Antisignal Recognition Particle Antibodies–Related Cardiomyopathy

Abstract

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 B, Classic indirect immunofluorescence assay on HEp-2 cells in the serum showed a characteristic cytoplasmic staining pattern. Dot-blot analysis of the serum showed specific reactivity against the signal recognition particle (SRP).

Secondary cardiac involvement in anti-SRP-antibody-positive myopathy: an 87-year-old woman with heart failure symptoms as the first clinical presentation

“…In that case, the electrocardiogram demonstrated left ventricular hypokinesis, pericardial effusion, and diastolic dysfunction, similar to that in our case. These three findings can be related to myocarditis with anti-SRP-antibody-positive myopathy, as reported previously [10,11,18,20]. On the basis of these reports, the prevalence of cardiac involvement in anti-SRP-antibodypositive myopathy can be higher than expected.…”

“…We identified six case series reporting on patients with myopericarditis with anti-SRP-antibodies [9][10][11][18][19][20]. Three of the cases showed pericardial effusion like the present case [10,11,18], and two showed diastolic left ventricular dysfunction [18,20].…”

Anti-signal Recognition Particle Antibody-positive Necrotizing Myopathy with Secondary Cardiomyopathy: The First Myocardial Biopsy- and Multimodal Imaging-proven Case

“…We herein report the first myocardial biopsy-proven case of anti-SRP-positive necrotizing myopathy. Previous studies have described various cardiac symptoms in cases of IMNM including chest pain, palpitations, congestive heart failure, as well as electrocardiographic and echocardiographic changes and MRI changes (2,7,9,10). Cardiac fibrosis has also been reported, but no detailed pathological findings were provided (11).…”

Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts

“…One case with SRP-IMNM was complicated by cardiomyopathy, gradually developed heart failure, and is ultimately relieved after heart transplantation ( 52 ). Some case reports and studies suggest that patients with SRP-IMNM are susceptible to subclinical myocardial damage ( 32 , 52 – 55 ). Echocardiogram abnormalities usually appear in SRP-IMNM and account for 61% (25 of 41 patients), most presenting as diastolic dysfunction ( 32 ).…”