COVID-19 and Cardiac Arrhythmias: a Contemporary Review.

Purpose of Review: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions. Recent Findings: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Summary: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.

Administration of macrolide antibiotics increases cardiovascular risk.

Background: The increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades. Methods: Medline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model. Results: A total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use. Conclusion: Administration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.

Cardiac arrhythmias in viral infections.

BACKGROUND: The current COVID-19 pandemic has led to many studies examining its arrhythmogenic effects. However, there are many other viruses that are capable of inducing arrhythmias that have not received as much attention. The objective of this study was to review common viruses and identify studies highlighting their arrhythmogenic effects. METHODS AND RESULTS: In this review, we examined 15 viruses and the literature regarding their arrhythmogenic effects. The common mechanisms of action appear to be direct invasion of myocytes leading to immune mediated damage, infection of vascular endothelium, and alteration of cardiac ion channels. CONCLUSIONS: This review highlights the growing evidence that supports the involvement of other viral infections in the development of arrhythmia. Physicians should be aware of these potentially life-threatening effects when caring for patients with these viruses, some of which are very common. Additional studies are required to better understand the complex mechanism and risk factors of cardiac arrhythmias in patients suffered from viral infections to determine whether the processes can be reversed or even prevented.

Electrical Storm in a Patient with Brugada Syndrome and Coronavirus Disease 2019.

Brugada syndrome (BrS) is an inherited arrhythmia syndrome characterized by right bundle branch block and dynamic ST-segment changes in precordial leads V1-V3. In patients with BrS, fever is a known trigger that may induce arrhythmia. For patients with BrS who contract coronavirus disease 2019 (COVID-19), the inflammatory response poses the risk of causing ventricular arrhythmias. The following case discusses the management of a patient with BrS presenting with electrical storm after contracting COVID-19. Treatment should be focused on aggressive anti-pyretic management along with concomitant pharmacological therapy.

Utility of exercise testing to assess athletes for post COVID-19 myocarditis.

Purpose: This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection. Methods: We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days. Results: We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2max, left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis. Conclusions: Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.

Arrhythmogenic Cardiomyopathy as a Late Complication of COVID-19-Induced Myocarditis.

COVID-19 has become a global health problem. So far, more than 281 million COVID-19 cases have been confirmed. The vast majority of patients diagnosed with COVID-19 infection present only with respiratory signs and symptoms. A small amount of patients, however, show signs and symptoms of cardiovascular involvement like a myocardial injury. Myocarditis is one of the possible complications, and cases of clinically suspected myocarditis have been reported in the setting of COVID-19. Herein, we present a case of inflammatory cardiomyopathy, a different type of arrhythmogenic cardiomyopathy, in a 32-year-old man, 40 days after being diagnosed with COVID-19.

The Prevalence and Associated Death of Ventricular Arrhythmia and Sudden Cardiac Death in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Arrhythmia is a very common complication of coronavirus disease 2019 (COVID-19); however, the prevalence of ventricular arrhythmia and associated outcomes are not well-explored. Here, we conducted a systematic review and meta-analysis to determine the prevalence and associated death of ventricular arrhythmia and sudden cardiac death (SCD) in patients with COVID-19. METHODS: Databases of PubMed, Cochrane Library, Embase, and MdeRxiv were searched. Studies that could calculate the prevalence of ventricular arrhythmia/SCD during hospital admission or associated death in patients with COVID-19 were included. The study was registered with the PROSPERO (CRD42021271328). RESULTS: A total of 21 studies with 13,790 patients were included. The pooled prevalence of ventricular arrhythmia was 5% (95% CI: 4-6%), with a relatively high-SCD prevalence (1.8% in hospitalized COVID-19 and 10% in deceased cases of COVID-19). Subgroup analysis showed that ventricular arrhythmia was more common in patients with elevated cardiac troponin T [ES (effect size): 10%, 95% CI: -0.2 to 22%] and in European (ES: 20%, 95% CI: 11-29%) populations. Besides, ventricular arrhythmia was independently associated with an increased risk of death in patients with COVID-19 [odds ratio (OR) = 2.83; 95% CI: 1.78-4.51]. CONCLUSION: Ventricular arrhythmia and SCD resulted as a common occurrence with a high prevalence in patients with COVID-19 admitted to the hospital. Furthermore, ventricular arrhythmia significantly contributed to an increased risk of death in hospitalized patients with COVID-19. Clinicians might be vigilant of ventricular arrhythmias for patients with COVID-19, especially for severe cases. SYSTEMATIC REVIEW REGISTRATION: www.york.ac.uk/inst/crd, identifier: CRD42021271328.

Cardiotoxicity of azithromycin in COVID-19: an overall proportion meta-analysis.

INTRODUCTION: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. MATERIAL AND METHODS: We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of Covid19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. RESULTS: Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of > 60ms QTc prolongation from baseline was 13% (95% CI 9%-18%, I² = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%-11%, I² = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%-5%, I² = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. CONCLUSIONS: Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with Covid19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection.

The Effect of Hydroxychloroquine On Ventricular Repolarization Parameters Jtc And Jtpc Intervals In Patients With Covid-19

JT and JTp intervals are among the ventricular repolarization parameters and prolongation, just as the QT interval is related to ventricular arrhythmias. This study aims to examine the effect of hydroxychloroquine on JTc and JTpc intervals in individuals hospitalized with COVID-19. We involved 130 COVID-19 patients divided into two groups as the hydroxychloroquine treatment group and the control group, in this study. ECGs of the patients were recorded at admission and after a median of 48 hours following the initiation of hydroxychloroquine treatment. Then, QTc, JTc, and JTpc intervals were measured. Patients' average age was 48 (37-66 IQR), and 53% of the individuals were female. The median basal JTpc interval was 215 ms(195-230 IQR), while JTpc-Day 3 was 220 ms(195-238 IQR). The median basal JTc interval was 320 ms(301-334 IQR), while JTc-Day 3 was 328 ms(306-343 IQR). JTpc and JTc interval in the hydroxychloroquine group have prolonged significantly (p<0.001), while there were no significant changes in the control group for both values (p>0.05). There was a significant prolongation in the multivariable linear regression analysis in JTc-Day 3 and JTpc-Day 3 after hydroxychloroquine treatment. (ß=-2.589, 95%CI, 2.384-17.894, p=0.011, ß=2.195, 95%CI, 759 -14.752, p=0.030, respectively). In this study, we found significant prolongation in JTc and JTpc intervals in the patients who take hydroxychloroquine treatment. [ FROM AUTHOR] Copyright of Eastern Journal of Medicine is the property of Yuzuncu Yil University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A new predictor for indicating clinical severity and prognosis in COVID-19 patients: Frontal QRS-T angle.

OBJECTIVE: COVID-19; It spread rapidly around the world and led to a global pandemic. Indicators of poor prognosis are important in the treatment and follow-up of COVID-19 patients and have always been a matter of interest to researchers. The aim of this study was to investigate the relationship between frontal QRS-T angle values and clinical severity and prognosis in COVID-19 patients. METHODS: This prospective case-control study was conducted with 130 COVID-19 patients whose diagnosis was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and 100 healthy controls. The CURB-65 score was used as the clinical severity score. RESULTS: A total of 130 patients and 100 healthy controls were included in the study. When the patient and control groups were compared a significant difference was found between QT (378.07 ± 33.75 vs. 368.63 ± 19.65, p < 0.001), QTc (410.79 ± 28.19 vs. 403.68 ± 11.70, p < 0.001), QRS time (95.04 ± 21.67 vs. 91.42 ± 11.08, p < 0.001) and frontal QRS-T angle (36.57 ± 22.86 vs. 22.72 ± 14.08, p < 0.001). According to clinical severity scoring, QT (370.27 ± 25.20 vs. 387.75 ± 40.19, p = 0.003), QTc (402.18 ± 19.92 vs. 421.48 ± 33.08, p < 0.001), frontal QRS-T angle (32.25 ± 18.79 vs. 41.94 ± 26.27), p = 0.0.16) parameters were found to be significantly different. Age (odds ratio [OR], 1.201; 95% confidence interval [CI], 1.111-1.298; p < 0.001) and frontal QRS-T angle ([OR], 1.045; 95% [CI], 1.015-1.075; p = 0.003) values were found to be an independent predictor for the severity of the disease. Frontal QRS-T angle ([OR], 1.101; 95% [CI], 1.030-1.176; p = 0.004), and CRP ([OR], 1.029; 95% [CI], 1.007-1.051; p = 0.01) parameters were found to be independent predictors for the mortality of the disease. As a mortality indicator; for the frontal QRS-T angle of ≥44.5°, specificity and sensitivity were 93.8% and 84.2%, respectively. CONCLUSION: Frontal QRS-T angle can be used as a reproducible, convenient, inexpensive, new and powerful predictor in determining the clinical severity and prognosis of COVID-19 patients.

Evaluation of index of cardiac electrophysiological balance in COVID-19 patients.

AIM: The aim of the current study was to evaluate the index of Cardiac Electrophysiological Balance (iCEB) in hospitalized COVID-19 patients receiving Hydroxychloroquine / azithromycin (HCQ / AZ) combination therapy to determine the susceptibility to ventricular arrhythmia among these patients. METHOD: Sixty-seven COVID-19 patients admitted to the ward were included in the study. Electrocardiograms (ECGs) were obtained from all patients before the initiation of treatment and on treatment day 5. QT/QRS (iCEB) and QTc/QRS (iCEBc) ratios were calculated. RESULTS: QRS, QT and QTc intervals were significantly prolonged on day 5 measurements compared to pre-treatment period (p <0.05). Overall, mean iCEB was 3.6±0.4 before treatment and 3.8±0.4 on day 5 in the study population (p <0.001). Considering the iCEBc values, a significant increase was observed in patients receiving HCQ/AZ treatment compared to pre-treatment period (4.1±0.5 vs 4.4±0.6; p <0.001). CONCLUSIONS: To the best of our knowledge, this was the first study to investigate iCEB and iCEBc parameters in patients with COVID-19 on HCQ/AZ therapy. In this study, we demonstrated significantly increased iCEB and iCEBc values following HCQ/AZ treatment in COVID-19 patients. iCEB and iCEBc may serve as a noninvasive, simple, and novel biomarker for detecting increased pro-arrhythmia risk in COVID-19 patients (Tab. 3, Fig. 3, Ref. 36).

Comparison of ventricular repolarization parameters of Covid-19 patients diagnosed with chest CT and RT-PCR.

BACKGROUND AND OBJECTIVES: The aim of the comparison is to evaluate the marker of ventricular repolarization parameters such as QT, QTc, cQT, Tp-e, Tp-e/QT, Tp-e/QTc, Tp-e/JT and Tp-e/JTc ratios and the risk of ventricular arrhtythmias in patients with newly diagnosed Covid-19. METHODS: The study included 2 separate groups. The first one consisted of 96 positive reverse transcriptase polymerase chain reaction (RT-PCR) Covid-19 patients and the second one of 106 patients with negative PCR but positive chest computed tomography (CT) findings consistent with Covid-19. We measured QTmax, QTmin, QRS, JT and Tp-e intervals and estimated Tp-e/QT max, Tp- e/QTc max, Tp-e/JT and Tp-e/JTc rates and QTc max, QTc min, cQTd and JTc intervals. RESULTS: QT max, QT min, JT, cQTd, Tp-e, Tp-e/QT max, Tp-e/QTc max, Tp-e/JT, Tp-e/JTc values were significantly higher in RT-PCR Covid-19 patient group. CONCLUSION: Positive RT-PCR Covid-19 patients should be followed more closely, in terms of high ventricular repolarization parameters and preventing ventricular arrhythmias that may develop due to this.

QT Interval Monitoring with Handheld Heart Rhythm ECG Device in COVID-19 Patients.

Background: QTc prolongation is an adverse effect of COVID-19 therapies. The use of a handheld device in this scenario has not been addressed. Objectives: To evaluate the feasibility of QTc monitoring with a smart device in COVID-19 patients receiving QTc-interfering therapies. Methods: Prospective study of consecutive COVID-19 patients treated with hydroxychloroquine ± azithromycin ± lopinavir-ritonavir. ECG monitoring was performed with 12-lead ECG or with KardiaMobile-6L. Both registries were also sequentially obtained in a cohort of healthy patients. We evaluated differences in QTc in COVID-19 patients between three different monitoring strategies: 12-lead ECG at baseline and follow-up (A), 12-lead ECG at baseline and follow-up with the smart device (B), and fully monitored with handheld 6-lead ECG (group C). Time needed to obtain an ECG registry was also documented. Results: One hundred and eighty-two COVID-19 patients were included (A: 119(65.4%); B: 50(27.5%); C: 13(7.1%). QTc peak during hospitalization did significantly increase in all groups. No differences were observed between the three monitoring strategies in QTc prolongation (p = 0.864). In the control group, all but one ECG registry with the smart device allowed QTc measurement and mean QTc did not differ between both techniques (p = 0.612), displaying a moderate reliability (ICC 0.56 [0.19-0.76]). Time of ECG registry was significantly longer for the 12-lead ECG than for handheld device in both cohorts (p < 0.001). Conclusion: QTc monitoring with KardiaMobile-6L in COVID-19 patients was feasible. Time of ECG registration was significantly lower with the smart device, which may offer an important advantage for prevention of virus dissemination among healthcare providers.

Impact of COVID-19 on the incidence of cardiac arrhythmias in implantable cardioverter defibrillator recipients followed by remote monitoring.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a fast-growing worldwide pandemic. AIMS: We aimed to investigate the incidence of cardiac arrhythmias among a large French cohort of implantable cardioverter defibrillator recipients over the first 5 months of 2020. METHODS: Five thousand nine hundred and fifty-four implantable cardioverter defibrillator recipients were followed by remote monitoring during the COVID-19 period (from 01 January to 31 May 2020). Data were obtained from automated remote follow-up of implantable cardioverter defibrillators utilizing the Implicity® platform. For all patients, the type of arrhythmia (atrial fibrillation, ventricular tachycardia or ventricular fibrillation), the number of ventricular arrhythmia episodes and the type of implantable cardioverter defibrillator-delivered therapy were recorded. RESULTS: A total of 472 (7.9%) patients presented 4917 ventricular arrhythmia events. An increase in ventricular arrhythmia incidence was observed after the first COVID-19 case in France, and especially during weeks #10 and #11, at the time of major governmental measures, with an increase in the incidence of antitachycardia pacing delivered therapy. During the 11 weeks before the lockdown order, the curve of the percentage of live-stream television coverage of COVID-19 information matched the ventricular arrhythmia incidence. During the lockdown, the incidence of ventricular arrhythmia decreased significantly compared with baseline (0.05±0.7 vs. 0.09±1.2 episodes per patient per week, respectively; P<0.001). Importantly, no correlation was observed between ventricular arrhythmia incidence and the curve of COVID-19 incidence. No changes were observed regarding atrial fibrillation/atrial tachycardia episodes over time. CONCLUSIONS: An increase in ventricular arrhythmia incidence was observed in the 2 weeks before the lockdown order, at the time of major governmental measures. Ventricular arrhythmia incidence decreased dramatically during the lockdown.

Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study.

PURPOSE: We investigated the efficacy and safety of hydroxychloroquine for empirical treatment of outpatients with confirmed COVID-19. METHODS: In this prospective, single-center study, we enrolled ambulatory outpatients with COVID-19 confirmed by a molecular method who received hydroxychloroquine. The patients were divided into low- and moderate-risk groups based on the Tisdale risk score for drug-associated QT prolongation, and the QT interval was corrected for heart rate using the Bazett formula (QTc). The QTc interval was measured by electrocardiography both pretreatment (QTc1) and 4 h after the administration of hydroxychloroquine (QTc2). The difference between the QTc1 and QTc2 intervals was defined as the ΔQTc. The QTc1 and QTc2 intervals and ΔQTc values were compared between the two risk groups. RESULTS: The median and interquartile range (IQR) age of the patients was 47.0 (36.2-62) years, and there were 78 men and 74 women. The median (IQR) QTc1 interval lengthened from 425.0 (407.2-425.0) to 430.0 (QTc2; 412.0-443.0) milliseconds (ms). However, this was not considered an increased risk of ventricular tachycardia associated with a prolonged QTc interval requiring drug discontinuation, because none of the patients had a ΔQTc of >60 ms or a QTc2 of >500 ms. Moreover, the median (quartiles; minimum-maximum) ΔQTc value was higher in patients in the moderate-risk group than those in the low-risk group (10.0 [-4.0-18.0; -75.0-51.0] vs. 7.0 [-10.5-23.5; -53.0-59.0 ms]) (p = 0.996). Clinical improvement was noted in 91.4% of the patients, the exceptions being 13 patients who presented with non-serious adverse drug reactions or who had severe COVID-19 and were hospitalized. Adverse effects related to hydroxychloroquine were non-serious and occurred in 52.8% (n = 80) of the patients. CONCLUSIONS: Our findings show that hydroxychloroquine is safe for COVID-19 and not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation. Additionally, hydroxychloroquine was well tolerated, and there were no drug-related non-serious adverse events leading to treatment discontinuation in the majority of patients who were stable and did not require hospitalization.

Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic.

AIMS: Our objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19. METHODS AND RESULTS: In this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54-0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58-0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56-0.85, P < 0.001). CONCLUSIONS: During COVID-19, there was a 32% reduction in ventricular arrhythmias needing device therapies, coinciding with measures of social isolation. There was a 39% reduction in the proportion of patients with ventricular arrhythmias in states with higher COVID-19 incidence. These findings highlight the potential role of real-life stressors in ventricular arrhythmia burden in individuals with ICDs. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry; URL: https://www.anzctr.org.au/; Unique Identifier: ACTRN12620000641998.

Effects of Short-Term Hydroxychloroquine Plus Moxifloxacin Therapy on Corrected QT Interval and Tp-e Interval in Patients With COVID-19.

BACKGROUND: Limited data are available regarding hydroxychloroquine (HCQ) and moxifloxacin (MOX) in patients with possible coronavirus disease 2019, (COVID-19). Both drugs may increase risk of malignant ventricular arrhythmias associated with prolongation of QT interval. METHODS: A total of 76 subjects with chest tomography findings compatible with COVID-19 pneumonia were enrolled in the study. Standard 12-lead electrocardiogram (ECG) was repeated on days 2 and 5 in patients receiving a combination of HCQ + MOX. Heart rate, QT interval, Tp-e interval, and Tp-e/QT ratio were measured. RESULTS: The mean age of the patients was 61.7 ± 14.8 years and 54% had hypertension. Compared to day 2, ECG on day 5 showed significant increases in QT interval (370.8 ± 32.5 vs. 381.0 ± 29.3, respectively, P = 0.001), corrected QT (QTc) interval (424 (403 - 436) vs. 442 (420 - 468), respectively, P < 0.001), Tp-e interval (60 (55 - 70) vs. 65 (57 - 75), respectively, P < 0.001), cTp-e interval (72.2 ± 12.9 vs. 75.4 ± 12.7, respectively, P < 0.001). Moreover, a slight decrease in Tp-e/QT ratio was observed (0.17 ± 0.03 vs. 0.17 ± 0.02, P = 0.030). QTc was > 500 ms in 5% of the patients, and 8% of patients had an increase in QTc interval > 60 ms. Tp-e/QT ratio was > 0.23 in 4% of patients. Five patients died due to pulmonary failure without evidence of ventricular arrhythmia. No ventricular arrhythmia events, including torsades de pointes (TdP), were observed. CONCLUSIONS: HCQ + MOX combination therapy led to increases in QTc interval, Tp-e interval, and cTp-e interval. However, this therapy did not cause ventricular arrhythmia in the short-term observation.

Evaluation of electrocardiographic ventricular repolarization variables in patients with newly diagnosed COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease that has spread rapidly. COVID-19 has been associated with a number of cardiovascular complications, including arrhythmias. The mechanism of ventricular arrhythmias in patients with COVID-19 is uncertain. The aim of the present study was to evaluate the ventricular repolarization by using the Tp-e interval, QT dispersion, Tp-e/QT ratio, and Tp-e/QTc ratio as candidate markers of ventricular arrhythmias in patients with newly diagnosed COVID-19. In addition, the relationship between the repolarization parameters and the CRP (C-reactive protein) was investigated. METHODS: 75 newly diagnosed COVID-19 patients, 75 age and sex matched healthy subjects were included in the study between 20th March 2020 and 10th April 2020. The risk of ventricular arrhythmias was evaluated by calculating the electrocardiographic Tp-e and QT interval, Tp-e dispersion, corrected QT(QTc), QT dispersion (QTd), corrected QTd, Tp-e/QT and Tp-e/QTc ratios. CRP values were also measured in patients with newly diagnosed COVID-19. RESULTS: Tp-e interval (80.7 ±â€¯4.6 vs. 70.9 ±â€¯4.8; p < .001), Tp-e / QT ratio (0.21 ±â€¯0.01 vs. 0.19 ±â€¯0.01; p < .001) and Tp-e/QTc ratio (0.19 ±â€¯0.01 vs.0.17 ±â€¯0.01; p < .001) were significantly higher in patients with newly diagnosed COVID-19 than the control group. There was a significant positive correlation between Tp-e interval, Tp-e/QTc ratio and CRP in patients with newly diagnosed COVID-19 (rs = 0.332, p = .005, rs = 0.397, p < .001 consecutively). During their treatment with hydroxychloroquine (HCQ), azithromycin and favipiravir, ventricular tachycardia episodes were observed in in two COVID-19 patients during their hospitalization in the intensive care unit. CONCLUSION: Our study showed for the first time in literature that the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio, which are evaluated electrocardiographically in patients with newly diagnosed COVID-19, were prolonged compared with normal healthy individuals. A positive correlation was determined between repolarization parameters and CRP. We believe that pre-treatment evaluation of repolarization parameters in newly diagnosed COVID-19 would be beneficial for predicting ventricular arrhythmia risk.

Ventricular Arrhythmia Risk Based on Ethnicity in COVID-19 Patients on Hydroxychloroquine and Azithromycin Combination: Viewpoint.

There are many reports available now, which are mostly observational or registry trial outcomes having varied results on coronavirus 2019 (COVID-19) patients put on hydroxychloroquine and azithromycin combination. Some are showing increased in-hospital mortality and ventricular arrhythmia increase, while some are showing overall benefit with significant viral RNA load reduction. Everyday things are getting more complicated with the publication of these different outcomes. This needs to be addressed.