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.

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.

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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 (FAERS). We calculated the reporting odds ratio (ROR) with 95% confidence for four drugs that have the highest incidence of cardiovascular adverse events. Results: Among the medications that have approved for MM Between 2015-2020, four 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 versus all other drugs in FAERS. Conclusions: Our results demonstrated that the newly approved antimyeloma therapy (elotuzumab, Ixazomib, daratumumab, panobinostat) are significantly associated previously unknow 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.

Aim: Vaccines have been mainly described to provide cardioprotective effects with rare reports showing rare association with myopericarditis. However, vaccines have not been well studied regarding its effects on heart rhythm disorders. Methods: we used vaccine adverse event reporting system (VAERS) between 1990-2021 to search for atrial fibrillation and other less prevalent arrhythmia. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with 95% confidence interval (CI). Results: Over 1,300,000 adverse events were reported between 1990-2021. Among these events, atrial fibrillation was reported 2149 times in association with various vaccines. 90% of atrial fibrillation was associated with COVID-19 vaccines with ROR of 13.18 (CI 95%: 11.3 to 15.4) (P<0.0001). Interestingly, influenza vaccines, polyvalent polysaccharide pneumococcal (PPSV23) vaccine, pneumococcal 13-valent (PCV13) vaccine, zoster vaccine, and tetanus-containing vaccines were significantly associated with reduced atrial fibrillation. Finally, our analysis showed that COVID-19 vaccines were associated with much higher incidence of other cardiac arrhythmias compared with other vaccines. Conclusions: While vaccines have not been linked to heart rhythm disorders, the introduction of COVID-19 vaccines in 2020 showed significant association with atrial fibrillation. This study showed unprecedent detrimental effect of COVID-19 vaccines on atrial fibrillation and warrants the need to take that into consideration when prescribing COVID-19 vaccines.

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Vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance in combating the current coronavirus disease 2019 (COVID-19) pandemic. Syncopal episodes following routine vaccinations are well-reported; however, only a few cases of syncope following SARS-CoV-2 vaccines exist in the literature. This is a case report of a 21-year-old female patient who developed recurrent syncopal attacks over three months that started one day after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine (Pfizer, New York City; BioNTech, Mainz, Germany). Holter monitoring during successive episodes showed progressive bradycardia followed by a prolonged sinus arrest. The patient eventually required pacemaker placement that resulted in the total resolution of her symptoms. Further studies are required to investigate a possible correlation and the mechanisms involved.

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