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 Table of Contents  
INTERESTING CASE REPORT
Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 58-62

Cardiac Magnetic Resonance Depiction of Different Morphological Appearances of Becker Cardiomyopathy in Siblings


1 Department of Radiology and Imaging Sciences, KMCH, Tamil Nadu, India
2 Department of Radiology, Narayana Institute of Cardiac Sciences, Bengaluru, Karnataka, India
3 Department of Cardiology, Bangalore Baptist Hospital, Bengaluru, Karnataka, India

Date of Submission04-Jun-2020
Date of Decision26-Jul-2020
Date of Acceptance30-Aug-2020
Date of Web Publication04-Feb-2021

Correspondence Address:
Dr. Pudhiavan Arunachalam
Department of Radiology and Imaging Sciences, KMCH, 99, Avinashi Road, Coimbatore - 641 014, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiae.jiae_25_20

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  Abstract 

Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutation of the dystrophin gene. Cardiac involvement in BMD is frequent and represents the foremost cause of mortality. Two male siblings with severe left ventricular (LV) dysfunction and presence of deletion in the dystrophin gene underwent cardiac magnetic resonance (CMR) imaging, which revealed typical but varying imaging findings. The CMR revealed dilated left ventricle with severe global hypokinesis with preserved right ventricular (RV) function. Few patchy areas of septal edema were seen with typical epicardial enhancement along the LV lateral wall and the RV side of septum in one sibling. Both the siblings revealed an elevated myocardial native T1 values. CMR has the potential to detect cardiac involvement early by identifying and quantifying fibrosis, before wall motion abnormalities set in and determine prognosis in patients with muscular dystrophy and BMD carriers.

Keywords: Becker cardiomyopathy, Becker muscular dystrophy, cardiac magnetic resonance, Duchenne muscular dystrophy, dystrophin


How to cite this article:
Arunachalam P, Kothari R, Palaniappan S, Raj V. Cardiac Magnetic Resonance Depiction of Different Morphological Appearances of Becker Cardiomyopathy in Siblings. J Indian Acad Echocardiogr Cardiovasc Imaging 2021;5:58-62

How to cite this URL:
Arunachalam P, Kothari R, Palaniappan S, Raj V. Cardiac Magnetic Resonance Depiction of Different Morphological Appearances of Becker Cardiomyopathy in Siblings. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2021 [cited 2021 Jul 23];5:58-62. Available from: https://www.jiaecho.org/text.asp?2021/5/1/58/308727


  Introduction Top


Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders involving mutation of the dystrophin gene, located on chromosome Xp21.1. Patients with DMD have a large out of frame deletion in the DMD gene whereas in BMD, there is an in-frame deletion.[1] It codes for a scaffolding protein in the skeletal and cardiac muscle called dystrophin, which functions to link the contractile protein to the cell membrane.[2] In DMD, there is near complete absence of the dystrophin protein, whereas in BMD, the protein is reduced in amount or is dysfunctional. Both can cause cardiac involvement resulting in dilated cardiomyopathy (DCM). DMD affects early with predominant neuromuscular and respiratory muscle involvement resulting in respiratory failure as a leading cause of death. BMD can have a variable presentation of skeletal muscle involvement with cardiac involvement independent of the former and DCM as the leading cause of mortality.[3],[4],[5]


  Case report Top


A 23-year-old male presented with palpitations and breathlessness on exertion for the first time at the age of 15 years in 2010. He was not on any medications and there was no history of alcohol/drug abuse. He was performing well in school and was independent in daily life. Vital parameters were within normal limits and there was no cyanosis/clubbing/edema. This patient is referred to as Case 1.

Investigations

Echocardiography revealed left ventricular (LV) dysfunction with LV ejection fraction of 45% in 2010.

Initial management

At that time, he was diagnosed to have viral myocarditis and treated with steroids and anti-failure medications.

Initial follow-up

In 2012, Case 1 had persistent LV dysfunction. It was reclassified as dilated cardiomyopathy and put on anti-failure measures. As part of family screening, his brother was examined.

The younger brother was 14-years-old and asymptomatic. His echocardiography revealed mild LV dysfunction with LV ejection fraction of 48%. He is referred to as Case 2.

Both the siblings exhibited persistent low LV systolic function over time in spite of anti-failure medications. Hence, the option of gene testing was offered to them.

Gene testing

Gene testing revealed the presence of a deletion in the dystrophin gene involving multiple exons (48–49), consistent with the diagnosis of Duchenne/BMD in both brothers.

Cardiac magnetic resonance

CMR examination was performed on a 3-T Scanner (Philips Ingenia 3T system) for both siblings to depict the morphological appearance and as a baseline for future follow-up in 2018.

Cardiac magnetic resonance protocol

The CMR protocol used a three axis orthogonal plane survey and axial black blood sequence for screening the chest. Cine balanced steady state-free precision sequences were done in 2 chamber, 4 chamber, 3 chamber, and short axis views. T1 and T2 mapping sequence was done in a single mid cavity short axis plane. Gadolinium-based cyclic contrast (Dotarem–Gadoterate meglumine) was given at 0.2 ml/kg bodyweight followed by delayed enhancement imaging at 8–10 min using a phase sensitive inversion recovery (PSIR) sequence in short axis plane from base to apex without slice gap. An inversion time optimized to null the myocardium was used in PSIR sequence using a TI scout image. Phase contrast flow images across ascending aorta and main pulmonary artery was done for flow quantification. T1 mapping was done before administration of contrast to obtain native T1 values and 15 min post contrast for the calculation of extracellular volume (ECV) fraction. The T1 values were obtained by a manual endocardial and epicardial trace with software based motion correction (Intellispace Portal, Koninklijke Philips N. V.), excluding the trabeculations and epicardial fat. The normal native T1 values at 3T in our institution are 1250 ± 25 ms. The LV myocardial scar quantification was done using manual endo and epicardial tracing from base to apex in PSIR images and using a full-width half-maximum (FWHM) method.

CMR in case 1 revealed a dilated LV with diffuse global hypokinesis and LV ejection fraction of 38%. The indexed LV end diastolic volume was 113 ml/m2 and indexed LV end systolic volume was 70 ml/m2. The wall thickness along the anterior wall and septum were preserved with diffuse wall thinning and severe hypokinesia in the basal and mid cavity lateral and inferior walls [Figure 1]. Mild prominence of trabeculations were seen in the mid and apical cavity of LV. T1 mapping of the LV myocardium revealed a uniformly elevated native T1 value (1425 ms) and raised ECV (45%). T2 sequence revealed mild myocardial edema along the septum. Postcontrast delayed enhancement revealed linear mid myocardial enhancement along the septum. An extensive mid myocardial and epicardial enhancement was also seen along the lateral and inferior walls. LV myocardial scar quantification revealed an enhancing fibrotic burden of 20% of myocardial volume [Figure 2].
Figure 1: Cardiac magnetic resonance imaging in sibling 1. Cine-balanced steady state free precision sequence in 4 chamber (a and d), 2 chamber (b and e) and short axis (c and f) views. The images show dilated left ventricles in diastole (a-c) with hypokinesia and mild myocardial thickening in systole (d-f). The lateral and inferior walls show wall thinning in diastole with poor myocardial thickening in systole (arrowheads)

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Figure 2: Cardiac magnetic resonance imaging in sibling 1 shows, (a) Short TI inversion recovery short axis reveals myocardial edema in the anteroseptal segment, (b) native T1 mapping with manual contouring after motion correction showing diffusely raised T1 values, (c) phase sensitive inversion recovery short axis showing diffuse myocardial fibrosis seen as hyperintense areas in mid septum and lateral/inferior walls and (d) Bull's eye plot showing enhanced left ventricular myocardial percentage using full-width half-maximum method

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CMR in case 2 revealed a dilated LV with mild global hypokinesis and LV ejection fraction of 45%. The indexed LV end diastolic volume was 98 ml/m2 and indexed LV end systolic volume was 54 ml/m2. Wall thinning with severe hypokinesis was seen in the lateral wall in basal and mid cavity [Figure 3]. No significant LV hyper trabeculation was seen. T2 images revealed no myocardial edema. T1 mapping revealed diffuse mildly elevated native T1 values (1320 ms) and raised ECV (40%). Postcontrast delayed enhancement showed diffuse epicardial enhancement along the lateral and inferior walls and a focal area of enhancement in the right ventricular (RV) side of the septum. LV myocardial scar quantification revealed an enhancing fibrotic burden of 10% of myocardial volume [Figure 4].
Figure 3: Cardiac magnetic resonance imaging in sibling 2. Cine balanced steady state free precision sequence in 4 chamber (a and d), 2 chamber (b and e) and short axis (c and f) views. The images show dilated left ventricles in diastole (a-c) with mild hypokinesia and moderate myocardial thickening in systole (d-f). The lateral wall shows wall thinning in diastole with poor myocardial thickening in systole (arrowheads) with adequate systolic thickening of septum (arrow)

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Figure 4: Cardiac magnetic resonance imaging in sibling 2 shows, (a) Short TI inversion recovery short axis reveals no myocardial edema, (b) native T1 mapping with manual contouring after motion correction showing diffusely raised T1 values, (c) phase sensitive inversion recovery short axis showing diffuse myocardial fibrosis seen as hyperintense areas in lateral/inferior walls and (d) Bull's eye plot showing enhanced left ventricular myocardial percentage using full-width half-maximum method. Compared to sibling 1, the extent of fibrosis is less

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Management

Case 1 continues to have persistent exertional dyspnea. He has been on Losartan (angiotensin receptor blocker [ARB]), carvedilol, eplerenone, and furosemide. The troponin T has been within normal limits (0.1 ng/ml). Case 2 has remained asymptomatic and has been on losartan, carvedilol, and eplerenone.


  Discussion Top


Cardiac involvement in BMD can vary from subtle signs to severe cardiomyopathy requiring transplant. Although DMD and BMD are X-linked conditions, cardiac involvement and symptoms are also seen in female carriers of the DMD gene mutation with the prevalence of 10%–15%.[1] The primary pathology in BMD is diffuse myocardial degeneration and fibrosis.[6] There is preferential myocardial involvement of the inferolateral wall of LV, which is presumed to be due to increased mechanical stress in this region. The presence of LV hyper trabeculation (LVHT) is also common in both the DMD and BMD patients and in female carriers of dystrophinopathies with up to 40% of patients with DMD. LVHT also increases risk of heart failure, thromboembolism, arrhythmias, and sudden cardiac death.[1] Most patients of BMD have asymptomatic cardiac involvement, however, and very few patients present with heart failure features. In our patients, the elder sibling presented with heart failure, while the younger sibling had cardiac involvement but was asymptomatic. The typical electrocardiogram (ECG) features described in the literature are R: S ratio ≥1, tall R waves, deep Q wave, short PR interval, and longer QTc interval. Conduction abnormalities including bundle branch blocks are also seen. However, typical ECG changes are less common among patients with BMD-associated cardiomyopathy.[7]

CMR is more sensitive than echocardiography in assessing ventricular size and function and in the characterization of the myocardium. The clinical picture of dilatation and LV dysfunction are not early features of cardiac involvement in DMD and BMD as well as in the carriers of dystrophin gene mutation. However, fibrosis along the lateral LV wall as detected by CMR clearly predates the drop in LV ejection fraction.[8] CMR with a gadolinium-based delayed enhancement imaging can accurately detect myocardial damage, which causes reduction in myocardial contractility resulting in global LV systolic dysfunction. The gadolinium is an extra cellular contrast agent and there is pooling of contrast in the areas of fibrosis due to an expansion of the extra cellular space. The late gadolinium enhancement (LGE) images are obtained using a PSIR sequence after 8–10 min of contrast administration with nulling of the normal myocardium. The myocardial damage is seen as enhancement in the LGE images in CMR. The myocardial damage predominantly begins in the region of the subepicardium in the lateral wall of LV, which is picked up early in the CMR LGE images. T1 mapping sequence also helps in detecting subclinical myocardial fibrosis, when the LGE images are yet to demonstrate areas of fibrosis.[8] T1 mapping is a method of tissue characterization by measuring the T1 relaxation times of the myocardium. It provides pixel level T1 values of the myocardium using a shortened modified look locker sequence (Sh-Molli). The sequence is also repeated at 15 min post gadolinium contrast to give the T1-enhanced map which is used for deriving the ECV fraction of the myocardium. The native T1 values of the LV myocardium vary with the scan parameters and the hardware used and hence a single cut off value for disease prevalence is not possible. It is necessary to compute a normal range for a given hardware–sequence combination to determine the significance of elevated native T1 values. However, the ECV fraction is a ratio and is independent of these factors. CMR is also recommended as a tool for baseline quantification of myocardial fibrosis and in the follow-up. The amount of myocardial fibrosis can be quantified from the LGE images taken in short axis from base to apex.

Patients with cardiac involvement in BMD may have varying morphological appearances on CMR. In this instance, the siblings had different pattern of enhancement and different areas of myocardial involvement. The degree of fibrosis based on LGE and T1 mapping sequences may act as surrogate markers of prognosis in these patients. The native T1 and the amount of fibrosis were certainly higher in the elder sibling, who was more symptomatic compared to the younger sibling. The pattern of LGE perhaps, may also have an effect on the prognosis of the patient.

Angiotensin-converting enzyme inhibitors and ARBs have been shown to retard the progression of LV dysfunction and have also shown to have a mortality benefit.[9] Beta-blockers also have shown to have a beneficial effect in patients with dilated cardiomyopathy and are likely to benefit patients with BMD. CMR by demonstrating the features of cardiomyopathy early can help in the identification of patients who will most likely benefit from early institution of heart failure therapy. Timely and appropriate heart failure therapy has been shown to result in beneficial ventricular remodeling. There is improvement in LV systolic function or at least no progression of LV dysfunction.[10]


  Conclusion Top


CMR is more sensitive in detecting the myocardial damage in BMD and in characterizing the cardiomyopathy. In our series, both the siblings demonstrated varying morphological features of myocardial involvement which correlated with the severity of clinical presentation. Regular CMR evaluation in patients with BMD without overt cardiac symptoms can help in detecting early myocardial involvement and prompt institution of therapy to delay detrimental myocardial remodeling. Native T1 and degree of LGE may be useful in long term prognostication of these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Lim KR, Sheri N, Nguyen Q, Yokota T. Cardiac involvement in dystrophin-deficient females: Current understanding and implications for the treatment of dystrophinopathies. Genes (Basel) 2020;11:1-17.  Back to cited text no. 1
    
2.
Ho R, Nguyen ML, Mather P. Cardiomyopathy in Becker muscular dystrophy: Overview. World J Cardiol 2016;8:356-61.  Back to cited text no. 2
    
3.
Romfh A, McNally EM. Cardiac assessment in Duchenne and Becker muscular dystrophies. Curr Heart Fail Rep 2010;7:212-8.  Back to cited text no. 3
    
4.
Melacini P, Fanin M, Danieli GA, Villanova C, Martinello F, Miorin M, et al. Myocardial involvement is very frequent among patients affected with subclinical Becker's muscular dystrophy. Circulation 1996;94:3168-75.  Back to cited text no. 4
    
5.
Finsterer J, Bittner RE, Grimm M. Cardiac involvement in Becker's muscular dystrophy, necessitating heart transplantation, 6 years before apparent skeletal muscle involvement. Neuromuscul Disord 1999;9:598-600.  Back to cited text no. 5
    
6.
Rajdev A, Groh WJ. Arrhythmias in the muscular dystrophies. Physiol Behav 2017;176:139-48.  Back to cited text no. 6
    
7.
Yilmaz A, Gdynia HJ, Baccouche H, Mahrholdt H, Meinhardt G, Basso C, et al. Cardiac involvement in patients with Becker muscular dystrophy: New diagnostic and pathophysiological insights by a CMR approach. J Cardiovasc Magn Reson 2008;10:1-12.  Back to cited text no. 7
    
8.
Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, Camino E, Lehman KJ, et al. Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing. Int J Cardiol 2020;316:257-65.  Back to cited text no. 8
    
9.
Bosser G, Lucron H, Lethor JP, Burger G, Beltramo F, Marie PY, et al. Evidence of early impairments in both right and left ventricular inotropic reserves in children with Duchenne's muscular dystrophy. Am J Cardiol 2004;93:724-7.  Back to cited text no. 9
    
10.
Ramaciotti C, Heistein LC, Coursey M, Lemler MS, Eapen RS, Iannaccone ST, et al. Left ventricular function and response to enalapril in patients with Duchenne muscular dystrophy during the second decade of life. Am J Cardiol 2006;98:825-7.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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