14.6.1 Epidemiology and diagnosis
CA or amyloid cardiomyopathy is still an underdiagnosed cause of HF.
895,965,966The two most prevalent forms of CA are light chain immunoglobulin (AL) and transthyretin (ATTR) amyloidosis. ATTR includes the wild-type (>90% of cases), and the hereditary or variant type (<10% of cases). It is estimated that 6% to 16% of all patients Table 30 Aetiologies to be considered triggering acute
myocarditis
917 InfectiousViral Parvovirus B19, human herpes virus-6, Epstein- Barr virus, enteroviruses, (coxsackievirus, adenovirus), CMV, HIV, SARS-CoV-2 Others Borrelia, Coxiella burnetii(Q-fever) Systemic disease
Auto-immune and others
Sarcoidosis, giant cell myocarditis, eosinophilic myocarditis, SLE, ANCA-positive vasculitis, rheumatoid arthritis, any other auto-immune disease
Toxic
Medications Immune check point inhibitors, anthracyclines, clozapine, adrenergic drugs, 5-fluorouracil Other agents Alcohol, amphetamines, cocaine
ANCA = antineutrophil cytoplasmic antibody; CMV = cytomegalovirus; HIV = human immunodeficiency virus; SARS-CoV-2 = severe acute respiratory syn- drome coronavirus 2; SLE = systemic lupus erythematosus.
ESC 2021
Downloaded from https://academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 27 December 2023
.. ..
.. ..
.. ..
.. ..
.. ..
.. ..
.. .
with unexplained LVH or HFpEF at hospitalization or severe aortic stenosis undergoing aortic valve replacement, aged above 65 years, may have wtTTR-CA.
967972Diagnosis and treatment of CA were recently reviewed.
973Age
>65 years and HF along with a LV wall thickness >12 mm at echocar- diography are major criteria for the suspicion of CA.
973Criteria for a suspicion of CA and to confirm diagnosis are reported in Table 35, Supplementary Table 25, and Figure 21.
973,974Cardiac imaging and EMB or extra-cardiac biopsy are needed for the diagnosis of AL-CA
in patients with abnormal haematological tests (Figure 21).
Technetium-labelled
99mTc-PYP or DPD or HMDP scintigraphy with planar and SPECT imaging has a specificity and positive predictive value for TTR-CA of up to 100%.
975In contrast, CMR has a sensitivity and specificity of 85% and 92%, respectively.
966,976The hereditary form should be excluded by genetic testing. EMB is the gold standard for the diagnosis of TTR-CA with nearly 100% sensitivity and specific- ity if specimens are collected from >4 multiple sites and tested for amyloid deposits by Congo red staining.
966However, a biopsy is not Table 31 Diagnostic workup in suspected acute myocarditis
Definition of suspected acute myocarditis
Clinical presentationþ>_1 mandatory diagnostic test being positive (by preference CMR) in the absence of significant coronary artery, valvular or congenital heart disease, or other causes.
Sensitivity Specificity Clinical presentation
Acute/new onset chest pain, dyspnoea, signs of left and/or right HF, and/or unexplained arrhythmias or aborted sudden death. Low Low Mandatory diagnostic tests
ECG New and dynamic ST-T abnormalities, including pseudo-infarct ST seg-
ment elevation, atrial or ventricular arrhythmias, AV blocks, QRS abnormalities.
High Low
Laboratory tests Elevated troponins with dynamic changes consistent with myocardial necrosis.
Standard tests including white blood cells count to exclude eosinophilia.919,954
Intermediate Low
Echocardiography New structural or function abnormalities, regional wall motion abnormal- ities or global ventricular dysfunction without ventricular dilatation or with, generally mild, dilatation, increased wall thickness due to myocardial oedema, pericardial effusion, intracardiac thrombi, not explained by other conditions (e.g., CAD, ACS or valvular heart disease).
High Low
CMR Oedema, inflammation and fibrosis detection, quantification and localiza-
tion through T1 and T2 mapping, extracellular volume assessment and LGE (seeTable33).955,956
High Intermediate
Additional diagnostic tests
Coronary angiography or CTCA Excludes significant CAD or ACS in clinically suspected myocarditis. High High Endomyocardial biopsy For diagnosis and indication to specific treatment (seeTable32). Intermediate High Cardiac PET May be useful in patients who cannot undergo CMR or with suspected
systemic autoimmune disease or cardiac sarcoidosis.919,957
Low Low
Additional laboratory test Skeletal muscle enzymes, liver and renal function, natriuretic peptides, thyroid function tests, iron status, markers of systemic autoimmune disease.
Low Low
CRP elevated in 8090% patients.919,954 Intermediate Low
PCR testing of common cardiotropic viruses. It can detect systemic infec- tion but does not prove cardiac infection and cannot substitute viral genome analysis on EMB samples.917
Circulating IgG antibodies to cardiotropic viruses are common in the absence of viral myocarditis. Very limited diagnostic usefulness.917,918 Specific test for SARS-CoV-2, Borrelia, HIV or CMV if clinical suspicion.
Low Low
ACS = acute coronary syndrome; AV = atrio-ventricular; CAD = coronary artery disease; CMR = cardiac magnetic resonance; CMV = cytomegalovirus; CRP = C-reactive pro- tein; CTCA = computed tomography coronary angiography; ECG = electrocardiogram; EMB = endomyocardial biopsy; HF = heart failure; HIV = human immunodeficiency virus;
IgG = immunoglobulin G; LGE = late gadolinium enhancement; PCR = polymerase chain reaction; PET = positron emission tomography; QRS = Q, R and S waves (combination of three of the graphical deflections); SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; ST = ST segment of the electrocardiogram; ST-T = ST segment and T wave of the electrocardiogram.
ESC 2021
Downloaded from https://academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 27 December 2023
Management of patients with heart failure and suspected myocarditis
Clinical history, signs and symptoms, ECG, laboratory, echocardiography, CMR imaging, coronary CT/CAGa
Treatment of CAD if present and indicated
Suspected auto-immunity, infectious, toxic
HF treatment
Clinical stabilization EMB if any doubt
about diagnosis
Maintain HF treatment Consider immunosuppressive
therapy or anti-infection Y
N
Consider MCS
Figure 20 Management of patients with heart failure and acute myocarditis. ACS = acute coronary syndrome; CAD = coronary artery disease; CAG = coronary artery angiogram; CMR = cardiac magnetic resonance; CT = computed tomography; ECG = electrocardiogram; EMB = endomyocardial biopsy;
HF = heart failure; MCS = mechanical circulatory support.
aTo exclude CAD/ACS.
Table 32 Endomyocardial biopsy in patients with suspected myocarditis
Indication(see alsosection 4.3).Progressive or persistent severe cardiac dysfunction and/or life-threatening ventricular arrhythmias and/or Mobitz type 2 second-degree or higher AV block with lack of short-term (<1-2 weeks) expected response to usual medical treatment.
The aim is to identify aetiology and to indicate specific treatment (e.g. giant cell myocarditis, eosinophilic myocarditis, cardiac sarcoidosis, systemic inflamma- tory disorders).97,98,917,918,958
Number and sites of the samples
A minimum of 5 but possibly at least 7 samples, 3 for pathology, 2 for infections (DNA, PCR) and 2 for RNA viruses/viral replication. Left and/or right ven- tricle. CMR or PET guided sampling may be considered.919
Aetiology
Quantitative PCR viral genome analysis for common cardiotropic viruses (parvovirus B19, HHV4, HHV6, enteroviruses, adenovirus and coxsackievirus) by rtPCR.
Viral mRNA for active viral replication may be assessed although it has low sensitivity.
On indication, search for CMV, HIV,Borrelia, Coxiella burnetii(Q-fever) and SARS-CoV-2.
Diagnosis of inflammation
Immunohistochemistry with staining for anti-CD3-, CD4-, CD8- or CD45 antibodies for lymphocytes and anti-CD68 antibodies for macrophages and anti- HLA-DR antibodies.907,917,918,959
Therapeutic implications
Immunosuppressive therapymay be indicated based on the results of EMB as in giant cell myocarditis or eosinophilic myocarditis and, possibly, also in sarcoidosis, vasculitis or selected patients with increased cardiac inflammation of unknown origin based upon multidisciplinary counselling.98,917919,954
Antibiotics:Borrelia(Lyme disease).
Antiviral therapy:HIV, CMV, HHV6 pending on load and viral replication (mRNA).
CMR = cardiac magnetic resonance; CMV = cytomegalovirus; DNA = deoxyribonucleic acid; EMB = endomyocardial biopsy; HHV = human herpes virus; HIV = human immuno- deficiency virus; HLA-DR = human leucocyte antigen-DR isotype; mRNA = messenger ribonucleic acid; PCR = polymerase chain reaction; PET = positron emission tomography;
RNA = ribonucleic acid; rtPCR = reverse transcriptase polymerase chain reaction; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
ESC 2021