OBJECTIVES

: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disease, where patients commonly experience delayed diagnosis and misdiagnosis. This targeted literature review assessed the extent and consequences of diagnostic delays and errors.

METHODS

: The Embase database was searched together with proceedings of 8 cardiology conferences. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and clinical/economic outcomes and healthcare resource use whilst undiagnosed/misdiagnosed. Searches were restricted to English language publications in adults with ATTR-CM.

RESULTS

: 629 records were screened and 23 met the inclusion criteria. Mean time to diagnosis (8 studies) ranged from 1.3-7.2 years for wild-type (wt)ATTR-CM, 1.8-6.5 years for hereditary (h)ATTR-CM, and 0.8-5.7 years in mixed populations. Median delays (8 studies) were 0.8-3.9, 2.1-3.7 and 1.2-2.9 years for wtATTR-CM, hATTR-CM and mixed populations. In wtATTR-CM, a delay of ≥3 months was associated with significantly higher NYHA classification at diagnosis, indicating more advanced disease. Additional findings include a trend toward shorter delay with non-invasive diagnosis. Misdiagnosis occurred in 34-57% of patients (4 studies). Three studies reported use of ACE inhibitors and/or beta blockers in 26-51% of misdiagnosed patients, which may be inappropriate or poorly tolerated. Three studies reported healthcare provider visits. In one, 32% of patients saw ≥6 providers before diagnosis, with a median of 3 general practitioner and 2 cardiologist visits. In another, 23% of hATTR-CM and 8% of wtATTR-CM patients saw ≥5 physicians before diagnosis. Another study reported hospital visits, with a median 17 attendances, including 3 inpatient admissions, in the 3 years before diagnosis.

CONCLUSIONS

: The ATTR-CM diagnostic journey is characterized by delay, misdiagnosis, and evaluation by multiple healthcare providers before a diagnosis is confirmed. Efforts to shorten the patient journey and provide early diagnosis are needed to enable patients to benefit from early access to disease-modifying therapies.