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Electrocardiographic abnormalities associated with myotonic dystrophy
Clinic al communications
Electrocardiographic associated
with
abnormalities mptonic
dystrophy
Charles A. Payne, M.D.* Joseph C. Greenjield, Jr., M.D.** Bethesda, Md.
S
everal of the neuromuscular disorders havebeen shown to affect organ systems other than skeletal muscle and the nervous system. Among these, myotonic dystrophy,’ pseudohypertrophic muscular dystrophy,2 myasthenia gravis,3 and Friedreich’s ataxia4 are all known to affect the heart. A high incidence of electrocardiographic abnormalities has been found in patients with myotonic dystrophy who otherwise have no clinical evidence of cardiac pathology. In 1950, De Wind and Jones5 collected from the literature and their own observations 98 cases of myotonic dystrophy and noted that the incidence of electrocardiographic abnormalities was 62 per cent. Common among these abnormal findings were a low P wave, a prolonged P-R interval, delayed intraventricular conduction, S-T segment abnormalities, and various arrhythmias. Also, both Evans6 and Spillane’ noted in their patients the frequent occurrence of left axis deviation. Forty-seven patients with documented myotonic dystrophy have been studied by the Medical Neurology Branch of the National Institute of Neurological Diseases and Blindness. This review was undertaken to clarify the incidence and nature of the electrocardiographic abFrom
normalities associated with myotonic dystrophy, and to determine whether clinically significant heart disease exists in these patients. Method
The diagnosis of myotonic dystrophy was established by the following criteria: family history (the disease is strongly dominant), the classic clinical physical features (distal weakness, gonadal atrophy, early balding, cataracts), and the presence of reflex and percussion myotonia. In evidence of addition, electromyographic electrical myotonia and myopathic disease and/or histologic evidence of myopathy by muscle biopsy was present in all patients. Forty-seven patients (32 males and 15 females) who ranged in age from 2 to 61 years satisfied the above-mentioned criteria. The hospital records of each of these were reviewed for evidence of cardiovascular signs or symptoms. A chest roentgenogram was available on each patient. One or more standard twelve-lead electrocardiograms, taken when the patient was not receiving drugs known to alter myocardial conduction (e.g., procaine amide or quinine), were analyzed for each patient. The heart rate, rhythm, P-wave amplitude,
the Medical Neurology Branch, National Institute of Neurological Diseases and Blindness, Branch, National Heart Institute. Clinical Center, National Institutes of Health. Bethesda, Md. Received for publication May 29. 1962. *Present address: Department of Mrdicine, Sertion of NeurrAogy. liniversity of Puerto Rico Schn~nl Juan, Puerto Rico. **Present address: Department of Medicitw, I1uke linivcrsity Mrdical Cvntrr, I~urh~~m, N. C.
436
and
Cardiology
of M?dicinr.
Snll
ECG abnormalities
Fig. 1. Electrocardiogram of a 3%year-old dystrophy, i.e., left axis deviation, prolonged
man, demonstrating several of the abnormalities P-R interval, and S-T segment elevation.
6oi 50
associated with myotonic dystrophy
noted
437
in myotonic
P-R interval, QRS duration, S-T segment elevation, and the Q-T interval were determined. The tables of Ashman and Hull8 were used as the normal standard. The S-T segment was considered to be abnormal if the junction was elevated from the base line more than 1.5 mm. The mean spatial vectors of both QRS and ‘1’ were estimated by the method of Grant.s A mean QRS deviation of -30 degrees or more was defined as left axis deviation.‘” The criteria of Sokolow and ILyon11 were used to determine the presence of left ventricular hypertrophy.
00 h
Results 0
IO
20
DURATION
OF
30 SYMPTOMS
40 -
50
YEARS
Fig. 2. Graph correlating electrocardiographic abnormalities with the age and duration of symptoms.
Fig.
3. Electrocardiogram
of a Z-year-old
boy
with
Twenty-one patients (14 males and 7 females) were found to have electrocardiographic abnormalities, as listed in Table I. Their ages ranged from 2 to 61 years. The
myotonic
dystrophy,
demonstrating
left
axis
deviation.
438
Payne and Greenfield
tracing from one of these patients with multiple electrocardiographic abnormalities is illustrated in Fig. 1. In this group, 1 patient was hypertensive (Case l), 2 had x-ray evidence of minimal cardiomegaly (Cases 1 and 13), and 1 had a history of previous myocardial infarction (Case 1) (see Table I). None of the patients gave a history of congestive heart failure or significant cardiac symptoms. Physical examinations of the heart were unremarkable in all patients, except as mentioned above. No definite relation between the duration of the myotonic symptoms and the presence of electrocardrographic abnormalities was demonstrated (see Fig. 2). The electrocardiogram was abnormal in all 5 patients who were older than 51 years. .
Discussion
The incidence of electrocardiographic left axis deviation in 11 of these patients (23 per cent) is unusually high. In 3 such patients the QRS duration was prolonged
to 0.11 second, and in 2 patients the QRS measured 0.14 second. However, in all of the patients the angle between the mean QRS and T vectors was less than 150 degrees; thus, the conduction defect did not suggest typical left bundle branch block. In 1956, GrantlO proposed that left axis deviation of the mean QRS vector more negative than -30 degrees denotes cardiac pathology and is due to a “parietal block” or conduction defect located in the superior branch of the left bundle. This concept has recently been supported by Samson and Bruce,12 who noted the frequent acute onset of left axis deviation after the use of an aortic valve dilator. These authors postulated that the mechanical injury to the left bundle conduction system in the aortic outflow tract produced the conduction defect. In his pathologic correlation study of left axis deviation, GrantlO noted that when myocardial infarction could be excluded as the cause, the remaining hearts
Table I
Case wez4-
Age (yr.)
Sex
“LOW” P wave
Prolonged P-R
Sinus bradycar&a
Abnormal S-T segment
Left axis deviation
interval
1. 2. 3. 4. .5 . 6. 7. 8. 9. 10. 11. 12. 13. 14.
61 30 30 57 5.5 49 49 19 2 46 38 41 48 43
M F M F F M F F M M M M M F
1.5. 16. 17. 18. 19. 20. 21.
44 5.5 51 38 33 21 46
M M M M F M M
Total
X
x
s s
X
s
s
s s
s
9 s s
Left ventricular hypertrophy
X s s s s s s s s s s as
s s s x x x
X X
4
5
7
3
11
3
QRS duration (sec.) 0.14 0.14 0.10 0.08 0.11 0.08 0.11 0.08 0.08 0.08 0.11 0.08 0.07 0.10
0.08 0.10 0.10 0.08 0.06 0.06 0.06
Comment
“1,ow”
See Fig.
ntrial
pacemaker
3
See Fig. 1 Mean QRS axis - 20” Mean QRS axis - 20” Occasional premature atrial contractions Mean Atria1
QRS axis - 20” fibrillation
ECG abnormalities
demonstrated myocardial fibrosis usually related to diffuse coronary artery disease. In the present group, coronary artery disease as the only cause for the left axis deviation is unlikely, since 5 of these patients were under 40 years of age, and 1 was only 2 years old. Numerous possibilities could account for the conduction abnormality noted in these patients. Focal pathology of the Purkinje network, myocardial damage, biochemical changes of the muscle proteins, and physiologic alterations in the conduction properties in the cell membrane have all been suggested, but a satisfactory explanation remains to be found. Because of the strong dominant inheritance and the involvement of multiple systems, a genetically determined biochemical abnormality is currently an attractive hypothesis offered in explanation of the changes in skeletal muscle, and one that also could be applied to abnormalities of cardiac muscle. To our knowledge, no specific pathologic study of the cardiac conduction system in this disease has been published. The published descriptions of pathologic finding in hearts from patients with myotonic dystrophy have usually been nonspecific.13p14Fisch and EvansI and, more recently, Cannon16 have demonstrated a diffuse myocardial fibrosis in 2 patients with myotonic dystrophy. Of particular interest in this group is the 2-year-old patient (Case 9) who was being screened for myotonic dystrophy because of subtle hypotonia and a positive family history. No myotonia had been found clinically and the picture was more suggestive of mental retardation than of primary muscle disease. Because of the electrocardiographic finding of left axis deviation (Fig. 3) in the absence of other evidence of congenital heart disease, further studies were undertaken. A peripheral muscle biopsy revealed myopathic changes, and electromyography revealed electrical myotonia. Thus, the diagnosis in the youngest patient in this group was suggested because of this electrocardiographic abnormality. Other electrocardiographic abnormalities, i.e., low P waves, prolonged P-R intervals, were somewhat less frequent than previously reported. This discrepancy
associated with myotonic dystrophy
439
may be due in part to the use of nlore rigid criteria for abnormality. The incidence of arrhythmias is in agreement with findings reported by others.5 S-T segment elevation was noted in 3 patients. In 1 patient this finding was transient, and in the other 2 it persisted. The etiology of the change in the S-T segment is unknown, but it was not related clinically to acute myocardial injury. Summary
Of 47 patients with myotonic muscular dystrophy, 21 were found to have electrocardiographic abnormalities as determined by application of standard criteria. None was found to have clinical evidence of significant heart disease which could be attributed primarily to the myotonic dystrophy. The most common finding was left axis deviation, which was seen in 11 patients (23 per cent). Other less frequent findings are tabulated (Table I). The finding of left axis deviation in a 2-year-old child who had no evidence of congenital heart disease suggested the diagnosis of myotonic dystrophy. The authors wish to express to Dr. G. Milton Shy and Dr. for their help in the preparation
their appreciation Eugene Braunwald of this manuscript.
REFERENCES 1. Waring, J. J., Ravin, A., and Walker, C. E.: Studies in dystrophia myotonica: clinical features and treatment, Arch. Int. Med. 65:763, 1940. 2. Globus, J. H.: The pathologic findings in heart muscle in progressive muscular dystrophy, Arch. Neural. & Psychiat. 9:50, 1923. 3. Ask-Upmark, E.: Cardiovascular observations in myasthenia gravis and dystrophia myotonica, Acta med. scandinav. 116~502, 1944. 4. Nadas, A. S., Alimurung, M. M., and Sieracki, L. A.: Cardiac manifestations of Friedreich’s ataxia, New England J. Med. 244:239, 1951. 5. De Wind, L. T., and Jones, R. J.: Cardiovascular observations in dystrophia myotonica, J.A.M.A. 144:299, 1950. W.: The heart in myotonia atrophica, 6. Evans, Brit. Heart J. 6:41, 1944. 7. Spillane, J. D.: The heart in myotonia atrophica, Brit. Heart J. 13:343, 1951. 8. Ashman, R., and Hull, E.: Essentials of electrocardiography, ed. 2, New York, 1947, The Macmillan Company. 9. Grant, R. P.: Clinical electrocardiography, The spatial vector approach, New York, 1957, McGraw-Hill Book Co.. Inc. 10. Grant, R. P.: Left axis deviation, Circulation 14:233, 1956.
440
11.
12.
13.
Payne
and Greenfield
Sol~olow, M., alid Lyon, ‘I‘. I’.: ‘l‘he \-entricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads, AM. HEART J. 37:161, 1949. Samson, W. E., and Bruce, R. A%.: Left ventricular parietal block produced by transventricular aortic commissurotomy, AM. HEART J. 63:41, 1962. Black, W. C., and Ravin, A.: Studies in dystrophia myotonica, VII. Autopsy observa-
14.
15.
16.
tions in live cases, Arch. I’ath. 44:176, 1047. Kilpatrick, J. A., and Caughey, J. E.: Changes in the heart in dystrophia myotonica, Australasian Ann. Med. 4:200, 1955. Fisch, C., and Evans, P.: The heart and dystrophia myotonica, New England J. Med. 251:527,1954. Cannon, P. J.: The heart and lungs in myotonic muscular dystrophy, Am. J. Med. 34:765, 1962.
Electrocardiographic associated
with
abnormalities mptonic
dystrophy
Charles A. Payne, M.D.* Joseph C. Greenjield, Jr., M.D.** Bethesda, Md.
S
everal of the neuromuscular disorders havebeen shown to affect organ systems other than skeletal muscle and the nervous system. Among these, myotonic dystrophy,’ pseudohypertrophic muscular dystrophy,2 myasthenia gravis,3 and Friedreich’s ataxia4 are all known to affect the heart. A high incidence of electrocardiographic abnormalities has been found in patients with myotonic dystrophy who otherwise have no clinical evidence of cardiac pathology. In 1950, De Wind and Jones5 collected from the literature and their own observations 98 cases of myotonic dystrophy and noted that the incidence of electrocardiographic abnormalities was 62 per cent. Common among these abnormal findings were a low P wave, a prolonged P-R interval, delayed intraventricular conduction, S-T segment abnormalities, and various arrhythmias. Also, both Evans6 and Spillane’ noted in their patients the frequent occurrence of left axis deviation. Forty-seven patients with documented myotonic dystrophy have been studied by the Medical Neurology Branch of the National Institute of Neurological Diseases and Blindness. This review was undertaken to clarify the incidence and nature of the electrocardiographic abFrom
normalities associated with myotonic dystrophy, and to determine whether clinically significant heart disease exists in these patients. Method
The diagnosis of myotonic dystrophy was established by the following criteria: family history (the disease is strongly dominant), the classic clinical physical features (distal weakness, gonadal atrophy, early balding, cataracts), and the presence of reflex and percussion myotonia. In evidence of addition, electromyographic electrical myotonia and myopathic disease and/or histologic evidence of myopathy by muscle biopsy was present in all patients. Forty-seven patients (32 males and 15 females) who ranged in age from 2 to 61 years satisfied the above-mentioned criteria. The hospital records of each of these were reviewed for evidence of cardiovascular signs or symptoms. A chest roentgenogram was available on each patient. One or more standard twelve-lead electrocardiograms, taken when the patient was not receiving drugs known to alter myocardial conduction (e.g., procaine amide or quinine), were analyzed for each patient. The heart rate, rhythm, P-wave amplitude,
the Medical Neurology Branch, National Institute of Neurological Diseases and Blindness, Branch, National Heart Institute. Clinical Center, National Institutes of Health. Bethesda, Md. Received for publication May 29. 1962. *Present address: Department of Mrdicine, Sertion of NeurrAogy. liniversity of Puerto Rico Schn~nl Juan, Puerto Rico. **Present address: Department of Medicitw, I1uke linivcrsity Mrdical Cvntrr, I~urh~~m, N. C.
436
and
Cardiology
of M?dicinr.
Snll
ECG abnormalities
Fig. 1. Electrocardiogram of a 3%year-old dystrophy, i.e., left axis deviation, prolonged
man, demonstrating several of the abnormalities P-R interval, and S-T segment elevation.
6oi 50
associated with myotonic dystrophy
noted
437
in myotonic
P-R interval, QRS duration, S-T segment elevation, and the Q-T interval were determined. The tables of Ashman and Hull8 were used as the normal standard. The S-T segment was considered to be abnormal if the junction was elevated from the base line more than 1.5 mm. The mean spatial vectors of both QRS and ‘1’ were estimated by the method of Grant.s A mean QRS deviation of -30 degrees or more was defined as left axis deviation.‘” The criteria of Sokolow and ILyon11 were used to determine the presence of left ventricular hypertrophy.
00 h
Results 0
IO
20
DURATION
OF
30 SYMPTOMS
40 -
50
YEARS
Fig. 2. Graph correlating electrocardiographic abnormalities with the age and duration of symptoms.
Fig.
3. Electrocardiogram
of a Z-year-old
boy
with
Twenty-one patients (14 males and 7 females) were found to have electrocardiographic abnormalities, as listed in Table I. Their ages ranged from 2 to 61 years. The
myotonic
dystrophy,
demonstrating
left
axis
deviation.
438
Payne and Greenfield
tracing from one of these patients with multiple electrocardiographic abnormalities is illustrated in Fig. 1. In this group, 1 patient was hypertensive (Case l), 2 had x-ray evidence of minimal cardiomegaly (Cases 1 and 13), and 1 had a history of previous myocardial infarction (Case 1) (see Table I). None of the patients gave a history of congestive heart failure or significant cardiac symptoms. Physical examinations of the heart were unremarkable in all patients, except as mentioned above. No definite relation between the duration of the myotonic symptoms and the presence of electrocardrographic abnormalities was demonstrated (see Fig. 2). The electrocardiogram was abnormal in all 5 patients who were older than 51 years. .
Discussion
The incidence of electrocardiographic left axis deviation in 11 of these patients (23 per cent) is unusually high. In 3 such patients the QRS duration was prolonged
to 0.11 second, and in 2 patients the QRS measured 0.14 second. However, in all of the patients the angle between the mean QRS and T vectors was less than 150 degrees; thus, the conduction defect did not suggest typical left bundle branch block. In 1956, GrantlO proposed that left axis deviation of the mean QRS vector more negative than -30 degrees denotes cardiac pathology and is due to a “parietal block” or conduction defect located in the superior branch of the left bundle. This concept has recently been supported by Samson and Bruce,12 who noted the frequent acute onset of left axis deviation after the use of an aortic valve dilator. These authors postulated that the mechanical injury to the left bundle conduction system in the aortic outflow tract produced the conduction defect. In his pathologic correlation study of left axis deviation, GrantlO noted that when myocardial infarction could be excluded as the cause, the remaining hearts
Table I
Case wez4-
Age (yr.)
Sex
“LOW” P wave
Prolonged P-R
Sinus bradycar&a
Abnormal S-T segment
Left axis deviation
interval
1. 2. 3. 4. .5 . 6. 7. 8. 9. 10. 11. 12. 13. 14.
61 30 30 57 5.5 49 49 19 2 46 38 41 48 43
M F M F F M F F M M M M M F
1.5. 16. 17. 18. 19. 20. 21.
44 5.5 51 38 33 21 46
M M M M F M M
Total
X
x
s s
X
s
s
s s
s
9 s s
Left ventricular hypertrophy
X s s s s s s s s s s as
s s s x x x
X X
4
5
7
3
11
3
QRS duration (sec.) 0.14 0.14 0.10 0.08 0.11 0.08 0.11 0.08 0.08 0.08 0.11 0.08 0.07 0.10
0.08 0.10 0.10 0.08 0.06 0.06 0.06
Comment
“1,ow”
See Fig.
ntrial
pacemaker
3
See Fig. 1 Mean QRS axis - 20” Mean QRS axis - 20” Occasional premature atrial contractions Mean Atria1
QRS axis - 20” fibrillation
ECG abnormalities
demonstrated myocardial fibrosis usually related to diffuse coronary artery disease. In the present group, coronary artery disease as the only cause for the left axis deviation is unlikely, since 5 of these patients were under 40 years of age, and 1 was only 2 years old. Numerous possibilities could account for the conduction abnormality noted in these patients. Focal pathology of the Purkinje network, myocardial damage, biochemical changes of the muscle proteins, and physiologic alterations in the conduction properties in the cell membrane have all been suggested, but a satisfactory explanation remains to be found. Because of the strong dominant inheritance and the involvement of multiple systems, a genetically determined biochemical abnormality is currently an attractive hypothesis offered in explanation of the changes in skeletal muscle, and one that also could be applied to abnormalities of cardiac muscle. To our knowledge, no specific pathologic study of the cardiac conduction system in this disease has been published. The published descriptions of pathologic finding in hearts from patients with myotonic dystrophy have usually been nonspecific.13p14Fisch and EvansI and, more recently, Cannon16 have demonstrated a diffuse myocardial fibrosis in 2 patients with myotonic dystrophy. Of particular interest in this group is the 2-year-old patient (Case 9) who was being screened for myotonic dystrophy because of subtle hypotonia and a positive family history. No myotonia had been found clinically and the picture was more suggestive of mental retardation than of primary muscle disease. Because of the electrocardiographic finding of left axis deviation (Fig. 3) in the absence of other evidence of congenital heart disease, further studies were undertaken. A peripheral muscle biopsy revealed myopathic changes, and electromyography revealed electrical myotonia. Thus, the diagnosis in the youngest patient in this group was suggested because of this electrocardiographic abnormality. Other electrocardiographic abnormalities, i.e., low P waves, prolonged P-R intervals, were somewhat less frequent than previously reported. This discrepancy
associated with myotonic dystrophy
439
may be due in part to the use of nlore rigid criteria for abnormality. The incidence of arrhythmias is in agreement with findings reported by others.5 S-T segment elevation was noted in 3 patients. In 1 patient this finding was transient, and in the other 2 it persisted. The etiology of the change in the S-T segment is unknown, but it was not related clinically to acute myocardial injury. Summary
Of 47 patients with myotonic muscular dystrophy, 21 were found to have electrocardiographic abnormalities as determined by application of standard criteria. None was found to have clinical evidence of significant heart disease which could be attributed primarily to the myotonic dystrophy. The most common finding was left axis deviation, which was seen in 11 patients (23 per cent). Other less frequent findings are tabulated (Table I). The finding of left axis deviation in a 2-year-old child who had no evidence of congenital heart disease suggested the diagnosis of myotonic dystrophy. The authors wish to express to Dr. G. Milton Shy and Dr. for their help in the preparation
their appreciation Eugene Braunwald of this manuscript.
REFERENCES 1. Waring, J. J., Ravin, A., and Walker, C. E.: Studies in dystrophia myotonica: clinical features and treatment, Arch. Int. Med. 65:763, 1940. 2. Globus, J. H.: The pathologic findings in heart muscle in progressive muscular dystrophy, Arch. Neural. & Psychiat. 9:50, 1923. 3. Ask-Upmark, E.: Cardiovascular observations in myasthenia gravis and dystrophia myotonica, Acta med. scandinav. 116~502, 1944. 4. Nadas, A. S., Alimurung, M. M., and Sieracki, L. A.: Cardiac manifestations of Friedreich’s ataxia, New England J. Med. 244:239, 1951. 5. De Wind, L. T., and Jones, R. J.: Cardiovascular observations in dystrophia myotonica, J.A.M.A. 144:299, 1950. W.: The heart in myotonia atrophica, 6. Evans, Brit. Heart J. 6:41, 1944. 7. Spillane, J. D.: The heart in myotonia atrophica, Brit. Heart J. 13:343, 1951. 8. Ashman, R., and Hull, E.: Essentials of electrocardiography, ed. 2, New York, 1947, The Macmillan Company. 9. Grant, R. P.: Clinical electrocardiography, The spatial vector approach, New York, 1957, McGraw-Hill Book Co.. Inc. 10. Grant, R. P.: Left axis deviation, Circulation 14:233, 1956.
440
11.
12.
13.
Payne
and Greenfield
Sol~olow, M., alid Lyon, ‘I‘. I’.: ‘l‘he \-entricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads, AM. HEART J. 37:161, 1949. Samson, W. E., and Bruce, R. A%.: Left ventricular parietal block produced by transventricular aortic commissurotomy, AM. HEART J. 63:41, 1962. Black, W. C., and Ravin, A.: Studies in dystrophia myotonica, VII. Autopsy observa-
14.
15.
16.
tions in live cases, Arch. I’ath. 44:176, 1047. Kilpatrick, J. A., and Caughey, J. E.: Changes in the heart in dystrophia myotonica, Australasian Ann. Med. 4:200, 1955. Fisch, C., and Evans, P.: The heart and dystrophia myotonica, New England J. Med. 251:527,1954. Cannon, P. J.: The heart and lungs in myotonic muscular dystrophy, Am. J. Med. 34:765, 1962.