Aims Multiple myeloma accounts for over 10–15% of haematological malignancies. Continued molecular advances have resulted in the development of new drugs for treatment of multiple myeloma. Four drugs were approved by the Food and Drug Administration (FDA) in 2015, but their safety is not well defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. Methods We reviewed the adverse cardiac events of newly approved FDA drugs since 2015 using the US FDA Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval (CIs) for the drugs that have the highest incidence of cardiovascular adverse events. Results Among the medications that have approved for multiple myeloma between 2015 and 2020, 4 novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, ixazomib, daratumumab and panobinostat compared to other FAERS drugs was 5.8 (4.4–7.7), 1.9 (1.5–2.3), 4.8 (4.2–5.6) and 5.7 (4.1–8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4–10.5), 4.7 (4.1–5.4), 5.8 (4.9–6.7) and 5.6 (3.8–8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9–3.9), 2.7 (2.3–3.2), 2.3 (1.9–2.8) and 4.6 (3.2–6.6) due to elotuzumab, ixazomib, daratumumab and panobinostat compared to all other drugs in FAERS. Conclusion Our results demonstrated that certain newly approved antimyeloma therapies are significantly associated with previously unknown cardiotoxicity. These results warrant further studies and highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.
The role of lymphatic vessels in myocarditis is largely unknown, while it has been shown to play a key role in other inflammatory diseases. We aimed to investigate the role of lymphatic vessels in myocarditis using in vivo model induced with Theiler's murine encephalomyelitis virus (TMEV) and in vitro model with rat cardiac lymphatic muscle cells (RCLMC). In the TMEV model, we found that upregulation of a set of inflammatory mediator genes, including interleukin (IL)-1β, tumor necrosis factor (TNF)-αand COX-2 were associated with disease activity. Thus, using in vitro collagen gel contraction assays, we decided to clarify the role(s) of these mediators by testing contractility of RCLMC in response to IL-1β and TNF-α individually and in combination, in the presence or absence of: IL-1 receptor antagonist (Anakinra); cyclooxygenase (COX) inhibitors inhibitors (TFAP, diclofenac and DuP-697). IL-1β impaired RCLMC contractility dose-dependently, while co-incubation with both IL-1β and TNF-α exhibited synergistic effects in decreasing RCLMC contractility with increased COX-2 expression. Anakinra maintained RCLMC contractility; Anakinra blocked the mobilization of COX-2 induced by IL-1β with or without TNF-α. COX-2 inhibition blocked the IL-1β-mediated decrease in RCLMC contractility. Mechanistically, we found that IL-1β increased prostaglandin (PG) E release dose-dependently, while Anakinra blocked IL-1β mediated PGE release. Using prostaglandin E receptor 4 (EP4) receptor antagonist, we demonstrated that EP4 receptor blockade maintained RCLMC contractility following IL-1β exposure. Our results indicate that IL-1β reduces RCLMC contractility via COX-2/PGE signaling with synergistic cooperation by TNF-α. These pathways may help provoke inflammatory mediator accumulation within the heart, driving progression from acute myocarditis into dilated cardiomyopathy.
and cardiogenic shock. Symptoms and cardiac function improved with intravenous beta-blockers and diuresis along with the removal of the trigger agent. Our case highlights the rare but possible scenario in which a beta-2 agonist triggers TC. 4 For these patients, systemic corticosteroids, inhaled anticholinergics, and aminophylline might be considered as first-line treatment for COPD exacerbations to avoid administration of inhaled beta-2 agonist administration (see Videos, Supplemental
Introduction: the role of vaccines in preventing diseases is well-established. However, the evolving techniques and types of vaccine necessitate the search for its safety more than ever. While cases of takotsubo cardiomyopathy and COVID-19 vaccine have been described, a comprehensive study to investigate the role of vaccination with cardiomyopathy and heart failure is lacking. The aim of this study is to investigate the link between the current vaccines and heart failure. Method: we utilized vaccine adverse event reporting system (VAERS) to search for cardiomyopathy, cardiac failure or ventricular dysfunction. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with 95% confidence interval (CI). Results: VAERS reported over 1,300,000 adverse events between 1990-2021. Heart failure was reported over 2000 times in association with multiple vaccines. 56% of vaccine-related heart failure reported in males; 88% were serious; 19% mortality rate. The majority of reported heart failure was related to COVID-19 vaccines with ROR of 21.6 (CI: 18.3 to 25.4, P<0.0001). Smallpox was also significant with ROR 7.2 (CI 5.5-9.6, P<0.0001) On the other hand, heart failure was minimally described to be associated with other vaccines (influenza, zoster, tetanus, human papillomavirus (PPV)). Conclusions: Our study showed for the first time that vaccines maybe associated with heart failure. In particular, we show that covid-19 and smallpox vaccines are associated with increased risk of heart failure. Vaccines against Influenza, zoster, tetanus and (PPV) are associated with reduced heart failure. These data warrant longitudinal studies to delineate the association between heart failure and vaccines.
Background: Multiple myeloma accounts for over 15% of hematological malignancies. In attempt to tackle this malady, the FDA approved four drugs in 2015 which has propagated further development of new anti-multiple myeloma since. However, the health safety of these new agents is still ill-defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. Methods: We searched the cardiac adverse events of the newly approved FDA drugs since 2015 using the U.S. Food and Drug Administration Adverse Events Reporting System database. We calculated the reporting odds ratio (ROR) with 95% confidence for four drugs that have the highest incidence of cardiovascular adverse events. Results: Between 2015-2020, the FDA approved six novel agents for multiple myeloma which includes elotuzumab, Ixazomib, daratumumab, panobinostat, Isatuximab, and belantamab mafodotin. Among all these medications, elotuzumab, Ixazomib, daratumumab, and panobinostat showed the highest incidence of cardiovascular complications. After vetting all the cardiac adverse events, our analysis revealed that atrial fibrillation, heart failure, and coronary disease were the highest reported cardiac events with significant odds ratio. Conclusions: The newly approved multiple myeloma therapy (elotuzumab, Ixazomib, daratumumab, panobinostat) are significantly associated with cardiotoxicity. These results highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.