Characterizing the Journey to Diagnosis for Patients with Transthyretin Amyloidosis and Accompanying Congestive Heart Failure

Abstract

Introduction Transthyretin (ATTR) amyloidosis is a rare, systemic, progressive, and fatal condition in which misfolded transthyretin proteins deposit as amyloid in nervous, cardiac, and other tissue. The deposition of amyloid in cardiac tissue results in cardiomyopathy (CM). Hypothesis The journey to diagnosis for patients with ATTR amyloidosis and accompanying CM (ATTR-CM) is long and complex and may result in delayed treatment initiation due to misdiagnosis. Methods Adult patients in the US and Canada with ATTR amyloidosis were enrolled in an online, longitudinal observational survey study. Analyses were based on initial survey responses from a subset of patients with self-reported cardiac involvement (n=68). Journey to diagnosis was assessed in terms of: age at symptom onset, types of initial symptoms, time to diagnosis, number and types of healthcare providers (HCPs) consulted, frequency of visits to HCPs prior to diagnosis, types of HCPs who provided diagnosis, and types of diagnostic procedures performed by HCPs while seeking a diagnosis. Results were summarized descriptively. Results and Conclusions On average, patients were 60.9 years of age at the time of symptom onset. Self-reported initial symptoms included cardiac (n=40, 59%), peripheral or autonomic neuropathy (n=16, 24%), and carpal tunnel syndrome (n=5, 7%). Cardiac was predominantly the initial symptom experienced by patients with wild type ATTR amyloidosis (75%) while cardiac (48%) or neuropathy (38%) were the initial symptoms experienced most often by patients with hereditary ATTR amyloidosis. Only one-quarter (n=17) of patients received their diagnosis within 6 months of their initial symptom onset (mean=3.6 years), and 5 (7%) patients were identified through genetic testing before symptom onset. Twenty-two (32%) patients reported seeing 6 or more HCPs before receiving their ATTR amyloidosis diagnosis; more than two-thirds (n=47, 69%) of the sample reported seeing 3 or more HCPs before diagnosis. Patients commonly visited primary care providers (n=52) and cardiologists (n=51) with a median of 3 visits to primary care providers and 2 visits to cardiologists before receiving their diagnosis; however, cardiologists most often made or confirmed final diagnoses of ATTR amyloidosis (n=49, 72%). Of the reported diagnostic procedures, the most common were echocardiogram (n=50), biopsy (n=45), MRI or CMR (n=34), genetic testing (n=30), cardiac biomarkers (n=18); and radionuclide imaging (PYP/DPD; n=13); among biopsy locations, cardiac (n=29) and fat pad (n=22) biopsies were the most frequently reported. Conclusions These results indicate that the journey to a diagnosis for patients with ATTR-CM is complicated and delays in diagnosis are common. Increased awareness of ATTR amyloidosis among cardiologists may help to raise early suspicion, reduce the time to an accurate diagnosis, and initiate early treatment.