IAEA Transthyretin Amyloid Cardiomyopathy Study – The I-TAC study

Heart failure (HF) with preserved ejection fraction (HFpEF) is a major public health problem with no effective therapy until recently, and substantial underdiagnosis. One of the deadliest forms of HFpEF, estimated to affect 13-18% of adults >65 years with HFpEF, is transthyretin amyloid cardiomyopathy (ATTR-CMP) with a median survival of 25-41 months. Fortunately,  recent therapeutic breakthrough— tafamidis— has improved survival, alleviated symptoms, and reduced HF hospitalizations from ATTR-CMP. However, we are unable to effectively harness the recent therapeutic breakthroughs to treat this important cause of HFpEF due to a key barrier—underdiagnosis of ATTR-CMP. The two key factors contributing to underdiagnosis as well as a delay in diagnosis of cardiac amyloidosis are (1) a lack of knowledge about amyloidosis due to its perceived rarity and (2) a lack of expertise in Tc-99m-PYP imaging. Tc-99m-PYP SPECT is a simple nuclear cardiology test that can accurately diagnose ATTR-CMP and has virtually eliminated the need for endomyocardial biopsy. Although access to Tc-99m-PYP SPECT and technical expertise exists, the practical application of PYP imaging to diagnose ATTR-CMP remains limited in many countries. Moreover, the current multisocietal diagnostic criteria were developed by physicians with amyloidosis expertise from Europe and America; whether these same criteria are valid in an ethnically and/or socio-economic diverse cohort of individuals in the rest of world, is not known. We expect this project to build expertise on high-quality Tc-99m-PYP SPECT imaging. The goal of this project is to develop sustainable global expertise to perform high quality PYP imaging to accurately diagnose ATTR-CMP.
Rationale of the coordinated research project
Despite availability of non-invasive methods, timely diagnosis of ATTR-CMP remains challenging. The challenge of accurate and timely diagnosis of ATTR-CMP was recently highlighted in a patient-focused survey conducted by the Amyloidosis Research Consortium (ARC).33 Before a correct diagnosis was made, 57% of hereditary (h)ATTR and 39% of wild type (wt)ATTR patients received a misdiagnosis. Of those patients who were misdiagnosed, a majority (76%, wtATTR; 75%, hATTR) received treatment for the misdiagnosed condition. 43% and 26% of patients reported being treated with beta blockers and ACE inhibitors, respectively; both of these medications are poorly tolerated in ATTR and may result in worse outcomes. 44% of patients saw ≥3 physicians before receiving the correct diagnosis, and 17% saw ≥5, suggesting missed opportunities for diagnosis.33 The lack of consideration of ATTR-CMP at the time of interpretation of echo, due to misdiagnosis of left ventricular wall thickening from amyloidosis as left ventricular myocyte hypertrophy from hypertensive heart disease, particularly in African Americans, remains a critical barrier to early diagnosis. Lack of familiarity with the protocols for Tc-99m-PYP and a lack of its validation in low-to-middle-income (LMC) nations may be a major reason for underutilization of Tc-99m-PYP and underdiagnosis of ATTR-CMP in many countries.