Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review

Abstract

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic delay and misdiagnosis in ATTR-CM.

Methods: The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed.

Results: Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34-57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic "red flags" were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences.

Conclusion: ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies.

Keywords: Cardiac amyloidosis; Diagnosis; Heart failure; Misdiagnosis; Transthyretin amyloid cardiomyopathy.

Fig. 1

PRISMA flow diagram

Fig. 2

Overall study population diagnostic delays

Fig. 3

NYHA class distribution at diagnosis by delay duration. Data source: Ladefoged et al. [36]