Prognostic Value of T wave Positivity in Lead aVR in COVID-19 Pneumonia (preprint)

Background: T wave positivity in the lead aVR is a marker of ventricular repolarization abnormality and provides information on short and long-term cardiovascular mortality in patients who have heart failure, anterior myocardial infarction, and receive hemodialysis for various reasons. The aim of this study was to investigate the relationship between T wave positivity in the lead aVR on superficial ECG and mortality from COVID-19 pneumonia. Methods: This study retrospectively included 130 patients who were diagnosed with COVID-19 and treated as an outpatient or in the thoracic diseases ward in a single center between January 2021 and June 2021. All patients included in the study had clinical and radiological features and signs of COVID-19 pneumonia. The COVID-19 diagnosis of all patients was confirmed by polymerase chain reaction (PCR) studied from an oropharyngeal swab Results: A total of 130 patients were included in this study. Patients were divided into 2 groups: survived and deceased. There were 55 patients (with a mean age of 64.76-14.93 years, 58.18% male, 41.12% female) in the survived group, while there were 75 patients (with a mean age of 65-15 years, 58.67% male, 41.33% female) in the deceased group. The univariate and multivariate regression analyses showed that positive TAVR (OR: 5.151, 95% CI: 1.001-26.504, p: 0.0012), lactate dehydrogenase (LDH) (OR: 1.006, 95% CI: 1.001-1.010, p: 0.012) and D-dimer (OR:1.436, 95% CI: 1.115-1.848, p: 0.005) were independent risk factors for mortality Conclusions: positive TAaVR is useful in risk stratification for COVID-19 pneumonia mortality. KEY WORLD:Electrocardıographıa, positive TAaVR, COVID-19 pneumonia, mortality

Impact of Hypocalcemia on the Prognosis of Patients with Acute Myocarditis.

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.

Amplitude Spectrum Area of ventricular fibrillation to guide defibrillation: a small open-label, pseudo-randomized controlled multicenter trial.

BACKGROUND: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. METHODS: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. FINDINGS: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18-4.90]). No adverse events were reported. INTERPRETATION: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. TRIAL REGISTRATION: NCT03237910. FUNDING: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Defibrillation Strategies for Refractory Ventricular Fibrillation.

BACKGROUND: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation. METHODS: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge. RESULTS: A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively). CONCLUSIONS: Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation. (Funded by the Heart and Stroke Foundation of Canada; DOSE VF ClinicalTrials.gov number, NCT04080986.).

COVID-19 Vaccination-Induced Ventricular Fibrillation in an Afebrile Patient With Brugada Syndrome.

A 43-year-old man presented with cardiac arrest 2 days after the second coronavirus disease 2019 (COVID-19) vaccination with an mRNA vaccine. Electrocardiograms showed ventricular fibrillation and type 1 Brugada pattern ST segment elevation. The patient reported having no symptoms, including febrile sensation. There were no known underlying cardiac diseases to explain such electrocardiographic abnormalities. ST segment elevation completely disappeared in two weeks. Although there were no genetic mutations or personal or family history typical of Brugada syndrome, flecainide administration induced type 1 Brugada pattern ST segment elevation. This case suggests that COVID-19 vaccination may induce cardiac ion channel dysfunction and cause life threatening ventricular arrhythmias in specific patients with Brugada syndrome.

Ventricular Tachycardia or Fibrillation Storm in Coronavirus Disease (preprint)

Ventricular tachycardia (VT) or ventricular fibrillation (VF) storm associated with severe acute respiratory syndrome coronavirus-2 infection is a potentially fatal complication; the correlation of these 2 disorders, however, has not been well studied. This retrospective case series examined outcomes of 2 patients who were admitted for repeated implantable cardioverter-defibrillator shocks with or without syncope and observed to have VT/VF storms with COVID-19. Mechanisms of VT/VF storms in COVID-19 are multifactorial including myocarditis, systemic inflammation, hyperadrenergic state, hemodynamic instability, hypoxia, acidosis, and proarrhythmic drugs. A higher incidence of VT/VF storm is observed in patients with comorbidities and those requiring critical care, with some studies reporting increased mortality. In our cohort, 1 of the 2 patients succumbed to the complications from COVID-19 and the other patient was discharged to home in stable condition. Monitoring of life-threatening arrhythmias in the setting of COVID-19 may need to be adopted to prevent morbidity and mortality.

Current and investigational therapies for the treatment of refractory ventricular fibrillation.

PURPOSE: Esmolol, dual sequential defibrillation, vector change defibrillation, and left stellate ganglion block are presented and reviewed for the treatment of refractory ventricular fibrillation. SUMMARY: Although no formal definition has been established for refractory ventricular fibrillation, the literature describes it as a pulseless ventricular arrhythmia that persists despite 3 standard defibrillation attempts, administration of amiodarone 300 mg intravenously, and provision of three 1-mg intravenous doses of epinephrine. Evolving literature surrounding resuscitation in this particular subset of cardiac arrest challenges the efficacy of traditional therapies, such as epinephrine, and suggests that other treatment modalities may improve outcomes. Case reports, case series, and small retrospective studies have pointed to benefit when utilizing a variety of therapies, namely, esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block, in patients with refractory ventricular fibrillation arrest. CONCLUSION: A mounting, although limited, body of evidence suggests that esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block may be effective at terminating refractory ventricular fibrillation and improving patient outcomes. Further evidence is required before these therapies can be adopted as standard practice; however, as key members of the code response team, it is imperative for pharmacists to be familiar with the supporting evidence, safety considerations, and logistical challenges of utilizing these treatments during arrest.

Impact of COVID-19 Pandemic on Severe Ventricular Arrhythmia and Icd Therapy (preprint)

BACKGROUND AND OBJECTIVES The regular clinical follow-up of the patient with the implantable cardioverter-defibrillator (ICD) device was seriously affected by the COVID-19 outbreak. Due to the high risk of contamination, patients didn’t admit to the clinics for the ICD device control. It has been observed that arrhythmic events increased during the COVID-19 outbreak. In this study, we aimed to investigate the frequency of severe ventricular arrhythmias and ICD device therapy in COVID-19 patients with ICD. METHODS In this single center-observational study, we assessed severe ventricular arrhytmias and ICD therapies by analyzing recorded data of 33 patients (24 males, 72.7%) 3 months before and after getting COVID-19 during the COVID-19 pandemic in Van, Turkey, between 15 August 2020 and 15 January 2021. RESULTS Before the diagnosis of COVID-19, 6 ventricular tachycardias and 1 ventricular fibrillation were observed. When we analyzed the records after the diagnosis COVID-19, 17 ventricular tachycardia and 3 ventricular fibrillation episodes were observed. Considering the the ICD device therapies, 5 of these severe tachyarrhythmias were terminated by antitachycardia pacing (ATP) and 2 with shock therapy before the diagnosis of COVID-19. After the COVID-19, 14 of them were terminated by ATP and 6 of them ere terminated by shock therapy. CONCLUSION The effects of the COVID-19 pandemic, especially on ventricular arrhythmia, have not been reported sufficiently. In our study, it was observed that life-threatening ventricular arrhythmias and the ICD therapies were increased in patients with COVID-19, especially in the first month after the diagnosis COVID-19.

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.

Cardiac arrhythmias in hospitalized patients with COVID-19: A prospective observational study in the western United States.

Arrhythmias have been reported frequently in COVID-19 patients, but the incidence and nature have not been well characterized. Patients admitted with COVID-19 and monitored by telemetry were prospectively enrolled in the study. Baseline characteristics, hospital course, treatment and complications were collected from the patients' medical records. Telemetry was monitored to detect the incidence of cardiac arrhythmias. The incidence and types of cardiac arrhythmias were analyzed and compared between survivors and non-survivors. Among 143 patients admitted with telemetry monitoring, overall in-hospital mortality was 25.2% (36/143 patients) during the period of observation (mean follow-up 23.7 days). Survivors were less tachycardic on initial presentation (heart rate 90.6 ± 19.6 vs. 99.3 ± 23.1 bpm, p = 0.030) and had lower troponin (peak troponin 0.03 vs. 0.18 ng/ml. p = 0.004), C-reactive protein (peak C-reactive protein 97 vs. 181 mg/dl, p = 0.029), and interleukin-6 levels (peak interleukin-6 30 vs. 246 pg/ml, p = 0.003). Sinus tachycardia, the most common arrhythmia (detected in 39.9% [57/143] of patients), occurred more frequently in non-survivors (58.3% vs. 33.6% in survivors, p = 0.009). Premature ventricular complexes occurred in 28.7% (41/143), and non-sustained ventricular tachycardia in 15.4% (22/143) of patients, with no difference between survivors and non-survivors. Sustained ventricular tachycardia and ventricular fibrillation were not frequent (seen only in 1.4% and 0.7% of patients, respectively). Contrary to reports from other regions, overall mortality was higher and ventricular arrhythmias were infrequent in this hospitalized and monitored COVID-19 population. Either disease or management-related factors could explain this divergence of clinical outcomes, and should be urgently investigated.

Absence of relevant QT interval prolongation in not critically ill COVID-19 patients.

SARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404-433), and after treatment QTc was prolonged to 423 ms (405-438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14.1%) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.

Incidence and treatment of arrhythmias secondary to coronavirus infection in humans: A systematic review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro-arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID-19, as well as barriers to implementation. METHODS: Our search of scientific databases identified relevant published studies from 1 January 2000 until 1 June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded. RESULTS: The incidence and nature of arrhythmias in the setting of COVID-19 were poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug-induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) were reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc). CONCLUSION: Patients with SARS-CoV-2 are at an increased risk of arrhythmias. Drug therapy is pro-arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision-making.

Ventricular Fibrillation Storm in Coronavirus 2019.

Cardiac arrhythmia is a known manifestation of novel coronavirus 2019 (COVID-19) infection. Herein, we describe the clinical course of an otherwise healthy patient who experienced persistent ventricular tachycardia and fibrillation which is believed to be directly related to inflammation, as opposed to acute myocardial injury or medications that can prolong the QT interval.

COVID-19: Electrophysiological mechanisms underlying sudden cardiac death during exercise with facemasks.

The mandatory use of facemasks is a public health measure implemented by various countries in response to the novel coronavirus disease 19 (COVID-19) pandemic. However, there have been case reports of sudden cardiac death (SCD) with the wearing of facemasks during exercise. In this paper, we hypothesize that exercise with facemasks may increase the risk of ventricular tachycardia/ventricular fibrillation (VT/VF) leading to SCD via the development of acute and/or intermittent hypoxia and hypercapnia. We discuss the potential underlying mechanisms including increases in adrenergic stimulation and oxidative stress leading to electrophysiological abnormalities that promote arrhythmias via non-reentrant and reentrant mechanisms. Given the interplay of multiple variables contributing to the increased arrhythmic risk, we advise avoidance of a facemask during high intensity exercise, or if wearing of a mask is mandatory, exercise intensity should remain low to avoid precipitation of lethal arrhythmias. However, we cannot exclude the possibility of an arrhythmic substrate even with low intensity exercise especially in those with established chronic cardiovascular disease in whom baseline electrophysiological abnormalities may be found.

Beta-Adrenergic Receptor Stimulation Limits the Cellular Proarrhythmic Effects of Chloroquine and Azithromycin (preprint)

Background: The antimalarial drug chloroquine and antimicrobial drug azithromycin have received significant attention during the current COVID-19 pandemic. Both drugs can alter cardiac electrophysiology and have been associated with drug-induced arrhythmias. Meanwhile, sympathetic activation is commonly observed during systemic inflammation and oxidative stress (e.g., in SARS-CoV-2 infection), and may influence the electrophysiological effects of chloroquine and azithromycin. Here, we investigated the effect of beta-adrenergic stimulation on proarrhythmic properties of chloroquine and azithromycin using a detailed in silico model of ventricular electrophysiology. Methods: Concentration-dependent chloroquine and azithromycin-induced alterations in ion-channel function were incorporated into the Heijman canine ventricular cardiomyocyte model. Single and combined drug effects on action-potential (AP) properties were analyzed using a population of 592 models accommodating inter-individual variability. Sympathetic stimulation was simulated by an increase in pacing rate and experimentally validated isoproterenol-induced changes in ion-channel function. Results: At 1 Hz pacing, therapeutic doses of chloroquine and azithromycin (5 and 20 µM, respectively) individually prolonged AP duration (APD) by 33% and 13%. Their combination produced synergistic APD prolongation (+161%) with incidence of proarrhythmic early afterdepolarizations in 53.5% of models. Increasing the pacing frequency to 2 Hz shortened APD and together with 1 µM isoproterenol corrected the drug-induced APD prolongation. No afterdepolarizations occurred following increased rate and simulated application of 0.1-1 µM isoproterenol. Conclusion: Sympathetic stimulation limits chloroquine- and azithromycin-induced proarrhythmia by reducing their APD-prolonging effect, suggesting the importance of heart rate and autonomic status monitoring in particular conditions (e.g., COVID-19).

Baseline echocardiographic assessment of left ventricle kinetics alteration and mortality risk in a cohort of critically ill COVID-19 patients (preprint)

Background SARS-CoV2 infection are frequently associated with cardiovascular manifestations, in particular with symptomatic acute coronary syndromes, cardiac arrhythmias and acute heart failure. However, the elevation of serum troponin seems to be non specific, and a cardiologic diagnostic workup should be performed. We aimed to assess the clinical characteristic and the prevalence of left ventricular (LV) dyssynergy patterns in a cohort of hospitalized non-critically ill COVID-19 patientsMethods Consecutive patients with an objective diagnosis of COVID-19, from February to April 2020. Baseline characteristics and comorbidities was collected. In case of increased troponin levels or symptoms suggestive for a concomitant cardiac syndrome, patients undergo to serial electrocardiograms, serial Troponin tests and bedside transthoracic echocardiogram.Results 402 consecutive patients were enrolled: 55 patients underwent an echocardiographic exam because of an increase in troponin levels or a suspected myocardial injury. Segmental left ventricular abnormalities were found in 10 (median WMSI 2.03 IQR 1.38-2.75) with a median LV ejection fraction was 30.1 % IQR, median troponin level was 3083 ng/L, median BNP was 761 ng/L. Death for any cause occurred in 4 patients among patients with regional LV abnormalities and in 3 with normal regional function (p= 0,02).Discussion A single bedside transthoracic echocardiogram performed in non critically ill COVID-19 patients with suspected cardiac injury has the potential to better assist clinicians in their challenging decision process. As an isolated increase of troponin levels is common in COVID patients, a bed-side echocardiographic evaluation of cardiac function should be routinely implemented during their early evaluation.