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.

Predictive Value of Myocardial injury in Patients with COVID-19 Admitted to a Quaternary Hospital in the City of Rio de Janeiro

Abstract Background In Brazil the factors involved in the risk of death in patients with COVID-19 have not been well established. Objective To analyze whether elevations of high-sensitivity troponin I (hTnI) levels influence the mortality of patients with COVID-19. Methods Clinical and laboratory characteristics of hospitalized patients with COVID-19 were collected upon hospital admission. Univariate and binary logistic regression analyzes were performed to assess the factors that influence mortality. P-value<0.05 was considered significant. Results This study analyzed192 patients who received hospital admission between March 16 and June 2, 2020 and who were discharged or died by July 2, 2020. The mean age was 70±15 years, 80 (41.7%) of whom were women. In comparison to those who were discharged, the 54 (28.1%) who died were older (79±12 vs 66±15years; P=0.004), and with a higher Charlson´s index (5±2 vs 3±2; P=0.027). More patients, aged≥60years (P <0.0001), Charlson´s index>1 (P=0.004), lung injury>50% in chest computed tomography (P=0.011), with previous coronary artery disease (P=0.037), hypertension (P=0.033), stroke (P=0.008), heart failure (P=0.002), lymphocytopenia (P=0.024), high D-dimer (P=0.024), high INR (P=0.003), hTnI (P<0.0001), high creatinine (P<0.0001), invasive mechanical ventilation (P<0.0001), renal replacement therapy (P<0.0001), vasoactive amine (P<0.0001), and transfer to the ICU (P=0.001), died when compared to those who were discharged. In logistic regression analysis, elevated hTnI levels (OR=9.504; 95% CI=1.281-70.528; P=0.028) upon admission, and the need for mechanical ventilation during hospitalization (OR=46.691; 95% CI=2.360-923.706; P=0.012) increased the chance of in-hospital mortality. Conclusion This study suggests that in COVID-19 disease, myocardial injury upon hospital admission is a harbinger of poor prognosis.

[Cardiohemodynamic Changes and Cardiac Arrhythmias After Coronavirus Infection].

Aim      To study changes in cardiohemodynamic alterations of the myocardium and heart rhythm disorders at 3 and 6 months following the coronavirus infection.Material and methods   EchoCG, ECG Holter monitoring, and Doppler ultrasonography of hepatolienal blood vessels were performed for 77 patients (mean age, 35.9 years) at 3 and 6 months after coronavirus infection. The patients were divided into the following groups: group 1, with injury of the upper respiratory tract; group 2, with bilateral pneumonia (CТ1, 2), and group 3, with severe pneumonia (CТ3, 4). Statistical analysis was performed with a SPSS Statistics Version 25.0 software package.Results At 6 months after the disease onset, the patients noted an improvement of their general condition. In patients with moderate pneumonia, early peak diastolic velocity (p=0.09), right ventricular isovolumic diastolic time (р=0.09), and pulmonary artery systolic pressure (р=0.005) where decreased, while tricuspid annular peak systolic velocity was, in contrast, increased (р=0.042). Both segmental systolic velocity of the LV mid-inferior segment (р=0.006) and the mitral annular Em / Am ratio were decreased. In patients with severe disease at 6 months, right atrial indexed volume was reduced (р=0.036), tricuspid annular Em / Am was decreased (р=0.046), portal and splenic vein flow velocities were decreased, and inferior vena cava diameter was reduced. Late diastolic transmitral flow velocity was increased (р=0.027), and LV basal inferolateral segmental systolic velocity was decreased (р=0.046). In all groups, the number of patients with heart rhythm disorders was decreased, and parasympathetic autonomic influences prevailed.Conclusion      At 6 months after coronavirus infection, practically all patients noted improvement of their general condition; incidence rate of arrhythmia and cases of pericardial effusion were decreased; and autonomic nervous system activity recovered. In patients with moderate and severe disease, morpho-functional parameters of the right heart and the hepatolienal blood flow were normalized, however, occult disorders of LV diastolic function remained, and LV segmental systolic velocity was reduced.

Autonomic dysfunction in COVID-19 patients receiving mechanical ventilation: A cross-sectional study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can damage cardiac tissue by increasing troponin levels and inducing arrhythmias, myocarditis, and acute coronary syndrome. OBJECTIVES: To analyze the impact of COVID-19 on cardiac autonomic control in mechanically ventilated intensive care unit (ICU) patients. DESIGN AND SETTING: This cross-sectional analytical study of ICU patients of both sexes receiving mechanical ventilation was conducted in a tertiary hospital. METHODS: Patients were divided into COVID-19-positive (COVID(+)) and COVID-19-negative (COVID(-)) groups. Clinical data were collected and heart rate variability (HRV) records obtained using a heart rate monitor. RESULTS: The study sample comprised 82 subjects: 36 (44%) in the COVID(-) group (58.3% female; median age, 64.5 years) and 46 (56%) in the COVID(+) group (39.1% females; median age, 57.5 years). The HRV indices were lower than the reference values. An intergroup comparison identified no statistically significant differences in the mean normal-to-normal (NN) interval, standard deviation of the NN interval, or root mean square of successive differences in NN intervals. The COVID(+) group had an increased low frequency (P = 0.05), reduced high frequency (P = 0.045), and increased low frequency/high frequency (LF/HF) ratio (P = 0.048). There was a weak positive correlation between LF/HF and length of stay in the COVID(+) group. CONCLUSION: Patients who received mechanical ventilation had lower overall HRV indices. COVID(+) patients who received mechanical ventilation had lower vagal HRV components. These findings likely indicate clinical applicability, as autonomic control impairments are associated with a greater risk of cardiac death.

Cardiac Arrhythmias in Post-COVID Syndrome: Prevalence, Pathology, Diagnosis, and Treatment.

An increase in post-COVID patients with late sequelae of acute COVID-19 infection is emerging as an ongoing challenge for physicians and healthcare professionals. Since the beginning of the pandemic, it has rapidly become evident that the acute infection is not limited to the respiratory tract but that several organs, including the cardiovascular system, can be affected. Moreover, in a significant proportion of patients (ranging from about 10 to up to 50%) with former COVID-19, cardiopulmonary symptoms such as dyspnea, palpitations, restricted physical capacity, and cardiac arrhythmias can persist weeks and months after the acute SARS-CoV-2 infection. The spectrum of COVID-19-associated arrhythmias is rather wide, most likely due to various pathomechanisms. In this article, the prevalence of cardiac arrhythmias and underlying pathologies are reviewed, including direct myocardial injury and abnormal consequences with an impact on cardiac electric instability. The hyperinflammatory reaction of the host immune system is specifically considered. Moreover, several distinct rhythm disorders occurring in post-COVID patients are discussed with regard to their clinical management.

Arrhythmia occurring as the sole presenting feature in Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection is observed to be associated with several cardiac complications. Cardiac arrhythmias are frequently observed in critically ill patients and are usually associated with myocarditis. We report two patients with Covid-19, in whom serious arrhythmias were the sole presenting feature, in the absence of any of the known manifestations of the disease. Further research is required into this yet unknown mechanism of the effect of Covid-19 on the conduction system. Thus, managing patients with acute-onset arrhythmias of unexplained aetiology, even when they present without known clinical features of Covid-19, should be done with care.

Electrocardiographic changes in hospitalised children with COVID-19.

OBJECTIVES: Cardiac manifestations of the coronavirus disease 2019 (COVID-19) have mainly been reported in adults. Therefore, we aimed to determine the electrocardiographic abnormalities in hospitalised paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children. METHODS: We retrospectively evaluated hospitalised paediatric patients <18 years of age with a diagnosis of COVID-19 (n = 168) and multisystem inflammatory syndrome in children (n = 48) between March 2021 and December 2021. A daily electrocardiography was performed for the patients who had electrocardiographic abnormalities on admission or developed electrocardiographic abnormality on the follow-up. The characteristics of these patients, underlying predisposing conditions, and clinical course were also examined. RESULTS: Two-hundred sixteen paediatric patients (55% were male) with a mean age of 10.7 ± 4.69 years were evaluated. There was an underlying disease in 84 (38.8%) patients and 51 (23.6%) required paediatric ICU admission. Electrocardiography abnormality was detected in 12 (5.5%) which were as follows: 7 (3.2%) had sinus bradycardia, 3 (1.4%) patients had transient ST elevation and concomitant T negativity, and 2 (0.9%) developed first-degree Atrioventricular (AV) block. The median time from the onset of disease symptoms to detecting electrocardiographic abnormality was 9 days. Electrocardiographic abnormalities returned to normal uneventfully 3 days later. CONCLUSIONS: The prevalence of arrhythmia in paediatric patients with COVID-19 was detected in 5.5% of the patients. While two-thirds of the electrocardiography abnormalities were sinus bradycardia, ST elevation was remarkable (1.4%). Clinicians should be aware of electrocardiographic abnormalities and consider electrocardiographic monitoring in paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children.

Tachyarrhythmias During Hospitalization for COVID-19 or Multisystem Inflammatory Syndrome in Children and Adolescents.

Background Cardiac complications related to COVID-19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID-19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID-19-related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID-19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4-17.4] versus 10.0 [range, 5.4-14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID-19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.

New-Onset Atrial Arrhythmias Are Independently Associated With In-Hospital Mortality in Veno-Venous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To explore if atrial arrhythmias are associated with in-hospital mortality in veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients. DESIGN: Retrospective observational cohort study. SETTING: Quaternary care academic medical center. PARTICIPANTS: Patients with respiratory failure requiring VV-ECMO for >24 hours between January 1, 2016, and January 1, 2019. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen VV-ECMO patients were included. Patients were stratified by absence or presence of clinically significant atrial arrhythmias during the VV-ECMO run. Atrial arrhythmias were defined as either atrial fibrillation or atrial flutter that occurred during VV-ECMO and required pharmacologic or electrical intervention. The primary outcome was in-hospital mortality. Secondary outcomes included a composite of thrombotic events, which included ischemic stroke and on-pump arterial thrombosis. Other objectives of this analysis included characterization of atrial arrhythmia incidence, risk factors, and management. A total of 67 patients (30.5%) experienced new-onset atrial arrhythmias post-ECMO cannulation. Age, male sex, and norepinephrine use were independently associated with atrial arrhythmia development. In-hospital mortality was significantly higher in the atrial arrhythmia group (38.8% v 19.1%; p = 0.003). In the multivariate logistic regression analysis, atrial arrhythmias during VV-ECMO were independently associated with increased odds of in-hospital mortality (odds ratio, 2.21; 95% confidence interval, 1.08-4.55; p = 0.03), after controlling for Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score, acute renal failure, total norepinephrine dose, and total cannulation time. CONCLUSIONS: New-onset atrial arrhythmias are a frequent complication during VV-ECMO and are independently associated with excessive in-hospital mortality. Thus, their presence may serve as an important prognostic tool in this patient population.

Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.

Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.

Coronavirus disease 2019 and the cardiologist.

PURPOSE OF REVIEW: There continues to be extensive clinical and epidemiological data to suggest that coronavirus disease 2019 (COVID-19) infection is associated with numerous different types of cardiac involvement. RECENT FINDINGS: Myocardial injury has been reported in over 25% of patients hospitalized due to COVID-19 infection and is not only associated with a worse prognosis but with higher mortality, approaching 40%. Currently proposed mechanisms of myocardial injury include direct viral infection, cytokine storm, endothelial inflammation, demand ischemia, interferon-mediated response and stress cardiomyopathy. COVID-19 infection is associated with new-onset arrhythmias and heart failure regardless of history of previous cardiovascular disease. Echocardiographic findings can be useful to predict mortality in COVID-19 patients and cardiac MRI is an effective tool to both assess COVID-19 induced myocarditis and to follow-up on cardiac complications of COVID-19 long-term. Although there is an association between COVID-19 vaccination and myocarditis, pericarditis or arrhythmias, the risk appears lower when compared to risk attributable to the natural infection. SUMMARY: Patients with cardiovascular disease are not only more likely to suffer from severe COVID-19 infection but are at increased risk for further complications and higher mortality. Further data compilation on current and emerging treatments of COVID-19 will have additional impact on cardiovascular morbidity and mortality of COVID-19 infection.

The use of telemedicine to assess a paediatric patient with arrhythmia presenting to a remote community coronavirus assessment centre.

In 2020, a girl aged 5 years presented to the coronavirus assessment centre on a remote Scottish island with symptoms consistent with novel coronavirus 2019 (COVID-19). Her mother was concerned as she had noted the patient to have an irregular pulse. COVID-19 has been shown to cause cardiac arrhythmia, and so after discussion with tertiary paediatric cardiology services an ECG was recommended. In order to minimise potential spread of coronavirus in the healthcare setting a portable ECG device was immediately delivered to the patient, with the ECG tracing being sent electronically to a cardiologist. A formal diagnosis was then communicated to the parents within 2 hours of the initial contact.

Incidence, Mortality, and Imaging Outcomes of Atrial Arrhythmias in COVID-19.

Atrial arrhythmias (AAs) are common in hospitalized patients with COVID-19; however, it remains uncertain if AAs are a poor prognostic factor in SARS-CoV-2 infection. In this retrospective cohort study from 2014 to 2021, we report in-hospital mortality in patients with new-onset AA and history of AA. The incidence of new-onset congestive heart failure (CHF), hospital length of stay and readmission rate, intensive care unit admission, arterial and venous thromboembolism, and imaging outcomes were also analyzed. We further compared the clinical outcomes with a propensity-matched influenza cohort. Generalized linear regression was performed to identify the association of AA with mortality and other outcomes, relative to those without an AA diagnosis. Predictors of new-onset AA were also modeled. A total of 6,927 patients with COVID-19 were included (626 with new-onset AA, 779 with history of AA). We found that history of AA (adjusted relative risk [aRR] 1.38, confidence interval [CI], 1.11 to 1.71, p = 0.003) and new-onset AA (aRR 2.02, 95% CI 1.68 to 2.43, p <0.001) were independent predictors of in-hospital mortality. The incidence of new-onset CHF was 6.3% in history of AA (odds ratio 1.91, 95% CI 1.30 to 2.79, p <0.001) and 11.3% in new-onset AA (odds ratio 4.01, 95% CI 3.00 to 5.35, p <0.001). New-onset AA was shown to be associated with worse clinical outcomes within the propensity-matched COVID-19 and influenza cohorts. The risk of new-onset AA was higher in patients with COVID-19 than influenza (aRR 2.02, 95% CI 1.76 to 2.32, p <0.0001), but mortality associated with new-onset AA was higher in influenza (aRR 12.58, 95% CI 4.27 to 37.06, p <0.0001) than COVID-19 (aRR 1.86, 95% CI 1.55 to 2.22, p <0.0001). In a subset of the patients with COVID-19 for which echocardiographic data were captured, abnormalities were common, including valvular abnormalities (40.9%), right ventricular dilation (29.6%), and elevated pulmonary artery systolic pressure (16.5%); although there was no evidence of a difference in incidence among the 3 groups. In conclusion, new-onset AAs are associated with poor clinical outcomes in patients with COVID-19.

Prospective arrhythmia surveillance after a COVID-19 diagnosis.

BACKGROUND: Cardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease. OBJECTIVE: To determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis. METHODS: Adults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations. RESULTS: A total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34-126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5-13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of <1%; one participant had a 2.8% supraventricular ectopic burden and one had a 15.4% ventricular ectopic burden. While 47 (92%) participants triggered their monitor for palpitation symptoms, 78% of these triggers were for either sinus rhythm or sinus tachycardia. CONCLUSIONS: We did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

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.

Emergency activations for chest pain and ventricular arrhythmias related to regional COVID-19 across the US.

Evidence that patients may avoid healthcare facilities for fear of COVID-19 infection has heightened the concern that true rates of myocardial infarctions have been under-ascertained and left untreated. We analyzed data from the National Emergency Medical Services Information System (NEMSIS) and incident COVID-19 infections across the United States (US) between January 1, 2020 and April 30, 2020. Grouping events by US Census Division, multivariable adjusted negative binomial regression models were utilized to estimate the relationship between COVID-19 and EMS cardiovascular activations. After multivariable adjustment, increasing COVID-19 rates were associated with less activations for chest pain and non-ST-elevation myocardial infarctions. Simultaneously, increasing COVID-19 rates were associated with more activations for cardiac arrests, ventricular fibrillation, and ventricular tachycardia. Although direct effects of COVID-19 infections may explain these discordant observations, these findings may also arise from patients delaying or avoiding care for myocardial infarction, leading to potentially lethal consequences.