The Role of Left Anterior Oblique Imaging in the Diagnosis of Transthyretin Cardiac Amyloidosis with Tc-99m Pyrophosphate Scintigraphy: A Pilot Study

Background and aim Transthyretin cardiac amyloidosis (ATTR) is a debilitating condition characterized by the accumulation of misfolded transthyretin (TTR) amyloid fibrils in the myocardium, resulting in restrictive cardiomyopathy and heart failure. Although Tc-99m-pyrophosphate (PYP) cardiac amyloidosis scintigraphy (CAS) has transformed the non-invasive diagnosis of ATTR, existing imaging protocols predominantly utilize anterior-posterior (AP) planar projections, which are susceptible to limitations due to anatomical overlap and extracardiac activity. The aim of this study was to explore the diagnostic utility of left anterior oblique (LAO) imaging in Tc-99m-PYP CAS for enhancing the identification and characterization of myocardial amyloid deposits. Materials and methods A retrospective analysis was conducted on 152 patients who underwent Tc-99m-PYP CAS. Static images were obtained from both AP and LAO projections at 1 and 3 hours following Tc-99m-PYP administration. Semi-quantitative assessment was conducted utilizing heart-to-contralateral (H/CL) ratio measurements, and the results were correlated with echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and visual amyloidosis grading. Multivariate logistic regression was employed to identify independent predictors of PYP positivity, while receiver operating characteristic (ROC) curve analysis was utilized to assess diagnostic performance. Results LAO imaging exhibited significantly higher H/CL ratios compared to AP imaging at both time points (p < 0.001), indicating enhanced of myocardial tracer uptake. Among patients with PYP-positive scans, the 1-hour LAO H/CL ratio emerged as a robust independent predictor of amyloidosis (OR = 14.1, 95% CI: 3.31–60.10, p < 0.001), surpassing the predictive value of the 3-hour measurement (OR = 7.1, 95% CI: 1.80–28.13, p < 0.001). Bland-Altman analysis revealed a systematic bias towards higher uptake values in LAO projections compared to AP projections, with a mean difference of 39% H/CL. ROC analysis demonstrated superior sensitivity for 1-hour LAO imaging (80.4%) relative to 3-hour imaging (60.9%), suggesting that early-phase LAO projections enhance diagnostic accuracy and may facilitate more efficient scan protocols. Conclusion This pilot investigation provides novel systematic evidence that LAO imaging enhances diagnostic accuracy in Tc-99m-PYP CAS for ATTR by reducing extracardiac interference. These preliminary findings also suggest that 1-hour LAO imaging could optimize CAS protocols and may ultimately decrease the need for invasive biopsy particularly in borderline cases. This innovation holds promise for advancing early ATTR detection and streamlining clinical decision-making. Further validation through prospective multicenter studies is required to confirm these observations and standardize LAO integration into clinical practice.