Antisignal Recognition Particle Antibodies–Related Cardiomyopathy
A 63-year-old woman was referred to our center for the workup of a 6-month history of diffuse myalgia and severe proximal weakness. Physical examination did not find any sign of heart failure. The patient had a medical history of diabetes mellitus. Serum creatine kinase and aldolase levels were increased at 2262 U/L (normal <195 U/L) and 19.9 U/L (normal <7.6 U/L), respectively. ECG showed sinus rhythm at 91 beats per minute with frequent ventricular extrasystoles and normal repolarization. Muscle biopsy of the quadriceps revealed necrotizing myopathy (Figure 1A) and antisignal recognition particle (SRP) antibodies were identified in serum (Figure 1B), consistent with the diagnosis of anti-SRP necrotizing myopathy. Cardiac involvement was documented at diagnosis with increased troponin level at 451 pg/mL (normal <14 pg/mL), and transmural gadolinium enhancement and hypokinesia of the anteroseptal wall on cardiac magnetic resonance (CMR) imaging (Movie I in the online-only Data Supplement). Coronary angiography was normal. The patient received 1 mg/kg/d of prednisone, plasma exchanges, and rituximab with a good efficacy. Clinical and biological relapse occurred 5 months later, leading to adjunction of methotrexate with a remission of the disease.
Six months later, after discontinuating all treatments by herself, she presented a new relapse of myopathy with proximal weakness, chest pain, and increased serum creatine kinase (1710 U/L) and troponin levels (616 pg/mL). ECG remained stable with sinus rhythm, flattened T waves in apical and lateral regions, and frequent ventricular extrasystoles (Figure 2A and 2B). Cardiac ultrasonography disclosed mild global hypokinesia predominating in anterior and septal territories with 40% left ventricular ejection fraction (Movies II and III in the online-only Data Supplement) associated with septal thickening and infiltration (Figure 3A and 3B) and transmural infiltration of anteroseptal wall (Figure 3C). CMR showed severe global hypokinesia with 23% left ventricular ejection fraction (Movie IV), with an early and late transmural gadolinium enhancement of the anterolateral and anteroseptal walls (Figure 4A and 4B and Movie V in the online-only Data Supplement), associated with circumferential subendocardial enhancement and pericardial effusion (Figure 3C). Combination therapy with rituximab, prednisone, and methotrexate was reintroduced, with an improvement of muscle proximal weakness and the normalization of creatine kinase (145 U/L) and troponine (<14 pg/mL) levels.
Cardiac involvement is recognized as a major clinical manifestation and 1 of the most frequent causes of death in patients with inflammatory or necrotizing myopathies, although its actual frequency is still uncertain, ranging from 6 to 75%.1,2 Anti-SRP antibodies represent one of the muscle-specific autoantibodies, and was associated in previous studies with a more acute and severe form of necrotizing myopathy and more frequent cardiac involvement.3 This particular form of myopathy is characterized by a necrotizing myopathy with regenerating and degenerating fibers contrasting with the absence of inflammatory infiltrates. In contrast to these earlier studies, recent findings revealed that the frequency of cardiac involvement did not differ between patients with necrotizing myopathy associated with anti-SRP antibodies and those with other inflammatory myopathies.4 However, no description of the specific cardiac involvement in patients with anti-SRP necrotizing myopathy is available in the literature. In the present case, we report for the first time findings from cardiac ultrasonography and CMR imaging in a patient with anti-SRP necrotizing myopathy, showing a severe specific cardiomyopathy with severe global hypokinesia, early and late transmural gadolinium enhancement of the anterolateral and anteroseptal wall, and circumferential subendocardial enhancement. Transmural infarction is usually associated with atherosclerosis involving a major coronary artery, what was excluded in the present case as indicated by normal coronary angiography. In contrast, this transmural involvement could be the consequence of the necrosis of myocardial fibers that could lead to congestive heart failure or conduction disturbances. In conclusion, this case illustrates the specific and severe cardiomyopathy that can be observed in patients with anti-SRP necrotizing myopathy, characterized by severe global hypokinesia and transmural myocardial infiltration, and the importance of considering this disorder in the differential diagnosis of myocardial pathology with transmural infiltration and necrosis.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.112.118877/-/DC1.
- © 2013 American Heart Association, Inc.