Delayed Diagnosis of Transthyretin Cardiac Amyloidosis in Recurrent Heart Failure with Preserved Ejection Fraction: A Narrative Review of Multimodality Imaging Pathways
DOI:
https://doi.org/10.5281/zenodo.22205963Keywords:
Transthyretin Amyloidosis, Heart Failure with Preserved Ejection Fraction, Multimodality Imaging, Bone ScintigraphyAbstract
Transthyretin amyloid cardiomyopathy (ATTR-CM) is no longer a rare curiosity of the autopsy room. It is a treatable cause of heart failure with preserved ejection fraction (HFpEF) that is still recognised years after the first decompensation, by which time irreversible myocardial infiltration has occurred and the therapeutic window has narrowed. Objectives: To review the published evidence on the diagnostic performance and optimal sequencing of electrocardiography, echocardiography with deformation imaging, cardiovascular magnetic resonance and bone-avid radiotracer scintigraphy in patients presenting with recurrent HFpEF, and to identify where in that pathway diagnostic delay is generated. Material and Methods: A narrative review was undertaken. MEDLINE, Embase and the Cochrane Library were searched from January 2005 to May 2026 for prevalence studies, diagnostic accuracy studies, consensus recommendations and randomised outcome trials in ATTR-CM. Prevalence estimates, sensitivity and specificity values and trial endpoints were extracted from the primary reports and tabulated without pooling. Results: Reported ATTR-CM prevalence in HFpEF cohorts with ventricular wall thickening ranges from 3% to 16.8%, driven largely by age, wall-thickness threshold and whether screening was systematic. Median diagnostic delay is 3.4 years in wild-type disease and misdiagnosis is reported
in 34-57% of patients. Grade 2 or 3 uptake on bone scintigraphy with absence of a monoclonal protein carries a specificity and positive predictive value of 100%, removing the need for biopsy in most patients. Relative apical sparing of longitudinal strain and elevated extracellular volume identify infiltration earlier than wall thickness alone, but neither distinguishes transthyretin from light-chain deposition. Conclusion: The tools required to identify ATTR-CM in HFpEF are widely available and well validated; the delay is generated by failure to suspect the diagnosis rather than by any deficiency of the tests. A protocolised pathway triggered by clinical red flags, in which immunofixation with free light chains is requested at the same time as scintigraphy, is the single change most likely to shorten time to treatment. Abbreviations: ATTR-CM – Transthyretin Amyloid Cardiomyopathy, HFpEF – Heart Failure with Preserved Ejection Fraction, CMR – Cardiovascular Magnetic Resonance, ECV – Extracellular Volume, LGE – Late Gadolinium Enhancement, RALS – Relative Apical Longitudinal Strain.
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