Recognizing Potential Clinical Markers of Hereditary Transthyretin Amyloidosis for Early Diagnosis

Hereditary transthyretin amyloidosis (ATTRv) is frequently underdiagnosed and misdiagnosed, with up to several years in reported diagnostic delays despite promising treatments. ATTRv symptoms affect an array of body systems, leading to cardiac, gastrointestinal, ocular, and musculoskeletal damage. The wide range of symptom manifestations, coupled with low levels of disease awareness among healthcare professionals, can lead to misdiagnoses. By understanding the patient journey prior to diagnosis, clinicians may be able to intervene earlier and promote more widespread efforts.

To this end, Vera-Llonch and colleagues assessed the clinical characteristics and healthcare utilization of patients before they received a diagnosis of ATTRv.

Patients who were aged ≥18 years and newly diagnosed with ATTRv were identified using a claims-based algorithm. The researchers based a diagnosis on the patient having ≥1 medical claims with a relevant amyloidosis diagnosis code (excluding light chain and wild-type amyloidosis) and either evidence of ≥15 days of diflunisal treatment without a >30-day gap or liver transplant during the identification period during a 6-year time frame spanning from 2011 to 2017.

The date of first claim with an amyloidosis diagnosis code was considered to be the index date. For ≥5 years before the index date (look-back period), patients must have had continuous enrollment in a healthcare plan.

Healthcare utilization (testing, emergency department visits, and hospitalization) as well as selected comorbid conditions and symptoms were identified during the look-back period; demographics, physician specialty, and Charlson comorbidity index were identified 1-year pre-index. Excluded from the study were patients with an International Classification of Diseases, Ninth Revision (ICD-9) or ICD-10 amyloidosis code during the look-back period.

From a random sample of enrollees who lacked any diagnosis of amyloidosis, an ATTRv-free reference cohort was created and matched 3:1 to ATTRv patients based on age, gender, and region to provide reference values; as a match, the same index and enrollment requirements were implemented.

For the matched controls (N = 423) and qualifying patients with ATTRv (N = 141), the majority (53.9%) were female, and the mean age was 62.5 years. For the ATTRv cohort, the mean Charlson comorbidity index was 2.7 compared with 1.1 among the control cohort, P <.001. During the look-back period when compared with the control group, selected comorbidities, acute care and emergency department visits, and hospitalization were more common among patients with ATTRv. Relative to controls, cardiac imaging, biopsy or genetic testing, and blood/urine testing use was higher in each of the look-back years.

The investigators concluded that patients with ATTRv experience an array of neurologic, cardiovascular, and other clinical symptomatology requiring testing and hospitalization before being correctly diagnosed. This case highlights the critical need for clinicians to recognize common markers of illness that typically present 1 year prior to diagnosis. The detection and identification of common markers of early disease could motivate more extensive screening efforts, with the ensuing result being accelerated diagnosis and treatment of ATTRv.

Source: Vera-Llonch M, Reddy SR, Chang E, et al. The patient journey toward a diagnosis of hereditary transthyretin (ATTRv) amyloidosis. Orphanet J Rare Dis. 2021;16:25.