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........................... with unexplained LVH or HFpEF at hospitalization or severe aortic stenosis undergoing aortic valve replacement, aged above 65 years, may have wtTTR-CA.967972

Diagnosis and treatment of CA were recently reviewed.973 Age >65 years and HF along with a LV wall thickness >12 mm at echocardiography are major criteria for the suspicion of CA.973 Criteria for a suspicion of CA and to confirm diagnosis are reported in Table 35, Supplementary Table 25, and Figure 21.973,974 Cardiac 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%.975 In contrast, CMR has a sensitivity and specificity of 85% and 92%, respectively.966,976 The hereditary form should be excluded by genetic testing. EMB is the gold standard for the diagnosis of TTR-CA with nearly 100% sensitivity and specificity if specimens are collected from >4 multiple sites and tested for amyloid deposits by Congo red staining.966 However, a biopsy is not

Table 31 Diagnostic workup in suspected acute myocarditis

Definition of suspected acute myocarditis Clinical presentation þ >_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 segment 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 abnormalities 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 (see Table 33).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 (see Table 32). 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 cardiotrophic viruses. It can detect systemic

infection but does not prove cardiac infection and cannot substitute viral genome analysis on EMB samples.917 Circulating IgG antibodies to cardiotrophic 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 protein; 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 academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026