According to prevalence estimates for the United States, idiopathic inflammatory myopathies (IIM) affect an estimated 14.0 to 17.4 per 100,000 individuals, although rates vary widely across studies, types of IIM, and populations.1 There are 4 main types of IIM: dermatomyositis, inclusion body myositis, polymyositis, and necrotizing autoimmune myopathy.1 These diseases share the “underlying common manifestation of proximal muscular weakness usually in conjunction with elevated serum muscle enzymes,” wrote the investigators in a review and case series published in the Journal of Clinical Rheumatology.2

In addition, many patients suffer from extramuscular manifestations such as articular, dermatologic, and pulmonary diseases. Cardiac manifestations include congestive heart failure, arrhythmias, and coronary artery disease, among other conditions.1 Results of various studies suggest that cardiovascular disease is the main cause of death in these patients, with associated mortality rates of 14% to 55%.1,3

Treatment of IIM typically involves high-dose corticosteroids as the first-line therapy, often combined with a second agent such as methotrexate, calcineurin inhibitors, or azathioprine.2 Emerging research has indicated that rituximab may be an effective treatment option for refractory cases of IIM, particularly interstitial lung disease and skeletal muscle myositis.2 However, there is a dearth of evidence regarding treatment of refractory cardiac manifestations in IIM with rituximab or other agents. 

In the new paper, the investigators reported on the use of rituximab for refractory cardiac manifestations in 3 patients with IIM who were treated at a single center.2 Each patient received rituximab 1 g intravenously on days 0 and 7 in addition to standard therapies, with subsequent rituximab dosing as needed. In one case, the patient’s myocarditis had resolved as indicated by cardiac magnetic resonance imaging performed 8 months following the initial administration of rituximab. Another patient showed improved left ventricular function (from a 40% to 45% ejection fraction to 58% after initial rituximab dosing). The third patient demonstrated resolution of atrial fibrillation after a second course of rituximab. Sustained treatment response was observed in each case.

Although these results, along with those of several previous case studies “support a role for rituximab in [patients with] IIM complicated by cardiac inflammation, randomized clinical trials are required to confirm these observations,” the researchers concluded.2 “With the available data in the literature, rituximab should be considered as a viable option to treat refractory cardiac manifestations attributed to the inflammatory myopathies.”

Rheumatology Advisor spoke with Jemima Albayda, MD, assistant professor in the division of rheumatology and director of the Musculoskeletal Ultrasound and Injection Clinic at Johns Hopkins University School of Medicine in Baltimore, Maryland, to learn more about cardiac complications in IIM.

Rheumatology Advisor: What are some common cardiac manifestations of IIM, and how is management of these typically approached in clinical practice?

Jemima Albayda, MD: Cardiac manifestations in IIM are still relatively uncommon. As the Journal of Clinical Rheumatology study alludes to, the incidence varies widely per cohort and, generally speaking, clinically apparent heart involvement is quite rare (<10%). Our appreciation for subclinical heart disease has increased mainly because of the availability of more sensitive diagnostic techniques.

The more common manifestations include congestive heart failure, myocarditis, arrhythmias, cardiomyopathy, coronary artery disease, and pericarditis. Typically, treatment for these conditions requires collaboration and co-management with cardiology. If the involvement appears to be inflammatory, as is the case with myocarditis leading to heart failure, aggressive immunosuppression is needed in addition to congestive heart failure treatment. Treatment generally follows as per cardiac indications — such as a pacemaker or defibrillator for arrhythmias and conduction blocks — but the potential for improvement of these manifestations with better control of the inflammatory disease should always be considered. Some manifestations, however, can be the sequelae of prior damage and may not respond as well, and can also be teased out with diagnostic testing such as cardiac magnetic resonance imaging.

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Rheumatology Advisor: What are your thoughts about the recent study pointing to rituximab as a potential treatment for cardiac manifestation in some refractory cases of IIM? 

Dr Albayda: Because these conditions are rare, and cardiac involvement is even rarer, there have been no big studies as yet to guide treatment recommendations.

This study is a case series of patients who had cardiac involvement that improved with rituximab treatment. It is still important to show the efficacy of this medication in select cases, and we have seen this as well in our practice. We have treated patients with cardiomyopathy, myocarditis, congestive heart failure, and conduction blocks with rituximab with sustained efficacy. I think the key here is to use it in refractory cases as standard therapy with steroids and first-line immunosuppression like methotrexate, azathioprine, and mycophenolate mofetil, which has also shown benefit in some cases.

Rheumatology Advisor: What are additional treatment considerations for clinicians treating these patients? 

Dr Albayda: Although cardiac involvement in the inflammatory myopathies is rare, it is a significant cause of morbidity and mortality in this population. As subclinical heart disease is common, screening for heart involvement should be performed via a good history and physical exam. A baseline echocardiogram and electrocardiogram should also be considered, as well as additional cardiology evaluation as indicated.

Rheumatology Advisor: What are remaining research needs pertaining to this topic?

Dr Albayda: There are still many needs in this area. Because cardiac involvement is not routinely assessed in every patient with myositis, we do not know the true prevalence of different cardiac manifestations in all comers. We do not have guidance on how to initially screen for cardiac disease or how to follow it. Furthermore, we do not know how each of these manifestations develop, how they can be prevented, and what the optimal treatment strategy is. 

References

  1. Jayakumar D, Zhang R, Wasserman A, Ash J. Cardiac manifestations in idiopathic inflammatory myopathies: An overview. Card Review. 2019;27(3):131-137.
  2. Motley SA, Sidari A, Hildebrand B, Ward IM. Cardiac manifestations of idiopathic inflammatory myopathy treated with rituximab: A single-center case series and review of the literature [published online July 26, 2019]. J Clin Rheumatol. doi:10.1097/RHU.00000000000011413.     
  3. Oldroyd AGS, Cooper R, Parker B, Bruce IN, New P, Chinoy H. Profile of cardiovascular burden in myositis: A case-control study [abstract]. Arthritis Rheumatol. 2016;68 (suppl 10). https://acrabstracts.org/abstract/profile-of-cardiovascular-burden-in-myositis-a-case-control-study Accessed August 16, 2019.