Vignarajah, Aravinthan

Background: Transvenous lead extraction (TLE) is the standard of care for cardiac implantable electronic device (CIED) infections. Data regarding the optimal timing of CIED reimplantation after TLE are not well established. Objective: This study aims to assess the 5-year outcomes of early (≤7 days) versus non-early (>7 days) CIED reimplantation following TLE for CIED infection using a multi-national database. Methods: Using the TriNetX Analytics Research Network, we included patients aged ≥18 years who underwent TLE for CIED infection between 1/1/2014 and 1/1/2020. Patients were further categorized into two groups: early CIED reimplantation (≤7 days from TLE) and non-early CIED reimplantation. Propensity score matching (PSM) was performed by including patient demographics, LVEF, cardiac comorbidities and medications. The study outcomes included all-cause mortality and cardiac adverse events during a 5-year study period. Results: A total of 1668 patients in the early CIED reimplantation group and 1550 in the non-early group were identified. After PSM, 1327 patients in each group were analyzed. Compared to non-early group, early CIED reimplantation group was associated with significantly higher odds of all-cause hospitalization (odds ratio [OR]: 1.837, 95% confidence interval [CI]: 1.532-2.203) and repeated device infection (OR: 1.569, 95% CI: 1.314-1.873) at 5-year follow-up. However, no significant differences were observed in all-cause mortality (OR: 0.927, 95% CI: 0.778-1.104), HF exacerbation (OR: 1.021, 95% CI: 0.855-1.218), cardiac arrest (OR:0.924, 95% CI: 0.739-1.157), stroke (OR: 1.169, 95% CI: 0.915-1.494), cardiac thrombus (OR: 1.163, 95% CI: 0.749-1.808), major bleeding (OR: 1.079, 95% CI: 0.857-1.358) and venous thromboembolism (OR: 0.923, 95% CI: 0.759-1.123) between the two groups. Conclusion: Early reimplantation of CIED following TLE of infected devices was associated with worse outcomes in all-cause hospitalization and repeated device infection. Further large prospective studies are needed to define the optimal timing of device reimplantation.

e19524 Background: Carfilzomib, a second-generation proteasome inhibitor, has emerged as one of the therapeutic agents in the treatment of relapsed or refractory multiple myeloma (MM). Despite its known cardiotoxicity, real-world data on its long-term cardiovascular outcomes remain limited. This study aimed to evaluate the real-world cardiovascular outcomes in patients with relapsed or refractory MM treated with carfilzomib. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with relapsed or refractory MM between January 1, 2014, and January 1, 2019. We further categorized the patients into two groups: patients exposed to carfilzomib and patients not exposed to carfilzomib. Inclusion in the carfilzomib group required exposure to carfilzomib during the 5-year study period. Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes were cardiovascular outcomes, including acute heart failure, acute myocardial infarction, cerebrovascular accident, acute venous thromboembolism, all-cause hospitalization, and all-cause mortality over the 5-year follow-up duration. Results: A total of 151,802 patients with relapsed or refractory MM were identified, including 6,386 patients (mean age 64.8 ± 10.6 years) who were exposed to carfilzomib and 145,416 patients (mean age 66.1 ± 12.7 years) who were not. After propensity score matching, there were 4,559 (65.3 ± 10.8 years of age, 44.7% female, 18.2% African American [AA]) patients who were exposed to carfilzomib and 4,559 patients who were not (65.2 ± 12.2 years of age, 45.1% female, 17.0% AA). Exposure to carfilzomib was associated with higher odds of acute heart failure (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.48-1.77, P < 0.001), acute myocardial infarction (aOR: 1.24; 95% CI: 1.03-1.48, P = 0.020), cerebrovascular accident (aOR: 1.97; 95% CI: 1.47-2.64, P < 0.001), acute venous thromboembolism (aOR: 1.79; 95% CI: 1.58-2.03, P < 0.001), all-cause hospitalizations (aOR: 1.91; 95% CI: 1.75-2.09, P < 0.001), and all-cause mortality (aOR: 1.97; 95% CI: 1.80-2.16, P < 0.001). Conclusions: Patients with relapsed or refractory MM who were exposed to carfilzomib had poorer cardiovascular outcomes compared to those who did not.

e19515 Background: The prevalence of diabetes mellitus (DM) is significantly higher in patients with multiple myeloma (MM) compared to the general population. DM has been associated with worse outcomes in MM, including reduced overall survival and increased mortality. The impact of diabetes in patients with MM is further compounded by cardiotoxicity from proteasome inhibitors and the increased thromboembolic risk linked to immunomodulatory agents. Given the potential benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors, we hypothesized that their use in MM patients with DM could improve clinical outcomes and mitigate adverse events in this population. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with MM and DM between January 1, 2013, and January 1, 2019. We categorized the patients into SGLT2 inhibitors users and SGLT2 inhibitors users. Inclusion in the SGLT2 inhibitors group required exposure to SGLT2 inhibitors for at least 1 year. 1:1 Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes include all-cause mortality, all-cause hospitalization, acute venous thromboembolism (VTE), acute heart failure (HF), acute myocardial infarction (MI), cardiac arrhythmia, and cardiac arrest over the 5-year follow-up duration. Results: A total of 43,078 patients were identified, including 3,640 SGLT2 inhibitors users and 39,438 non-SGLT-2 inhibitors users. After 1:1 propensity-score matching, there were 3,379 SGLT-2 inhibitor users (68.9 ± 10.3 years of age, 38.0% female, 23.9% African American [AA]) and 3,379 non-SGLT-2 inhibitor users (68.9 ± 11.0 years of age, 35.9% female, 22.2% AA). SGLT-2 inhibitors users were associated with lower rates of all-cause mortality (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.30-0.39) and all-cause hospitalization (OR: 0.52, 95% CI: 0.47-0.58). Lower odds of acute VTE (OR: 0.59, 95% CI: 0.49-0.70), acute HF (OR: 0.89, 95% CI: 0.81-0.98), acute MI (OR: 0.81, 95% CI: 0.69-0.95), cardiac arrhythmia (OR: 0.82, 95% CI: 0.70-0.97), and cardiac arrest (OR: 0.57, 95% CI: 0.44-0.74) were reported among SGLT-2 inhibitors users compared to non-SGLT2 inhibitor users. Conclusions: Our study revealed that only 8.4% of patients with DM and MM were prescribed an SGLT-2 inhibitor. Our study also demonstrated that SGLT2 inhibitor use was associated with lower odds of all-cause mortality and hospitalization, reduced risk of VTE, and favorable cardiovascular outcomes in this patient population.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.