Remdesivir-associated bradycardia in COVID-19: a rapid review protocol.

INTRODUCTION: Remdesivir is an antiviral medication that is used in the treatment of severe COVID-19. Research has highlighted the potential cardiac side effects of remdesivir, including the occurrence of remdesivir-associated bradycardia (RAB), but these findings have not been consistent. In addition, very little is known about the clinical implications and outcomes of RAB. The aim of this rapid systematic review is to determine the event rate of developing bradycardia while receiving remdesivir treatment compared with not receiving remdesivir in patients diagnosed with COVID-19. METHODS AND ANALYSIS: This study follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol guidelines and will include original papers related to COVID-19, remdesivir and bradycardia. Only English language papers published from 1 December 2019 to 31 December 2022 will be included. The following databases will be searched using keywords and controlled vocabulary: Ovid MEDLINE, Ovid EMBASE, Scopus, Cochrane, PubMed and Web of Science. Two reviewers will independently perform screening and data abstraction. Data will be synthesised qualitatively as well as quantitatively. A random-effects model will be used to calculate the pooled estimates. ETHICS AND DISSEMINATION: This review will systematically analyse the clinical studies available to help better characterise RAB. The results will support a retrospective study investigating RAB that is currently being conducted at the University Medical Center of Southern Nevada in Las Vegas, Nevada. PROSPERO REGISTRATION NUMBER: This protocol has been submitted to and approved by PROSPERO (Protocol ID: CRD42022331614).

Clinical spectrum of COVID-19 complications in young adults: combined analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry and the Outcomes Registry for Cardiac Conditions in Athletes.

BACKGROUND: While young adults 18-24 years old bear a significant proportion of COVID-19 diagnoses, the risk factors for hospitalisation and severe COVID-19 complications in this population are poorly understood. OBJECTIVE: The objective of this study was to identify risk factors for hospitalisation and other COVID-19 complications across the health spectrum of young adults diagnosed with COVID-19 infection. STUDY DESIGN: Retrospective cohort study. PARTICIPANTS: Young adults (aged 18-24) with confirmed COVID-19 infection from the American Heart Association (AHA) COVID-19 Cardiovascular Disease Registry of hospitalised patients and the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study of collegiate athletes. The AHA registry included 636 young adults from 152 hospitals. The ORCCA registry consisted of 3653 competitive college athletes from 42 colleges and universities. INTERVENTION: None (exposure to COVID-19). PRIMARY AND SECONDARY OUTCOME MEASURES: Main outcomes included hospitalisation, death, major adverse cardiovascular events (MACE) and other severe clinical events. RESULTS: In comparison to the ORCCA registry, patients in the AHA registry were more likely to be female (59% vs 33%); had higher average body mass index (BMI) (32.4 vs 25.6); and had increased prevalence of diabetes (10% vs 0.4%), hypertension (7% vs 0.6%), chronic kidney disease (2% vs 0%) and asthma (14% vs 8%), all with p<0.01. There were eight (2%) deaths in the AHA hospitalised registry compared with zero in the ORCCA cohort. BMI was a statistically significant predictor of death in the hospitalised cohort (OR 1.05, 95% CI 1.00, 1.10). No significant predictors of MACE or other severe clinical events were identified. CONCLUSIONS: The risk of cardiac events in young adults aged 18-24 diagnosed with COVID-19 infection is low. Patients who were hospitalised (AHA registry) were more likely to have pre-existing medical comorbidities and higher BMI than healthy collegiate athletes (ORCCA registry). Once hospitalised, elevated BMI is associated with increased mortality although other drivers of MACE and other severe clinical events remain unclear.

Performance of digital early warning score (NEWS2) in a cardiac specialist setting: retrospective cohort study.

INTRODUCTION: Patients with cardiovascular diseases (CVD) are at significant risk of developing critical events. Early warning scores (EWS) are recommended for early recognition of deteriorating patients, yet their performance has been poorly studied in cardiac care settings. Standardisation and integrated National Early Warning Score 2 (NEWS2) in electronic health records (EHRs) are recommended yet have not been evaluated in specialist settings. OBJECTIVE: To investigate the performance of digital NEWS2 in predicting critical events: death, intensive care unit (ICU) admission, cardiac arrest and medical emergencies. METHODS: Retrospective cohort analysis. STUDY COHORT: Individuals admitted with CVD diagnoses in 2020; including patients with COVID-19 due to conducting the study during the COVID-19 pandemic. MEASURES: We tested the ability of NEWS2 in predicting the three critical outcomes from admission and within 24 hours before the event. NEWS2 was supplemented with age and cardiac rhythm and investigated. We used logistic regression analysis with the area under the receiver operating characteristic curve (AUC) to measure discrimination. RESULTS: In 6143 patients admitted under cardiac specialties, NEWS2 showed moderate to low predictive accuracy of traditionally examined outcomes: death, ICU admission, cardiac arrest and medical emergency (AUC: 0.63, 0.56, 0.70 and 0.63, respectively). Supplemented NEWS2 with age showed no improvement while age and cardiac rhythm improved discrimination (AUC: 0.75, 0.84, 0.95 and 0.94, respectively). Improved performance was found of NEWS2 with age for COVID-19 cases (AUC: 0.96, 0.70, 0.87 and 0.88, respectively). CONCLUSION: The performance of NEWS2 in patients with CVD is suboptimal, and fair for patients with CVD with COVID-19 to predict deterioration. Adjustment with variables that strongly correlate with critical cardiovascular outcomes, that is, cardiac rhythm, can improve the model. There is a need to define critical endpoints, engagement with clinical experts in development and further validation and implementation studies of EHR-integrated EWS in cardiac specialist settings.

Predictors of in-hospital mortality in critically ill patients with COVID-19: a large dual tertiary centre study.

OBJECTIVES: The aim of this study was to investigate the relationship of echocardiographic parameters, laboratory findings and clinical characteristics with in-hospital mortality in adult patients with COVID-19 admitted to the intensive care units (ICU) in two large collaborating tertiary UK centres. DESIGN: Observational retrospective study. SETTING: The study was conducted in patients admitted to the ICU in two large tertiary centres in London, UK. PARTICIPANTS: Inclusion criteria were: (1) patients admitted to the ICU with a COVID-19 diagnosis over a period of 16 weeks. and (2) underwent a transthoracic echocardiogram on the first day of ICU admission as clinically indicated.No exclusion criteria applied.Three hundred patients were enrolled and completed the follow-up. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure in this study was in-hospital mortality in patients admitted to the ICU with COVID-19 infection. RESULTS: Older age (HR: 1.027, 95% CI 1.007 to 1.047; p=0.008), left ventricular (LV) ejection fraction<35% (HR: 5.908, 95% CI 2.609 to 13.376; p<0.001), and peak C reactive protein (CRP) (HR: 1.002, 95% CI 1.001 to 1.004, p=0.001) were independently correlated with mortality in a multivariable Cox regression model. Following multiple imputation of variables with more than 5% missing values, random forest analysis was applied to the imputed data. Right ventricular (RV) basal diameter (RVD1), RV mid-cavity diameter (RVD2), tricuspid annular plane systolic excursion, RV systolic pressure, hypertension, RV dysfunction, troponin level on admission, peak CRP, creatinine level on ICU admission, body mass index and age were found to have a high relative importance (> 0.7). CONCLUSIONS: In patients with COVID-19 in the ICU, both severely impaired LV function and impaired RV function may have adverse prognostic implications, but older age and inflammatory markers appear to have a greater impact. A combination of echocardiographic and laboratory investigations as well as demographic and clinical characteristics appears appropriate for risk stratification in patients with COVID-19 who are admitted to the ICU.

Cardiopulmonary exercise testing excludes significant disease in patients recovering from COVID-19.

OBJECTIVE: Post-COVID-19 syndrome presents a health and economic challenge affecting ~10% of patients recovering from COVID-19. Accurate assessment of patients with post-COVID-19 syndrome is complicated by health anxiety and coincident symptomatic autonomic dysfunction. We sought to determine whether either symptoms or objective cardiopulmonary exercise testing could predict clinically significant findings. METHODS: 113 consecutive military patients were assessed in a comprehensive clinical pathway. This included symptom reporting, history, examination, spirometry, echocardiography and cardiopulmonary exercise testing (CPET) in all, with chest CT, dual-energy CT pulmonary angiography and cardiac MRI where indicated. Symptoms, CPET findings and presence/absence of significant pathology were reviewed. Data were analysed to identify diagnostic strategies that may be used to exclude significant disease. RESULTS: 7/113 (6%) patients had clinically significant disease adjudicated by cardiothoracic multidisciplinary team (MDT). These patients had reduced fitness (V̇O2 26.7 (±5.1) vs 34.6 (±7.0) mL/kg/min; p=0.002) and functional capacity (peak power 200 (±36) vs 247 (±55) W; p=0.026) compared with those without significant disease. Simple CPET criteria (oxygen uptake (V̇O2) >100% predicted and minute ventilation (VE)/carbon dioxide elimination (V̇CO2) slope <30.0 or VE/V̇CO2 slope <35.0 in isolation) excluded significant disease with sensitivity and specificity of 86% and 83%, respectively (area under the receiver operating characteristic curve (AUC) 0.89). The addition of capillary blood gases to estimate alveolar-arterial gradient improved diagnostic performance to 100% sensitivity and 78% specificity (AUC 0.92). Symptoms and spirometry did not discriminate significant disease. CONCLUSIONS: In a population recovering from SARS-CoV-2, there is reassuringly little organ pathology. CPET and functional capacity testing, but not reported symptoms, permit the exclusion of clinically significant disease.

Impact of health literacy and its interventions on health outcomes in those with atrial fibrillation: a systematic review protocol.

INTRODUCTION: Atrial fibrillation (AF) is associated with increased risk of stroke, heart failure and death. Health literacy, an aspect that falls within precision health, has been recognised as an important factor. We will be focusing on the impact of these interventions specifically to AF and its health outcomes. METHODS AND ANALYSIS: This protocol is informed by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. The results will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to determine the impacts of health literacy interventions on AF outcomes. Searches will be carried out on databases including MEDLINE, EMBASE, Web of Science, CINAHL, Emcare, Cochrane Library and Google Scholar. Citations will be collected via Endnote 20, then into Covidence for duplicate removal, and article screening. Extraction will occur using a standardised extraction tool and studies will be synthesised using best evidence synthesis. Downs and Black's checklist will be used for risk of bias and assessment of overall quality of evidence will use the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Approval from human research ethics committee is not required. Dissemination will occur in peer-reviewed journals and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022304835.

Factors associated with poor medication adherence during COVID-19 pandemic among hypertensive patients visiting public hospitals in Eastern Ethiopia: a cross-sectional study.

OBJECTIVE: This study aimed to assess factors associated with poor medication adherence during the COVID-19 pandemic among hypertensive patients visiting public hospitals in Eastern Ethiopia. SETTING: Hospital-based cross-sectional study was conducted in Harari regional state and Dire Dawa Administration from 1 January to 30 February 2022. Both settings are found in Eastern Ethiopia. PARTICIPANTS: A total of 402 adult hypertensive patients who visited the chronic diseases clinic for follow-up were included in the study. MAIN OUTCOME MEASURES: The main outcome measure was poor medication adherence during the COVID-19 pandemic. RESULTS: The level of poor antihypetensive medication adherence was 63% (95% CI 48.1 to 67.9). Patients who had no formal education (adjusted OR (AOR)=1.56, 95% CI 1.03 to 4.30), existing comorbid conditions (AOR=1.98, 95% CI 1.35 to 4.35), self-funded for medication cost (AOR=2.05, 95% CI 1.34 to 4.73), poor knowledge about hypertension (HTN) and its treatment (AOR=2.67, 95% CI 1.45 to 3.99), poor patient-physician relationship (AOR=1.22, 95% CI 1.02 to 4.34) and unavailability of medication (AOR=5.05, 95% CI 2.78 to 12.04) showed significant association with poor medication adherence during the pandemic of COVID-19. CONCLUSION: The level of poor antihypertensive medication adherence was high in this study. No formal education, comorbidity, self-funded medication cost, poor knowledge about HTN and its treatment, poor patient-physician relationship, and unavailability of medication during the COVID-19 pandemic were factors significantly associated with poor adherence to antihypertensive medication. All stakeholders should take into account and create strategies to reduce the impact of the COVID-19 pandemic on medication adherence of chronic diseases.

Impact of a nurse-led teleconsultation strategy for cardiovascular disease management during COVID-19 pandemic in India: a pyramid model feasibility study.

OBJECTIVE: The COVID-19 pandemic necessitated the use of telemedicine to maintain continuity of care for patients with cardiovascular diseases (CVDs). This study aimed to demonstrate the feasibility of implementing a nurse-led teleconsultation strategy for CVD management during the COVID-19 pandemic in India and evaluated the impact of nurse-led teleconsultations on patient treatment satisfaction. DESIGN, SETTING AND PARTICIPANTS: We developed a two-stage teleconsultation strategy and tested the feasibility of implementing a nurse-led teleconsultation strategy to manage CVD in a northern state (Punjab) in India. A multidisciplinary team of experts developed the treatment protocol used for teleconsultations to manage CVD. Nurses were trained to provide teleconsultation, triaging of patients and referrals to the physicians. Patients with CVD who had an outpatient visit or hospitalisation between September 2019 and March 2020 at the Dayanand Medical College Hospital, Ludhiana, India, were contacted by phone and offered teleconsultations. Telemedicine strategy comprised: stage 1 nurse-led teleconsultations and stage 2 physician-led teleconsultations. Descriptive analysis was performed to report the proportion of patients triaged by the two-stage telemedicine strategy, and patient's clinical characteristics, and treatment satisfaction between the nurse-led versus physician-led teleconsultations. RESULTS: Overall, nurse-led stage 1 teleconsultations were provided to 12 042 patients with CVD. The mean (SD) age of the participants was 58.9 years (12.8), and men were 65.4%. A relatively small proportion of patients (6.3%) were referred for the stage-2 physician-led teleconsultations and of these only 8.4% required hospitalisations. During stage 1 nurse-led teleconsultations, patients were referred to the physicians due to uncontrolled diabetes (24.9%), uncontrolled hypertension (18.7%) and congestive heart failure (16.2%). The patient's treatment satisfaction was similar between the nurse-led versus physician-led teleconsultations (p=0.07). CONCLUSION: This study showed that a nurse-led telemedicine strategy is feasible to implement in a resource-constraint setting for triaging patients with CVD and reduces physician's burden.

Changes in QTc interval after hydroxychloroquine therapy in patients with COVID-19 infection: a large, retrospective, multicentre cohort study.

OBJECTIVE: To evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths. DESIGN: A large-scale cohort study with retrospective analysis of baseline and on-therapy QT interval corrected using Bazett and Fridericia formulas. SETTING: A multicentre study involving eight secondary and tertiary care hospitals of the Abu Dhabi Health Services Company (SEHA), United Arab Emirates. PARTICIPANTS: 2014 patients consecutively admitted with PCR-confirmed SARS-CoV-2 infection between 1 March 2020 and 1 June 2020. INTERVENTIONS: Treatment with hydroxychloroquine alone or in combination with azithromycin for at least 24 hours and with a baseline ECG and at least one ECG after 24 hours of therapy. MAIN OUTCOME MEASURES: Maximal QTc interval prolongation and its relationship to clinical severity, polymorphic ventricular tachycardia and sudden arrhythmic death while on treatment. RESULTS: The baseline QTc(Bazett) was 427.6±25.4 ms and the maximum QTc(Bazett) during treatment was 439.2±30.4 ms (p<0.001). Severe QTc prolongation (QTc ≥500 ms) was observed in 1.7%-3.3% of patients (Fridericia and Bazett, respectively). There were no cases of polymorphic ventricular arrhythmia or hydroxychloroquine-related arrhythmic death. QTc prolongation was more pronounced in combination therapy compared with hydroxychloroquine alone (22.2 ms vs 11.0 ms, p<0.001) and in patients with higher COVID-19 clinical severity (asymptomatic: 428.4±25.4 ms, severe COVID-19 infection: 452.7±35.7 ms, p<0.001). The overall in-hospital mortality was 3.97% and deceased patients had longer on-therapy QTc(Bazett) than survivors (459.8±21.4 ms vs 438.4±29.9 ms, p<0.001). CONCLUSIONS: The incidence of severe QTc prolongation with hydroxychloroquine was low and not associated with ventricular arrhythmia. The safety concerns surrounding the use of hydroxychloroquine may have been overestimated; however, caution should be exercised when using hydroxychloroquine in patients with risk factors for QT prolongation.

Heart Watch Study: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04468321.

Cohort study of the characteristics and outcomes in patients with COVID-19 and in-hospital cardiac arrest.

OBJECTIVE: We studied characteristics, survival, causes of cardiac arrest, conditions preceding cardiac arrest, predictors of survival and trends in the prevalence of COVID-19 among in-hospital cardiac arrest (IHCA) cases. DESIGN AND SETTING: Registry-based observational study. PARTICIPANTS: We studied all cases (≥18 years of age) of IHCA receiving cardiopulmonary resuscitation in the Swedish Registry for Cardiopulmonary Resuscitation during 15 March 2020 to 31 December 2020. A total of 1613 patients were included and divided into the following groups: ongoing infection (COVID-19+; n=182), no infection (COVID-19-; n=1062) and unknown/not assessed (n=369). MAIN OUTCOMES AND MEASURES: We studied monthly trends in proportions of COVID-19 associated IHCAs, causes of IHCA in relation to COVID-19 status, clinical conditions preceding the cardiac arrest and predictors of survival. RESULTS: The rate of COVID-19+ patients suffering an IHCA increased to 23% during the first pandemic wave (April), then abated to 3% in July, and then increased to 19% during the second wave (December). Among COVID-19+ cases, 43% had respiratory insufficiency or infection as the underlying cause of the cardiac arrest, compared with 18% among COVID-19- cases. The most common clinical sign preceding cardiac arrest was hypoxia (57%) among COVID-19+ cases. OR for 30-day survival for COVID-19+ cases was 0.50 (95% CI 0.33 to 0.76), compared with COVID-19- cases. CONCLUSION: During pandemic peaks, up to one-fourth of all IHCAs are complicated by COVID-19, and these patients have halved chance of survival, with women displaying the worst outcomes.

How has technology been used to deliver cardiac rehabilitation during the COVID-19 pandemic? An international cross-sectional survey of healthcare professionals conducted by the BACPR.

OBJECTIVE: To investigate whether exercise-based cardiac rehabilitation services continued during the COVID-19 pandemic and how technology has been used to deliver home-based cardiac rehabilitation. DESIGN: A mixed methods survey including questions about exercise-based cardiac rehabilitation service provision, programme diversity, patient complexity, technology use, barriers to using technology, and safety. SETTING: International survey of exercise-based cardiac rehabilitation programmes. PARTICIPANTS: Healthcare professionals working in exercise-based cardiac rehabilitation programmes worldwide. MAIN OUTCOME MEASURES: The proportion of programmes that continued providing exercise-based cardiac rehabilitation and which technologies had been used to deliver home-based cardiac rehabilitation. RESULTS: Three hundred and thirty eligible responses were received; 89.7% were from the UK. Approximately half (49.3%) of respondents reported that cardiac rehabilitation programmes were suspended due to COVID-19. Of programmes that continued, 25.8% used technology before the COVID-19 pandemic. Programmes typically started using technology within 19 days of COVID-19 becoming a pandemic. 48.8% did not provide cardiac rehabilitation to high-risk patients, telephone was most commonly used to deliver cardiac rehabilitation, and some centres used sophisticated technology such as teleconferencing. CONCLUSIONS: The rapid adoption of technology into standard practice is promising and may improve access to, and participation in, exercise-based cardiac rehabilitation beyond COVID-19. However, the exclusion of certain patient groups and programme suspension could worsen clinical symptoms and well-being, and increase hospital admissions. Refinement of current practices, with a focus on improving inclusivity and addressing safety concerns around exercise support to high-risk patients, may be needed.

Study protocol for COVID-RV: a multicentre prospective observational cohort study of right ventricular dysfunction in ventilated patients with COVID-19.

INTRODUCTION: COVID-19 can cause severe acute respiratory failure requiring management in intensive care unit with invasive ventilation and a 40% mortality rate. Cardiovascular manifestations are common and studies have shown an increase in right ventricular (RV) dysfunction associated with mortality. These studies, however, comprise heterogeneous patient groups with few requiring invasive ventilation. This study will investigate the prevalence and prognostic significance of RV dysfunction in ventilated patients with COVID-19 which may lead to targeted interventions to improve patient outcomes. METHODS AND ANALYSIS: This prospective multicentre observational cohort study will perform transthoracic echocardiography (TTE) in 150 patients with COVID-19 requiring invasive ventilation for more than 48 hours. RV dysfunction will be defined as TTE evidence of RV dilatation along with the presence of septal flattening. Baseline demographics, disease severity data and clinical information relating to proposed aetiological mechanisms of RV dysfunction (acute respiratory distress syndrome (ARDS), disordered coagulation, direct myocardial injury and ventilation) will be collected and analysed.Primary outcome measures include the prevalence of RV dysfunction and its association with 30-day mortality. Exploratory outcome measures will investigate the association of the proposed aetiological mechanisms of RV dysfunction to the primary outcomes.Prevalence of RV dysfunction will be determined along with 95% Clopper-Pearson CIs and 30-day survival will be analysed using logistic regression adjusting for patient demographics, phase of disease and baseline severity of illness. The role of potential aetiological factors (ARDS, disordered coagulation, direct myocardial injury and ventilation) in relation to the primary outcomes will be analysed using logistic regression. ETHICS AND DISSEMINATION: Approval was gained from Scotland A Research Ethics Committee (REC reference 20/SS/0059). Findings will be disseminated by various methods including webinars, international presentations and publication in peer-reviewed journals.

Optimal cut-off value of elevated cardiac troponin concentrations for myocardial injury predicts clinical outcomes in adult patients with COVID-19: a dose-response analysis protocol for systematic review.

INTRODUCTION: Acute myocardial injury in patients with COVID-19 infection has been recognised as one important complication associated with in-hospital mortality. The potential dose-response effect of cardiac troponin (cTn) concentrations on adverse clinical outcomes has not been systematically studied. Hence, we will conduct a comprehensive dose-response meta-analysis to quantitatively evaluate the relationship between elevated cTn concentrations and in-hospital adverse clinical outcomes in patients with COVID-19. METHODS: We will search PubMed, EMBASE, Cochrane Library and ISI Knowledge via Web of Science databases, as well as preprint databases (medRxiv and bioRxiv), from inception to October 2021, to identify all retrospective and prospective cohorts and randomised controlled studies using related keywords. The primary outcome will be all-cause mortality during hospitalisation. The secondary outcome will be major adverse event (MAE). To conduct a dose-response meta-analysis of the potential linear or restricted cubic spline regression relationship between elevated cTn concentrations and all-cause mortality or MAE, studies with three or more categories of cTn concentrations will be included. Univariable or multivariable meta-regression and subgroup analyses will be conducted to compare elevated and non-elevated categories of cTn concentration. Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of all-cause mortality or MAE. ETHICS AND DISSEMINATION: In accordance with the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital, ethical approval was waived for this systematic review protocol. This meta-analysis will be disseminated through a peer-reviewing process for journal publication and conference communication. PROSPERO REGISTRATION NUMBER: CRD42020216059.

COVID-19 and the burning issue of drug interaction: never forget the ECG.

The coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), has been rapidly escalating, becoming a relevant threat to global health. Being a recent virus outbreak, there are still no available therapeutic regimens that have been approved in large randomised trials and so patients are currently being treated with multiple drugs. This raises concerns regarding drug interaction and their implication in arrhythmic burden. In fact, two of the actually used drugs against SARS-CoV2, such as chloroquine and the combination lopinavir/ritonavir, might determine a QT (the time from the start of the Q wave to the end of the T wave) interval prolongation and they show several interactions with antiarrhythmic drugs and antipsychotic medications, making them prone to an increased risk of developing arrhythmias. This brief review focuses the attention on the most relevant drug interactions involving the currently used COVID-19 medications and their possible association with cardiac rhythm disorders, taking into account also pre-existing condition and precipitating factors that might additionally increase this risk. Furthermore, based on the available evidence and based on the knowledge of drug interaction, we propose a quick and simple algorithm that might help both cardiologists and non-cardiologists in the management of the arrhythmic risk before and during the treatment with the specific drugs used against SARS-CoV2.