Introduction

Amyloidosis is a disease in which abnormal proteins infiltrate organs, causing dysfunction. Amyloid is categorized by the type of protein and its folding. One of the most common types of amyloidosis is amyloid light chain (AL) amyloidosis. In AL amyloidosis plasma cell dyscrasias create excess immunoglobulin light chain fragments, which form abnormal proteins which deposit in tissues (1). The worst prognosis in AL amyloidosis occurs with infiltration of the heart, which leads to myocardial thickening and heart failure (2). The definitive treatment of AL amyloidosis is autologous hematopoietic stem cell transplantation, which prevents further deposition of abnormal proteins. Organ response and progression is currently monitored with multiple, limited, insensitive, non-specific biomarkers. Amyloid infiltration is widely accepted to cause increased tissue stiffness (3), including within the heart. Dysregulation of myocardial stiffness plays an important role in cardiac function and can lead to congestive heart failure (4), contribute to left ventricular (LV) remodeling, and a significant challenge in treating myocardial infarction (5). Shear wave elastography is an emerging imaging approach for measuring myocardial stiffness in vivo (6-15). Recently, cardiac magnetic resonance elastography (MRE) reported that patients with cardiac amyloidosis have significantly elevated myocardial stiffness (14) compared to healthy age-matched controls. The goal of this study is to evaluate the feasibility of using cardiac magnetic resonance elastography (MRE) to monitor changes in left ventricular myocardial stiffness after stem cell transplantation for treatment of AL amyloidosis.

Methods

Five patients with AL cardiac amyloidosis were enrolled in this study prior to undergoing hematopoietic stem cell transplantation, and after receiving institutional review board and written informed consent approval. All subjects underwent cardiac MRI/MRE prior to therapy (baseline) and at their scheduled approximate 3 month follow-up visit. The mean age at time of enrollment was 58 (median: 59, max: 66, min: 51), with a mean follow-up time of 117.6 days (median: 114, max: 130, min: 106). MRE imaging was conducted at a vibration frequency of 140 Hz using the same procedure as previously described (16). Exams with an octahedral shear strain signal-to-noise ratio (OSS-SNR) (17,18) above 1.1 were considered in the analysis. A paired Student’s t-test was performed on the mean left ventricular myocardial stiffness at baseline and follow-up. A p-value of less than 0.05 was considered statistically significant. The estimated percentage change in myocardial stiffness per 100 days was calculated to help compensate for the slight differences in follow-up times.

Results

Systolic center-slice magnitude and elastogram images for all 5 volunteers at baseline and at their follow-up visit are shown in Figure 1. Quantitative stiffness maps demonstrate the decrease in left-ventricular myocardial stiffness post-therapy in all 5 patients. Quantitative mean LV myocardial stiffness values at baseline and at follow-up are plotted in Figure 2. Myocardial stiffness as a function of days after each patent’s first imaging session is plotted in Figure 3. The measured percentage change in stiffness at follow-up and the calculated expected change per 100 days post therapy have been plotted in Figure 4. The mean LV myocardial stiffness decreased by 17.0±7.4% (median: 15.1%, max: 28.4%, min: 8.2%) at follow-up (14.4±5.9% per 100 days), across patients. The mean absolute change in myocardial stiffness was calculated to be -1.6±0.7 kPa (median: -1.3 kPa, max: -2.4 kPa, min: -0.9 kPa) from baseline to follow-up. This decrease in stiffness was found to statistically significant (p = 0.007).

Discussion and Conclusions

This study demonstrates there is a statistically significant (p=0.007) decrease in LV myocardial stiffness (mean: 1.6±0.7 kPa, 17.0±7.4%) post hematopoietic stem cell transplantation as measured by MRE. These results not only suggest that stem cell therapy is affecting the biomechanics of the heart, but also that CMRE is a sensitive non-invasive monitoring technique capable of detecting these changes within a short follow-up time (~117 days post-therapy). These results motivate future investigations of cardiac MRE in larger patient cohorts, to monitor treatment response, and potentially as a means to detect early stages of cardiac diseases.

Acknowledgements

We would like to thank Kathy Brown for recruiting and scheduling all patient exams. This work was supported by the National Institutes of Health grants K12HD65987-11 and by internal grants funded by Mayo Clinic, Department of Radiology.

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