Duchenne Muscular Dystrophy: Prevalence and Patterns of Cardiac Involvement
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《美国医学杂志》
Departments of Pediatrics and Cardiology, All India Institute of Medical Sciences, New Delhi, India
Abstract
Abstract. In about 10% cases of Duchenne muscular dystrophy (DMD), death is due to cardiac dysfunction. The recognition of cardiomyopathy in DMD is thus important. Objective: To assess cardiac involvement in DMD patients by clinical, radiographic, electrocardiographic (ECG) and echocardiographic monitoring and correlate clinical parameters, CPK levels, presence of gene deletion and steroid therapy with cardiac involvement. Methods: Thirty patients beyond 6 years age, with DMD in advanced stage disease/non-ambulatory were recalled. A detailed clinical evaluation, CPK levels, gene deletion studies were carried out. Cardiac investigations included Chest X-ray, 12 lead ECG and echocardiography. Results: Nineteen patients were non-ambulatory at the time of enrollment. Symptoms or signs suggestive of cardiac dysfunction were seen in only 10%. Gene deletion was identified in 70.3%. Around one-third patients had cardiomegaly. ECG abnormalities were present in 93.3% patients and commonest abnormality was R> 4 mm in V1. Ejection fraction (EF) < 55% was observed in 64.2% and EF < 50% in 17.8%. Conclusion: Cardiomyopathy of DMD is characterized by lack of symptoms and few physical signs. Presence of subtle changes like sinus tachycardia may suggest early cardiac involvement. Thus echocardiography is required for evaluation of cardiac dysfunction. Presence of gene deletion was associated with higher CT ratio. Older children have been found to have higher heart rates. No other significant correlation with clinical parameters, CPK levels, genotype and steroid therapy was observed. Early detection possibly leads to appropriate treatment thus reducing the morbidity
Keywords: : Duchenne muscular dystrophy; Cardiomyopathy; Electrocardiographic; Echocardiographic
Duchenne muscular dystrophy (DMD), an X-linked recessive disorder, is the most common hereditary neuromuscular disease occuring in approximately 1 of every 3,300-4,000 live births due to a defect in the P21 band of the X chromosome that is responsible for dystrophin production.[1-6] Dystrophin is a cytosolic protein associated with the external membrane of skeletal, cardiac and smooth muscle cells and of some neurons.[7-8] DMD has onset in early childhood, proximal distribution of weakness and a progressive course.[1]
Cardiac involvement in DMD is common, its onset is usually after the age of 10 years and increases in incidence with age affecting almost all patients beyond the age of 18.[9-21] Death in Duchenne muscular dystrophy most commonly results from pulmonary insufficiency and respiratory infections. In about 10% of cases, death is due to cardiac dysfunction. The recognition of cardiomyopathy in Duchenne muscular dystrophy is thus important and requires active cardiac investigation. It is not clear whether cardiac involvement becomes evident prior to non-ambulation, it's relation to severity of the disease, creatine phosphokinase (CPK) levels, gene deletion and steroid therapy.
There is paucity of data regarding cardiac involvement as well as its pattern in DMD patients from India. The objectives of this study were to assess cardiac involvement in DMD patients by clinical, radiographic, electrocardiographic (ECG) and echocardiographic monitoring and correlate clinical parameters, CPK levels, presence of gene deletion and steroid therapy with cardiac involvement.
Materials and Methods
0Subjects
Patients beyond 6 years of age enrolled in the Muscle Clinic in Child Neurology Division of a tertiary care hospital were studied. The diagnostic criteria were typical history of proximal muscle weakness with onset in early childhood, objective signs of girdle weakness, calf pseudohypertrophy and elevated CPK levels. A total of 30 patients with DMD in advanced stage disease/non ambulatory were recalled. A detailed clinical evaluation was performed in addition to investigations listed below.
Clinical Evaluation
The clinical profile included age at onset, course of disease, details of motor disability, history of respiratory complaints and developmental history. Cardiac symptomatology was recorded including history of dyspnea and palpitations. Family history of similar involvement especially in maternal uncles and siblings was recorded. Physical examination included observation for myopathic facies, pseudohypertrophy, pattern of muscle atrophy and muscle charting. Systemic examination with special reference to cardiovascular system was done. Motor disability was assessed using 8 grade Swinyard-Dever criteria. The applicability of this classification for evaluating cardiac status in patients with DMD has been confirmed by previous reports. [20,22-23]
Investigations
CPK level and muscle biopsy were done for diagnosis. Genetic studies were done by deletion screening for 25 exons of the DMD gene using multiplex PCR method.
Cardiac investigations included Chest x-ray for cardiomegaly and pulmonary venous hypertension (PVH), 12 lead ECG and echocardiography .
Electrocardiogram: All subjects had a 12 lead ECG recorded while recumbent. The heart rate, characteristics of R waves, S waves, R/S ratios, Q waves, P-R interval, Q-T interval were measured manually in many ECG leads and were interpreted on the basis of published standard age- matched normal values.[24]
Echocardiography: Hewlett Packard Sonos 5,500 and Advanced technology laboratories model ultramark 9 with 3.5 MHz or 5 MHz transducer was used. The measurements of aorta, left atrium (end systole), left ventricular (end diastole and end systole), interventricular septum (end diastole), and posterior wall (end diastole) were done according to the recommendations of the American Society of Echocardiography. [25],[26] Valve morphology was assessed and presence of mitral valve prolapse or any left ventricular wall motion abnormality was looked for on 2D Echocardiogra(Gulati Sheffali, Saxena A)
Abstract
Abstract. In about 10% cases of Duchenne muscular dystrophy (DMD), death is due to cardiac dysfunction. The recognition of cardiomyopathy in DMD is thus important. Objective: To assess cardiac involvement in DMD patients by clinical, radiographic, electrocardiographic (ECG) and echocardiographic monitoring and correlate clinical parameters, CPK levels, presence of gene deletion and steroid therapy with cardiac involvement. Methods: Thirty patients beyond 6 years age, with DMD in advanced stage disease/non-ambulatory were recalled. A detailed clinical evaluation, CPK levels, gene deletion studies were carried out. Cardiac investigations included Chest X-ray, 12 lead ECG and echocardiography. Results: Nineteen patients were non-ambulatory at the time of enrollment. Symptoms or signs suggestive of cardiac dysfunction were seen in only 10%. Gene deletion was identified in 70.3%. Around one-third patients had cardiomegaly. ECG abnormalities were present in 93.3% patients and commonest abnormality was R> 4 mm in V1. Ejection fraction (EF) < 55% was observed in 64.2% and EF < 50% in 17.8%. Conclusion: Cardiomyopathy of DMD is characterized by lack of symptoms and few physical signs. Presence of subtle changes like sinus tachycardia may suggest early cardiac involvement. Thus echocardiography is required for evaluation of cardiac dysfunction. Presence of gene deletion was associated with higher CT ratio. Older children have been found to have higher heart rates. No other significant correlation with clinical parameters, CPK levels, genotype and steroid therapy was observed. Early detection possibly leads to appropriate treatment thus reducing the morbidity
Keywords: : Duchenne muscular dystrophy; Cardiomyopathy; Electrocardiographic; Echocardiographic
Duchenne muscular dystrophy (DMD), an X-linked recessive disorder, is the most common hereditary neuromuscular disease occuring in approximately 1 of every 3,300-4,000 live births due to a defect in the P21 band of the X chromosome that is responsible for dystrophin production.[1-6] Dystrophin is a cytosolic protein associated with the external membrane of skeletal, cardiac and smooth muscle cells and of some neurons.[7-8] DMD has onset in early childhood, proximal distribution of weakness and a progressive course.[1]
Cardiac involvement in DMD is common, its onset is usually after the age of 10 years and increases in incidence with age affecting almost all patients beyond the age of 18.[9-21] Death in Duchenne muscular dystrophy most commonly results from pulmonary insufficiency and respiratory infections. In about 10% of cases, death is due to cardiac dysfunction. The recognition of cardiomyopathy in Duchenne muscular dystrophy is thus important and requires active cardiac investigation. It is not clear whether cardiac involvement becomes evident prior to non-ambulation, it's relation to severity of the disease, creatine phosphokinase (CPK) levels, gene deletion and steroid therapy.
There is paucity of data regarding cardiac involvement as well as its pattern in DMD patients from India. The objectives of this study were to assess cardiac involvement in DMD patients by clinical, radiographic, electrocardiographic (ECG) and echocardiographic monitoring and correlate clinical parameters, CPK levels, presence of gene deletion and steroid therapy with cardiac involvement.
Materials and Methods
0Subjects
Patients beyond 6 years of age enrolled in the Muscle Clinic in Child Neurology Division of a tertiary care hospital were studied. The diagnostic criteria were typical history of proximal muscle weakness with onset in early childhood, objective signs of girdle weakness, calf pseudohypertrophy and elevated CPK levels. A total of 30 patients with DMD in advanced stage disease/non ambulatory were recalled. A detailed clinical evaluation was performed in addition to investigations listed below.
Clinical Evaluation
The clinical profile included age at onset, course of disease, details of motor disability, history of respiratory complaints and developmental history. Cardiac symptomatology was recorded including history of dyspnea and palpitations. Family history of similar involvement especially in maternal uncles and siblings was recorded. Physical examination included observation for myopathic facies, pseudohypertrophy, pattern of muscle atrophy and muscle charting. Systemic examination with special reference to cardiovascular system was done. Motor disability was assessed using 8 grade Swinyard-Dever criteria. The applicability of this classification for evaluating cardiac status in patients with DMD has been confirmed by previous reports. [20,22-23]
Investigations
CPK level and muscle biopsy were done for diagnosis. Genetic studies were done by deletion screening for 25 exons of the DMD gene using multiplex PCR method.
Cardiac investigations included Chest x-ray for cardiomegaly and pulmonary venous hypertension (PVH), 12 lead ECG and echocardiography .
Electrocardiogram: All subjects had a 12 lead ECG recorded while recumbent. The heart rate, characteristics of R waves, S waves, R/S ratios, Q waves, P-R interval, Q-T interval were measured manually in many ECG leads and were interpreted on the basis of published standard age- matched normal values.[24]
Echocardiography: Hewlett Packard Sonos 5,500 and Advanced technology laboratories model ultramark 9 with 3.5 MHz or 5 MHz transducer was used. The measurements of aorta, left atrium (end systole), left ventricular (end diastole and end systole), interventricular septum (end diastole), and posterior wall (end diastole) were done according to the recommendations of the American Society of Echocardiography. [25],[26] Valve morphology was assessed and presence of mitral valve prolapse or any left ventricular wall motion abnormality was looked for on 2D Echocardiogra(Gulati Sheffali, Saxena A)