Secondary bacterial infections are a leading factor triggering New Onset Atrial Fibrillation in intubated ICU Covid-19 ARDS patients.

BACKGROUND: Cardiac arrhythmias, mainly atrial fibrillation (AF), is frequently reported in COVID-19 patients, more often in Intensive Care Unit (ICU) patients, yet causality has not been virtually explored. Moreover, non-Covid ICU patients frequently present AF, sepsis being the major trigger. We aimed to examine whether sepsis or other factors-apart from Covid-19 myocardial involvement-contribute to elicit New Onset AF (NOAF) in intubated ICU patients. METHODS: Consecutive intubated, Covid-19ARDS patients, were prospectively studied for factors triggering NOAF. Demographics, data on Covid-19 infection duration, laboratory findings (troponin as well), severity of illness and ARDS were compared between NOAF and control group (no AF) on admission. In NOAF patients, echocardiographic findings, laboratory and secondary infection data on the AF day were compared to the preceding days and/or ICU admission data. RESULTS: Among 105 patients screened, 79 were eligible; nineteen presented NOAF (24%). Baseline characteristics did not differ between the NOAF and control groups. Troponin levels were mildly elevated upon ICU admission in both groups. Left ventricular global longitudinal strain was impaired (<16.5%) in 63% vs 78% in the two groups, respectively. The right ventricle was mildly dilated, and pericardial effusion was present in 52 vs 43%, respectively. NOAF occurred on the 18 ± 4.8 days from Covid-19 symptoms' onset, and the 8.5 ± 2.1 ICUday. A septic secondary infection episode occurred in 89.5% of the patients in the NOAF group ( vs 41.6% in the control group (p < 0.001). In fact, NOAF occurred concurrently with a secondary septic episode in 84.2% of the patients. Sepsis presence was the only factor associated to NOAF occurrence (OR 16.63, p = 0.002). Noradrenaline, lactate and inflammation biomarkers gradually increased in the days before AF (all p < 0.05). Echocardiographic findings did not change on NOAF occurrence. CONCLUSION: Secondary infections seem to be major contributors for NOAF occurrence in Covid-19 patients, probably playing the role of the "second hit" in an affected myocardium from Covid-19.

A double-blind randomised controlled trial on the effect of Tocovid, a tocotrienol-rich capsule on postoperative atrial fibrillation at the National Heart Institute, Kuala Lumpur: an interim blinded analysis.

INTRODUCTION: Post-operative atrial fibrillation (POAF) is associated with poorer outcomes, increased resource utilisation, morbidity and mortality. Its pathogenesis is initiated by systemic inflammation and oxidative stress. It is hypothesised that a potent antioxidant and anti-inflammatory agent such as tocotrienol, an isomer of Vitamin E, could reduce or prevent POAF. AIMS: The aim of this study is to determine whether a potent antioxidative and anti-inflammatory agent, Tocovid, a tocotrienol-rich capsule, could reduce the incidence of POAF and affect the mortality and morbidity as well as the duration of ICU, HDU and hospital stay. METHODS: This study was planned as a prospective, randomised, controlled trial with parallel groups. The control group received placebo containing palm superolein while the treatment group received Tocovid capsules. We investigated the incidence of POAF, the length of hospital stay after surgery and the health-related quality of life. RESULTS: Recruitment commenced in January 2019 but the preliminary results were unblinded as the study is still ongoing. Two-hundred and two patients have been recruited out of a target sample size of 250 as of January 2021. About 75% have completed the study and 6.4% were either lost during follow-up or withdrew; 4% of participants died. The mean age group was 61.44 ± 7.30 years with no statistical difference between the groups, with males having a preponderance for AF. The incidence of POAF was 24.36% and the mean time for developing POAF was 55.38 ± 29.9 h post-CABG. Obesity was not a predictive factor. No statistically significant difference was observed when comparing left atrial size, NYHA class, ejection fraction and the premorbid history. The mean cross-clamp time was 71 ± 34 min and the mean bypass time was 95 ± 46 min, with no difference between groups. There was a threefold increase in death among patients with POAF (p = 0.008) and an increase in the duration of ICU stay (p = 0.01), the total duration of hospital stay (p = 0.04) and reintubation (p = 0.045). CONCLUSION: A relatively low incidence rate of POAF was noted although the study is still ongoing. It remains to be seen if our prophylactic intervention using Tocovid would effectively reduce the incidence of POAF. Clinical Registration Number: US National Library of Medicine. Clinical Trials - NCT03807037. Registered on 16th January 2019. Link: https://clinicaltrials.gov/ct2/show/NCT03807037.

COVID-19 and Cardiac Arrhythmias.

Since the coronavirus disease (COVID-19) pandemic spread unrelentingly all over the world, millions of cases have been reported. Despite a high number of asymptomatic cases, the course of the disease can be serious or even fatal. The affection of the myocardium, called myocardial injury, is caused by multiple triggers. The occurrence of cardiac arrhythmias in COVID-19 patients with myocardial involvement and a critical course is common. In this review, potential mechanisms, incidence, and treatment options for cardiac arrhythmias in COVID-19 patients will be provided by performing a literature research in MESH database and the National Library of Medicine. Common cardiac arrhythmias in COVID-19 patients were sinus tachycardia, atrial fibrillation (AF), ventricular tachycardia (VT), ventricular fibrillation (VF), atrioventricular block, sinusoidal block or QTc prolongation. AF was the most common heart rhythm disorder. About 10% of COVID-19 patients develop new-onset AF and 23 to 33% showed recurrence of AF in patients with known AF. One retrospective trial revealed the incidence of VT or VF to be 5.9% in hospitalized patients. Both AF and VT are clearly associated with worse outcome. Several mechanisms such as hypoxia, myocarditis, myocardial ischemia, or abnormal host immune response, which induce cardiac arrhythmias, have been described. The effect of QT-prolonging drugs in inducing cardiac arrhythmias has become mitigated as these medications are no longer recommended. Acute management of cardiac arrhythmias in COVID-19 patients is affected by the reduction of exposure of health care personnel. More prospective data are desirable to better understand pathophysiology and consecutively adapt management.

Effect of Continuous Electrocardiogram Monitoring on Detection of Undiagnosed Atrial Fibrillation After Hospitalization for Cardiac Surgery: A Randomized Clinical Trial.

Importance: Postoperative atrial fibrillation (POAF) occurring after cardiac surgery is associated with adverse outcomes. Whether POAF persists beyond discharge is not well defined. Objective: To determine whether continuous cardiac rhythm monitoring enhances detection of POAF among cardiac surgical patients during the first 30 days after hospital discharge compared with usual care. Design, Setting, and Participants: This study is an investigator-initiated, open-label, multicenter, randomized clinical trial conducted at 10 Canadian centers. Enrollment spanned from March 2017 to March 2020, with follow-up through September 11, 2020. As a result of the COVID-19 pandemic, enrollment stopped on July 17, 2020, at which point 85% of the proposed sample size was enrolled. Cardiac surgical patients with CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex) score greater than or equal to 4 or greater than or equal to 2 with risk factors for POAF, no history of preoperative AF, and POAF lasting less than 24 hours during hospitalization were enrolled. Interventions: The intervention group underwent continuous cardiac rhythm monitoring with wearable, patch-based monitors for 30 days after randomization. Monitoring was not mandated in the usual care group within 30 days after randomization. Main Outcomes and Measures: The primary outcome was cumulative AF and/or atrial flutter lasting 6 minutes or longer detected by continuous cardiac rhythm monitoring or by a 12-lead electrocardiogram within 30 days of randomization. Prespecified secondary outcomes included cumulative AF lasting 6 hours or longer and 24 hours or longer within 30 days of randomization, death, myocardial infarction, ischemic stroke, non-central nervous system thromboembolism, major bleeding, and oral anticoagulation prescription. Results: Of the 336 patients randomized (163 patients in the intervention group and 173 patients in the usual care group; mean [SD] age, 67.4 [8.1] years; 73 women [21.7%]; median [interquartile range] CHA2DS2-VASc score, 4.0 [3.0-4.0] points), 307 (91.4%) completed the trial. In the intent-to-treat analysis, the primary end point occurred in 32 patients (19.6%) in the intervention group vs 3 patients (1.7%) in the usual care group (absolute difference, 17.9%; 95% CI, 11.5%-24.3%; P < .001). AF lasting 6 hours or longer was detected in 14 patients (8.6%) in the intervention group vs 0 patients in the usual care group (absolute difference, 8.6%; 95% CI, 4.3%-12.9%; P < .001). Conclusions and Relevance: In post-cardiac surgical patients at high risk of stroke, no preoperative AF history, and AF lasting less than 24 hours during hospitalization, continuous monitoring revealed a significant increase in the rate of POAF after discharge that would otherwise not be detected by usual care. Studies are needed to examine whether these patients will benefit from oral anticoagulation therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02793895.

Evaluation of P-wave dispersion in patients with newly diagnosed coronavirus disease 2019.

AIM: The aim of the current study was to evaluate P-wave dispersion (PWD) as a predictor of atrial fibrillation in patients with newly diagnosed COVID-19. In addition, the relationship between the PWD and inflammation parameters was investigated. METHODS: A total of 140 newly diagnosed COVID-19 patients and 140 age- and sex-matched healthy individuals were included in the study. The risk of atrial fibrillation was evaluated by calculating the electrocardiographic PWD. C-reactive protein (CRP), white blood cell, neutrophil and neutrophil-to-lymphocyte ratio (NLR) were measured in patients with newly diagnosed COVID-19. RESULTS: PWD, white blood cell, NLR and CRP levels were significantly higher in the COVID-19 group than the control group. There was a significant positive correlation between PWD and CRP level (rs = 0.510, P < 0.001) and NLR in COVID-19 group (rs = 0.302, P = 0.001). In their follow-up, 13 (9.3%) patients, 11 of whom were in the ICU, developed new atrial fibrillation. CONCLUSION: Our study showed for the first time in literature that the PWD, evaluated electrocardiographically in patients with newly diagnosed COVID-19, was prolonged compared with normal healthy individuals. A positive correlation was found between PWD, CRP level and NLR. We believe that pretreatment evaluation of PWD in patients with newly diagnosed COVID-19 would be beneficial for predicting atrial fibrillation risk.

Atrial fibrillation in patients with SARS-CoV-2 infection.

INTRODUCTION AND OBJECTIVE: the SARS-CoV-2 infection ranges from asymptomatic to critical forms and several prognostic factors have been described. Atrial fibrillation (AF) is common in acute situations where it is linked with more complications and mortality. We aimed to evaluate the prognostic information of AF in this population. METHODS: retrospective analysis of a cohort of 517 patients consecutively admitted in a tertiary hospital due to SARS-CoV-2 infection. We divided the patients in two groups according the development of AF and compared the main features of both groups. An univariable and multivariable analysis of mortality were also performed. RESULTS: among 517 patients with SARS-CoV-2 infection admitted in a tertiary center, 54 (10.4%) developed AF. These patients are older (81.6 vs 66.5 years old, p<0.001) and present more hypertension (74% vs 47%, p<0.001), cardiomyopathy (9% vs 1%, p=0.002), previous heart failure admission (9% vs 0.4%, p<0.001), previous episodes of AF (83% vs 1%, p<0.001) and bigger left atrium (47.8 vs 39.9mm, p<0.001). AF COVID-19 patients present more acute respiratory failure (72% vs 40%, p<0.001) and higher in-hospital mortality (50% vs 22%, p<0.001). Predictors of AF development are age and previous AF. AF is not an independent predictor of in-hospital mortality. Predictors are age, creatinine>1.5mg/dL at admission, LDH>250UI/L at admission and acute respiratory failure. CONCLUSION: Atrial fibrillation appears in 10% of hospitalized patients with SARS-CoV-2 infection. These patients present more comorbidities and two-fold increase in hospital mortality. Atrial fibrillation is not an independent prognostic factor.

Cardiac Injury and Outcomes of Patients With COVID-19 in New York City.

BACKGROUND: Prior studies demonstrated that elevated troponin in patients with COVID-19 was associated with increased in-hospital mortality. However, the association of cardiac injury and electrocardiogram (ECG) changes remains unclear. The aim of this study was to investigate the association of cardiac injury with ECG abnormality and with in-hospital mortality. METHODS: We conducted a retrospective cohort study of patients who were hospitalised with COVID-19 between 13 March and 31 March 2020. Those patients with troponin I measurement were included in the study and divided into those who had elevated troponin I (cardiac injury group) and those who did not (no cardiac injury group). Statistical analyses were performed to compare differences between the groups, and a multivariate logistic regression model was constructed to assess the effect of cardiac injury on in-hospital mortality. RESULTS: One hundred and eight-one (181) patients were included, 54 of whom were in the cardiac injury group and 127 in the no cardiac injury group. The mean age was 64.0±16.6 years and 55.8% were male. The cardiac injury group was more likely to be older, have a history of coronary artery disease, atrial fibrillation and congestive heart failure compared to the no cardiac injury group (all p<0.05); there was no difference in presence of chest pain (cardiac injury group versus no cardiac injury group: 17.0% versus 22.5%, p=0.92); the cardiac injury group had a significantly higher value of brain natriuretic peptide, procalcitonin, interleukin-6 and D-dimer (all p<0.05); they had numerically more frequent ECG abnormalities such as T wave inversion (13.2% versus 7.5%, p=0.23) and ST depression (1.9% versus 0.0%, p=0.13) although statistically not significant; they had significantly higher in-hospital mortality (42.3% versus 12.6%, p<0.001). With a multivariate logistic regression model, age (odds ratio [95% confidence interval]: 1.033 [1.002-1.065], p=0.034) and cardiac injury (3.25 [1.40-7.54], p=0.006) were independent predictors of in-hospital mortality. CONCLUSIONS: Patients with COVID-19 with elevated troponin I had a relatively low proportion of chest pain and ECG abnormality. Cardiac injury was independently associated with in-hospital mortality.

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.

Atrial fibrillation in COVID-19: A review of possible mechanisms.

A relationship between COVID-19 infection and an increasing incidence of atrial fibrillation has been observed. However, the underlying pathophysiology as a precipitant to AF has not been reviewed. This paper will consider the possible pathological and immunological AF mechanisms as a result, of COVID-19 infection. We discuss the role myocardial microvascular pericytes expressing the ACE-2 receptor and their potential for an organ-specific cardiac involvement with COVID-19. Dysfunctional microvascular support by pericytes or endothelial cells may increase the propensity for AF via increased myocardial inflammation, fibrosis, increased tissue edema, and interstitial hydrostatic pressure. All of these factors can lead to electrical perturbances at the tissue and cellular level. We also consider the contribution of Angiotensin, pulmonary hypertension, and regulatory T cells as additional contributors to AF during COVID-19 infection. Finally, reference is given to two common drugs, corticosteroids and metformin, in COVID-19 and how they might influence AF incidence.

New-onset atrial fibrillation: incidence, characteristics, and related events following a national COVID-19 lockdown of 5.6 million people.

AIM: To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown. METHODS AND RESULTS: Using nationwide Danish registries, we included all patients, aged 18-90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12-1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56-0.78), 0.53 (0.45-0.64), and 0.41 (0.34-0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93-2.12). CONCLUSIONS: Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.

Atrial Arrhythmias in a Patient Presenting With Coronavirus Disease-2019 (COVID-19) Infection.

The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has significant potential cardiovascular implications for patients. These include myocarditis, acute coronary syndromes, cardiac arrhythmias, cardiomyopathies with heart failure and cardiogenic shock, and venous thromboembolic events. We describe a Caribbean-Black gentleman with COVID-19 infection presenting with atrial arrhythmias, namely, atrial flutter and atrial fibrillation, which resolved with rate and rhythm control strategies, and supportive care.