Echocardiographic predictors of transthyretin cardiac amyloidosis

Transthyretin cardiac amyloidosis (TTR-CA) is an under-recognized cause of heart failure. Technetium pyrophosphate (PYP) scintigraphy provides a method of diagnosing TTR-CA non-invasively while transthoracic echocardiography (TTE) is often the imaging modality that first raises the suspicion of TTR-CA. We aimed to compare the clinical and echocardiographic characteristics of patients with TTR-CA versus those with suspected but no TTR-CA among patients who underwent PYP scans. We performed a retrospective cohort study of consecutive patients with suspected TTR-CA who underwent PYP scans at three tertiary care hospitals in Vancouver, Canada from 2017 to 2021. Baseline clinical and echocardiographic characteristics were obtained from electronic medical records. Left ventricular (LV) longitudinal strain (LS) analysis was retrospectively repeated on all available echocardiograms with sufficient image quality by a Level III echocardiographer blinded to the result of the PYP scans. We identified 503 patients (mean age 74 years, 35% female) with suspected TTR-CA who underwent TTE and PYP scans within 1 year, of whom 77 patients were diagnosed with TTR-CA. A diagnosis of TTR-CA was associated with older age (79.9 vs 72.6 years, p < 0.001), male gender (83.1 vs 61.5%, p < 0.001), NYHA class III/IV (34.7 vs 22.3%, p < 0.02), and a history of atrial fibrillation (71.4 vs 49.8%, p< 0.001). Conventional echocardiographic features predictive of a TTR-CA diagnosis included higher indexed LV mass (144.4 vs 106.6 g/m2, p < 0.001), higher LV wall thickness (15.6 vs 11.2 mm, p < 0.001), and higher indexed right atrial volume (46.7 vs 38.5 ml/m2). Among the patients with echocardiograms sufficient for strain analysis (n=388), patients with TTR-CA showed significantly lower mid LS (-11.6 vs -15.3, p < 0.001) and basal LS (-7.97 vs -14.4, p < 0.001), and a higher apical to basal LS ratio (3.36 vs 1.48, p < 0.001). Relative apical sparing by visual estimate demonstrated a 76% sensitivity and 91% specificity to identify TTR-CA, and a 74% sensitivity and 84% specificity based on a calculated apical to basal LS ratio >2. We identified clinical and echocardiographic features associated with a diagnosis of TTR-CA and report the test characteristics of relative apical sparing in a large cohort of undifferentiated patients with suspected TTR-CA referred for PYP scans.