Prevalence and Outcomes of Cardiac Amyloidosis in All-Comer Referrals for Bone Scintigraphy

Abstract

The prevalence of cardiac amyloidosis (CA) in the general population and associated prognostic implications remain poorly understood. We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Consecutive all-comers undergoing 99m Tc-3,3diphosphono-1,2-propanodicarboxylic-acid ( 99m Tc-DPD) bone scintigraphy between 2010 and 2020 were included. Perugini grade 1 was defined as low-grade uptake and grade 2 or 3 as confirmed CA. Allcause mortality, cardiovascular death, and heart failure hospitalization (HHF) served as endpoints. Results: In total, 17,387 scans from 11,527 subjects (age, 61 6 16 y; 63.0% women, 73.6% cancer) were analyzed. Prevalence of 99m Tc-DPD positivity was 3.3% (n 5 376/11,527; grade 1: 1.8%, grade 2 or 3: 1.5%), and was higher among cardiac than noncardiac referrals (18.2% vs. 1.7%). In individuals with more than 1 scan, progression from grade 1 to grade 2 or 3 was observed. Among patients with biopsy-proven CA, the portion of light-chain (AL)-CA was significantly higher in grade 1 than grade 2 or 3 (73.3% vs. 15.4%). After a median of 6 y, clinical event rates were: 29.4% mortality, 2.6% cardiovascular death, and 1.5% HHF, all independently predicted by positive 99m Tc-DPD. Overall, adverse outcomes were driven by confirmed CA (vs. grade 0, mortality: adjusted hazard ratio [AHR] 1.46 [95% CI 1.12-1.90]; cardiovascular death: AHR 2.34 [95% CI 1.49-3.68]; HHF: AHR 2.25 [95% CI 1.51-3.37]). One-year mortality was substantially higher in cancer than noncancer patients. Among noncancer patients, also grade 1 had worse outcomes than grade 0 (HHF/death: AHR 1.45 [95% CI 1.01-2.09]), presumably because of longer observation and higher prognostic impact of early infiltration. Conclusion: Positive 99m Tc-DPD was identified in a substantial number of consecutive 99m Tc-DPD referrals and associated with adverse outcomes.

Diagnostic Accuracy of Bone Scintigraphy for the Histopathological Diagnosis of Cardiac Transthyretin Amyloidosis—A Retrospective Austrian Multicenter Study

“…In fact, AL CA can lead to significant myocardial tracer uptake and it is not possible to exclude AL with the use of scintigraphy [ 15 ]. In line with this, in another recent study by Nitsche and colleagues, up to 15% of biopsy-proven AL CA had a Perugini score ≥ 2 [ 16 ]. One patient in our cohort had AL CA without any evidence of monoclonal protein in the FLC assessment, as reported previously [ 17 ].…”

Echocardiographic tracking of transthyretin cardiomyopathy: which parameters matter the most?

“…These These results add to the emerging body of literature focusing on the pivotal role of cardiac valves in ATTR-CM. In patients with aortic stenosis, a significantly higher prevalence of concomitant ATTR 3,4 has been reported when compared to estimates for the general population, [5][6][7][8] whereas a potential contributing role of amyloid infiltration to the progression of stenosis severity remains controversial. Moreover, mitral regurgitation (MR) due to structural changes described above is a frequent finding in ATTR-CM as highlighted by data from the present study, where around two thirds of patients were affected by at least mild MR at baseline.…”

How prevalent is cardiac amyloidosis and which patients should be screened?

“…This highlights the utmost importance of additional single positron emission computed tomography (SPECT) in case of any cardiac uptake to confirm a myocardial tracer origin (as opposed to blood pool, ribs, or sternum). Nevertheless, even if we take into consideration patients with low‐grade cardiac uptake, there remains a large gap between prevalence estimates in elderly patients from bone scintigraphy on the one hand 3,4 and autopsy studies on the other hand 5,6 . One possible explanation may be a high prevalence of ‘subclinical’ amyloid deposits in the elderly, which are not accessible to current imaging techniques.…”

“…Comparable studies reported an ATTR prevalence of 1-3% in individuals ≥80 years old. 3,4 Moreover, the prevalence of 'early' ATTR infiltration, as indicated by low-grade cardiac tracer uptake, accounted for an additional ∼3% in these elderly patients. 3 However, we have to keep in mind the lower diagnostic accuracy of planar bone scintigraphy for a correct CA diagnosis in a low-risk population compared to patients with a high pre-test probability (e.g.…”