Acute cardiac complication in a patient with antimitochondrial M2 antibody-positive myositis on immunosuppressive therapy

Abstract

As the emerging disease concept of antimitochondrial M2 antibody (AMA-M2)-positive myositis gains wider recognition, reports of its cardiac complications are increasing. However, the clinical course and optimal management of cardiac involvements in patients with AMA-M2-positive myositis remain unclear. We report the case of a 53-year-old male with AMA-M2-positive myositis who had been receiving immunosuppressive therapy for four years. He presented with cardiogenic shock with an atypical clinical course that responded to corticosteroid pulse therapy. This case report provides valuable insights into the clinical course and potential treatment option for cardiac involvement in patients with AMA-M2-positive myositis.

Learning objectives

This case highlights the unique clinical course of cardiac involvement in a patient with antimitochondrial M2 antibody-positive myositis under long-term immunosuppressive therapy, and suggests the potential efficacy of corticosteroid pulse therapy in the setting of acute exacerbations. Physicians should consider abrupt cardiac complications even during maintenance therapy. Rapid recognition and aggressive steroid treatment may yield favorable outcomes even in these complex cases.

Introduction

Antimitochondrial M2 antibody (AMA-M2) is a diagnostic biomarker for primary biliary cholangitis (PBC). Some studies have shown that approximately 10% of patients with idiopathic inflammatory myositis also presented AMA-M2 positive even without the diagnosis of PBC [1], [2]. AMA-M2-positive myositis is characterized by a high prevalence of cardiac involvements, including heart failure, left ventricular dysfunction and atrial/ventricular arrhythmias, which is reported as high as 30–50% [1], [2]. Therefore, as suggested in some case reports, there are increasing clinical settings where cardiologists need to tackle cardiac complications in patients with AMA-M2-positive myositis [3], [4]. However, the cardiac features, clinical course, and treatment of this condition remain unknown.

Here we present a case of AMA-M2-positive myositis complicated by cardiogenic shock despite ongoing immunosuppressive therapy over a follow-up period of 4 years.

Case report

A 53-year-old man presented to our hospital with dyspnea and anorexia. He had a history of heart failure hospitalization at the age of 49 years. Left ventricular ejection fraction (LVEF) was preserved, and atrial fibrillation was considered the cause of heart failure. Six months after the hospitalization, he developed generalized arthralgia and myalgia in both lower limbs, leading to referral to the rheumatology department at our hospital. Blood tests showed an elevated creatinine kinase level (469 IU/L), and following a comprehensive work-up including a muscle biopsy, he was diagnosed with AMA-M2-positive myositis. He was referred to our cardiovascular medicine department for further cardiac evaluation. Echocardiography revealed preserved LVEF of 63% with hypokinesis in the anterior wall. Cardiac magnetic resonance imaging (CMR) demonstrated delayed contrast enhancement (late gadolinium enhancement; LGE) predominantly in the epicardial side of the anterior wall (Fig. 1A). Right heart catheterization (RHC) showed no pulmonary hypertension and preserved cardiac index (CI) of 3.0 L/min/m². The myocardial biopsy revealed trivial fibrosis and slight lymphocytic infiltration. Treatment with prednisolone (PSL) at a dose of 60 mg and tacrolimus for myositis were initiated, which promptly improved his symptoms. With PSL tapered to 5 mg, he remained asymptomatic until the age of 53 years.

Fig. 1.

Cardiac MRI findings showing LGE 4 years prior (A), LGE during the current hospitalization (B), and T2 mappings and native T2 values during the current hospitalization (C).

Cardiac MRI revealed more extensive LGE predominantly in the anterior and partly transmural compared to 4 years prior (A and B), and furthermore it revealed a prolongation of T2 relaxation time in whole myocardium (C), which satisfied the diagnostic criteria of myocarditis.

LGE, late gadolinium enhancement; MRI, magnetic resonance imaging.

He developed a wet cough and fever, two weeks after which he felt dyspnea and anorexia. On the first hospital visit, he was stable with a C-reactive protein (CRP) level of 1.08 mg/dL, and chest computed tomography (CT) showed ground-glass opacities in the lower lungs, diagnosed as pneumonia. Antibiotics were prescribed and he returned home, but, that night, his dyspnea worsened, leading to his transfer to the emergency room. Vital signs were as follows: body temperature 36.6 °C, blood pressure 112/81 mmHg, heart rate 118/min, respiratory rate 36/min, and oxygen saturation 97% (4 L/min mask). Blood tests revealed elevated levels of aminotransferases, creatinine, N-terminal pro–B-type natriuretic peptide (NT-pro BNP), and CRP, all of which dramatically changed from the previous day (Table 1). The chest CT showed bilateral lung ground-glass opacity but no pleural effusion.

Table 1.

Trajectories of laboratory findings, right heart catheterization, and vital signs during hospitalization.

Evaluated items	Day
	X-1	X	X + 6	X + 13	X + 27	X + 40	X + 61
Laboratory findings
White blood cell, /μL	8200	15,800	8500	10,900	15,400	9000	9500
Hemoglobin, g/dL	14.2	15.2	13.9	11.7	12.9	11.6	11.6
Platelet, 104/μL	26.5	25.6	12.1	12.0	10.5	79	70
Aspartate aminotransferase, IU/L	28	7826	263	48	39	45	36
Alanine aminotransferase, IU/L	13	2822	866	103	80	76	56
γ-Glutamyl transpeptidase, IU/L	39	86	125	84	221	195	278
Lactate dehydrogenase, IU/L	314	8435		466	467	543	574
Creatine phosphokinase, IU/L	173	322	180	100	43	78	54
Total protein, g/dL	6.9	6.8	6.2	5.2	5.4	5.1	5.6
Albumin, g/dL	3.8	3.8	3.1	2.7	3.3	3.1	3.5
Blood urea nitrogen, mg/dL	18	37	88	47	39	28	25
Creatinine, mg/dL	1.24	2.68	2.82	1.39	0.88	0.64	0.66
Estimated glomerular filtration rate, ml/min/1.73m2	49.1	21.1	20	43.3	71.4	101.2	97.8
Sodium, mEq/L	140	134	138	138	140	138	145
Potassium, mEq/L	4.4	6.1	4.4	3.8	4.5	3.9	4.2
C-reactive protein, mg/dL	1.08	1.72	2.17	2.51	0.08	104	106
NT-pro BNP, pg/mL		3332	5690	4472	1895	5081	3270
Troponin T, pg/mL			0.069		0.074	0.280	0.060
Right Heart Catheterization				(X + 12)
PAWP, mmHg				41		16
Mean PAP, mmHg				41		21
Mean RAP, mmHg				20		10
Cardiac output, L/min				2.52		4.67
Cardiac index, L/min/m2				1.29		2.59
Vital signs
Body temperature, °C		36.6	36.1	36.2	36.0	36.3	36.2
Blood pressure, mmHg		112/81	117/87	112/86	90/62	97/71	103/67
Heart rate, /min		118	82	100	70	78	74
Respiratory rate, /min		36	14	14	16	14	14
Oxygen saturation, %		97 (4 L/min mask)	96 (2 L/min nasal)	96 (2 L/min nasal)	98 (room air)	96 (room air)	98 (room air)

NT-pro BNP, N-terminal pro–B-type natriuretic peptide; PAWP, pulmonary artery wedge pressure; PAP, pulmonary artery pressure; RAP, right atrial pressure.

Suspected of worsening pneumonia, he was admitted to the hospital and started on supplemental fluids resuscitation and intravenous antibiotics administration. However, blood test demonstrated persistently-elevated creatinine levels with improved aminotransferases, and his shortness of breath remained with deterioration by slight exercise. An echocardiogram revealed a reduced LVEF of 31% and pulmonary hypertension [estimated pulmonary artery pressure (PAP) 51 mmHg], prompting transfer to our department. Electrocardiogram showed atrial fibrillation, complete right bundle branch block, and left axis deviation. Coronary angiography performed on day 13 of admission revealed no significant coronary artery stenosis, while RHC showed high pulmonary artery wedge pressure (PAWP) of 41 mmHg, mean PAP of 41 mmHg, and low CI of 1.3 L/min/m² (Table 1).

Despite having a blood pressure of 112/86 mmHg, he presented with cardiogenic shock, characterized by low cardiac output, markedly elevated PAWP, and ongoing end-organ dysfunction. He was transferred to the cardiac care unit, where an intra-aortic balloon pump (IABP) and inotropes were initiated. Upon consultation with the rheumatology department, one course of intravenous methylprednisolone (mPSL) pulse therapy (1000 mg for 3 days) with subsequent high-dose PSL treatment was administered, considering that AMA-M2-positive myositis could have caused LV dysfunction. Great diuretic response was observed with prompt improvement in his symptoms of heart failure and laboratory findings including creatinine levels (Table 1). Following decongestion, he was weaned off from IABP on day 24 of admission and discontinued inotropic drugs on day 27.

CMR revealed more extensive LGE predominantly in the anterior and partly transmural compared to 4 years prior, and furthermore it revealed a prolongation of T2 relaxation time in whole myocardium (Fig. 1B and C), which satisfied the diagnostic criteria of myocarditis. Myocardial biopsy showed moderate to severe fibrosis in the interstitium and mild CD3 lymphocytic infiltration (CD4-positive cells ≥CD8-positive cells) without CD20-positive cells (Fig. 2). Follow-up RHC showed improved intracardiac pressure including PAWP and mean PAP, and increased cardiac output under no cardiac support. Blood tests showed a temporary decrease in the level of NT-pro BNP after the intravenous mPSL pulse therapy, but it began to rise during the process of tapering PSL. Troponin T levels also remained high during the hospitalization (Table 1). Despite these elevations in cardiac biomarkers, no signs/symptoms of heart failure were observed, and after PSL being tapered at the dose of 40 mg, he was discharged on Day 83.

Fig. 2.

Pathology images and immunohistochemical staining of myocardial biopsy samples prior to corticosteroid pulse therapy.

(A) Hematoxylin and eosin (HE) staining showed mild lymphocytic infiltration, while (B) Azan staining revealed marked fibrosis. Immunohistochemical staining demonstrated T-cell infiltration, with a predominance of CD4-positive cells (C) over CD8-positive cells (D).

At the time of discharge, echocardiography was reassessed, showing improvement in LVEF to 45%. After discharge, his heart failure symptoms remained stable, and NT-pro BNP levels remained unchanged during the follow-up period, with a value of 2205 pg/mL at three months after discharge.

Discussion

This case is characterized by two aspects: (1) cardiogenic shock with atypical features, and (2) potential effectiveness of corticosteroid pulse therapy despite maintenance immunosuppressive therapy in a patient with AMA-M2-positive myositis.

The clinical course of this case is consistent with myocarditis, characterized by rapid multiple organ dysfunction within a single day and acute-onset left ventricular failure confirmed by RHC. The presence of preceding symptoms consistent with an upper respiratory tract infection mimics typical viral myocarditis. However, at the emergency room, no symptoms including hypotension or altered level of consciousness were observed, leading to underdiagnosis of cardiac complication. Furthermore, he survived the very acute phase with only fluid resuscitation and intravenous antibiotics administration, although persistent organ dysfunction and high PAWP suggested that he had required earlier hemodynamic support. Despite markedly high PAWP and low CI, the patient maintained normal blood pressure, implying potential hemodynamic compensation from an underlying chronic process. Myocardial biopsy showed mild lymphocyte infiltration only, making classic viral myocarditis unlikely. The tissue pattern—predominantly CD4+ T-cell infiltration and considerable fibrosis—fit autoimmune cardiac involvement. CMR supported myocardial inflammation, and progressive LGE on serial imaging despite immunosuppression indicated ongoing disease activity. Furthermore, the LGE pattern on CMR was similar to that observed four years earlier, suggesting that both cardiac episodes may share a common underlying etiology. Taken together, these findings suggest that the clinical picture is not merely de-novo acute myocarditis, but may represent an acute exacerbation of immune-mediated chronic cardiomyopathy.

Although there have been a few studies focusing on the clinical course of cardiac complications in AMA-M2 positive myocarditis, two case series indicated that cardiac involvement in patients with AMA-M2 positive myositis was characterized by a chronic course [1], [2], which was inconsistent with our case. However, one case with PBC and polymyositis presented myocarditis which recovered from steroid therapy [5], that was similar to our case except for the lack of diagnosis with PBC. A case of AMA-M2-positive myositis reported presentations of cardiac arrest and refractory ventricular arrythmia comorbid heart failure [6], which may partly account for the risk of acute cardiac complications.

Despite three years of low-dose PSL (5 mg/day) and tacrolimus (5 mg/day) without evidence of myositis symptoms, he finally experienced this acute cardiac complication. The clinical course was similar to some cases in that progressive myocardial damage over several years was observed despite immunosuppressive therapy, even in the absence of myositis symptoms [3], [7]. However, the previous cases presented chronic progressive cardiac dysfunction, which was inconsistent with our case. Furthermore, our case was characterized by the fact that following one course of mPSL pulse therapy approximately two weeks after admission, he could be weaned from cardiac support with improved cardiac function, which was also consistent with previous cases reporting improvement in LVEF after immunosuppressive treatments including initiating high-dose PSL or intravenous steroid pulse therapy [5], [8]. While both of these cases suggested the potential efficacy of steroid therapy in steroid-naïve patients, our case suggested the potential efficacy of mPSL pulse therapy with subsequent high-dose PSL treatment even in patients already taking low-dose PSL and tacrolimus. Notably, NT-pro BNP and troponin T rose during steroid taper, even as weight and symptoms improved, suggesting silent progression. Persistent troponin T elevation in myocarditis usually indicates ongoing inflammation and underscores the need for careful follow-up [9].

Conclusion

We describe a patient with AMA-M2-positive myositis, under long-term immunosuppression, who developed cardiogenic shock and was successfully treated with corticosteroid pulse therapy. Physicians should consider abrupt cardiac complications even during maintenance therapy. Rapid recognition and aggressive steroid treatment may yield favorable outcomes even in these complex cases.

Patient consent statement

Written informed consent was obtained from the patient.

Funding

None.

Previous presentations

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Declaration of competing interest

Authors declare no conflict of interest for this article.