Cardiac arrest in patients with myalgia and dyspnea is actually not uncommon!

*For medical professionals only, what is the source of recurrent progressive diffuse myalgia, sudden onset seizures, and cardiac arrest? ! 01 First sight - unclear etiology Female, in her 30s, complained of "fatigue, diffuse myalgia, and dyspnea for 2 months, progressively worsening for 1 month" [1]
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 The patient reported having a viral upper respiratory tract infection 3 months ago, and symptoms of fatigue, diffuse myalgia, and dyspnea gradually developed and worsened within 2 months
.

No fever, chills, abdominal pain, nausea, vomiting, constipation and diarrhea
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He was admitted to our hospital, and the physical examination and auxiliary examination were completed: ▌Physical examination: no positive signs were found; ▌laboratory examination: high-sensitivity troponin T (hs-TNT) 130ng/L, N-terminal brain natriuretic peptide precursor ( NT-proBNP) 1667pg/ml, aspartate aminotransferase (AST) 57 U/L, antinuclear antibody (ANA) 1:640, speckled, anti-ribonuclear antibody (anti-RNP)>8.
0, anti Double-stranded DNA (anti-dsDNA), anti-Ro and anti-La antibodies assayed negative
.

Creatine kinase (CK) was not examined
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▌ Imaging examination: chest X-ray: heart enlargement; transthoracic echocardiography (TTE): ejection fraction (EF) of 63% and a small amount of pericardial effusion; cardiac MRI showed diffuse patchy midwall late gadolinium enhancement
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The initial diagnosis was considered to be viral myopericarditis.
In view of the mild symptoms, paracetamol treatment was given, but the treatment effect was not good
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 One month ago, the patient reappeared with persistent chest pain, fatigue, and diffuse myalgia
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Rash, hair loss, mouth ulcers, photosensitivity, arthralgia, and abnormal weight changes were denied
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Denies use of statins
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The examination of the patient was perfected again: ▌Physical examination: sinus tachycardia, grade 3/5 proximal muscle weakness of the limbs
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▌Laboratory tests: leukopenia, CK3619 U/L, hs-TNT 527ng/L, NT-proBNP 3102pg/ml, aldolase 27.
7U/L, AST 142 U/L, alanine aminotransferase (ALT) ) 52 U/L
.

Anti-Scl-70 antibodies, anti-Smith antibodies, C3/C4 complement, and myositis tests including anti-signal recognition particle (SRP) antibodies were all within normal limits
.

Rheumatoid factor was elevated to 17.
0 U/ml and anti-cyclic citrullinated peptide (anti-CCP) IgG/IgA was negative
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▌ Imaging examination: bilateral upper extremity MRI showed diffuse mild myositis in the right deltoid and infraspinatus
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For such a newly admitted patient, what would your initial diagnosis consider? Myositis? However, myositis-related immune markers were all negative
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Myasthenia Gravis? However, the patient's symptoms were mainly myalgia, and there were no typical symptoms of myasthenia gravis
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Also, don't forget the patient's previous heart problems
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So can monism explain it? These questions also revolved around the patient's doctor's mind
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Considering that the patient was a young woman with progressive myalgia, although seroimmune negative, a monistic "immune myositis" explanation was considered
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Therefore, the patient was temporarily given prednisone 80 mg/day for diagnostic treatment
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 02 Treatment - a life-and-death struggle On the fourth day of hospitalization, the patient developed cardiac decompensation due to worsening tachycardia, fever and hypoxemia
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Emergency check of heart failure indicators and related examinations: Heart failure indicators: lactic acidosis, CK5137 U/L, hs-TNT 2999ng/L, NT-proBNP 28 205pg/ml
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ECG showed no ST-segment changes
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Chest radiograph showed new patchy infiltrates and edema
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TTE showed global hypokinesia with reduced EF to 32%
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On the evening of day 4, the patient developed epileptiform activity and was responding with disapproval
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ECG monitoring showed bradycardia to 30 beats/min, followed by cardiac arrest
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 Immediately transfer the patient to the intensive care unit for rescue with vasopressors and intravenous diuretics
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Left and right heart catheterization showed normal filling pressures and a cardiac index as low as 1.
8 L/min
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Intra-aortic balloon pumping (IABP) was initiated and the endocardial myocardium was biopsied
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Steroid therapy was escalated to methylprednisone 1 g/day for 5 days, and intravenous immune globulin (IVIG) was given for 2 days for myositis
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 On day 6, the patient's CK showed a decreasing trend and hemodynamics improved
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Vasopressors were discontinued and dobutamine started
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Endomyocardial biopsy showed mononuclear (lymphocyte and monocyte) myocarditis with active myocyte damage and patchy fibrosis replacing myocytes
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 On day 9, the catheter was extubated, and IABP support was discontinued
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 On day 10, the patient developed heart failure again, with worsening cardiogenic shock, reintubation, repeated IABP support, and resumption of methylprednisone 125 mg every 6 hours
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 Subsequently, the patient's condition gradually stabilized
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On day 13, steroids were de-escalated to prednisone 80 mg/day
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On day 16, deltoid muscle biopsy was performed
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On day 20, the catheter was extubated and dobutamine was discontinued
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Deltoid muscle biopsy results report: less immune inflammatory necrotizing myopathy with patchy major histocompatibility complex (MHC1) expression on muscle fibers
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The necrotic fibers were randomly distributed and the period of necrosis was heterogeneous, including all stages of acute necrosis, myophagy, and regeneration
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Specific features of dermatomyositis, polymyositis, or inclusion body myositis, such as perifascicular atrophy, lymphocytic infiltration in muscle fibers, or marginal vacuoles, were not detected
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On day 24, 1 g of rituximab was started; on days 34-35, IVIG 2 g/kg was used for 2 days despite the use of glucocorticoids because of the tendency of CK to rise
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On the 37th day, he was transferred to the ward
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 During the time when the patient's condition is gradually improving, complete examinations: CT examination: exclude the possibility of tumor; anti-β-hydroxyβ-methylglutaryl-CoA (HMG-CoA) reductase and SRP antibodies are negative; infection tests are negative (withdrawal of empiric antibiotics 10 days after negative infection test): Repeat blood culture, C.
difficile toxin, histoplasma antigen, tuberculosis interferon-gamma release test, respiratory syncytial virus/influenza, HIV and HCV antibody tests all Negative; serology positive for hepatitis B IgG core antibody (starting prophylactic entecavir); on day 52, the second dose of rituximab 1g was injected, and the prednisone dose was gradually reduced to 20mg/day
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She regained full 5/5 of strength in all her muscles except the hip flexors (4/5 bilaterally)
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discharge
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 At follow-up 3 months after discharge, the muscle strength of the limbs was normal, TTE showed the recovery of biventricular function, and the EF was 54%
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 03 The first case was reported, but it is not a rare disease.
With the thrilling diagnosis and treatment process of this patient, we gradually clarified the real cause - idiopathic inflammatory myopathy (IIM)
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 IIM is a heterogeneous family of rare diseases characterized by muscle weakness, elevated muscle enzymes, and inflammatory infiltration in muscle biopsies
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In 2017, the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) proposed the use of a scoring scale to diagnose IIM, which is a major progress in the diagnosis of IIM [2]
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This criterion uses a scoring and weighting approach and can be used when symptoms and signs are not better explained
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 Table 1: EULAR/ACR proposed IIM classification criteria for adults and children [3] ( muscle biopsy)] is defined as the cut-off value for the diagnosis of IIM
.

If the total score is ≥ 7.
5 (without muscle biopsy) or ≥ 8.
7 (with muscle biopsy), the diagnosis of IIM (90% probability of diagnosis); ≥5.
5 (without muscle biopsy) or ≥6.
7 (with muscle biopsy) probable IIM (diagnostic probability 55%, <90%); if total score ≥5.
3 (without muscle biopsy) or ≥6.
5 ( With muscle biopsy) suspected IIM (diagnostic probability ≥50%, <55%); probability of diagnosis of IIM if total score <5.
3 (without muscle biopsy) or <6.
5 (with muscle biopsy) below 50%
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 The adult types of IIM are divided into dermatomyositis (DM), polymyositis (PM) (including immune-mediated necrotizing myopathy (IMNM)), inclusion body myositis (IBM), amyopathic dermatomyositis ( ADM)
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 Figure 1: 2017 EULAR/ACR classification flow chart of inflammatory myopathy subtypes Lymphocyte-infiltrating, immune-mediated necrotizing myopathy (IMNM) belonging to the IMM subtype
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 IMNM is further subdivided into: patients with SRP autoantibodies, HMG-CoA reductase autoantibodies, or no autoantibodies
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Seronegative IMNM is associated with a significantly increased risk of malignancy (which is why a CT scan is added later to assess for malignancy)
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 Cardiac involvement was reported in 9% of 1715 IIM cases in a case registry [4]
.

In reality, however, the prevalence of cardiac complications in IIM and IMNM appears to be higher than previously thought
.

In an autopsy study, 25%–30% of patients with IIM had cardiac pathology consistent with myocarditis, with histopathology showing mononuclear cell infiltration in the endomysial and perivascular areas of the myocardium, as well as degenerative and necrotizing lesions
.

Although most of these patients presented with congestive symptoms, myocarditis was also found in patients without cardiac symptoms [5]
.

 From the case presented in this article, IMNM complicated with myocarditis, which can lead to severe mortality
.

So how to diagnose this condition early? Cardiac MRI is the imaging modality of choice when evaluating myocarditis
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 However, there are currently no specific guidelines for the management of cardiac manifestations of IIM
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The main clinical treatments include the use of steroids and disease-modifying antirheumatic drugs to address the underlying inflammatory myositis
.

Treatment of cardiac complications includes nonsteroidal anti-inflammatory drugs or colchicine for pericarditis, guideline-directed medical therapy for heart failure, and pacemaker therapy for conduction abnormalities
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Critically ill patients may require more aggressive supportive care, including inotropic and mechanical support
.

Depending on the severity of cardiac manifestations, IVIG and rituximab may be considered
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 Returning to our case, the patient's treatment process was complex, including inotropic therapy and mechanical circulatory support with IABP
.

In addition, the patient had an inadequate response to the first round of immunosuppression with IVIG and high-dose methylprednisone, necessitating repeated treatment with IVIG, rituximab, and additional high-dose steroids
.

Fortunately, the patient finally recovered, the pain disappeared, and the muscle strength and heart function returned
.

 Finally, to summarize our key knowledge from this case: ■ Myocardial involvement in IIM (including IMNM) is common, often subclinical, and associated with poor prognosis
.

■ IMNM presents with fulminant myocarditis and cardiogenic shock, requiring positive inotropic and mechanical circulatory support and high-dose immunosuppressive agents
.

Reference [1] Tsang D, Malladi CL, Patel K, Bajaj P.
Seronegative immune-mediated necrotising myopathy complicated by fulminant myocarditis resulting in cardiogenic shock and cardiac arrest.
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com/usercenter/paper/show?paperid=1a1y0ce0ak1y0r80xk1j0mc034146921[4]Lilleker JB, Vencovsky J, Wang G, Wedderburn LR, Diederichsen LP, Schmidt J, Oakley P, Benveniste O, Danieli MG, Danko K, Thuy NTP, Vazquez-Del Mercado M, Andersson H, De Paepe B,deBleecker JL, Maurer B, McCann LJ, Pipitone N, McHugh N, Betteridge ZE, New P, Cooper RG, Ollier WE, Lamb JA, Krogh NS, Lundberg IE, Chinoy H; all EuroMyositis contributors.
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Am J Cardiol.
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https:/ /pubmed.
ncbi.
nlm.
nih.
gov/7137049/an international collaborative tool to facilitate myositis research.
Ann Rheum Dis.
2018 Jan;77(1):30-39.
doi: 10.
1136/annrheumdis-2017-211868.
Epub 2017 Aug 30.
https://pubmed.
ncbi.
nlm.
nih.
gov/28855174/[5]Haupt HM, Hutchins GM.
The heart and cardiac conduction system in polymyositis-dermatomyositis: a clinicopathologic study of 16 autopsied patients.
Am J Cardiol.
1982 Nov;50(5):998-1006.
https://pubmed.
ncbi.
nlm.
nih.
gov/7137049/an international collaborative tool to facilitate myositis research.
Ann Rheum Dis.
2018 Jan;77(1):30-39.
doi: 10.
1136/annrheumdis-2017-211868.
Epub 2017 Aug 30.
https://pubmed.
ncbi.
nlm.
nih.
gov/28855174/[5]Haupt HM, Hutchins GM.
The heart and cardiac conduction system in polymyositis-dermatomyositis: a clinicopathologic study of 16 autopsied patients.
Am J Cardiol.
1982 Nov;50(5):998-1006.
https://pubmed.
ncbi.
nlm.
nih.
gov/7137049/