Yield of bone scintigraphy screening for transthyretin‐related cardiac amyloidosis in different conditions: Methodological issues and clinical implications

BACKGROUND: Transthyretin‐related cardiac amyloidosis (TTR‐CA) is thought to be particularly common in specific at‐risk conditions, including aortic stenosis (AS), heart failure with preserved ejection fraction (HFpEF), carpal tunnel syndrome (CTS) and left ventricular hypertrophy or hypertrophic cardiomyopathy (LVH/HCM). METHODS: We performed a systematic revision of the literature, including only prospective studies performing TTR‐CA screening with bone scintigraphy in the above‐mentioned conditions. Assessment of other forms of CA was also evaluated. For selected items, pooled estimates of proportions or means were obtained using a meta‐analytic approach. RESULTS: Nine studies (3 AS, 2 HFpEF, 2 CTS and 2 LVH/HCM) accounting for 1375 screened patients were included. One hundred fifty‐six (11.3%) TTR‐CA patients were identified (11.4% in AS, 14.8% in HFpEF, 2.6% in CTS and 12.9% in LVH/HCM). Exclusion of other forms of CA and use of genetic testing was overall puzzled. Age at TTR‐CA recognition was significantly older than that of the overall screened population in AS (86 vs. 83 years, p = .04), LVH/HCM (75 vs. 63, p < .01) and CTS (82 vs. 71), but not in HFpEF (83 vs. 79, p = .35). In terms of comorbidities, hypertension, diabetes and atrial fibrillation were highly prevalent in TTR‐CA‐diagnosed patients, as well as in those with an implanted pacemaker. CONCLUSIONS: Screening with bone scintigraphy found an 11–15% TTR‐CA prevalence in patients with AS, HFpEF and LVH/HCM. AS and HFpEF patients were typically older than 80 years at TTR‐CA diagnosis and frequently accompanied by comorbidities. Several studies showed limitations in the application of recommended TTR‐CA diagnostic algorithm, which should be addressed in future prospective studies.