Background: Apical sparing in longitudinal strain imaging is a recognized feature of cardiac amyloidosis (CA) but is often obtained visually without clearly defined quantitative parameters. We aimed to assess the diagnostic potential of multiple novel quantitative strain-derived ratios to differentiate transthyretin cardiac amyloidosis (ATTR-CM) from non-amyloidosis heart failure.
Methods: In this retrospective single-center study, biopsy- or scintigraphy-confirmed ATTRwt-CM patients were compared with non-CA HFpEF/HFmrEF controls of similar age, sex, and ejection fraction. Global, basal, mid-, and apical longitudinal strain values were recalculated from raw echocardiographic images. The primary endpoint was the Apical Sparing Ratio (ASR = apical / (mid + basal). In total, nine strain-derived ratios were analyzed, including four innovative indices, notably the Relative Apical Retention (RAR = (apical - basal) / GLS) and the Apical-to-Basal-to-Global Ratio (ABG= (apical / basal) / GLS). Depending on data distribution, unpaired Student’s t-test or Mann–Whitney U-test were applied. Receiver-operating-characteristic (ROC) curves were used to evaluate diagnostic performance with area under the curve (AUC) determination. Data are shown as mean ± standard deviation or median (interquartile range). The study was approved by the Ethics Committee of the University of Duisburg–Essen, Germany (25-12656-BO).
Results: A total of 172 patients were included (mean age 80 ± 4 years, 84 % male patients). Median left ventricular ejection fraction (LVEF) was 55 % (49-59) without significant variation between both groups (p = 0.311). Mean global longitudinal strain (GLS) was lower in ATTRwt-CM patients compared to non-CA controls (−14.03 ± 2.82 % vs. −18.38 ± 2.86 %; p < 0.001). Both basal strain (ATTRwt-CM -8.02 % [-5.83 to -11.14] vs. non-CA control -18.03 % [-14.27 to -20.76], p < 0.001) and midventricular longitudinal strain values (ATTRwt-CM -12,38 % [-10,60 to -14,89] vs. non-CA control -17 % [-15,34 to -19,38], p < 0.001) were lower in ATTR-CM than in non-CA controls, while apical strain remained similar between groups (p > 0.325). Addressing apical variability through strain-derived ratios enabled a more precise assessment of apical sparing, with all ratios differing significantly between ATTRwt-CM and non-CA controls (ASR: 0.98 [0.75–1.11] vs. 0.53 [0.44–0.67], p < 0.001; RAR: 0.82 ± 0.39 vs. 0.06 ± 0.40 % p < 0.001; ABG: 0.17 [0.12–0.27] vs. 0.06 [0.04–0.08], p < 0.001). ROC analysis revealed the highest discriminatory performance for the ABG (AUC =0.95, 95 % CI 0.92–0.98, p < 0.001) followed by the ASR (AUC = 0.92, 95% CI 0.88–0.96 p < 0.001) and RAR (AUC = 0.92 (95 % CI 0.88–0.96).
Conclusion: The diagnostic assessment of ATTR-CM is often limited by the lack of sufficient objective parameters. In this study, novel strain-derived ratios were introduced to enable a more objective and load-independent quantification of longitudinal strain. All analyzed ratios showed significant differences between the ATTRwt-CM and control groups, with the novel indices ABG and RAR demonstrating excellent diagnostic accuracy, supporting a more objective and quantitative evaluation of ATTR-CM in clinical practice.
