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Cardiac manifestations in the neuromuscular diseases include conduction defects, ventricular dilatation and cardiomyopathy. While electrocardiographic (ECG) abnormalities are quite prevalent, abnormalities are usually benign in most disorders, with a low frequency of clinical cardiac problems. The disorders in which there are significant heart problems are Duchenne dystrophy (DMD), Becker's dystrophy (BMD), Emery-Dreifuss dystrophy (EDMD), myotonic dystrophy (MMD) and Friedreich's ataxia. The results regarding specific diseases in this review were based on data obtained during a ten year study at this Research & Training Center.
Amyotrophic Lateral Sclerosis (ALS): In 31 patients, 17 (55%) of the initial ECGs were reported as abnormal, although most showed minor findings such as non-specific T wave changes. The other most significant abnormalities were abnormal Q waves (31%) and bradycardia (26%).
Twenty-four percent had a history of cardiovascular complications such as dyspnea, chest pain or palpitations. There was no age or disease duration effect on either ECG abnormalities or cardiac complications, and no relationship between ECG abnormalities and cardiovascular complications.
There have not been any previous reports of cardiac function in ALS. The low frequency of cardiac complications and the relatively minor ECG findings indicates that the heart is probably not involved in ALS.
Spinal Muscular Atrophy, Types II and III (SMA): In 41 patients, 26 (63%) of the initial ECGs for both types were reported as abnormal, although most had minor findings such as baseline irregularity (100%). Abnormalities were greater in SMA Type II. The most frequent abnormalities were increased R/S ratio in V3 (68%) and a prolonged Qtc (62%).
Only 12 percent had a history of cardiovascular complications such as dyspnea, palpitations, and chest pain. There was no age or disease duration effect on either ECG abnormalities or cardiac complications, and no correlation between ECG abnormalities and cardiovascular complications.
ECG findings were consistent with previous reports and indicate that non-specific abnormalities are common in SMA, but are not associated with any significant cardiovascular complications. Although ECG findings consistent with atrial and ventricular chamber enlargement were found in our study (16%), atrial or ventricular dilation has not been reported in echocardiograms. This discrepancy and the presence of baseline irregularities makes ECG interpretation difficult, and it is not clear that the heart is involved in SMA.
Hereditary Motor & Sensory Neuropathy, Types I and II (HMSN): In 47 patients, 14 (30%) of the initial ECGs were reported as abnormal. The most frequent abnormality was abnormal Q waves (32%).
Only 7% had a history of cardiovascular complications. There was no age or disease duration effect on either ECG abnormalities or cardiac complications, and no correlation between ECG abnormalities and cardiovascular complications. Previous studies have also shown a low incidence of cardiac involvement and indicate that the heart is probably not involved in HMSN.
Duchenne Muscular Dystrophy (DMD): In 91 patients, 72 (79%) of the initial ECGs were reported as abnormal. The most frequent abnormalities were abnormal Q waves (63%), resting tachycardia (25%), increased R/S ratio in V1 (25%), infranodal conduction defects (22%) and prolonged Qtc (69%). When analyzed by ages 13 and below and 14 and above years, a significant age and disease duration increase was found in the frequency of resting tachycardia, abnormal R/S ratio, infranodal conduction defects, and the presence of any ECG abnormality (91%). Abnormalities were found as early as three years of age. Deep lateral Q waves, elevated ST segments, and poor progression of R waves were the earliest manifestations. Abnormal R/S ratio was the next finding most likely to occur, and resting tachycardia and conduction defects appeared later.
Only 30%, however, had a history of cardiovascular complications which were also age related. Of those with clinical symptoms, 67% were 16 years of age or older, 24% were ages 11-15 years, and only 9% were ten years old or younger. There was no relationship between ECG abnormality and cardiovascular complications.
The type of abnormalities found in this study were similar to those reported by other investigators although the frequency of shortened PR intervals was less. The early appearance and progression of ECG abnormalities with age has also been previously reported by others. In spite of significant ECG abnormalities, a relatively low frequency of individuals with DMD in this and other studies had a history of clinical cardiovascular complications. The myocardial impairment apparently remains clinically silent until late in the course of the disease, possibly due to the absence of exertional dyspnea secondary to lack of physical activity. Death has, however, been attributed to congestive heart failure in as many as 40-50% of patients with DMD by some investigators.
Becker's Muscular Dystrophy (BMD): In 15 patients, 11 (73%) of the initial ECGs were reported as abnormal. The most frequent abnormalities were abnormal Q waves (60%), left ventricular hypertrophy (40%), increased R/S ratio in V1 (20%), night ventricular hypertrophy (20%), and infranodal conduction defects (15%).
Twenty-five percent had a history of cardiovascular complications. There was no age or disease duration effect on either ECG abnormalities or cardiac complications, and no relationship between ECG abnormalities and cardiovascular complications.
The findings in our study are consistent with studies reported by other investigators, including a pattern of occasional life-threatening cardiac involvement. A significant number of BMD individuals develop cardiac disease, and the rate of progression of cardiac failure may be more rapid than the progression of the skeletal muscle weakness.
Although not included in our study, Emery-Dreifuss muscular dystrophy, also a rare X-linked recessive dystrophy, is well known to have clinically significant heart involvement with marked sinus node impulse abnormality. In one study of 17 individuals, all had severe cardiac arrhythmia, usually a persistent atrial paralysis. Bradycardia and syncope frequently occur and occasionally result in cerebral emboli and stroke. A permanent cardiac pacemaker is required when bradycardia and syncope occur.
Facioscapulohumeral Dystrophy (FSHD): In 32 patients, 24 (74%) of the initial ECGs were reported as abnormal. The most frequent abnormalities were resting bradycardia (38%), abnormal Q waves (25%), increased R/S ratio in V1 (25%), and infranodal conduction defects (22%). Sixty nine percent of the abnormal ECGs occurred in individuals with a disease duration greater than 15 years.
Twenty five percent had a history of cardiovascular complications. There was no age or disease duration effect, and no correlation between complications and ECG findings.
The few reports of cardiac function in FSHD by other investigators indicated that significant clinical cardiac involvement is unusual except for occasional atrial paralysis and A-V conduction defects. The clinical significance of the 25% history of cardiac complications is unknown, and the electrical problems found on ECG are unlikely to cause these complaints and are usually benign. The disease is not associated with cardiac muscle failure.
Myotonic Muscular Dystrophy (MMD): In 75 patients with non-congenital MMD, 55 (74%) of the initial ECGs were reported as abnormal. The most frequent findings were infranodal conduction defects (57%), widened QRS intervals (37%), abnormal Q waves (36%) and prolonged PR intervals (33%). Twenty-nine (39%) had a history of cardiovascular complications. While there was no age or disease duration effect on the ECGs, 68% of the individuals with complications had a disease duration greater than 15 years and 92% of these had abnormal ECGs.
In 16 congenital MMD patients, 14(87%) of the initial ECGs were reported as abnormal. The most frequent abnormalities were similar to those found in the non-congenital MMD group. Twenty five percent had a history of cardiovascular complications. There was no age or disease duration effect on either the ECGs or cardiac complications, and no relationship between complications and ECG findings.
Frequent and significant ECG abnormalities in MMD have been extensively reported by other investigators, and our data is consistent with prior studies. Although relatively few individuals show clinical complications, sudden deaths do occur in even young individuals, and bundle of His conduction delays have been reported.
Congenital Myopathy: In 17 patients, 12 (70%) of the initial ECGs were reported as abnormal although most showed minor findings such as non-specific T wave changes and poor R wave progression. The only possibly significant abnormality was abnormal Q waves (47%). Only 9% had a history of cardiovascular complications. There was no age or disease duration effect on either ECG findings or cardiac complications, and no relationship between complications and ECG abnormalities.
The structural congenital myopathies are numerous, do not represent a homogeneous group of muscle diseases, and include the congenital muscular dystrophies. The only significant finding, abnormal q waves, was seen mostly in congenital muscular dystrophy. With the possible exception of the congenital muscular dystrophies, it is doubtful that the heart is involved in the structural congenital myopathies.
Limb Girdle Syndrome (LGS): In 26 pelvifemoral (PF), 19 autosomal recessive muscular dystrophy of childhood (ARMDC) and 11 autosomal dominant late onset (ADLO) patients with LGS, 62% to 73% of the initial ECGs were reported as abnormal. Conduction defects were noted in 15% in PF, 37% in ARMDC, and 18% in ADLO. ADLO patients had the highest percentage of right ventricular hypertrophy, (36%) while 22% of those with ARMDC showed evidence of left atrial enlargement and left ventricular hypertrophy. All three types had a high percentage of abnormal Q waves (16 to 23%).
Only 20% of the patients had a history of cardiovascular complications. There was no age or disease duration effect on either the ECG findings or the clinical cardiac complications, and no correlation between ECG abnormalities and cardiac complications.
Cardiac involvement has only recently been recognized in LGS, but is difficult to interpret due to the several types of LGS and the various types of inheritance. The lack of any relationship between the ECG findings and the clinical cardiac complications as well as the low frequency of the latter, indicates that the electrical abnormalities are usually benign.
Hereditary Spinal Cerebellar Ataxia (HSCA): In 30 patients with HSCA, 19 (63%) of the initial ECGs were reported as abnormal, and all individuals with Friedreich's Ataxia (FA) had abnormal ECGs at some time during the 10 year study. The most frequent abnormalities were tachycardia (33%), bradycardia (20%), increased R/S ratio in V1 (20%) and abnormal Q waves (20%).
Forty three percent had a history of cardiovascular complications. There was no age or disease duration effect on either the ECG findings or the cardiovascular complications, and no correlation between the clinical complications and the ECG abnormalities.
Most of the ECG abnormalities and cardiac complications occurred in the individuals with FA. The cardiomyopathy of FA is well known, and the incidence of terminal congestive heart failure is substantial.
Summary and Management: The significance of a high frequency of ECG abnormalities in most neuromuscular disorders is unknown since the incidence of clinical evidence of cardiac involvement is relatively low, and there is no correlation between cardiovascular complications and ECG findings or a disease duration effect. Furthermore, some of the ECG abnormalities are considered to be relatively benign. This uncertainty about the significance of the electrical findings is compounded by the lack of studies using more sophisticated cardiac tests and pathologic studies in diseases such as SMA, FSHD, and LGS. Significant and clinically important involvement of the heart has, however, been clearly demonstrated by pathologic and other studies in DMD, BMD, EDMD, MMD and FA.
Management, therefore, involves careful periodic follow-up in diseases at high risk, early identification of potentially serious abnormalities, such as conduction defects, and symptomatic treatment.
RRTC Neuromuscular Diseases Staff.
