Introduction

Amyloidosis is characterized by systemic amyloid deposition, with light-chain amyloidosis being common and impacting multiple organs^1,2. Cardiac involvement is a critical factor in patient survival³. Cardiac Magnetic Resonance (CMR) has emerged as a valuable modality for diagnosing and predicting outcomes in patients with cardiac amyloidosis. Feature tracking (CMR-FT) has gained prominence due to its simplicity and reliability in quantifying left ventricular (LV) strain using SSFP sequences⁴. Notably, myocardial strain has demonstrated superior prognostic value in specific clinical contexts involving patients with AL-CA⁵. Despite advancements, the research on prognostic implications of myocardial strain in various segments of cardiac amyloidosis remains limited.

Methods

Seventy-five consecutive patients, comprising 50 males with an average age of 55.6 ± 10.0 years, who had undergone CMR examinations and were histologically confirmed to have systemic AL-CA, were enrolled from January 2014 to November 2022. CMR scans were performed using both 3.0-T scanners (Philips Ingenia, GE Discovery MR750, SIEMENS MAGNETOM Prisma) and 1.5-T scanners (SIEMENS MAGNETOM Aera), employing either cardiac or abdominal coils. Subsequently, CMR images were imported into CVI42 v5.14.2 software for in-depth analysis.
To assess myocardial function, global and segmental longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) of the left ventricle were quantified using SSFP cine sequences. This analysis including the basal, middle, and apical segments, in line with the American Heart Association's 16-segment model for segmental myocardial motion evaluation (Figure 1). The period between the CMR examination date and the occurrence of a patient's demise was regarded as the event time, divided into survivors and non-survivors groups. The prognostic significance of LV strain parameters was assessed using Cox proportional hazards regression and visually depicted through Kaplan–Meier curves.

Results

After a median follow-up period of 34 months, 16 out of 75 patients reached the endpoint of mortality, who classified into survivor and non-survivor groups. Baseline and CMR characteristics of patients with AL amyloidosis were summarized in Table 1. Among these patients, there was a notable change in LV strain parameters when compared survivor with non-survivor groups, including RS_global, CS_global, RS_basal, RS_middle, CS_basal, CS_middle, LS_basal, and LS_apical, P < 0.05 for all (Table 1). Furthermore, significant variations in strain measurements were observed within specific myocardial segments (Figure 2).
In a multivariate Cox analysis, BNP (hazard ratio, 1.001; 95% CI: 1.001, 1.002; p < 0.001), RS_global (hazard ratio, 4.440; 95% CI: 1.128, 17.477; p = 0.003), and RS in the basal lateral segment (RS_bas-lateral) (hazard ratio, 5.953; 95% CI: 1.245, 28.471; p = 0.025) remained significant as independent predictors of all-cause mortality (Table2). The cut-off values were identified as 354.5 for BNP, 24.97% for RS_global, and 20.97% for RS_bas-lateral. After categorizing AL patients into two groups by using the defined cut-off values, Kaplan-Meier survival curves revealed significantly reduced event-free survival for individuals in the lower cut-off groups for RS_global and RS_bas-lateral (P = 0.013, P < 0.001, respectively) (Figure 3).

Discussion

In patients who reached the study endpoint, notable alterations in myocardial strain patterns were observed, characterized by reduced radial strain coupled with increased circumferential and longitudinal strains in the basal myocardial segments. These findings corroborate existing research in the field^6,7. Moreover, distinctions in radial and circumferential strains at the apical segments between survivors and non-survivors were relatively minimal, with the exception of longitudinal strains. It is evident that basal segments are more susceptible to involvement, and the change in strains in these segments may serve as an early indication of amyloid infiltration^8,9. Intriguingly, significant disparities in segmental strains across the 16 myocardial segments were identified between the two groups, with a pronounced emphasis on the septal and lateral walls, necessitating further exploration of the underlying mechanisms. The study's results unveiled the independent associations of RS_global, RS_bas-lateral, and BNP with all-cause mortality. RS_global, reflecting myocardial fiber deformation toward the heart's central cavity, exhibited a correlation with changes in myocardial fiber thickness¹⁰. The novel contribution of this study lies in the potential utility of RS_bas-lateral for risk stratification in AL amyloidosis patients. This suggests that the lateral wall might be particularly susceptible to experiencing early or intensified pathological structural and functional changes¹¹. Nonetheless, the comprehensive mechanistic understanding of this phenomenon remains to be elucidated. Consequently, it is important to highlight that the measurement of RS_bas-lateral remains a valuable approach for routine assessment of AL-CA prognosis.

Conclusions

Global radial strain and radial strain in the basal lateral segment, assessed through CMR, exhibit potential as noninvasive markers for independently predicting all-cause mortality in AL amyloidosis patients.

Acknowledgements

None

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