Impact of coronavirus disease 19 outbreak on arrhythmic events and mortality among implantable cardioverter defibrillator patients followed up by remote monitoring: a single center study from the Veneto region of Italy.

BACKGROUND: The 2020 severe acute respiratory syndrome coronavirus 2 outbreak entailed reduced availability of traditional (in-office) cardiology consultations. Remote monitoring is an alternative way of caring that may potentially mitigate the negative effects of the epidemic to the care of cardiovascular diseases. We evaluated the outcome of implantable cardioverter defibrillator (ICD) carriers followed up remotely in 2020 (epidemic period) versus 2019 (control). METHODS: We included all patients with an ICD who remained remotely monitored from the beginning to the end of each year. The combined end point included: new-onset atrial fibrillation; sustained ventricular tachycardia >170 bpm without ICD intervention; appropriate ICD intervention (either shock or antitachycardia pacing); any-cause death. Multiple events in the same patients were counted separately if occurring ≥48 h apart. RESULTS: In 2020, 52 end points occurred in 37 of 366 (10%) ICD carriers [0.14/patient (95% confidence interval [CI] = 0.11-0.19)] versus 43 end points in 32 of 325 (10%) ICD carriers in 2019 [0.13/patient (95% CI = 0.10-0.18) P  = 0.75]. There was no difference between the distribution of any individual end point in 2020 versus 2019 although a nonsignificant mortality increase was observed (from 2.8% to 4.6%, P  = 0.19). The lowest weekly event rate occurred during the national lock down in spring 2020 but a similar trend occurred also in 2019 suggesting that the effect may not be linked to social distancing measures. CONCLUSIONS: We did not observe an increase in a combined end point including arrhythmic events and mortality in ICD carriers who were remotely monitored in 2020, compared to 2019, despite the negative impact of the coronavirus disease 2019 outbreak on the healthcare system.

Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases.

Inflammatory diseases including COVID-19 are associated with a cytokine storm characterized by high interleukin-6 (IL-6) titers. In particular, while recent studies examined COVID-19 associated arrhythmic risks from cardiac injury and/or from pharmacotherapy such as the combination of azithromycin (AZM) and hydroxychloroquine (HCQ), the role of IL-6 per se in increasing the arrhythmic risk remains poorly understood. The objective is to elucidate the electrophysiological basis of inflammation-associated arrhythmic risk in the presence of AZM and HCQ. IL-6, AZM and HCQ were concomitantly administered to guinea pigs in-vivo and in-vitro. Electrocardiograms, action potentials and ion-currents were analyzed. IL-6 alone or the combination AZM + HCQ induced mild to moderate reduction in heart rate, PR-interval and corrected QT (QTc) in-vivo and in-vitro. Notably, IL-6 alone was more potent than the combination of the two drugs in reducing heart rate, increasing PR-interval and QTc. In addition, the in-vivo or in-vitro combination of IL-6 + AZM + HCQ caused severe bradycardia, conduction abnormalities, QTc prolongation and asystole. These electrocardiographic abnormalities were attenuated in-vivo by tocilizumab (TCZ), a monoclonal antibody against IL-6 receptor, and are due in part to the prolongation of action potential duration and selective inhibition of Na+, Ca2+ and K+ currents. Inflammation confers greater risk for arrhythmia than the drug combination therapy. As such, in the setting of elevated IL-6 during inflammation caution must be taken when co-administering drugs known to predispose to fatal arrhythmias and TCZ could be an important player as a novel anti-arrhythmic agent. Thus, identifying inflammation as a critical culprit is essential for proper management.

COVID-19-related arrhythmias and the possible effects of ranolazine.

The COVID-19 pandemic has become a burden to the global healthcare community. Despite the severity of the complications associated with COVID-19, no antiviral agent is yet available for the treatment of this disease. Several studies have reported arrhythmias as one of the numerous manifestations associated with COVID-19 infection. Clinicians use different therapeutic agents in the management of COVID-19 patients with arrhythmias, apart from ranolazine; however, some of these drugs are administered with caution because of their significant side effects. In this study, we reviewed the potential antiarrhythmic effects of ranolazine in the management of cardiac arrhythmias associated with COVID-19. Ranolazine is a second-line drug approved for the treatment of chronic stable angina pectoris. Previous studies have shown that ranolazine produces its beneficial cardiac effects without any significant impact on the body's hemodynamics; hence, blood pressure is not altered. Due to its reduced side effects, ranolazine may be more effective than other drugs in producing the desired relief from COVID-19 related arrhythmias, since it produces its antiarrhythmic effect by modulating sodium, potassium and calcium channels, and suppressing cytokine expression.

ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy.

COVID-19 is an infectious respiratory illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and until now, there is no effective therapy against COVID-19. Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding domain-containing spike S1 and ACE-2. Accordingly, wild type (wt), but not mutated (m), AIDS peptide inhibited SARS-CoV-2 spike S1-induced activation of NF-κB and expression of IL-6 in human lungs cells. Interestingly, intranasal intoxication of C57/BL6 mice with recombinant SARS-CoV-2 spike S1 led to fever, increase in IL-6 in lungs, infiltration of neutrophils into the lungs, arrhythmias, and impairment in locomotor activities, mimicking some of the important symptoms of COVID-19. However, intranasal treatment with wtAIDS, but not mAIDS, peptide reduced fever, protected lungs, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of ACE2-to-SARS-CoV-2 interaction by wtAIDS may be beneficial for COVID-19.

Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society.

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.