Abstract
Background Amyloidosis refers to the extracellular deposition of fibrils composed of low molecular weight protein subunits (5 to 25 kD) of a variety of serum proteins. These fibrils adopt a beta-pleated sheet configuration that leads to characteristic histological changes. Amyloid deposits can occur in a variety of organs, with the involvement of the heart, kidney, liver, and autonomic nervous system most often being responsible for morbidity and mortality. Cardiac amyloidosis is most commonly associated with light-chain (AL) and transthyretin (ATTR) deposition in the United States, and is associated with an increased risk of heart failure, arrhythmias, and conduction defects. The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is higher in older age, men and African Americans. There is insufficient data describing the prevalence and characteristics of MGUS in patients with cardiac ATTR amyloidosis. This study aims to identify the prevalence and characteristics of secondary MGUS in patients with cardiac ATTR amyloidosis. The secondary endpoint for the study is to assess for overall survival comparing patients with ATTR and MGUS versus patients with ATTR alone.
Methods We conducted a multicentric retrospective descriptive study, including all patients with cardiac amyloidosis treated in an academic healthcare system from January 2009 to September 2021. Patients who did not have biopsy proven cardiac amyloidosis, or had another type of amyloidosis were excluded from the study. An exemption from the Institutional Review Board for obtaining individual subjects' consent was procured. We obtained data from chart review of patients who were diagnosed with amyloidosis. Statistical analysis was reported using means for descriptive data.
Results We analyzed a total of 122 patients, of which 54 patients had biopsy proven cardiac ATTR amyloidosis. 8 of these 54 patients had MGUS diagnosed with an abnormal serum-free light chain ratio and/or serum immunofixation electrophoresis. The predominant monoclonal proteins were immunoglobulins G kappa (IgG K), A kappa (IgA K) and G lambda (IgG λ) seen in 3, 3 and 2 patients respectively. The mean age of patients at the time of extraction was 79±7 years. Of 8 patients with MGUS, 7 patients were males (87.5%) and 7 patients were African American (87.5%). The average duration of being diagnosed with MGUS from cardiac ATTR amyloidosis was 419 days. The mean M spike was 3.85±4.76. 5 out of these 8 patients died of end stage heart failure.
Conclusion Although previous studies such as by Phull et al have demonstrated an increased incidence of MGUS in patients with cardiac ATTR amyloidosis, there was no race stratification in those studies. Our study shows a higher prevalence of secondary MGUS in African American patients with cardiac ATTR amyloidosis. Furthermore, our study also highlights the time gap between the diagnoses of cardiac ATTR amyloidosis and MGUS. These findings highlight the importance of a thorough diagnostic evaluation in patients with amyloidosis to determine the precursor protein, as the clinical course and treatment of AL and ATTR cardiac amyloidosis are very different, as AL amyloidosis involves treatment with bortezomib-based chemotherapy and autologous hematopoietic cell transplant (AHCT) while ATTR amyloidosis involves treatment with transthyretin stabilizers such as Tafamidis to reduce cardiovascular mortality and cardiovascular-related hospitalization. Given the small sample size of our study, further large-scale studies are required to establish the incidence of secondary MGUS in patients with cardiac ATTR amyloidosis, especially in African Americans.
Disclosures
Catlett:Electra Therapeutics: Research Funding.
