Another Obesity Paradox: In Cardiac AL Amyloid a Higher BMI Is Associated with a Lower Rate of Cardiac Response
Authors: Kim So Yeon , Vest Amanda , Comenzo Raymond L , Varga Cindy 
Published: November 2019

Background:Light-chain amyloidosis (AL) is a clonal plasma cell disorder in which Ig light chains cause organ-specific disease due to toxic misfolded light-chain aggregates and extracellular deposition of amyloid fibrils derived from light chain proteins. The majority of amyloid patients present in various stages of heart failure and survival is largely driven by the extent of cardiac involvement. In the general heart failure population, overweight and mild/moderate obesity is associated with lower mortality, termed the obesity survival paradox. Conversely for patients with multiple myeloma, a disease similar in pathophysiology to AL, obesity is a risk factor for hematological progression. Hypothesis:We hypothesized that patients with cardiac amyloidosis would exhibit an obesity survival paradox and sought to determine the impact of BMI on hematological and cardiac responses to anti-plasma cell treatment. Methods:We conducted a single tertiary center retrospective study of consecutive patients with cardiac AL amyloidosis, referred between 1/1/2009 and 09/30/2018. We collected demographics and BMI prior to treatment. We recorded the date of diagnosis and subsequent dates of hematological and/or cardiac response, mortality or end of follow-up. We constructed a Cox proportional hazards model examining the association between BMI and mortality with a restricted cubic spline function curve. Three logistic regression models were constructed to examine the association between high BMI (>/=25 kg/m2) and cardiac or hematological response, and mortality. Models were adjusted for age, sex and cardiac stage at the time of diagnosis. Results:Of 79 patients, 17 patients had BMI of 17-22.5, 19 a BMI of 22.6-25, 23 a BMI of 25.1-29.7, and 20 a BMI of >/=30 kg/m2. Crude mortality was 31/79 (39%). There was no relationship between BMI as a continuous variable and mortality (HR 0.98, 95% CI 0.91-1.06, p=0.625, adjusted for age and sex), although a survival paradox trend was suggested by the spline curve. While there was no relationship between high BMI and hematological response (adjusted OR 1.00, 0.37-2.75, p=0.996), there was a relationship between high BMI and lower likelihood of achieving cardiac response (adjusted OR 0.23, 0.07-0.71, p=0.011). Conclusions:In this small cohort of patients with AL cardiac amyloidosis, there was no significant relationship between BMI and mortality. Hematological response was unrelated to BMI, but patients with a higher BMI were significantly less likely to achieve a cardiac response. These findings suggest that obesity might be associated with poorer cardiac outcomes in AL amyloidosis, highlighting the importance of a multidisciplinary approach involving oncologists, cardiologists, and nutritionists in the treatment of this complex multi-organ disease.

Disclosures
Comenzo: Caelum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prothena Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Myself: Patents & Royalties: Patent 9593332, Pending 20170008966; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding.