Redefining the epidemiology of cardiac amyloidosis. A systematic review and meta-analysis of screening studies

Abstract

Aims: An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for CA. We examined the prevalence of CA in different settings based on literature data.

Methods and results: We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non-cardiac reasons (n = 5 studies), 1% (95% confidence interval [CI] 0%-1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%-20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%-15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%-4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%-10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%-9%); severe aortic stenosis (n = 7), 8% (95% CI 5%-13%); autopsy series of 'unselected' elderly individuals (n = 4), 21% (95% CI 7%-39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR-CA, but the average percentage of patients with amyloid light-chain (AL) CA was up to 18%.

Conclusions: Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR-CA accounts for many cases of CA across the different settings, but AL-CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women.

Keywords: Autopsy; Cardiac amyloidosis; Carpal tunnel syndrome; Diagnosis; Epidemiology; Heart failure; Hypertrophy; Red flags; Scintigraphy; Screening.

Figure 1

Prevalence of cardiac amyloidosis (CA) in different settings. Except for two specific settings (bone scintigraphy for non‐cardiac reasons and autopsy in unselected elderly individuals), the mean and 95% confidence interval (CI) or the range of prevalence of CA across studies (blue), the percentage of males out of all patients with CA (average and range; red), the mean/median age of patients with CA (brown), and the percentage of patients with amyloid light‐chain (AL) CA out of all patients with CA (green) are reported. Information on the original studies is reported in Table  1 . HCM, hypertrophic cardiomyopathy; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; M, men; W, women.

Figure 2

Prevalence of incidental myocardial uptake of bone tracers among men (M) and women (W) from the general population. See Table  1 for details on the original studies. CA, cardiac amyloidosis.

Figure 3

Prevalence of cardiac amyloidosis (CA) in patients with severe aortic stenosis referred to surgical or transcatheter aortic valve replacement. Prevalence values were calculated as the number of cases of CA among men (M) and women (W) divided by the number of M and W, respectively. In the study by Singal et al., no patient had CA diagnosed based on histology. Nitsche et al. considered the number of M and W with a Perugini score 2–3 instead of the number of M and W with CA (not provided). See Table  1 for further details on the original studies.