Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis

Abstract

or transthyretin (ATTR) 2-4 types in the vast majority of cases. ATTR amyloidosis may be acquired, associated with wild-type Background-Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of echocardiography and the traditional requirement for histological confirmation. It has long been recognized that technetium-labeled bone scintigraphy tracers can localize to myocardial amyloid deposits, and use of this imaging modality for the diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicenter study to ascertain the diagnostic value of bone scintigraphy in this disease. Methods and Results-Results of bone scintigraphy and biochemical investigations were analyzed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Of 857 patients with histologically proven amyloid (374 with endomyocardial biopsies) and 360 patients subsequently confirmed to have nonamyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with false positives almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and the absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (positive predictive value confidence interval, 98.0-100). Conclusions-Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for histology in patients who do not have a monoclonal gammopathy. We propose noninvasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease. Clinical Perspective on p 2412Autopsy studies have shown the presence of cardiac ATTR amyloid deposits in up to 25% of individuals >80 years of age, although in many of these hearts the amount of amyloid was small.8 Nevertheless, among patients with heart failure and preserved ejection fraction, postmortem examination indicates that cardiac amyloid deposition is commoner than in an age-matched autopsy group without heart failure. The majority of patients with cardiac amyloid on postmortem in these studies had not had amyloidosis diagnosed during their lifetime.9 Echocardiography, although a valuable and widely accessible tool for investigating heart failure, is neither sensitive nor specific for cardiac amyloidosis.10 Typical findings on echocardiography include thickening of ventricular walls, restrictive filling, abnormal left and right ventricular longitudinal strain, and atrial septal thickening.11 Cardiac magnetic resonance imaging (CMR) has much greater diagnostic value in cardiac amyloidosis, but false-positive and false-negative CMRs are not infrequent.12 Typical findings ...

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

“…Immunofixation and serum‐free light chains should always be measured when amyloidosis is suspected 32. Recently, the excellent diagnostic accuracy of cardiac magnetic resonance and bone scintigraphy was confirmed in several studies 6, 10, 11, 12. However, these modalities are expensive and available only in a limited number of institutions.…”

“…Cardiac amyloidosis was diagnosed by amyloid deposition in the myocardium or increased wall thickness (interventricular septum ≥12 mm) on echocardiography in the absence of any other cause of ventricular hypertrophy, providing that a histopathological diagnosis of amyloidosis has been made in at least one involved organ, such as the abdominal subcutaneous adipose tissue, skin, or gastrointestinal tract 1. The presence of global transmural or subendocardial late gadolinium enhancement on cardiac magnetic resonance and positive finding on 99m Tc‐pyrophosphate scintigraphy, if performed, added support to the diagnosis of cardiac amyloidosis 6, 10, 11, 12…”

“…In fact, the need to perform EMB in patients with suspected cardiac amyloidosis decreased following the introduction of various non‐invasive imaging modalities and feasibility of sampling other tissues 9. Recent improvements in the diagnostic accuracy of cardiac magnetic resonance imaging using late gadolinium enhancement and T1 mapping, and bone scintigraphy, have contributed to the diagnosis of cardiac amyloidosis 6, 10, 11, 12…”

Nuclear imaging of cardiac amyloidosis

“…Planar imaging alone or with single-photon emission computed tomography (SPECT) using nonamyloid-specific, bone-avid radiotracers ( 99m Tc-DPD [3,3- [8][9][10][11][12][13][14][15][16][17] Recent data indicate that the increased level of microcalcifications may explain the enhanced affinity of bone-seeking tracers for TTR over AL amyloidosis. 18 Amyloidspecific, positron emitting 18 F-and 11 C-tagged tracers have been used successfully with positron emission tomography (PET) imaging for the identification of both AL and TTR subtypes of CA.…”

Technetium 99m pyrophosphate radioisotope for diagnosis and prognosis of transthyretin cardiac amyloidosis: A call for collaboration

“…Thus, technetium-based radionuclide imaging can spare select patients the burden and risk associated with invasive endomyocardial biopsy, which can delay the diagnosis. 4 The quantitative H/CL chest ratio is a measure which has been found to confer [90% sensitivity and specificity for detection of ATTR (and differentiation from AL and HFpEF) as well as prognosticate survival in a multicenter analysis of Tc99m PYP cardiac imaging in the United States. 3 The authors of the current study performed a retrospective analysis in 75 patients with suspected ATTR cardiac amyloidosis who underwent planar Tc99 m PYP cardiac imaging, 48 of whom were reported to have ATTR, 12 with endomyocardial biopsy-proven disease.…”