Diagnostic lag and time to transthyretin stabilizer therapy in wild-type transthyretin amyloid cardiomyopathy
C Coleman, W L BakerAbstract
Background
Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive disease in which transthyretin protein misfolds and deposits as amyloid fibrils in the myocardium, leading to a restrictive cardiomyopathy (CM). These deposits cause diastolic dysfunction, heart failure (HF) symptoms, arrhythmias, conduction disorders, and ultimately increased morbidity and mortality if untreated. wtATTR-CM is often under-recognized due to its non-specific symptoms, leading to delayed diagnosis and initiation of transthyretin stabilizers (tafamidis or acoramidis). As a result, many patients start treatment in later HF stages, reducing the benefits of therapy.
Purpose
To quantify time intervals from initial HF to wtATTR-CM diagnosis and from wtATTR-CM diagnosis to first prescription for a transthyretin stabilizer.
Methods
Adults newly diagnosed with wtATTR-CM in the Veradigm Network EHR were included. Eligibility required ≥1 International Classification of Diseases-10th Revision (ICD-10) diagnosis code E85.82 between May 1, 2020, and May 1, 2025 (with the index date defined by the first E85.82 code), no prior E85.x code or ATTR-CM-directed therapy during the baseline period (January 1, 2010 to the index date, minimum of 365 days activity required), and ≥1 ICD-10 or SNOMED code for HF or CM preceding wtATTR-CM diagnosis. Patients with light chain amyloidosis, cerebral amyloid angiopathy, hematologic cancers/multiple myeloma, or end-stage renal disease were excluded. Patients were followed until transthyretin stabilizer prescription, loss to follow-up or end of data availability.
Results
In total, 127 patients newly diagnosed with wtATTR-CM were identified (Table 1). The median interval from first HF diagnosis to wtATTR-CM diagnosis was 181 (9, 642) days. Transthyretin stabilizers were prescribed in 89 (74.8%) patients during available follow-up. Among patients having a prescription entered for a transthyretin stabilizer, the median time from wtATTR-CM diagnosis was 49 (2, 115) days; 20 patients were prescribed therapy on the day of wtATTR-CM diagnosis and 61 patients by day 90 (Figure 1). Median time from wtATTR-CM diagnosis to stabilizer prescription was 86 (32, 199) days for wtATTR-CM diagnoses made in 2021–2022 and decreased to 39 (0, 93) days for diagnoses made between 2022 and 2025.
Conclusion
In this contemporary real-world cohort, patients with wtATTR-CM experienced prolonged delays from HF onset to diagnosis, and most were prescribed transthyretin stabilizers weeks to months after diagnosis. Time from wtATTR-CM diagnosis to transthyretin stabilizer prescription has shortened in recent years.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.