Myocarditis diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Varun Kumar M.B.B.S., Maliha Shakil, M.D. [2] Homa Najafi, M.D.[3]

Overview

Endomyocardial biopsy remains the gold standard test to evaluate for the presence of and to subclassify the type of myocarditis. A small tissue sample of the endocardium and myocardium is obtained via right sided cardiac catheterization. The sample is then evaluated by a pathologist using immunochemistry and special staining techniques as necessary. Histopathological features include abundant edema in the myocardial interstitium and an inflammatory infiltrate which is rich in lymphocytes and macrophages. Focal destruction of myocytes as a result of the inflammatory process results in left ventricular dysfunction. Endomyocardial biopsy is recommended when the results would identify an underlying disease that is amenable to therapy. Routine performance of endomyocardial biopsy is not recommended in all patients with myocarditis. The Canadian Cardiovascular Society has guidelines on the diagnosis of myocarditis and in which clinical scenarios myocarditis should be suspected as a diagnosis. They also outline the situations in which a patient should be referred for cardiac transplantation or mechanical circulatory support, as well as the guidelines for clinical follow-up.

Diagnostic Study of Choice

Study of choice

Endomyocardial Biopsy

  • The Heart Failure Society of America recommends that performance of endomyocardial biopsy should be considered when cardiac function deteriorates acutely with an unknown etiology that is unresponsive to medical therapy (Strength of Evidence = B).[1]
  • Non-specific findings such as hypertrophy, cell loss, and fibrosis may be noted on biopsy. However, biopsy findings that significantly impact patient management have not been conclusively established.[2] Although inflammatory changes in the myocardium may be detected in viral myocarditis, the majority of patients with biopsy proven myocarditis improve with supportive therapy alone without the need for antiviral or anti-inflammatory treatment.[3] Endomyocardial biopsy has a low sensitivity and specificity which could be explained by the focal and transient nature of the inflammatory infiltrates.[4][5]

Standardizing the Interpretation of Endomyocardial Biopsies: The Dallas Criteria

  • Histologically, both active inflammatory infiltrate within the myocardium and associated myocyte necrosis (the Dallas pathologic criteria) are present in myocarditis. Despite its limitations, the Dallas criteria have established uniform histologic criteria diagnosing myocarditis and have substantially reduced the variability in diagnosing the disease. Some of the criteria are as follows:[6]

Active myocarditis:

  • The presence of an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischaemic damage associated with coronary artery disease.

Borderline myocarditis:

  • The presence of an inflammatory infiltrate of the myocardium without necrosis or degeneration of adjacent myocytes.

Scenarios in Which Endomyocardial Biopsy May Be Useful[7][8]

Complications of Endomyocardial Biopsy

  • Complications may be as high as 6% as observed in a series where 546 patients with cardiomyopathy underwent right ventricular endomyocardial biopsy.[10] Several other studies reported the incidence of complications to be 0.5 to 1.5%.[11][12]
  • Complications of endomyocardial biopsy include:[11][13]

2009 ACC/AHA Focused Update and 2005 Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult (DO NOT EDIT) [14]

Endomyocardial Biopsy in Patients Presenting With Heart Failure (DO NOT EDIT) [14]

Class III (No Benefit)
" 1. Endomyocardial biopsy should not be performed in the routine evaluation of patients with heart failure.[13] (Level of Evidence: C) "
Class IIa
"1. Endomyocardial biopsy can be useful in patients presenting with heart failure when a specific diagnosis is suspected that would influence therapy.[13] (Level of Evidence: C) "

2007 AHA/ACCF/ESC Scientific Statement: The Role of Endomyocardial Biopsy (EMB) in Fourteen Clinical Scenarios[13]

Class I
"1. EMB should be performed in the setting of unexplained, new-onset heart failure of less than 2 weeks’ duration associated with a normal-sized or dilated left ventricle and hemodynamic compromise. (Level of Evidence: B) "
"2. EMB should be performed in the setting of unexplained, new-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks. (Level of Evidence: B) "
Class III (No Benefit)
"1. EMB should not be performed in the setting of unexplained atrial fibrillation. (Level of Evidence: C) "
Class IIa
"1. EMB is reasonable in the clinical setting of unexplained heart failure of more than 3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks. (Level of Evidence: C) "
"2. EMB is reasonable in the setting of unexplained heart failure associated with a dilated cardiomyopathy (DCM) of any duration associated with suspected allergic reaction and/or eosinophilia. (Level of Evidence: C) "
"3. EMB is reasonable in the setting of unexplained heart failure associated with suspected anthracycline cardiomyopathy. (Level of Evidence: C) "
"4. EMB is reasonable in the setting of heart failure associated with unexplained restrictive cardiomyopathy. (Level of Evidence: C) "
"5. EMB is reasonable in the setting of suspected cardiac tumors. (Level of Evidence: C) "
"6. EMB is reasonable in the setting of unexplained cardiomyopathy in children. (Level of Evidence: C) "
Class IIb
"1. EMB may be considered in the setting of unexplained, new-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle, without new ventricular arrhythmias or second- or third-degree heart block, that responds to usual care within 1 to 2 weeks. (Level of Evidence: B) "
"2. EMB may be considered in the setting of unexplained heart failure of more than 3 months’ duration associated with a dilated left ventricle, without new ventricular arrhythmias or second- or third-degree heart block, that responds to usual care within 1 to 2 weeks. (Level of Evidence: C) "
"3. EMB may be considered in the setting of heart failure associated with unexplained hypertrophic cardiomyopathy (HCM). (Level of Evidence: C) "
"4. EMB may be considered in the setting of suspected arrhythmogenic right ventricular dysplasia (ARVD/C). (Level of Evidence: C) "
"5. EMB may be considered in the setting of unexplained unexplained ventricular arrhythmias. (Level of Evidence: C) "

2009 Canadian Cardiovascular Society Guidelines on Myocarditis[15]

Class I

  1. Myocarditis should be suspected in the following clinical scenarios: (Level of evidence: C)
    • Cardiogenic shock due to LV systolic dysfunction (global or regional), where etiology is not apparent.
    • Acute or subacute development of LV systolic dysfunction (global or regional), where etiology is not apparent.
    • Evidence of myocardial damage not attributable to epicardial coronary artery disease or another cause.
  2. Referral to a centre with experience and expertise in the assessment and management of myocarditis should be considered for patients with suspected myocarditis (Level of evidence: C).
  3. Urgent referral for evaluation/consideration for cardiac transplantation or mechanical circulatory support should be considered for patients with heart failure and evidence of resulting progressive clinical deterioration or end-organ dysfunction (Level of evidence: C).
  4. Referral for further evaluation/consideration for transplantation or mechanical circulatory support should be considered for patients who remain in severe heart failure following implementation of standard heart failure therapy (Level of evidence: C).
  5. Best medical therapy, including supportive care is recommended for the treatment of myocarditis (Level of evidence: C).

Class IIa

  1. Expert clinical follow-up is required until myocarditis is determined to be resolved or until a chronic management plan is in place (Level of evidence: C).

Class III

  1. Routine use of general or specific immunological therapies directed toward myocarditis are not recommended, as this has not been shown to alter outcomes, and may lead to side effects or complications (Level of evidence: B).

Sources

  • Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: Diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials.[15]


Overview

Diagnostic Study of Choice

Study of choice

[Name of the investigation] is the gold standard test for the diagnosis of [disease name].

OR

The following result of [gold standard test] is confirmatory of [disease name]:

  • [Result 1]
  • [Result 2]

OR

[Name of the investigation] must be performed when:

  • The patient presents with [symptom/sign 1], [symptom/sign 2], and [symptom/sign 3].
  • A [name of test] is positive for [sign 1], [sign 2], and [sign 3] in the patient.

OR

[Name of the investigation] is the gold standard test for the diagnosis of [disease name].

OR

The diagnostic study of choice for [disease name] is [name of the investigation].

OR

There is no single diagnostic study of choice for the diagnosis of [disease name].

OR

There is no single diagnostic study of choice for the diagnosis of [disease name], but [disease name] can be diagnosed based on [name of the investigation 1] and [name of the investigation 2].

OR

[Disease name] is primarily diagnosed based on the clinical presentation.

OR

Investigations:

  • Among the patients who present with clinical signs of [disease name], the [investigation name] is the most specific test for the diagnosis.
  • Among the patients who present with clinical signs of [disease name], the [investigation name] is the most sensitive test for diagnosis.
  • Among the patients who present with clinical signs of [disease name], the [investigation name] is the most efficient test for diagnosis.

The comparison of various diagnostic studies for [disease name]

Test Sensitivity Specificity
Test 1 ...% ...%
Test 2 ...% ...%

[Name of test with higher sensitivity and specificity] is the preferred investigation based on the sensitivity and specificity

Diagnostic results

The following finding(s) on performing [investigation name] is(are) confirmatory for [disease name]:

  • [Finding 1]
  • [Finding 2]
Sequence of Diagnostic Studies

The [name of investigation] must be performed when:

  • The patient presented with symptoms/signs 1, 2, and 3 as the first step of diagnosis.
  • A positive [test] is detected in the patient, to confirm the diagnosis.

OR

The various investigations must be performed in the following order:

  • [Initial investigation]
  • [2nd investigation]

Name of Diagnostic Criteria

It is recommended that you include the criteria in a table. Make sure you always cite the source of the content and whether the table has been adapted from another source.

[Disease name] is primarily diagnosed based on clinical presentation. There are no established criteria for the diagnosis of [disease name].

OR

There is no single diagnostic study of choice for [disease name], though [disease name] may be diagnosed based on [name of criteria] established by [...].

OR

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

[Disease name] may be diagnosed at any time if one or more of the following criteria are met:

  • Criteria 1
  • Criteria 2
  • Criteria 3

OR

IF there are clear, established diagnostic criteria

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

IF there are no established diagnostic criteria

There are no established criteria for the diagnosis of [disease name].

References

  1. Heart Failure Society of America. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA; et al. (2010). "HFSA 2010 Comprehensive Heart Failure Practice Guideline". J Card Fail. 16 (6): e1–194. doi:10.1016/j.cardfail.2010.04.004. PMID 20610207. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  2. Chow LC, Dittrich HC, Shabetai R (1988). "Endomyocardial biopsy in patients with unexplained congestive heart failure". Ann Intern Med. 109 (7): 535–9. PMID 3421562.
  3. Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME; et al. (1995). "A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators". N Engl J Med. 333 (5): 269–75. doi:10.1056/NEJM199508033330501. PMID 7596370.
  4. Mahrholdt H, Goedecke C, Wagner A, Meinhardt G, Athanasiadis A, Vogelsberg H; et al. (2004). "Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology". Circulation. 109 (10): 1250–8. doi:10.1161/01.CIR.0000118493.13323.81. PMID 14993139. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  5. Hauck AJ, Kearney DL, Edwards WD (1989). "Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error". Mayo Clin Proc. 64 (10): 1235–45. PMID 2593714.
  6. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ; et al. (1987). "Myocarditis. A histopathologic definition and classification". Am J Cardiovasc Pathol. 1 (1): 3–14. PMID 3455232.
  7. Wu LA, Lapeyre AC, Cooper LT (2001). "Current role of endomyocardial biopsy in the management of dilated cardiomyopathy and myocarditis". Mayo Clin Proc. 76 (10): 1030–8. PMID 11605687.
  8. Magnani JW, Dec GW (2006). "Myocarditis: current trends in diagnosis and treatment". Circulation. 113 (6): 876–90. doi:10.1161/CIRCULATIONAHA.105.584532. PMID 16476862. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  9. Cooper LT, Berry GJ, Shabetai R (1997). "Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators". N Engl J Med. 336 (26): 1860–6. doi:10.1056/NEJM199706263362603. PMID 9197214.
  10. Deckers JW, Hare JM, Baughman KL (1992). "Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center". J Am Coll Cardiol. 19 (1): 43–7. PMID 1729344.
  11. 11.0 11.1 Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A; et al. (2010). "Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance". Circulation. 122 (9): 900–9. doi:10.1161/CIRCULATIONAHA.109.924167. PMID 20713901.
  12. Holzmann M, Nicko A, Kühl U, Noutsias M, Poller W, Hoffmann W; et al. (2008). "Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period". Circulation. 118 (17): 1722–8. doi:10.1161/CIRCULATIONAHA.107.743427. PMID 18838566.
  13. 13.0 13.1 13.2 13.3 Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U; et al. (2007). "The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology". Circulation. 116 (19): 2216–33. doi:10.1161/CIRCULATIONAHA.107.186093. PMID 17959655.
  14. 14.0 14.1 Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119 (14):1977-2016. DOI:10.1161/CIRCULATIONAHA.109.192064 PMID: 19324967
  15. 15.0 15.1 Howlett JG, McKelvie RS, Arnold JM, Costigan J, Dorian P, Ducharme A; et al. (2009). "Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials". Can J Cardiol. 25 (2): 85–105. PMC 2691911. PMID 19214293.


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