Background

Previous studies indicated that amyloid scintigraphy in combination with free light chain (FLC) assessment yields an excellent diagnostic accuracy for cardiac transthyretin (ATTR) amyloidosis. As a consequence, the diagnosis of ATTR amyloidosis is increasingly made without the actual gold-standard method endomyocardial biopsy (EMB). Whether this leads to misdiagnosis in real-world practice is currently underinvestigated. We aimed to describe the diagnostic accuracy of amyloid scintigraphy in a real world setting performing a multicenter retrospective study.

Methods

Seven tertiary care centers throughout Austria agreed to participate in the study and performed a systematic retrospective medical records search from 2017 to 2020 after ethical approval was obtained. Patients were included in case of available results of amyloid scintigraphy, FLC assessment and EMB, respectively. Amyloid scintigraphy was performed using a 99m-technetium-labelled tracer. Histological analysis was performed using immunohistochemistry.

Results

We enrolled 98 patients (19% females) with a mean age 72 ± 9 years and median NT-proBNP (IQR) of 4153 (2673 – 9140) pg/ml. The number of submitted subjects with complete data per center ranged from 2 to 46. The patient number increased with years, with 12 patients investigated in 2017 and 32 in 2020.

An abnormal Perugini Score (ie. grade II or III) was present in 54 patients (55%) and FLC assessment was indicative of monoclonal gammopathy in 44 patients (45%). The most common histopathological diagnoses were ATTR in 57 patients (58%) and cardiac light chain (AL) amyloidosis in 20 patients (20%). One further patient was diagnosed with concomitant AL and ATTR amyloidosis. Further diagnoses were ApoA4 (n=2) and AA amyloidosis (n=1), while cardiac amyloidosis was ruled out in 17 patients (17%).

ATTR was diagnosed in 52 patients with Perugini Score II or III compared with 6 patients with Perugini less than II, yielding a sensitivity of abnormal Perugini score for ATTR amyloidosis of 90%. Among patients with abnormal Perugini (n=54), 52 were diagnosed with ATTR and 2 with AL amyloidosis, yielding a positive predictive value (PPV) of 96% (see Table). One AL patient had Perugini Score of II and one had Perugini Score of III. When excluding patients with monoclonal gammopathy, the PPV of abnormal Perugini Score was 100%.

Conclusion

Our data confirm a PPV of abnormal amyloid scintigraphy of 100% for cardiac ATTR amyloidosis when monoclonal gammopathy was excluded. However, among subjects with monoclonal gammopathy, one of ten patients with abnormal scintigraphy has AL amyloidosis as the underlying condition. Our data underscore that tissue biopsy and histopathological analysis should be performed in every patient with suspected amyloidosis and monoclonal gammopathy even in case of Perugini Score II or III.