbidity and mortality in these patients [17,18,19,20].
Assessing myocardial strain using two-dimensional speckle-tracking echocardiography (2D STE) has been reported to be a reliable tool for identifying nascent myocardial injury, which is imperative in the early detection of subclinical cardiac dysfunction and prognosis of several cardiac diseases [21,22]. Longitudinal left ventricular (LV) function is a sensitive and well-documented clinical marker of early stage LV systolic dysfunction in subjects with ventricular hypertrophy, hypertensive remodeling, diabetic cardiomyopathy, and heart failure with preserved ejection fraction [23,24,25,26]. Consequently, using myocardial deformation imaging in clinical practice may be of value in the early diagnosis of myocardial dysfunction. However, STE has not yet been broadly used to evaluate myocardial mechanics in patients with MPS [21,27,28]. In this study, we aimed to determine the cardiac structure and function of Taiwanese patients with various MPS types using 2D STE and conventional echocardiography.

2. Materials and Methods

2.1. Study Population

Cardiac features of 53 patients with MPS (31 men and 22 women; median age of 16.0 years; age range 1.1–34.9 years) were evaluated using 2D STE and conventional echocardiography from December 2013 to December 2018 at MacKay Memorial Hospital. The diagnosis of MPS was confirmed by measuring the enzymatic activities of particular lysosomal hydrolases in leukocytes or skin fibroblasts using two-dimensional electrophoresis of the urinary GAGs and/or through mutational analysis [29,30]. Patients with MPS I were further subdivided into those with Hurler, H/S, or Scheie syndrome based on their clinical manifestations and mutation analysis. There were three patients with MPS I (H/S), four with MPS I (Scheie), 16 with MPS II, nine with MPS III, 14 with MPS IVA, and seven with MPS VI in our cohort. No patient had received hematopoietic stem cell transplantation. Twenty-two patients (one with MPS I, eight with MPS II, seven with MPS IVA, and six with MPS VI) were under enzyme replacement therapy (ERT) at the time of echocardiographic evaluation. Patients with MPS I received 0.58 mg/kg/week intravenous laronidase (Aldurazyme®, Genzyme Corporation, Cambridge, MA, USA), those with MPS II received 0.5 mg/kg/week intravenous idursulfase (Elaprase®, Shire Pharmaceutical Inc., Lexington, MA, USA), those with MPS IVA received 2.0 mg/kg/week intravenous elosulfase alfa (Vimizim®, BioMarin Pharmaceutical Inc., San Rafael, CA, USA), and those with MPS VI received 1.0 mg/kg/week intravenous galsulfase (Naglazyme®, BioMarin Pharmaceutical Inc., San Rafael, CA, USA). Written informed consent for cardiac evaluations was obtained from a parent if the patient was aged <18 years. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki of 1975, as revised in the year 2000. The Institutional Review Board of MacKay Memorial Hospital approved this study (14MMHIS281, approval date: 30 March 2015), and written informed consent was obtained from all of the patients or their parents who were included in the study

2.2. Measurements of Echocardiographic Parameters

2.2.1. 2D STE

We performed LV deformational imaging using baseline 2D STE from three LV apical views for longitudinal strain (EchoPAC version 10.8; GE Vingmed Ultrasound AS, Horten, Norway), as described in our previous work [31]. We manually traced the endomyocardial border with epicardial tracing automatically generated by algorithm, with minor adjustment to cover the whole myocardial wall thickness. Based on automated speckle-tracking algorithms, LV global longitudinal strain (GLS) was then averaged from the three individual LV apical views (two-, four-, and three-chamber views, respectively). The average frame rate in current analysis was 78.1 ± 3.1 frames/sec. Subsequently, these values were compared with the normal values based on a study by Marcus et al. [32].

2.2.2. Conventional Echocardiography

Echocardiography was performed using a Vividi system (GE Vingmed Ultrasound, Horten, Norway) equipped with a 2- to 4-MHz transducer (3S-RS) during the recruitment period of this study. Data were digitally stored and analyzed by one experienced cardiologist (CLH) to minimize any potential interobserver variations as described in our previous study [31]. The left ventricular (LV) diastolic and systolic diameters were measured by the M-mode. The systolic function of the LV was evaluated based on the ejection fraction according to the Simpson method. For children, an ejection fraction of <50% was defined as abnormal, whereas for adults, an ejection fraction of <52% for men and <54% for women was defined as abnormal [33]. A shortening fraction of <28% was considered abnormal in both adults and children. Diastolic filling was assessed using the E/A ratio by measuring the mitral-inflow according to the pattern-peak early filling (E) and late filling (A) velocities. Moreover, the systolic function was assessed according to the ejection and shortening fractions [34]. Existence of diastolic dysfunction was indicated by a reversed E/A ratio (E/A ratio <1). The severity of valvular stenosis and regurgitation was assessed and graded as follows: 0 (none), 1 (mild), 2 (moderate), and 3 (severe), based on the European Society of Cardiology guidelines [12,13,14,15,35,36]: mild aortic stenosis (AS) = a valve area > 1.5 cm2 and a mean gradient < 30 mmHg; moderate AS = a valve area of 1.0–1.5 cm2 and a mean gradient of 30–50 mmHg; severe AS = a valve area < 1.0 cm2 and a mean gradient > 50 mmHg; mild mitral stenosis (MS) = a valve area > 1.5 cm2 and a mean gradient < 5 mmHg; moderate MS = a valve area between 1.0–1.5 cm2 and a mean gradient between 5–10 mmHg; and severe MS = a valve area < 1.0 cm2 and a mean gradient >10 mmHg. Because the frequency of physiological tricuspid regurgitation is high in the general population, we did not include tricuspid regurgitation as a pathological finding in this study.
We recorded data on left ventricular mass index (LVMI), interventricular septal end-diastolic dimension (IVSd), left ventricular posterior wall end-diastolic dimension (LVPWd), left ventricular end-diastolic dimension (LVIDd), and aortic diameter obtained by echocardiographic evaluations. The relative wall thickness (RWT) was calculated as (2×LVPWd)/LVIDd. Three patterns of LV remodeling were determined based on measurements of the LVMI and RWT, namely, concentric remodeling (normal LVMI and RWT > 0.42), eccentric hypertrophy (LVMI z score >2 and RWT <= 0.42), and concentric hypertrophy (LVMI z score >2 and RWT >0.42) [37]. Measurements of the aorta were made on the sinus by leading-edge-to-leading-edge. The LVMI was calculated using the Devereux formula and indexed by the height z score with normal values according to the report by Foster et al. [38]. These values were compared with normal values according to the study by Kampmann et al. [39].
All echocardiographic parameters were transformed into a z score derived by subtracting the mean reference value from an individual observed value, then dividing the difference by the standard deviation from the reference value. A z score value between −2 and +2 was considered normal.

2.3. Data Analysis and Statistics

Sex, MPS type, age, height, weight, and the duration of receiving ERT at the time of echocardiographic assessments were recorded for each patient. Descriptive statistics, including the mean and standard deviation, of all echocardiographic parameters were calculated. The relationships between the age and various echocardiographic parameters were established using a Pearson’s correlation coefficient (r), and the significance was determined using the Fisher’s r–z transformations to obtain two-tailed p-values. All statistical analyses were conducted using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA), and any differences with a p < 0.05 were considered statistically significant.

3. Results

Table 1 shows clinical and echocardiographic features of the 53 patients with different MPS types. The mean z scores of the GLS, LVMI, IVSd, LVPWd, and aortic diameter in all 53 patients with MPS were 1.71, 0.35, 1.66, 1.03, and 3.15, respectively. Z scores of >2 were identified in 45%, 13%, 40%, 13%, and 70% of the GLS, LVMI, IVSd, LVPWd, and aortic diameter, respectively. The greatest deviation from the reference values of GLS was observed in the patients with MPS VI, followed by those with MPS II and MPS I. Patients with MPS II had the largest LVMI and IVSd, followed by those with MPS VI. Patients with MPS IVA had the largest aortic diameter, followed by those with MPS II (Table 2 and Figure 1). The GLS z score was positively correlated with the LVMI z score (p < 0.01) (Figure 2). Diastolic dysfunction (reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio < 1)) was identified in 12 patients (23%). Ejection and shortening fractions were abnormal in four (8%) and seven (13%) patients, respectively. Forty-nine (92%) patients with MPS had different types and degrees of severity of valvular heart disease. Mitral regurgitation (MR) (92%) was the most common presentation, followed by aortic regurgitation (AR) (57%), MS (21%), and AS (15%). All patients with MPS I, II, and VI had valvular heart disease, compared to 89% of those with MPS III and 79% of those with MPS IV. Patients with MPS VI had the highest severity of MS and MR, whereas those with MPS I (Scheie) had the highest severity of AS and AR (Table 3 and Figure 3). The z scores of GLS and LVMI and severity scores of MS, MR, AS, and AR were all positively correlated with increasing age (p < 0.05) (Figure 4 and Figure 5). Twenty patients (38%) had an LV remodeling pattern, including 13 (25%) with LV concentric remodeling, five (9%) with eccentric hypertrophy, and two (4%) with concentric hypertrophy. The remaining 33 patients (62%) had normal LV geometry. Among the various MPS types, most patients with MPS VI (71%) had LV remodeling, followed by those with MPS II (56%). However, no patient with MPS III had LV remodeling (Table 4 and Figure 6).

4. Discussion

To the best of our knowledge, this is the first study to delineate the cardiac structure and function of Asian patients with various MPS types in a single population using 2D STE and conventional echocardiography and compare the results with normal values, including young adults, based on the reports of Marcus et al. [32] and Kampmann et al. [39]. In this study, we evaluated the LV contractile function according to myocardial deformation imaging using a 2D STE technique in patients with different MPS types and ages. We found that the ejection and shortening fractions were abnormal in 8% and 13% of patients with MPS, respectively. However, a GLS z score of >2 was observed in 45% of these patients. The findings of a GLS z score of >2 in the absence of LV ejection and shortening fraction abnormalities suggests that 2D STE is an early marker for LV dysfunction in patients with MPS. We demonstrated early stage systolic dysfunction using the more sensitive LV deformation parameter, GLS z score, which preceded global LV systolic dysfunction as traditionally assessed using LV ejection and shortening fractions. Additionally, we observed that the GLS z score as a measure of myocardial deformation was significantly associated with the LVMI z score and age. In addition, diastolic dysfunction (E/A ratio < 1) was identified in 12 patients (23%). MPS was related to myocardial deformation and more impaired diastolic function and a decline in the global LV systolic mechanics, despite globally preserved LV ejection and shortening fractions. These results were consistent with those of previous studies [21,27,28].
Conventional two-dimensional echocardiography is a clinically useful tool, however its use in determining the early stages of myocardial dysfunction is limited. In recent years, 2D STE imaging has been used to independently identify early stage LV dysfunction before conventional echo parameters become abnormal. Conventional echocardiography can detect overt global systolic dysfunction with regard to the reduced LV ejection fraction in patients with MPS; however, it is not sufficiently sensitive to identify early stage LV dysfunction. Diastolic function parameters may be useful; however, they are only indirect measures of LV contractile function and are considerably affected by hemodynamic load conditions. Accordingly, STE may help in the identification of early stage LV systolic dysfunction in patients with MPS before the development of obvious heart failure and is more reliable and practicable [26].
All patients with MPS in the present study had cardiac abnormalities. Overall, 40% of these patients had an IVSd z score of >2, whereas only 13% had an LVMI z score of >2. IVSd is related to the LVMI, and the clinical significance of an isolated increase in IVSd may be caused by a LV remodeling pattern in these patients. Our results revealed that the most significant LV myocardial deformation, hypertrophy, and valvular heart disease were observed in patients with MPS VI, II, and I, followed by those with MPS IV, and that patients with MPS III had the mildest manifestations. Deformed mitral or aortic valves with varying degrees of severity were commonly noted (92%) in our patients with MPS. In this cohort, mitral valve abnormalities (92%) were more prevalent than aortic valve abnormalities (57%), and valvular regurgitation (92%) was more common than valvular stenosis (28%), which is consistent with previous studies [4,5,6,7,8]. The most prevalent cardiac valve abnormality was MR (92%), followed by AR (57%), MS (21%), and AS (15%). Consistent with the report by Mohan et al. [9], valvular stenosis and regurgitation in our patients with MPS worsened with increasing age, which is in accordance with the progressive nature of this disease. Among the various MPS types, all patients with MPS I, II, and VI had valvular heart disease, compared to 89% of those with MPS III and 79% of those with MPS IV. Patients with MPS VI had the highest severity of MS and MR, whereas those with MPS I (Scheie) had the highest severity of AS and AR. Previous studies have reported that abnormal catabolism of dermatan sulfate in patients with MPS I, II and VI leads to dermatan-sulfate GAG accumulation in the cardiac valves, resulting in valvular thickening and other cardiac defects [7,8]. As valvular heart diseases have been shown to contribute to worsened global ventricular deformations, we speculated that more impaired GLS in MPS VI, II, and I may be partly attributable to the accompanied valvular lesions [40]. The major storage products of MPS III and MPS IV are heparan sulfate and keratan sulfate, respectively. Therefore, cardiac lesions may be less prominent in patients with MPS III and IV than in those with MPS I, II, and VI [14,15,41].
Aortic root dilatation classically evolves through cystic medial degeneration and migration of the smooth muscle cells from the tunica media to the tunica intima with age [42]. Bolourchi et al. [43] reported that aortic root dilatation was highly prevalent in all patients with MPS (35%) and that those with MPS IVA had the highest prevalence of aortic root dilatation (62.5%), which is consistent with our results (aortic diameter z score >2 in 70% of patients with all MPS types and 93% of those with MPS IVA). Routine screening for this potentially critical observation should be integrated into the multidisciplinary care of patients with MPS.
Ventricular remodeling leads to alterations in the ventricular architecture with associated increases in volume and altered chamber configuration, thereby causing myocyte hypertrophy and apoptosis, myofibroblast proliferation, and interstitial fibrosis [44]. Few reports have described the LV remodeling pattern in patients with MPS. In our cohort, 38% of patients with MPS had LV remodeling pattern, including 25% with LV concentric remodeling, 9% with eccentric hypertrophy, and 4% with concentric hypertrophy. Among all MPS types, most patients with MPS VI (71%) had LV remodeling, followed by those with MPS II (56%), MPS IVA (29%), and MPS I (29%). Each of these patterns was associated with a higher risk of subsequent cardiovascular events than a normal LV morphology, with each of these three patterns carrying a progressively worse prognosis [44].
The ERT for some MPS disorders appears to be effective in stabilizing or reducing cardiac hypertrophy, and better results may be associated with initiating the ERT at a younger age. There is currently no definitive evidence of the effects of ERT on valvulopathy [10,13,14]. However, due to the progressive nature of MPS, starting the ERT before the occurrence of irreversible cardiac damage may contribute to a better clinical outcome. As such, it is essential to make an early diagnosis via screening programs for high-risk populations or newborns [45,46,47,48].

5. Limitations

In this study, there was no healthy control group to compare the echocardiographic parameters with those of our patients. Further, not all patients in our study cohort had echocardiographic data before the ERT. Consequently, we used reference values from a Caucasian population due to the lack of data from an Asian population, under the recognition that longitudinal strain values from single four-chamber may be highly consistent from those averaged from three planes based on the systemic review [49,50]. The small sample size of patients with each type of MPS reflects the rare nature of this genetic disorder. Additionally, both the age range (1.1–34.9 years) and degree of disease severity differed widely. Therefore, further studies with larger cohorts and longer follow-up periods are warranted to validate our findings.

6. Conclusions

Our results showed that a substantial proportion of patients with MPS had myocardial deformation, cardiac hypertrophy, aortic dilatation, and valvular heart disease. Assessing the LV function using 2D STE to evaluate myocardial deformation may help to stratify the risk of MPS. STE was more sensitive than global LV ejection fraction and fractional shortening, and its derived parameter, GLS, may prove especially useful in patients with subclinical LV dysfunction prior to the development of obvious systolic dysfunction. Cardiac abnormalities in our patients worsened with increasing age in accordance with the progressive nature of this disease. The most significant LV myocardial deformation, hypertrophy and valvular heart disease, were observed in patients with MPS VI, II, and I, followed by those with MPS IV, whereas those with the MPS III had the mildest manifestations. Despite the globally preserved LV ejection and shortening fractions, MPS was associated with myocardial deformation, more impaired diastolic function, and decline in the global LV systolic mechanics.

Author Contributions

H.-Y.L. performed acquisition, statistical analysis and interpretation of data, and drafting of the manuscript. C.-L.H. and S.-P.L. participated in design of the study, interpretation of the data and helped to draft the manuscript. C.-K.C., C.-L.L., M.-R.C., K.-T.S., S.-M.L., C.J.-Y.H., D.-M.N. and T.-M.C. were responsible for patient screening and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This study was supported by research grants from the Ministry of Science and Technology, Executive Yuan, Taiwan (MOST-108-2314-B-195-012, MOST-108-2314-B-195-014, MOST-106-2314-B-195-015-MY2, MOST-105-2628-B-195-001-MY3, MOST-101-2314-B-195-020-MY1, MOST-103-2314-B-010-005-MY3, MOST-103-2314-B-195-006-MY3, and MOST-106-2314-B-195-008-MY2) and MacKay Memorial Hospital (MMH-E-108-16 and MMH-107-82).

Acknowledgments

We acknowledge the participation of study patients and their families. The authors thank Tsai-Feng Ho for her professional assistance in biostatistics.

Conflicts of Interest

The authors declare no conflict of interest. The authors confirm independence from the sponsors. The contents of the article, including the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, have not been influenced by the sponsors.

Abbreviations

MPSMucopolysaccharidosis
GAGsGlycosaminoglycans
H/SHurler-Scheie
2D STETwo-dimensional speckle-tracking echocardiography
LVLeft ventricular
ERTEnzyme replacement therapy
GLSGlobal longitudinal strain
E/ARatio between early and late (atrial) ventricular filling velocity
ASAortic stenosis
MSMitral stenosis
LVMILeft ventricular mass index
IVSdInterventricular septal end-diastolic dimension
LVPWdLeft ventricular posterior wall end-diastolic dimension
LVIDdLeft ventricular end-diastolic dimension
RWTRelative wall thickness

References

  1. Neufeld, E.F.; Muenzer, J. The mucoplysaccharidoses. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed.; Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D., Childs, B., Kinzler, K.W., Vogelstein, B., Eds.; McGraw-Hill: New York, NY, USA, 2001; pp. 3421–3452. [Google Scholar]
  2. Muenzer, J. Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 2011, 50 (Suppl. 5), v4–v12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Lin, H.Y.; Lin, S.P.; Chuang, C.K.; Niu, D.M.; Chen, M.R.; Tsai, F.J.; Chao, M.C.; Chiu, P.C.; Lin, S.J.; Tsai, L.P.; et al. Incidence of the mucopolysaccharidoses in Taiwan, 1984–2004. Am. J. Med. Genet. A 2009, 149, 960–964. [Google Scholar] [CrossRef] [PubMed]
  4. Dangel, J.H. Cardiovascular changes in children with mucopolysaccharide storage diseases and related disorders--clinical and echocardiographic findings in 64 patients. Eur. J. Pediatr. 1998, 157, 534–538. [Google Scholar] [CrossRef] [PubMed]
  5. Fesslová, V.; Corti, P.; Sersale, G.; Rovelli, A.; Russo, P.; Mannarino, S.; Butera, G.; Parini, R. The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses. Cardiol. Young 2009, 19, 170–178. [Google Scholar] [CrossRef]
  6. Wippermann, C.F.; Beck, M.; Schranz, D.; Huth, R.; Michel-Behnke, I.; Jüngst, B.K. Mitral and aortic regurgitation in 84 patients with mucopolysaccharidoses. Eur. J. Pediatr. 1995, 154, 98–101. [Google Scholar] [CrossRef]
  7. Braunlin, E.A.; Harmatz, P.R.; Scarpa, M.; Furlanetto, B.; Kampmann, C.; Loehr, J.P.; Ponder, K.P.; Roberts, W.C.; Rosenfeld, H.M.; Giugliani, R. Cardiac disease in patients with mucopolysaccharidosis: Presentation, diagnosis and management. J. Inherit. Metab. Dis. 2011, 34, 1183–1197. [Google Scholar] [CrossRef] [Green Version]
  8. Leal, G.N.; de Paula, A.C.; Leone, C.; Kim, C.A. Echocardiographic study of paediatric patients with mucopolysaccharidosis. Cardiol Young 2010, 20, 254–261. [Google Scholar] [CrossRef]
  9. Mohan UR, Hay AA, Cleary MA, Wraith JE, Patel RG: Cardiovascular changes in children with mucopolysaccharide disorders. Acta Paediatr. 2002, 91, 799–804. [CrossRef]
  10. Brands, M.M.; Frohn-Mulder, I.M.; Hagemans, M.L.; Hop, W.C.; Oussoren, E.; Helbing, W.A.; van der Ploeg, A.T. Mucopolysaccharidosis: Cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI. J. Inherit. Metab. Dis. 2013, 36, 227–234. [Google Scholar] [CrossRef] [Green Version]
  11. Chen, M.R.; Lin, S.P.; Hwang, H.K.; Yu, C.H. Cardiovascular changes in mucopolysaccharidoses in Taiwan. Acta Cardiol. 2005, 60, 51–53. [Google Scholar] [CrossRef]
  12. Lin, S.M.; Lin, H.Y.; Chuang, C.K.; Lin, S.P.; Chen, M.R. Cardiovascular abnormalities in Taiwanese patients with mucopolysaccharidosis. Mol. Genet. Metab. 2014, 111, 493–498. [Google Scholar] [CrossRef]
  13. Lin, H.Y.; Chuang, C.K.; Chen, M.R.; Lin, S.M.; Hung, C.L.; Chang, C.Y.; Chiu, P.C.; Tsai, W.H.; Niu, D.M.; Tsai, F.J.; et al. Cardiac structure and function and effects of enzyme replacement therapy in patients with mucopolysaccharidoses I, II, IVA and VI. Mol. Genet. Metab. 2016, 117, 431–437. [Google Scholar] [CrossRef] [PubMed]
  14. Lin, H.Y.; Chen, M.R.; Lin, S.M.; Hung, C.L.; Niu, D.M.; Chuang, C.K.; Lin, S.P. Cardiac Features and Effects of Enzyme Replacement Therapy in Taiwanese Patients with Mucopolysaccharidosis IVA. Orphanet. J. Rare Dis. 2018, 13, 148. [Google Scholar] [CrossRef] [PubMed]
  15. Lin, H.Y.; Chen, M.R.; Lin, S.M.; Hung, C.L.; Niu, D.M.; Chang, T.M.; Chuang, C.K.; Lin, S.P. Cardiac Characteristics and Natural Progression in Taiwanese Patients with Mucopolysaccharidosis III. Orphanet. J. Rare Dis. 2019, 14, 140. [Google Scholar] [CrossRef] [PubMed]
  16. Braunlin, E.A.; Berry, J.M.; Whitley, C.B. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am. J. Cardiol. 2006, 98, 416–418. [Google Scholar] [CrossRef] [PubMed]
  17. Jones, S.A.; Almássy, Z.; Beck, M.; Burt, K.; Clarke, J.T.; Giugliani, R.; Hendriksz, C.; Kroepfl, T.; Lavery, L.; Lin, S.P.; et al. Mortality and cause of death in mucopolysaccharidosis type II-a historical review based on data from the Hunter Outcome Survey (HOS). J. Inherit. Metab. Dis. 2009, 32, 534–543. [Google Scholar] [CrossRef]
  18. Lavery, C.; Hendriksz, C. Mortality in patients with Morquio syndrome A. JIMD Rep. 2015, 15, 59–66. [Google Scholar]
  19. Lin, H.Y.; Chuang, C.K.; Huang, Y.H.; Tu, R.Y.; Lin, F.J.; Lin, S.J.; Chiu, P.C.; Niu, D.M.; Tsai, F.J.; Hwu, W.L.; et al. Causes of death and clinical characteristics of 34 patients with Mucopolysaccharidosis II in Taiwan from 1995–2012. Orphanet. J. Rare Dis. 2016, 11, 85. [Google Scholar] [CrossRef] [Green Version]
  20. Lin, H.Y.; Lin, S.P.; Chuang, C.K.; Chen, M.R.; Chen, B.F.; Wraith, J.E. Mucopolysaccharidosis I under enzyme replacement therapy with laronidase-a mortality case with autopsy report. J. Inherit. Metab. Dis. 2005, 28, 1146–1148. [Google Scholar] [CrossRef]
  21. Andrade, M.F.A.; Guimarães, I.C.B.; Acosta, A.X.; Leão, E.K.E.A.; Moreira, M.I.G.; Mendes, C.M.C. Left ventricular assessment in patients with mucopolysaccharidosis using conventional echocardiography and myocardial deformation by two-dimensional speckle-tracking method. J. Pediatr. (Rio J.) 2019, 95, 475–481. [Google Scholar] [CrossRef] [PubMed]
  22. Mor-Avi, V.; Lang, R.M.; Badano, L.P.; Belohlavek, M.; Cardim, N.M.; Derumeaux, G. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. Eur. J. Echocardiogr. 2011, 12, 167–205. [Google Scholar] [CrossRef] [PubMed]
  23. Wang, J.; Khoury, D.S.; Yue, Y.; Torre-Amione, G.; Nagueh, S.F. Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure. Eur. Heart. J. 2008, 29, 1283–1289. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Kouzu, H.; Yuda, S.; Muranaka, A.; Doi, T.; Yamamoto, H.; Shimoshige, S.; Hase, M.; Hashimoto, A.; Saitoh, S.; Tsuchihashi, K.; et al. Left ventricular hypertrophy causes different changes in longitudinal, radial, and circumferential mechanics in patients with hypertension: A two-dimensional speckle tracking study. J. Am. Soc. Echocardiogr. 2011, 24, 192–199. [Google Scholar] [CrossRef] [PubMed]
  25. Vinereanu, D.; Nicolaides, E.; Tweddel, A.C.; Mädler, C.F.; Holst, B.; Boden, L.E.; Cinteza, M.; Rees, A.E.; Fraser, A.G. Subclinical left ventricular dysfunction in asymptomatic patients with Type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin. Sci. (Lond) 2003, 105, 591–599. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Chen, M.R.; Ko, H.S.; Chao, T.F.; Liu, H.C.; Kuo, J.Y.; Bulwer, B.E.; Yeh, H.I.; Hung, C.L. Relation of myocardial systolic mechanics to serum ferritin level as a prognosticator in thalassemia patients undergoing repeated transfusion. Echocardiography 2015, 32, 79–88. [Google Scholar] [CrossRef] [PubMed]
  27. Nijmeijer, S.C.M.; de Bruin-Bon, R.H.A.C.M.; Wijburg, F.A.; Kuipers, I.M. Cardiac disease in mucopolysaccharidosis type III. J. Inherit. Metab. Dis. 2019, 42, 276–285. [Google Scholar] [CrossRef] [PubMed]
  28. Borgia, F.; Pezzullo, E.; Schiano Lomoriello, V.; Sorrentino, R.; Lo Iudice, F.; Cocozza, S.; Della Casa, R.; Parenti, G.; Strisciuglio, P.; Trimarco, B.; et al. Myocardial deformation in pediatric patients with mucopolysaccharidoses: A two-dimensional speckle tracking echocardiography study. Echocardiography 2017, 34, 240–249. [Google Scholar] [CrossRef]
  29. Chuang, C.K.; Lin, S.P.; Lin, S.J.; Wang, T.J. MPS screening methods, the Berry spot and acid turbidity tests, cause a high incidence of false-negative results in sanfilippo and morquio syndromes. J. Clin. Lab. Anal. 2002, 16, 253–258. [Google Scholar]
  30. Chuang, C.K.; Lin, H.Y.; Wang, T.J.; Tsai, C.C.; Liu, H.L.; Lin, S.P. A modified liquid chromatography/tandem mass spectrometry method for predominant disaccharide units of urinary glycosaminoglycans in patients with mucopolysaccharidoses. Orphanet. J. Rare Dis. 2014, 9, 135. [Google Scholar] [CrossRef] [Green Version]
  31. Hung, C.L.; Goncalves, A.; Lai, Y.J.; Lai, Y.H.; Sung, K.T.; Lo, C.I.; Liu, C.C.; Kuo, J.Y.; Hou, C.J.Y.; Chao, T.F.; et al. Light to Moderate Habitual Alcohol Consumption Is Associated with Subclinical Ventricular and Left Atrial Mechanical Dysfunction in an Asymptomatic Population: Dose-Response and Propensity Analysis. J. Am. Soc. Echocardiogr. 2016, 29, 1043–1051. [Google Scholar] [CrossRef]
  32. Marcus, K.A.; Mavinkurve-Groothuis, A.M.; Barends, M.; van Dijk, A.; Feuth, T.; de Korte, C.; Kapusta, L. Reference values for myocardial two-dimensional strain echocardiography in a healthy pediatric and young adult cohort. J. Am. Soc. Echocardiogr. 2011, 24, 625–636. [Google Scholar] [CrossRef] [PubMed]
  33. Lang, R.M.; Badano, L.P.; Mor-Avi, V.; Afilalo, J.; Armstrong, A.; Ernande, L.; Flachskampf, F.A.; Foster, E.; Goldstein, S.A.; Kuznetsova, T.; et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur. Heart. J. Cardiovasc. Imaging 2015, 16, 233–270. [Google Scholar] [CrossRef] [PubMed]
  34. Eidem, B.W.; McMahon, C.J.; Cohen, R.R.; Wu, J.; Finkelshteyn, I.; Kovalchin, J.P.; Ayres, N.A.; Bezold, L.I.; Smith, E.O.B.; Pignatelli, R.H. Impact of cardiac growth on Doppler tissue imaging velocities: A study in healthy children. J. Am. Soc. Echocardiogr. 2004, 17, 212–221. [Google Scholar] [CrossRef] [PubMed]
  35. Baumgartner, H.; Hung, J.; Bermejo, J.; Chambers, J.B.; Evangelista, A.; Griffin, B.P.; Iung, B.; Otto, C.M.; Pellikka, P.A.; Quiñones, M. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J. Am. Soc. Echocardiogr. 2009, 22, 1–23. [Google Scholar] [CrossRef]
  36. Lancellotti, P.; Tribouilloy, C.; Hagendorff, A.; Popescu, B.A.; Edvardsen, T.; Pierard, L.A.; Badano, L.; Zamorano, J.L. Recommendations for the echocardiographic assessment of native valvular regurgitation: An executive summary from the European Association of Cardiovascular Imaging. Eur. Heart J. Cardiovasc. Imaging 2013, 14, 611–644. [Google Scholar] [CrossRef] [Green Version]
  37. Lang, R.M.; Bierig, M.; Devereux, R.B.; Flachskampf, F.A.; Foster, E.; Pellikka, P.A.; Picard, M.H.; Roman, M.J.; Seward, J.; Shanewise, J.S.; et al. Recommendations for chamber quantification: A report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J. Am. Soc. Echocardiogr. 2005, 18, 1440–1463. [Google Scholar]
  38. Foster, B.J.; Mackie, A.S.; Mitsnefes, M.; Ali, H.; Mamber, S.; Colan, S.D. A novel method of expressing left ventricular mass relative to body size in children. Circulation 2008, 117, 2769–2775. [Google Scholar] [CrossRef] [Green Version]
  39. Kampmann, C.; Wiethoff, C.M.; Wenzel, A.; Stolz, G.; Betancor, M.; Wippermann, C.F.; Huth, R.G.; Habermehl, P.; Knuf, M.; Emschermann, T. Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart 2000, 83, 667–672. [Google Scholar] [CrossRef] [Green Version]
  40. Singh, A.; Voss, W.B.; Lentz, R.W.; Thomas, J.D.; Akhter, N. The Diagnostic and Prognostic Value of Echocardiographic Strain. JAMA Cardiol. 2019, 4, 580–588. [Google Scholar] [CrossRef]
  41. Lin, H.Y.; Lee, C.L.; Lo, Y.T.; Wang, T.J.; Huang, S.F.; Chen, T.L.; Wang, Y.S.; Niu, D.M.; Chuang, C.K.; Lin, S.P. The Relationships between Urinary Glycosaminoglycan Levels and Phenotypes of Mucopolysaccharidoses. Mol. Genet. Genomic. Med. 2018, 6, 982–992. [Google Scholar] [CrossRef]
  42. Collins, J.A.; Munoz, J.V.; Patel, T.R.; Loukas, M.; Tubbs, R.S. The anatomy of the aging aorta. Clin. Anat. 2014, 27, 463–466. [Google Scholar] [CrossRef] [PubMed]
  43. Bolourchi, M.; Renella, P.; Wang, R.Y. Aortic Root Dilatation in Mucopolysaccharidosis I-VII. Int. J. Mol. Sci. 2016, 17, 2004. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Konstam, M.A.; Kramer, D.G.; Patel, A.R.; Maron, M.S.; Udelson, J.E. Left ventricular remodeling in heart failure: Current concepts in clinical significance and assessment. JACC Cardiovasc. Imaging 2011, 4, 98–108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Lin, S.P.; Lin, H.Y.; Wang, T.J.; Chang, C.Y.; Lin, C.H.; Huang, S.F.; Tsai, C.C.; Liu, H.L.; Keutzer, J.; Chuang, C.K. A Pilot Newborn Screening Program for Mucopolysaccharidosis Type I in Taiwan. Orphanet. J. Rare Dis. 2013, 8, 147. [Google Scholar] [CrossRef] [Green Version]
  46. Chuang, C.K.; Lin, H.Y.; Wang, T.J.; Huang, Y.H.; Chan, M.J.; Liao, H.C.; Lo, Y.T.; Wang, L.Y.; Tu, R.Y.; Fang, Y.Y.; et al. Status of newborn screening and follow up investigations for Mucopolysaccharidoses I and II in Taiwan. Orphanet. J. Rare Dis. 2018, 13, 84. [Google Scholar] [CrossRef] [Green Version]
  47. Chan, M.J.; Liao, H.C.; Gelb, M.H.; Chuang, C.K.; Liu, M.Y.; Chen, H.J.; Kao, S.M.; Lin, H.Y.; Huang, Y.H.; Kumar, A.B. Taiwan National Newborn Screening Program by Tandem Mass Spectrometry for Mucopolysaccharidoses Types, I, II, and VI. J. Pediatr. 2019, 205, 176–182. [Google Scholar] [CrossRef]
  48. Lin, H.Y.; Lee, C.L.; Lo, Y.T.; Tu, R.Y.; Chang, Y.H.; Chang, C.Y.; Chiu, P.C.; Chang, T.M.; Tsai, W.H.; Niu, D.M.; et al. An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan. Diagnostics 2019, 9, 140. [Google Scholar] [CrossRef] [Green Version]
  49. Levy, P.T.; Machefsky, A.; Sanchez, A.A.; Patel, M.D.; Rogal, S.; Fowler, S.; Yaeger, L.; Hardi, A.; Holland, M.R.; Hamvas, A.; et al. Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis. J. Am. Soc. Echocardiogr. 2016, 29, 209–225. [Google Scholar] [CrossRef] [Green Version]
  50. Cantinotti, M.; Scalese, M.; Giordano, R.; Franchi, E.; Assanta, N.; Marotta, M.; Viacava, C.; Molinaro, S.; Iervasi, G.; Santoro, G.; et al. Normative Data for Left and Right Ventricular Systolic Strain in Healthy Caucasian Italian Children by Two-Dimensional Speckle-Tracking Echocardiography. J. Am. Soc. Echocardiogr. 2018, 31, 712–720. [Google Scholar] [CrossRef]
Diagnostics 10 00062 g001 550
Figure 1. The z scores of LVMI, IVSd, and LVPWd by MPS type in the 53 patients. MPS, mucopolysaccharidosis; LVMI, left ventricular mass index; IVSd, interventricular septum thickness in diastole; LVPWd, left ventricular posterior wall thickness in diastole; H/S: Hurler-Scheie.
Figure 1. The z scores of LVMI, IVSd, and LVPWd by MPS type in the 53 patients. MPS, mucopolysaccharidosis; LVMI, left ventricular mass index; IVSd, interventricular septum thickness in diastole; LVPWd, left ventricular posterior wall thickness in diastole; H/S: Hurler-Scheie.
Diagnostics 10 00062 g001
Diagnostics 10 00062 g002 550
Figure 2. The LVMI z score is positively correlated with the GLS z score (n = 53, r = 0.469, p < 0.01). LVMI, left ventricular mass index; GLS, global longitudinal strain. The red line represents the trendline.
Figure 2. The LVMI z score is positively correlated with the GLS z score (n = 53, r = 0.469, p < 0.01). LVMI, left ventricular mass index; GLS, global longitudinal strain. The red line represents the trendline.
Diagnostics 10 00062 g002
Diagnostics 10 00062 g003 550
Figure 3. (A) Incidence of valvular heart disease by MPS type in the 53 patients. (B) Mean severity scores of valvular heart disease by MPS type in the 53 patients. Severity of valvular stenosis and regurgitation (MS, MR, AS, AR) was estimated and graded as follows: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). MPS, mucopolysaccharidosis; MS, mitral stenosis; MR, mitral regurgitation; AS, aortic stenosis; AR, aortic regurgitation; H/S: Hurler-Scheie.
Figure 3. (A) Incidence of valvular heart disease by MPS type in the 53 patients. (B) Mean severity scores of valvular heart disease by MPS type in the 53 patients. Severity of valvular stenosis and regurgitation (MS, MR, AS, AR) was estimated and graded as follows: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). MPS, mucopolysaccharidosis; MS, mitral stenosis; MR, mitral regurgitation; AS, aortic stenosis; AR, aortic regurgitation; H/S: Hurler-Scheie.
Diagnostics 10 00062 g003
Diagnostics 10 00062 g004 550
Figure 4. (A) The GLS z score is positively correlated with age (n = 53, r = 0.323, p < 0.05). (B) The LVMI z score is positively correlated with age (n = 53, r = 0.335, p < 0.05). GLS, global longitudinal strain; LVMI, left ventricular mass index. The red line represents the trendline.
Figure 4. (A) The GLS z score is positively correlated with age (n = 53, r = 0.323, p < 0.05). (B) The LVMI z score is positively correlated with age (n = 53, r = 0.335, p < 0.05). GLS, global longitudinal strain; LVMI, left ventricular mass index. The red line represents the trendline.
Diagnostics 10 00062 g004
Diagnostics 10 00062 g005 550
Figure 5. The relationships between age and severity of cardiac valve abnormalities in the 53 patients with mucopolysaccharidosis (severity score: 3: severe, 2: moderate, 1: mild, 0: normal). (A) MS, mitral stenosis (r = 0.314, p < 0.05); (B) MR, mitral regurgitation (r = 0.410, p < 0.01); (C) AS, aortic stenosis (r = 0.579, p < 0.01); (D) AR, aortic regurgitation (r = 0.371, p < 0.01). The blue dot represents the value of age and severity of cardiac valve abnormalities in the 53 patients.
Figure 5. The relationships between age and severity of cardiac valve abnormalities in the 53 patients with mucopolysaccharidosis (severity score: 3: severe, 2: moderate, 1: mild, 0: normal). (A) MS, mitral stenosis (r = 0.314, p < 0.05); (B) MR, mitral regurgitation (r = 0.410, p < 0.01); (C) AS, aortic stenosis (r = 0.579, p < 0.01); (D) AR, aortic regurgitation (r = 0.371, p < 0.01). The blue dot represents the value of age and severity of cardiac valve abnormalities in the 53 patients.
Diagnostics 10 00062 g005
Diagnostics 10 00062 g006 550
Figure 6. Percentages of left ventricular remodeling patterns in various MPS types. MPS, mucopolysaccharidosis.
Figure 6. Percentages of left ventricular remodeling patterns in various MPS types. MPS, mucopolysaccharidosis.
Diagnostics 10 00062 g006
Table
Table 1. Clinical and echocardiographic features of the 53 patients with MPS.
Table 1. Clinical and echocardiographic features of the 53 patients with MPS.
No.GenderMPS TypeAge (Years)ERT Duration (Years)GLS z ScoreLVMI z ScoreIVSd z ScoreLVPWd z ScoreAoD z ScoreEF (%)SF (%)E/A RatioRWTLeft Ventricular Remodeling PatternMSMRASAR
1FI (H/S)1.1 1.9 1.42.92.1−0.1 54273.22 0.413Normal geometry0201
2FI (H/S)1.1 0.8 −0.42.31.7 3.671351.44 0.449Concentric remodeling0100
3FI (H/S)33.9 2.70.31.0 1.1 4.462330.940.337Normal geometry3312
4MI (Scheie)13.2 2.80.51.1 0.7 0.4 71402.56 0.346Normal geometry0202
5FI (Scheie)22.5 0.3 −0.91.7 0.2 −0.4 71401.71 0.423Concentric remodeling0131
6MI (Scheie)33.2 4.01.41.7 0.7 1.4 66371.16 0.376Normal geometry1231
7MI (Scheie)34.9 0.0 −0.20.7 0.4 0.9 60320.910.380Normal geometry0231
8MII (mild)6.9 1.2 1.13.21.5 3.374421.05 0.434Concentric remodeling0101
9MII (mild)7.3 2.2−1.60.8 −0.2 7.068371.44 0.348Normal geometry0100
10MII (mild)10.0 5.0 0.0 −1.4−0.9 −0.1 2.971391.73 0.335Normal geometry0100
11MII (mild)10.6 6.5 3.00.32.41.4 2.0 62321.13 0.455Concentric remodeling0200
12MII (mild)11.6 5.7 2.52.81.6 1.7 4.241200.890.351Eccentric hypertrophy0202
13MII (mild)17.4 2.4 2.922.31.2 5.373422.61 0.349Normal geometry0103
14MII (mild)19.8 3.533.72.44.274432.92 0.421Concentric hypertrophy0100
15MII (mild)20.6 7.4 2.01.30.5 0.3 0.7 50261.36 0.309Normal geometry0202
16MII (mild)20.7 2.4 4.52.72.61.9 4.751261.45 0.381Eccentric hypertrophy0203
17MII (mild)24.0 6.5 1.2 11.9 1.4 3.762330.850.391Normal geometry1112
18MII (mild)25.6 3.5 3.41.82.71.7 1.3 73410.670.451Concentric remodeling2.51.500
19MII (severe)3.1 −1.3 −0.50.7 0.9 3.863331.17 0.359Normal geometry0101
20MII (severe)3.2 2.62.44.32.53.863331.48 0.421Concentric hypertrophy0200.5
21MII (severe)14.7 3.70.84.12.12.476440.950.4204Concentric remodeling12.500.5
22MII (severe)17.9 1.7 1.41.4 1.5 2.676441.42 0.382Normal geometry0102
23MII (severe)26.9 3.51.33.92.16.065351.14 0.444Concentric remodeling0312
24FIIIA8.7 2.4−3.2 0.0 −0.6 0.9 52261.31 0.301Normal geometry00.500
25FIIIB10.5 0.0 −0.41.4 0.7 1.8 71401.46 0.366Normal geometry0102
26FIIIB12.9 1.4 −1.60.1 0.4 1.3 75431.06 0.391Normal geometry00.500.5
27MIIIA13.6 1.5 0.50.9 0.4 1.7 73421.26 0.338Normal geometry0103
28MIIIA16.4 4.2−0.22.0 0.9 5.268381.37 0.382Normal geometry00.500
29FIIIB18.5 2.50.62.41.5 2.460320.880.345Normal geometry00.502
30FIIIB19.1 0.7 −0.71.0 0.1 2.669380.890.349Normal geometry0200
31FIIIB19.1 0.8 −0.60.2 0.8 3.872410.930.382Normal geometry0201
32MIIIC26.5 2.6−0.90.5 −0.1 2.756291.08 0.333Normal geometry0000
33MIVA2.3 0.3 − 40.4 0.5 2.562311.11 0.476Concentric remodeling0000
34MIVA3.2 1.7 −0.9 −0.70.4 0.3 2.572401.73 0.312Normal geometry0000
35MIVA4.5 1.7 −2.5 −1.50.1 0.5 2.581491.24 0.347Normal geometry0000
36FIVA7.8 −1.0 0.82.31.9 1.0 56281.10 0.394Normal geometry0100
37FIVA8.2 0.3 03.51.6 3.771391.16 0.429Concentric remodeling0100
38MIVA9.1 1.8 0.8 −0.90.0 −0.2 3.961311.40 0.297Normal geometry0100
39FIVA14.8 1.8 −1.11.3 0.6 2.672401.82 0.373Normal geometry0100
40MIVA15.9 2.0 0.3 −0.91.2 0.8 8.470381.42 0.375Normal geometry0100
41FIVA17.0 2.2 1.8 1.60.7 0.1 5.376451.42 0.255Normal geometry0102
42FIVA17.8 1.2 1.32.92.74.968371.19 0.448Concentric remodeling0101
43FIVA19.0 2.2 0.1 1.11.3 0.5 5.370391.06 0.349Normal geometry0100
44FIVA19.3 4.61.51.2 0.5 4.567361.29 0.312Normal geometry00.500
45FIVA20.0 1.2 −0.80.5 0.1 6.878451.06 0.323Normal geometry0200.5
46MIVA28.0 2.3 0.1 2.62.11.0 6.353261.06 0.324Eccentric hypertrophy01.502
47MVI5.0 −0.5 −20.1 0.0 1.0 65340.910.321Normal geometry1200
48MVI15.2 7.7 3.90.53.33.23.872399.40 0.510Concentric remodeling2100
49FVI15.5 1.5 4.20.42.81.2 1.2 75430.810.424Concentric remodeling3200
50MVI16.0 7.7 4.52.52.31.5 4.676441.11 0.371Eccentric hypertrophy1302
51FVI21.6 9.9 2.33.92.21.5 2.650250.830.323Eccentric hypertrophy22.513
52FVI24.7 8.0 2.20.72.11.5 3.072401.35 0.463Concentric remodeling1201
53FVI29.8 3.3 0.6 −0.52.0 1.1 0.2 76441.22 0.379Normal geometry0332
MPS, mucopolysaccharidosis; ERT, enzyme replacement therapy; GLS, global longitudinal strain; LVMI, left ventricular mass index; IVSd, interventricular septal end-diastolic dimension; LVPWd, left ventricular posterior wall end-diastolic dimension; AoD, aortic diameter; EF, ejection fraction; SF, shortening fraction; E/A: ratio between early and late (atrial) ventricular filling velocity; RWT, relative wall thickness; MS, mitral stenosis; MR, mitral regurgitation; AS, aortic stenosis; AR, aortic regurgitation; H/S: Hurler-Scheie. Severity of valvular stenosis and regurgitation (MS, MR, AS, AR) were estimated and graded on the following scores: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The abnormal values are presented in boldface, which include: z score >2 or <−2; EF: for children < 50%; for adults < 52% for men and < 54% for women; SF < 28%; E/A ratio < 1; RWT > 0.420.
Table
Table 2. The z scores of GLS, LVMI, IVSd, LVPWd, and aortic diameter by MPS type in the 53 patients. Values are displayed as mean (standard deviation).
Table 2. The z scores of GLS, LVMI, IVSd, LVPWd, and aortic diameter by MPS type in the 53 patients. Values are displayed as mean (standard deviation).
MPS TypenGender (M/F)Age (Years)Age Range (Years)GLS z ScoreLVMI z ScoreIVSd z ScoreLVPWd z ScoreAoD z Score
MPS I (H/S)30/312.0 (18.9)1.1–33.91.82 (0.93)0.43 (0.91)2.04 (0.95)1.67 (0.50)2.62 (2.38)
MPS I (Scheie)43/126.0 (10.1)13.2–34.91.78 (1.95)0.20 (0.98)1.31 (0.47)0.51 (0.25)1.69 (1.66)
MPS II1616/015.0 (7.7)6.9–26.92.29 (1.48)1.15 (1.39)2.20 (1.47)1.39 (0.81)3.61 (1.66)
MPS III93/616.1 (5.4)8.7–26.51.77 (1.25)−0.72 (1.15)0.95 (0.86)0.45 (0.64)2.49 (1.33)
MPS IVA146/813.3 (7.6)2.3–28.00.58 (1.65)−0.07 (1.69)1.29 (1.06)0.79 (0.78)4.30 (2.02)
MPS VI73/418.3 (8.0)5.0–29.82.48 (1.90)0.79 (1.93)2.13 (0.99)1.45 (0.95)2.35 (1.59)
Total5331/2215.3 (8.2)1.1–34.91.71 (1.66)0.35 (1.57)1.66 (1.20)1.03 (0.84)3.15 (1.93)
MPS, mucopolysaccharidosis; M/F, male/female; GLS, global longitudinal strain; LVMI, left ventricular mass index; IVSd, interventricular septum thickness in diastole; LVPWd, left ventricular posterior wall thickness in diastole; AoD, aortic diameter; H/S: Hurler-Scheie.
Table
Table 3. Mean severity scores of valvular heart disease by MPS type in the 53 patients. 0, normal; 1, mild; 2, moderate; 3, severe. Values are displayed as mean (standard deviation).
Table 3. Mean severity scores of valvular heart disease by MPS type in the 53 patients. 0, normal; 1, mild; 2, moderate; 3, severe. Values are displayed as mean (standard deviation).
MPS TypenGender (M/F)Age (Years)MSMRASAR
MPS I (H/S)30/312.0 (18.9)1.00 2.00 0.33 1.00
MPS I (Scheie)43/126.0 (10.1)0.25 1.75 2.25 1.25
MPS II1616/015.0 (7.7)0.28 1.56 0.13 1.19
MPS III93/616.1 (5.4)0.00 0.89 0.00 0.94
MPS IVA146/813.3 (7.6)0.00 0.86 0.00 0.39
MPS VI73/418.3 (8.0)1.43 2.21 0.57 1.14
Total5331/2215.3 (8.2)0.35 1.39 0.30 0.92
MPS, mucopolysaccharidosis; M/F, male/female; MS, mitral stenosis; MR, mitral regurgitation; AS, aortic stenosis; AR, aortic regurgitation; H/S: Hurler-Scheie.
Table
Table 4. Number and percentages of left ventricular remodeling patterns in various MPS types.
Table 4. Number and percentages of left ventricular remodeling patterns in various MPS types.
Left Ventricular Remodeling PatternNormalConcentric RemodelingEccentric HypertrophyConcentric Hypertrophy
MPS I (n = 7)5 (71%)2 (29%)00
MPS II (n =16)7 (44%)5 (31%)2 (13%)2 (13%)
MPS III (n = 9)9 (100%)000
MPS IVA (n = 14)10 (71%)3 (21%)1 (7%)0
MPS VI (n = 7)2 (29%)3 (43%)2 (29%)0
Total (n = 53)33 (62%)13 (25%)5 (9%)2 (4%)
MPS, mucopolysaccharidosis.

Share and Cite

MDPI and ACS Style

Lin, H.-Y.; Chuang, C.-K.; Lee, C.-L.; Chen, M.-R.; Sung, K.-T.; Lin, S.-M.; Hou, C.J.-Y.; Niu, D.-M.; Chang, T.-M.; Hung, C.-L.; et al. Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses. Diagnostics 2020, 10, 62. https://doi.org/10.3390/diagnostics10020062

AMA Style

Lin H-Y, Chuang C-K, Lee C-L, Chen M-R, Sung K-T, Lin S-M, Hou CJ-Y, Niu D-M, Chang T-M, Hung C-L, et al. Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses. Diagnostics. 2020; 10(2):62. https://doi.org/10.3390/diagnostics10020062

Chicago/Turabian Style

Lin, Hsiang-Yu, Chih-Kuang Chuang, Chung-Lin Lee, Ming-Ren Chen, Kuo-Tzu Sung, Shan-Miao Lin, Charles Jia-Yin Hou, Dau-Ming Niu, Tung-Ming Chang, Chung-Lieh Hung, and et al. 2020. "Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses" Diagnostics 10, no. 2: 62. https://doi.org/10.3390/diagnostics10020062

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop