Cardiovascular Disease Burden Prior To Hereditary Transthyretin Amyloidosis Diagnosis

Introduction Hereditary transthyretin amyloidosis (ATTRv) is often associated with progressive infiltrative cardiac involvement, with cardiac symptoms occurring sometimes years prior to diagnosis. Hypothesis ATTRv patients demonstrate significant cardiovascular symptom manifestations and healthcare utilization prior to diagnosis. Methods Newly diagnosed ATTRv patients in IBM® MarketScan® Commercial and Medicare Supplemental data (US) were identified using a claims-based algorithm. Diagnosis required ≥1 claim with relevant amyloidosis diagnosis code (ICD-10-CM: E85.0-.4, E85.89, E85.9) during identification (ID) period (1/2016-12/2017), and the occurrence of ≥1 qualifying criteria during 2011-2017: ≥15 days diflunisal use, liver transplant, or claim with code E85.1 (neuropathic heredofamilial amyloidosis) or E85.2 (heredofamilial amyloidosis unspecified). Index date was defined as date of first claim with amyloidosis code in ID period, and the pre-index period as the 5 years prior to index date. Patients with an ICD-9/10 amyloidosis code during this period were excluded to focus on the newly diagnosed. Control subjects without ATTRv were identified and matched (age, gender, region) to ATTRv patients (ratio 3:1); meeting the same index and enrollment requirements. Frequency of selected cardiovascular (CV) conditions and healthcare use were measured in the pre-index period; demographics and Charlson comorbidity index (CCI) were measured 1 year pre-index. Results Among 141 patients with ATTRv and 423 matched controls, mean (SD) age was 62.5 (14.2) years and 53.9% were female. Mean CCI for ATTRv patients was 2.7 (3.0) vs 1.1 (1.9) for controls. In the pre-index period, CV conditions were more common among ATTRv patients relative to controls: chest pain (51.8 vs. 28.1%), dyspnea (49.6 vs 25.8%), bleeding (41.8 vs 21.3%), edema (27.0 vs 12.8%), heart failure (23.4 vs 5.9%), ventricular hypertrophy (19.9 vs 5.7%), hypotension (18.4 vs 6.1%), atrial fibrillation/flutter (18.0 vs 8.9%), stroke (12.8 vs 6.1%), and aortic stenosis (10.6 vs 4.5%); conditions were relatively higher in each pre-index year. Hospitalization (47.5 vs. 24.3%), emergency department visits (60.3 vs. 47.0%) and cardiac testing (81.6 vs. 65.7%) were also more frequent among ATTRv patients. Median time (months) to ATTRv diagnosis from initial symptom manifestation were largest for chest pain (43.0), dyspnea (41.1), aortic stenosis (39.2), and atrial fibrillation/flutter (34.3). Conclusions ATTRv patients have considerable CV disease burden in the 5 years preceding diagnosis. Increased awareness of characteristic CV manifestations may increase clinical suspicion, leading to early diagnosis and prompt intervention.