A combined threshold of 3D global longitudinal strain and extracellular volume identifies the highest-risk phenotype in light-chain cardiac amyloidosis
F Meng, J Li, R Zhao, Y Liu, Y Wu, H Chen, X Shu, P Liu, C Pan, J GeAbstract
Background
Risk stratification in light-chain cardiac amyloidosis (AL-CA) remains challenging. Three-dimensional speckle-tracking echocardiography (3D-STE) and cardiac magnetic resonance extracellular volume (ECV) are emerging prognostic tools, but their precise threshold values and combined prognostic utility in AL-CA are not fully defined.
Purpose
This study aimed to identify optimal threshold values for 3D-STE parameters and ECV, and to evaluate their combined prognostic utility in predicting all-cause mortality in patients with AL-CA.
Methods
This prospective study included patients with biopsy-confirmed AL-CA (2022–2025). All participants underwent comprehensive echocardiography prior to standard chemotherapy initiation. 3D-STE parameters —global longitudinal strain (GLS), global circumferential strain (GCS), left ventricular ejection fraction (LVEF)—were quantified using dedicated software (4D LV-Function 3, Ultrasound Workspace). The primary study endpoint was all-cause mortality.
Results
A total of 248 patients (mean age: 63.09 ± 9.82; 73.39% male) were included, with 124 reaching the primary endpoint. Ninety patients underwent cardiovascular magnetic resonance and 3D-STE within seven days prior to initiation of chemotherapy. Median follow-up was 211 days. Restricted cubic spline analysis revealed significant inflection points where mortality risk increased: 3D GLS > -11.9% (P for nonlinearity = 0.223), 3D GCS > -19.1% (P = 0.593), 3D LVEF < 45% (P = 0.153), and ECV > 53% (P for nonlinearity = 0.880). Kaplan-Meier analysis confirmed that patients with impaired parameters (below inflection points for strain/EF, above for ECV) had significantly worse survival (all Log-rank P < 0.05). Furthermore, combined stratification using both ECV (53%) and 3D GLS (-11.9%) identified a very high-risk subgroup (ECV ≥53% and 3D GLS > -11.9%) with the poorest prognosis (Log-rank, P = 0.041).
Conclusion
In AL-CA, specific thresholds of 3D-STE parameters (GLS= -11.9%, GCS= -19.1%, LVEF=45%) and ECV (53%) are critically associated with survival. The combination of elevated ECV and impaired 3D GLS effectively identifies patients at the highest risk, suggesting a synergistic prognostic value of myocardial tissue characterization and functional assessment.