Further examinations for diagnosing amyloidosis

Further examinations
Further cardiac examinations can give reason to suspect amyloidosis but only anatomopathological diagnosis can confirm this. Echocardiographs, MRIs and scintigraphs help diagnosis but do not help determine exactly what type of amyloidosis is present.
Classic signs of amyloidosis are a micro-voltage QRS, pseudo- Q waves, fragmented QRS and conduction disorders in the atrioventricular block. These anomalies can help guide diagnosis, especially when the echocardiograph shows a significant cardiac hypertrophy which then contrasts the low voltage and/or the lack of electrical activity in cardiac hypertrophy (Sokolov-Lyon Index < 35mm).
Cardiac Biomarkers
There is often an increase in natriuretic peptides in severe cases of amyloid cardiomyopathy. Levels of troponin I and T are often raised in CA when coronary artery disease is not present. An increase in these markers indicates that the cardiomyocytes are being damaged as a result of myocardial infiltration. If troponin levels increase as well as the pseudo Q waves detected in the ECG, this often means that a coronagraph must be carried out. If the coronagraph comes back normal, then an echocardiograph must be carried out to see if the myocardium has thickened. This increase in markers means that it has been possible to develop a scale of severity for AL amyloidosis (Mayo Clinic) which outlines the chemotherapy regimen and treatment. The number of markers will decrease if the body responds to chemotherapy and this is a good sign for prognosis.
M-mode and 2D imaging echocardiography are used to detect significant thickening of the myocardium. Left ventricular hypertrophy is generally concentric and linked to right ventricular hypertrophy. Amyloid deposits can cause valves to thicken. As a result, the myocardium has a ‘granular sparkling’ appearance in echocardiograms. However, this is not specific to amyloidosis and can be seen in other cardiac pathologies. Pericardial effusion is present less than 30% of the time. The combination of three hypertrophies (in the left and right ventricles and the pericardial effusion) is very suggestive of amyloidosis but when it is late-onset, the transmitral velocity (measured by pulsed Doppler) usually shows a restrictive pattern (E/A>2), in contrast to its early-onset presentation which is either normal or <1. Myocardial velocities are reduced in tissue doppler imaging. The ejection fraction only alters in the later stages, which explains why diagnosis is often late. Close analysis of contractility using deformation indices (2D-strain) is more precise than that of left ventricle ejection fraction. In amyloidosis, the global 2D strain of the left ventricle is reduced and shows apical sparing pattern.
Cardiac MRI
Noncontrast T1 mapping has high diagnosis accuracy for detecting cardiac amyloidosis. Elevated myocardial T1 may represent a direct marker of cardiac amyloid load. One of the difficulties, or even the impossibility, with this procedure is correctly regulating the inversion time to discriminate the blood-pool from the myocardium because of the gadolinium retention.
Myocardial scintigraph using diphosphonate
Bone tracers (DPD, HMDP) used in scintigraphs indicate where the amyloids are deposited. It is not known why they fixate on the heart. This behaviour seems to be more particular to transthyretin amyloid deposits than to light chains. If the scintigraph shows intense myocardial fixation, this tends to indicate transthyretin amyloidosis (hereditary or senile), equally is the case if the tests for AL amyloidosis come back negative and an extra-cardiac biopsy finds amyloid deposits, with positive markers for transthyretin antibodies. Lack of fixation does not eliminate AL amyloidosis as a diagnosis.
Extra-cardiac biological examinations
Diagnosing AL amyloidosis requires protein electrophoresis, immunofixation, tests for serum free light chain assay and tests for the Bence Jones protein in the urine. Blood tests indicate the monoclonal spike and measure the amount of kappa and lambda chains. It is necessary to carry out analysis and sequencing of the transthyretin gene in order to make a diagnosis of hereditary transthyretin amyloidosis.
Biopsies and anatomopathological diagnosis
An anatomopathological examination and a biopsy are needed to diagnose amyloid cardiopathy. Initially, biopsies are non-invasive (salivary glands, abdominal fat). If these biopsies come back negative, this does not necessarily eliminate diagnosis, rather it means that further examinations are needed according to the localisation and type of the amyloidosis, whether it be renal, osteospinal or indeed cardiac.