Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts

Background-Primary (AL) amyloidosis is a plasma cell dyscrasia characterize d by clonal production of immunoglobulin light chains (LC) resulting in the subsequent systemic deposition of extracellular amyloid fibrils. Cardiac i nvolvement is marked by the hemodynamic pattern of impaired diastolic filli ng and restrictive cardiomyopathy. Although cardiac death in patients with AL amyloidosis is usually associated with extensive myocardial infiltration , the infiltration alone does not correlated with the degree of heart failu re or survival. We hypothesized that circulating monoclonal LC may directly impair cardiac function, in addition to any mechanical effects of amyloid fibril deposition. Therefore, we examined the effects of amyloid LC protein s on diastolic and systolic cardiac function, as measured in an isolated mo use heart model. Methods and Results-LC were obtained from patients with nonamyloid disease or from those with noncardiac, mild cardiac. and severe cardiac involved AL amyloidosis. Saline or LC (100 mug/mL) was infused into a Langendorff-perf used, isovolumically contracting mouse heart. Saline and control, noncardia c, and mild-cardiac LC infusions did not alter ex vivo cardiac function. In contrast, infusion of sever cardiac LC resulted in marked impairment of ve ntricular relaxation with preservation of contractile function. Conclusion-These results demonstrate that infusion of LC from patients with AL amyloidosis result in diastolic dysfunction similar to that observed in patients with cardiac involved AL amyloidosis, and they suggest that amylo id LC proteins may contribute directly to the pathogenesis and the rapid pr ogression of amyloid cardiomyopathy, independent of extracellular fibril de position.