Critical insights on myocardial work indices in the short‐term prognosis of light‐chain cardiac amyloidosis

We read with great interest the article by Meng et al., ‘Myocardial work indices in the short-term prognosis of light-chain cardiac amyloidosis’.1 The authors longitudinally evaluated 96 biopsy-proven AL cardiac amyloidosis (AL-CA) patients and revealed that decreased global work index (GWI) and global constructive work (GCW) served as independent predictors of short-term mortality. Notably, these values enhanced the prognostic accuracy of standard staging systems, including the Mayo 2012 and Euro 2015 classifications. Their work demonstrates myocardial work (MW), derived from pressure–strain loops, as a valuable addition to risk evaluation in AL-CA. In spite of its strengths, several methodological aspects warrant further consideration. First, the lack of an independent validation cohort limits assurance in the reproducibility of the suggested cut-off values (GWI ≤840 mmHg% and GCW ≤1031 mmHg%). Clemmensen et al. demonstrated in a larger amyloidosis cohort that the prognostic ability of MW parameters differed according to the disease stage, emphasizing the need for external validation before cut-offs can be implemented in clinical practice.2 Lacking replication, Meng et al.'s cut-off may be cohort-specific rather than generalizable. Second, the study did not compare Myocardial Work Index (MWI) with cardiac magnetic resonance (CMR)–derived markers such as strain or extracellular volume (ECV), which continue to be the gold standard for myocardial tissue profiling in amyloidosis. The European Society of Cardiology (ESC) Working Group clearly recommends CMR-based ECV quantification as a complete prognostic tool.5 Dorbala et al. similarly highlighted the superiority of CMR for diffuse amyloid infiltration.3 Without comparison against these standard modalities, the incremental value of echocardiographic MWI remains unclear. Third, although all patients received bortezomib-based chemotherapy, outcomes were not categorized by haematological or cardiac therapeutic response. This is an important factor that could influence analysis, as treatment response has been regularly shown to outweigh baseline prognostic factors in AL amyloidosis. Gertz noted that haematological and organ responses stay the most influential predictors of survival in spite of baseline stage.4 Fourth, the use of all-cause mortality as the single end-point, without accounting for competing risks, may reduce the specificity of the outcomes. In AL-CA, deaths usually occur due to multi-organ involvement (renal, hepatic) than isolated cardiac failure. Competing risks modelling would help clarify whether MWI predicts cardiac-specific findings or highlights overall amyloid burden. Shi et al. similarly warn that systemic involvement complicates the interpretation of cardiac biomarkers in AL-CA.6 Finally, the homogeneity of the study population, taken mainly from a single Chinese centre, may limit the generalizability of findings. Garcia-Pavia et al. highlighted the variability of cardiac amyloidosis across ethnic and geographic backgrounds, where variability in genetic susceptibility, healthcare access and treatment access shapes prognosis.5 In conclusion, Meng et al. demonstrate the ability of MWI as a novel prognostic tool in AL-CA. However, for CMR comparison, treatment response stratification, competing risk adjustment and multi-ethnic representation, external validation is needed to confirm these conclusions. Future multicentre studies including these elements will be necessary to establish MWI as a reliable, clinically actionable biomarker in AL-CA. F.H. conceptualized and drafted the manuscript. Z.B. contributed to literature review, critical editing and final approval. Both authors approved the final version and are accountable for all aspects of the work. The authors received no specific funding for this work. The authors declare no conflicts of interest. Not applicable. This correspondence is based on previously published data and does not involve new human or animal research. Not applicable. This work does not contain any identifiable patient data. All data supporting the findings of this study are available from the corresponding author upon reasonable request.