Unravelling ATTR Cardiac Amyloidosis in Iceland : A Nationwide Epidemiological Study

Abstract

Introduction: Cardiac amyloidosis (CA) arises from the deposition of misfolded amyloid proteins in the heart's extracellular matrix, leading to significant cardiac disease. Recent data suggest that CA is under-recognised, and advances in treatment have increased focus on this condition with the intention of implementing treatment earlier to improve prognosis. There is limited knowledge regarding the prevalence of transthyretin CA (ATTR-CA) on a national level, particularly in Iceland. Therefore, this study represents the first nationwide effort to evaluate the baseline characteristics, diagnostics, and treatment of ATTR-CA in Iceland. Methods: A retrospective study of all patients diagnosed with ATTR-CA in Iceland from 6 May 2013 to 11 March 2024 was identified in the Icelandic Cardiac Amyloid Registry (ICE-CAR) created in 2023 by heart failure (HF) specialists at Landspitali University Hospital in Reykjavik, Iceland. Diagnosis was based on different combinations of transthoracic echocardiography, an elevated Perugini score on bone scintigraphy and heart biopsies, as well measurements of free light chains, M-component measurements in blood and urine. Patients were grouped according to the National Amyloidosis Centre (NAC) prognostic staging system for ATTR-CA. Results: In total, 65 patients with ATTR-CA were identified (males n = 60, females n = 5, median age 81.4 years [IQR 75.5-85.5 years]), all wild-type and no mutant variant. Diagnosis was made with myocardial biopsy in 7 cases. Upon diagnosis, 83% of the patients had an interventricular septum thickness of ≥15 mm and 92% showed a posterior wall thickness of ≥12 mm. Approximately 57% of patients belonged to New York Heart Association (NYHA) functional class I-II. The HF phenotypes according to left ventricular ejection fraction (LVEF) were distributed as follows: reduced (HFrEF) n = 24 (37%), mildly reduced (HFmrEF) n = 9 (14%), preserved (HFpEF) n = 29 (44.5%), and unknown LVEF n = 3 (4.5%). A total of 54 patients had reported NAC stage: stage I 23 (35.4%), stage II 20 (30.8%), stage III 11 (16.9%). Around 32% received disease-modifying treatment. Conclusion: Despite the low NYHA class observed in the study population, our findings in Iceland's nationwide assessment of ATTR-CA indicate more advanced age and lower LVEF at diagnosis compared to other studies. This highlights the critical need for early detection and appropriate therapeutic interventions in managing ATTR-CA.