1474
JACC Vol. 14, No. 6
November 15, 1989:14745
Editorial Comment
Coexistence of Skeletal Muscle
Abnormalities in
Cardiomyopathy*
girdle dystrophy. In patients with the former condition,
cardiac dysfunction is usually marked by conduction defects
and occasionally arrhythmias, whereas in the latter, more
heterogeneous group of patients, symptoms and signs of
congestive heart failure as well as cardiac arrhythmias have
been reported (6).
DAVID G. BENDITT,
Several other relatively uncommon but distinct clinical
syndromes exhibit both skeletal and cardiac muscle involvement. For example, type 2 glycogen storage disease (alpha-
ANN DUNNIGAN,
SIMON MILSTEIN,
CONSTANTINOS
Minneapolis,
MD, FACC,
MD,
MD,
LIMAS,
MD
Minnesota
Caforio et al. (1) in this issue of the Journal provide additional evidence for the concept that concomitant skeletal
muscle abnormalities are frequent in patients with cardiomyopathy. Their study provides indirect but suggestive support
for the view that the skeletal muscle findings are not attributable to a neurogenic origin, inadequate systemic blood
flow or disuse atrophy due to cardiac failure. Consequently,
if their observations and those of others (2-5) are confirmed
in larger patient groups, cardiomyopathy may ultimately be
considered to be part of a spectrum of generalized myopathies. As a corollary, if future studies indicate that the
observed skeletal muscle abnormalities are specific for cardiomyopathy and do not routinely accompany cardiac disease of other origins (e.g., ischemic or valvular disease),
then skeletal muscle biopsy or quantitative electromyography may prove a useful adjunctive diagnostic aid in patients
who have otherwise unexplained cardiac findings (e.g.,
cardiac arrhythmias in association with an “apparently
normal heart”).
Syndromes exhibiting concomitant skeletal and cardiac
myopathy. The best recognized associations of skeletal
muscle and cardiac dysfunction are the genetically determined muscular dystrophies. For example, cardiomyopathy
is nearly always present in patients with Duchenne muscular
dystrophy (6), although cardiac symptoms are rare until the
terminal stage of this illness. Cardiomyopathic findings are
also associated with both myotonic dystrophy and limb-
*Editorials published in Journal of the AmericanCollegeof Cardiology
reflect the views of the authors and do not necessarily represent the views of
JACC or the American College of Cardiology.
From the Departments of Medicine (Cardiovascular Division) and Pediatrics (Pediatric Cardiology), University of Minnesota Hospital and the
Variety Club Children’s Hospital, Minneapolis, Minnesota. This work was
supported in part by a grant-in-aid to Dr. Benditt from the American Heart
Association, Dallas, Texas.
Address for renrints: David G. Benditt, MD, Box 341, UMHC, University
of Minnesota, Minneapolis, Minnesota 55455.
01989 by the American College of Cardiology
1,4_glucosidase deficiency) is associated with massive accumulation of abnormal glycogen in skeletal and cardiac
muscle. In addition, Friedreich’s ataxia, an autosomal recessive degenerative disorder of the cerebellum and spinal cord,
has been associated with hypertrophic cardiomyopathy (68). In the latter condition, both disturbances of ventricular
function and cardiac arrhythmias contribute importantly to
the late clinical picture. In another group of disorders,
characterized as mitochondrial myopathies (6,9), muscle
biopsy reveals excessively numerous and large or bizarre
mitochondria in association with a variety of biochemical
abnormalities. Kearns-Sayre syndrome, the most widely
recognized of these disorders, includes conduction system
involvement among its many features (10). Similarly, cardiomyopathy has been associated with certain uncommon congenital skeletal muscle myopathies. For example, myotubular myopathy has been associated with a variety of
cardiovascular disturbances including congestive heart failure, right ventricular hypertrophy and arrhythmias.
Association of skeletal myopathy and cardiomyopathy.
Although cardiomyopathy is not usually a prominent presenting feature of patients with neuromuscular disorders,
physicians experienced in the care of these patients have
recognized the possibility of cardiac involvement. In contrast, physicians treating patients with cardiovascular disease generally have not been alert to the possibility that
overt symptomatic cardiomyopathy may be associated with,
and perhaps be a manifestation of, a generalized myopathy.
Nonetheless, several investigators have raised this issue.
For example, in their evaluation of six patients with cardiomyopathy, Shafiq et al. (2) found distinct histochemical and
electron microscopic abnormalities in skeletal muscle, although light microscopic findings were normal. Similarly,
among 11 patients with hypertrophic cardiomyopathy studied by Smith et al. (3), 8 exhibited abnormalities of skeletal
muscle by histochemical or electron microscopic evaluations. Mitochondrial abnormalities ranging from minor ultrastructural changes to prominent mitochondrial proliferation
and structural alterations were present. In addition, increased numbers of lipid droplets were detected in affected
muscle fibers.
Recently, Dunnigan et al. (4) studied histologic and
0735-1097/89/$3.50
BENDITT ET AL.
EDITORIAL COMMENT
JACC Vol. 14, No. 6
November 15, 1989:1474-S
biochemical features of skeletal muscle biopsy specimens in
10 young patients in whom cardiac arrhythmias appeared to
be the initial manifestation of cardiomyopathy. None of the
patients exhibited symptomatic skeletal myopathy, and only
one patient manifested findings of symptomatic left ventricular dysfunction. In all 10 patients, skeletal muscle biopsy
specimens were normal when stained with hematoxylineosin, but were abnormal on electron microscopic assessment. An increased frequency of lipid droplets was uniformly present, with endomysial fibrosis evident in 9 of the
10 cases. In addition, although fasting serum carnitine and
short- and long-chain acylcarnitine concentrations were normal in 9 of the 10 patients, 9 had an apparent decrease in
skeletal muscle long-chain acylcarnitine. The presence of
endomysial fibrosis in these patients suggested that the
skeletal muscle abnormality was relatively long standing and
was not secondary to an acute cardiac process. The increased lipid droplets and decreased skeletal muscle acylcarnitme levels, although nonspecific, suggested the potential for a systemic metabolic defect of lipid utilization.
Subsequently, Dunnigan et al. (5) compared cardiac and
skeletal muscle biopsy specimens in 22 patients with cardiomyopathy; 11 of these patients presented with ventricular
arrhythmias, and the other 11 had symptoms of severe
congestive heart failure. Cardiac biopsy specimens were
abnormal in all 22 patients, and the abnormalities were
comparable in the two groups. Skeletal muscle abnormalities
were widely evident and similar in each subset of patients,
with endomysial fibrosis and increased lipid deposition being
the predominant findings.
Clinical implications. The report by Caforio et al. (1)
again brings to our attention an apparent, but incompletely
understood, concordance of subtle skeletal muscle myopathy in patients with idiopathic cardiomyopathy. It is intriguing to contemplate the concept that common factors,
whether genetic infectious, humoral, immunologic or metabolic, may precipitate the reported cardiac and skeletal
muscle histochemical and histologic abnormalities. However, the limitations of this and previous studies should be
kept in mind: 1) the number of patients studied has been
small, and there has been insufficient comparison with
1475
findings in normal subjects or patients having other forms of
cardiac disease; 2) differences among various reports regarding involvement of type 1 and type 2 fibers need reconciliation; 3) the apparently similar association of skeletal muscle
abnormalities with both dilated and hypertrophic cardiomyopathies, conditions that are conventionally believed to have
different causes, needs clarification.
Finally, the potential contribution of disorderedfatty acid
metabolism needs further study. Whether disordered metab-
olism of this type represents the important functional
disturbance in certain cardiomyopathies or an epiphenomenologic “footprint” indicative of other intracellular
disturbances remains speculative, but it is clearly a subject
of potentially fruitful future research.
References
I. Caforio ALP, Rossi B, Risaliti R, et al. Type 1 fiber abnormalities in
skeletal muscle of patients with hypertrophic and dilated cardiomyopathy: evidence of subclinical myogenic myopathy. J Am Cob Cardiol
1989:14:1464-73.
2.
Shafiq SA, Sande MA, Carruthers RR, Killip T, Milhorat AT. Skeletal
muscle in idiopathic cardiomyopathy. J Neural Sci 1972;15:303-20.
3.
Smith ER, Heffernan LP, Sangalang VE, Vaughan LM, Flemington CS.
Voluntary muscle involvement in hypertrophic cardiomyopathy: a study
of eleven patients. Ann Intern Med 1976;85:566-72.
4.
Dunnigan A, Pierpont ME, Smith SA, Breningstall G, Benditt DG,
Benson DW Jr. Cardiac and skeletal myopathy associated with cardiac
dysrhythmias. Am J Cardiol 1984;53:731-7.
5.
Dunnigan A, Staley MA, Smith SA, et al. Cardiac and skeletal abnormalities in cardiomyopathy: comparison of patients with ventricular tachycardia or congestive heart failure. J Am Coil Cardiol 1987;10:608-18.
6.
Ziter FA, Tyler FH. Neuromuscular disorders. In: Pierpont MEM, Moller
JH, eds. Genetics of Cardiovascular Disease. Boston: Martinus Nijhoff,
1986:24143.
7.
Cote M, Davignon A, Pecko-Drovin K, et al. Cardiological signs and
symptoms in Friedreich’s ataxia. Can J Neural Sci 1976;3:319-21.
8.
Gottdiener JS, Hawley RJ, Maron BJ, Bertorini TF, Engel WK: Characteristics of the cardiac hypertrophy in Friedreich’s ataxia. Am Heart J
1982:103:525-31.
9.
Morgan-HughesJA, Hayes DJ, Clark JB. et al. Mitochondrial encephalomyopathies. Brain 1982;105:553-82.
10. Kearns TP, Sayre GP: Retinitis pigmentosa, external ophthalmotlegia,
and complete heart block: unusual syndrome with histologic study in one
of two cases. Arch Ophthalmol 1958;60:280-9.