Prognostic value of echocardiography in light chain cardiac amyloidosis: after adjusting for treatment status

The prognostic performance of biomarker-based staging systems in light chain cardiac amyloidosis (AL-CA) remains limited. In addition, the role of echocardiography in risk stratification has not been fully established in the era of contemporary therapies. This study aimed to identify echocardiographic parameters that independently predict adverse outcomes after accounting for treatment status, and to assess their incremental prognostic value beyond established biomarker-based staging systems.

Clinical data and two-dimensional echocardiography were collected from patients with AL-CA, who were staged according to the 2012 revised Mayo staging system. The primary endpoint was all-cause mortality. Treatment status was defined as a time-dependent covariate and categorized as on-treatment or off-treatment. Receiver operating characteristic (ROC) analyses were performed to determine optimal cutoffs for echocardiographic parameters.

Among 100 patients with AL-CA, the median follow-up was 35 [15, 46] months, during which 36 deaths occurred. Patients who experienced events showed more severe structural and functional cardiac impairment than those who remained event-free. After multivariable adjustment, only left ventricular ejection fraction (LVEF) [hazard ratio (HR): 0.963, 95% confidence interval (CI): 0.930-0.998, P=0.041], mitral s' (HR: 0.737, 95% CI: 0.596-0.911, P=0.005), and mid-cavity circumferential strain (CS) (HR: 1.125, 95% CI: 1.022-1.240, P=0.016) remained independent predictors of mortality. ROC analyses identified optimal cutoff values of 5 cm/s for mitral s' and -15.9% for mid-cavity CS in discriminating between patients with and without events. Kaplan-Meier curves demonstrated progressively worse survival with increasing Mayo stage (P<0.001). Likelihood ratio tests indicated that mitral s' ≤5 cm/s and mid-cavity CS >-15.9% provided significant incremental prognostic value over the revised Mayo staging system. Incorporating mitral s' ≤5 cm/s into the Mayo staging system further improved risk reclassification, with an overall net reclassification improvement (NRI) of 31.8%.

After adjusting for treatment status, mitral s' and mid-cavity CS remained independent prognostic markers in AL-CA, underscoring their potential to enhance current biomarker-based staging systems.