Impact of increased DPD scintigraphy on timing of diagnosis and prognosis of transthyretin cardiac amyloidosis over the course of ten years

Abstract

Abstract Background 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy is a sensitive non-invasive method for imaging transthyretin cardiac amyloidosis (ATTR-CA). The emergence of novel pharmacotherapies for ATTR-CA has resulted in much greater disease awareness. Objective We aimed to assess the level of increased demand for DPD scintigraphy and its influence on the clinical phenotype of patients diagnosed with ATTR-CA over the past 10 years. Methods This was a retrospective observational cohort study of patients referred to our centre (2012–2022) for DPD scintigraphy in whom ATTR-CA was a differential diagnosis. The protocol consisted of a planar whole-body acquisition performed at 3 hours after the injection, followed by single-photon emission computed tomography imaging of the thorax. Intensity of myocardial uptake on the planar 99mTc-DPD scan was categorized as 0 to 3 according to the Perugini grading system. A diagnosis of ATTR-CA was established on the basis of heart failure symptoms together with characteristic echocardiography or cardiac magnetic resonance imaging, and a grade 2 or 3 cardiac uptake on Tc99m-DPD in the absence of biochemical evidence of a monoclonal dyscrasia. Results As of December 2022, we identified 426 DPD scans performed in 421 patients (mean age 75 ± 12 yr, 72% male) referred for 99mTc-DPD, of whom 151 subsequently had a diagnosis of ATTR-CA confirmed. Patients diagnosed with AL-CA (n=2) were excluded for the purpose of this analysis. The number of DPD scans increased significantly in 2021-2022 (211 out of 426 studies) compared with previous 2 year periods (p<0.01) with an increasing proportion of referrals in this period made by cardiologists (p<0.05). In patients diagnosed with ATTR-CA, the proportion of grade 2 versus grade 3 Perugini scans increased in 2021-2022 compared with earlier years. There was no difference in survival among patients according to DPD grading (Figure 1; log rank p = 0.35). There was also no difference in survival between patients with ATTR-CA patients and DPD negative patients presenting with other forms of restrictive cardiomyopathy (Figure 2; HR 1.46, 95%CI [0.94-2.26], log rank p= 0.09). Conclusions Based on DPD grading, patients are being referred earlier by cardiologists with suspected ATTR-CA. DPD grading does not, however, carry prognostic significance in those patients subsequently diagnosed with ATTR-CA. Patients referred but who are not subsequently diagnosed with ATTR-CA have a similarly adverse prognosis to those with ATTR-CA; this forgotten cohort of non-specific restrictive cardiomyopathy is worthy of further follow up and investigation.5 year survival for all patients