Evolution of diagnoses
Infectious agent | % pos. in MMR | Comments Diagnosis made via: | |
---|---|---|---|
1. Infectious myocarditis | |||
Bacteria |
Chlamydia pneumoniae
| 0.03 | Serodiagnosis |
Mycobacterium tuberculosis
| 0.02 | IGRA (Quantiferon) or microscopy from sputum, pericardial fluid, in Africa more frequent | |
Haemophilus influenzae
| 0.002 | Serodiagnosis | |
Staphylococci | 0.03 | Blood culture, in sepsis or endocarditis | |
Streptococci | 0.02 | In rheumatic fever, in cooperation with Chandigarh | |
Spirochete | Syphilis | 0.001 | Serodiagnosis |
Borrelia burgdorferi
| 0.7 | ELISA and Western blot or PCR from EMB | |
Rickettsia |
Coxiella burnetiid
| 0.005 | Serodiagnosis, predominant pericarditis |
Fungi | Candida | 0.002 | In immunocompromised patients, diagnosed by culture |
Protozoa | Plasmodium falciparum (malaria) | 0.002 | Microscopy (thick blood film) |
Toxoplasma gondii
| 0.002 | Serodiagnosis | |
Helminthic infections | – | 0 | None in MMR |
Viruses (RNA subtype) | |||
Picornaviruses | Coxsackie A + B | 0.019 | All by PCR, epidemiologic shift in late 1990s, none since 2002 |
Echo | 0.005 | PCR | |
Hepatitis B and C | 0.002 | Serodiagnosis or PCR | |
Orthomyxoviruses | Influenza A or B | 0.002 | Serodiagnosis |
H1N1 | 0.001 | Serodiagnosis | |
Paramyxoviruses | Mumps | 0.001 | Serodiagnosis |
Measles | 0.002 | Serodiagnosis | |
Toga‑/Rubivirus | Rubella | 0.001 | Serodiagnosis |
Flavi‑/Arbovirus | Dengue | 0.001 | Serodiagnosis |
Viruses (DNA subtype) | |||
Adenoviruses | A1, 2, 3, 5 | 0.011 | PCR |
Erythroviruses | Parvovirus B19 types 1–3 | 28 | PCR |
Herpesviruses: human herpes 6 virus | 0.03 | PCR; sometimes together with PVB 19 virus | |
Cytomegalovirus | 0.02 | PCR or ISH | |
Epstein–Barr virus | 0.012 | PCR | |
Varicella zoster | 0.001 | Serodiagnosis | |
Retrovirus: HIV | 0.005 | PCR or by serodiagnosis | |
Rhabdovirus | 0.001 | – | |
2. Noninfectious myocarditis | Autoreactive myocarditis | 53 | Exclusion of microbial agents |
Systemic autoimmune diseases | Giant cell myocarditis | 0.03 | Histology |
Wegner’s granulomatosis | 0.01 | Histology | |
Sarcoid heart disease | 0.015 | Histology | |
Rheumatoid arthritis | 0.03 | Histology and serology | |
Sjögren syndrome | 0.02 | Serology | |
Systemic lupus | 0.05 | Serodiagnosis | |
Crohn’s disease | 0.02 | Serodiagnosis | |
Dermatomyositis | 0.02 | Serodiagnosis | |
Kawasaki syndrome | 0.015 | – | |
Rejection | After heart transplantation | 1 | In cooperation with Hannover Medical School |
After stem cell transplantation | 0.002 | – | |
Hypereosinophilic syndrome (HES) | Löffler’s endomyocarditis | 0.01 | Biopsy and histology |
Churg–Strauss syndrome | 0.01 | Biopsy and histology | |
3. Toxicity | |||
Alcohol | Alcoholic cardiomyopathy | 0.2 | History, negative PCR on microorganisms |
Drug toxicity | Aminophylline, amphetamine, anthracycline, chloramphenicol, cocaine, cyclophosphamide, d5-fluorouracil, mesylate, methyl sergide, phenytoin, trastuzumab, zidovudine, ipilimumab and nivolumab antibodies | 0.02 | Only anthracycline induced CMP in the MMR |
Hypersensitivity reaction (drugs) | Azithromycin, benzodiazepine, clozapine, cephalosporin, dobutamine, lithium, diuretics, methyldopa, mexiletine, streptomycin, sulfonamides, NSAIDs, tetracycline, tricyclic antidepressants | 0.001 | Only one patient with lithium intoxication in MMR |
Hypersensitivity reactions (venoms) | Bees, wasps, scorpions, snakes, spider | 0 | – |
Radiation injury | – | 0.015 | History + biopsy + imaging |
Metabolic disorder | Diabetic cardiomyopathy | 0.02 | History + biopsy + imaging in diabetes patients |
4. Other DCM patients | – | 16.62 | – |
Special considerations for complex diagnoses
Clinical syndromes associated with inflammatory cardiomyopathy and myocarditis
Clinical phenotype | Fulminant myocarditis | Acute myocarditis | Chronic active or persistent myocarditis |
---|---|---|---|
Syndrome | Life-threatening heart failure or rhythm disturbance | Acute chest wall syndrome or acute onset of heart failure; pericardial effusion (up to 10%); angina in parvovirus B19 myocarditis | Chronic heart failure, variable EF with LV dilatation, pericardial effusion (up to 10%); angina in parvovirus B19 myocarditis |
Dallas criteria [9] | Infiltrate (active myocarditis or giant cells), necrosis | Active, often focal lymphocytic myocarditis | Borderline myocarditis, focal small infiltrates |
≥50 infiltrating cells/mm², necrosis, possibly giant cells | ≥14 infiltrating cells, mostly lymphocytes, necrosis, necrosis likely | ≥14 infiltrating cells, lymphocytes and macrophages, necrosis and apoptosis not obligatory | |
Immunohistology | Immunoglobulin binding mostly IgM to sarcolemma and fibrils and complement fixation | Immunoglobulin (IgM, IgA and IgG) binding to sarcolemma and fibrils | Immunoglobulin (IgG) binding to sarcolemma and fibrils |
PCR of microbial pathogens | Negative in giant cell or autoreactive myocarditis, positive in up to one third of cases | Negative in autoreactive lymphocytic myocarditis, positive in up to one third of cases | Negative in autoreactive lymphocytic myocarditis, positive in up to one third of cases |
Course | Variable: from fatal outcome to spontaneous healing | Variable: from deterioration to defective healing | Chronic heart failure |
Treatment | 1. Immunosuppression in PCR-negative cases, 2. In virus-positive biopsies; ivIg, 3. In all patients: assist device and ICDs, if indicated; heart failure treatment | 1. Immunosuppression in PCR-negative cases, 2. In virus-positive biopsies; ivIg, 3. In all patients: assist device and ICDs, if indicated; heart failure treatment | 1. Immunosuppression in PCR-negative cases, 2. In viral myocarditis ivIg or IFN in controlled trials 3. In all patients: prophylactic ICDs, when EF < 35%; heart failure treatment |
Treatment
Restriction of physical activity
Heart failure therapy for inflammatory cardiomyopathy
Antiarrhythmic treatment
Device therapy
Immunosuppressive treatment
Idiopathic giant cell myocarditis
Cardiac sarcoidosis
Eosinophilic heart disease
Treatment in autoreactive, lymphocytic myocarditis
Immunosuppression
Author | Treatment | Endpoint | Patients/controls (n) | Result | Comment |
---|---|---|---|---|---|
Parillo et al. [21] | P | Function + mortality after 3 months | 60/62 | Improved 67% | No viral PCR |
Mason et al. (MTT) [22] | P + A/CyA | Function, mortality | 64/47 | No benefit, no harm | Underpowered, no viral PCR |
Wojnicz et al. [24] | P +A | EF + function, mortality | 41/43 | EF improved | No viral PCR |
Frustaci et al. (TIMIC) [25] | P +A | EF + mortality after 6 months | 43/42 | 88.3% improved | Treatment in virus-negative pts. only |
Maisch et al. (ESETCID) [26] | P +A | EF + function, MACE | 54/47 | EF + function improved after 2 years | Treatment in virus-negative pts. only |
Intravenous immunoglobulins
Authors | Study design | Patients (n) | Histology /PCR | ivIg dose | Outcome |
---|---|---|---|---|---|
Drucker et al. [40] | Retrospective | 46 children | Partly, no PCR | 2 g/kg single dose | Reduced LVEDD |
McNamara et al. [41] | Uncontrolled | 10 adults | Partly, no PCR | 2 g/kg single dose | Improved EF |
McNamara et al. [42] | RCT IMAC | 62 DCM, only 13 myocarditis | No PCR | 2 g/kg single dose | Both groups improved |
Case series | Total 9, 4 myocarditis | No PCR | 1–2 g/kg single dose | Improved NYHA and EF | |
Dennert et al. [49] | Uncontrolled | 25 | PVB19 positive | 2 g/kg single dose | Decreased viral load, improved EF |
Maisch et al. [51] | Uncontrolled | 90 PVB19 36 ADV | PCR-positive for PVB19 and ADV | 20 g per person at day 1 and 3 | Improved EF in 90%, eradication of ADV in 90%, of inflammation in 100%; PVB19 eradication in 40%, of inflammation in 70% |
Maisch et al. [52] | Controlled | 18/17 | CMV by PCR | 14 days, multiple doses | Improved EF, complete CMV eradication |
High-dose ivIG in cytomegalovirus myocarditis
Antiviral treatment with interferon beta
Practical conclusion
-
In inflammatory dilated cardiomyopathy and myocarditis, apart from heart failure and antiarrhythmic therapies, there is no real alternative to an etiologically driven specific treatment.
-
Diagnosis of the underlying microbial agent is a prerequisite for the initiation of treatment with antiviral agents or ivIg, which is the focus of this review.
-
If no virus but autoreactive myocardial inflammation is identified, immunosuppressive treatment is the treatment of choice.