Bandaru, Ravi

Abstract Background Depression has emerged as a critical risk factor for development and progression of various cardiovascular diseases; however, the association between depression and Hypertrophic Cardiomyopathy (HCM) outcomes is less clear. We aimed to determine the impact of comorbid depression on patients hospitalized with HCM. Methods The National Inpatient Sample (2020) was assessed to identify patients hospitalized with HCM using relevant ICD-10 codes. Propensity score matching of 1:1 was performed and the cohort was divided into two - those with comorbid depression (HCM-D+) and those without (HCM-D-). Baseline characteristics and comorbidities were compared between the two cohorts. Impact of comorbid depression on hospitalized HCM patients was evaluated using a multivariate regression analysis adjusting for confounders. Results We identified a cohort of 15530 in-hospital HCM patients with a median age of 67 years (66.9% females, 33.1% males, 74.6% whites, 19.1% blacks, 4.3% hispanics, 1.7% Asians). Amongst 15530, 85.5% admissions were non-elective. The HCM-D+ cohort had significantly higher rates of comorbidities such as hypertension (76.4% vs 71.4%), hyperlipidemia (62.5% vs 52.4%), obesity (27.9% vs 24.9%), smoking (28.1% vs 25.7%), dementia (8.2% vs 4.4%) and cancer (7.5% vs 5.8%) (p<0.001). When in-hospital outcomes were compared, HCM-D+ cohort paradoxically appeared to have 44% lower risk of all-cause mortality (OR-0.56; 95%CI: 0.37- 0.84), 22% lower risk of composite end points (all-cause mortality, heart failure, atrial fibrillation, cardiac arrest including ventricular fibrillation, acute ischemic stroke) (OR-0.78; 95%CI:0.66-0.91), 21% lower risk of atrial fibrillation alone (OR-0.79; 95%CI:0.67-0.92) (p<0.001). Conclusion Despite having higher rates of comorbidities, comorbid depression in HCM patients appeared to improve in-hospital outcomes. Further studies are needed to uncover the paradoxical protection provided by underlying depression.

Abstract Background. Third generation aromatase inhibitors (AIs) have been shown to be superior to tamoxifen in multiple randomized clinical trials and become the new standard of treatment for postmenopausal women with early or advanced endocrine-sensitive breast cancer. It is thus important to identify biomarkers predicting resistance to AIs so that alternative therapeutic options can be employed. A two gene expression index, HOXB13:IL17BR, and HOXB13 in particular, has been shown to be a negative predictor of clinical benefit from tamoxifen. It is unclear whether HOXB13:IL17BR or HOXB13 is also predictive of AI therapy.Methods. We performed a retrospective analysis of a phase II randomized neoadjuvant study of everolimus+letrozole vs. placebo+letrozole in patients with estrogen receptor-positive breast cancer. Total RNA was extracted from frozen tissue biopsies taken either prior to treatment or after 15 days of treatment. HOXB13:IL13BR and a molecular grade index (MGI) were measured in 107 pre-treatment samples and 111 samples after 15 days of treatment. Antiproliferative response as defined by a ln[Ki767] <1 at day 15 in the samples analyzed was correlated with these gene expression indices.Results. In the placebo+letrozole treatment arm, the antiproliferative response rate was 30% (14/47). Using a pre-specified cutpoint of 0.06, the response rate was 40% for low HOXB13:IL17BR patients, compared to 12% for high HOXB13:IL17BR patients (p=0.05). In the everolimus+letrozole arm, the antiproliferative response rate in the samples analyzed was 55% (33/60), and the response rates for low and high HOXB13:Il17BR patients were 70% and 37% (p=0.02), respectively. When examined separately, high HOXB13 expression was significantly associated with nonresponse to therapy (everolimus+letrozole arm, p=0.02; placebo+letrozle arm, p=0.03), but IL17BR was not (everolimus+letrozole arm, p=0.6; placebo+letrozle arm, p=0.88). As expected, we observed a significant correlation between MGI and Ki67 staining (Spearman r=0.67, p<0.0001).Conclusions. High HOXB13:IL17BR index and high HOXB13 expression may identify a possible subset of patients with estrogen receptor-positive tumor that could be less responsive to aromatase inhibitors such as letrozole. Furthermore, use of MGI may enable rapid assessment of antiproliferative response by fine needle aspiration. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2120.