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QTc Prolongation to Predict Mortality in Patients Admitted with COVID- 19 Infection: An Observational Study
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Background:
Cardiovascular involvement associated with SARS-COV-2 infection is related to unfavorable outcomes during hospitalization. Therefore, the measurement at the admission of the QTc interval on the 12-lead electrocardiogram may be a prognostic marker.
Objective:
To identify the relationship between QTc prolongation at admission during hospitalization and mortality from SARS-COV-2.
Method:
Observational study based on a retrospective cohort of patients with confirmed SARS-COV-2 infection from San Ignacio University Hospital, Bogotá (Colombia), between March 19, 2020, and July 31, 2021. Mortality was compared in patients with prolonged and normal QTc at admission after controlling by clinical variables and comorbidities using bivariate and multivariate logistic regression models. A p-value <0.05 was considered statistically significant.
Results:
1296 patients were analyzed, and 127 (9.8%) had prolonged QTc. Mortality was higher in patients with prolonged QTc (39.4% vs 25.3%, p=0.001), as was hospital stay (median 11vs.8 days; p=0.002). In the multivariate analysis, mortality was associated with prolonged QTc (OR 1.61, 95% CI: 1.02; 2.54, p=0.038), age (OR 1.03, 95% CI 1.02; 1.05, p<0.001), male sex (OR 2.15, 95% CI 1.60; 2.90, p <0.001), kidney disease (OR 1.32, 95% CI 1.05; 1.66, p =0.018) and Charlson comorbidity index > 3 (OR 1.49, 95% CI 1.03; 2.17, p=0.035).
Conclusions:
Hospital mortality due to SARS-COV-2 is associated with prolonging the QTc interval at the time of admission, even after adjusting for age, sex, comorbidities, and basal severity of infection. Additional research is needed to establish whether these findings are related to cardiac involvement by the virus, hypoxia, and systemic inflammation.
The coronavirus disease-2019 (COVID-19) pandemic has become a major global health problem. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibits pulmonary and extrapulmonary effects, including cardiovascular involvement. There are several attempts to identify drugs that could treat COVID-19. Moreover, many patients infected with COVID-19 have underlying diseases, particularly cardiovascular diseases. These patients are more likely to develop severe illnesses and would require optimized treatment strategies. The current study gathered information from various databases, including relevant studies, reviews, trials, or meta-analyses until April 2022 to identify the impact of SARS-CoV-2 treatment on the cardiovascular system. Studies have shown that the prognosis of patients with underlying cardiovascular disease is worsened by COVID-19, with some COVID-19 medications interfering with the cardiovascular system. The COVID-19 treatment strategy should consider many factors and parameters to avoid medication-induced cardiac injury, mainly in elderly patients. Therefore, this article provides a synthesis of evidence on the impact of different COVID-19 medications on the cardiovascular system and related disease conditions.
Background
QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known.
Purpose
To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection.
Materials and Methods
A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk.
Results
One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3–3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22–3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06–2.68, p = 0.027).
Conclusion
Prolonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.
Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality ( n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14–2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705–0.761) had a higher predictive value than AST ( p = 0.0018) and ALT ( p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553–0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659–0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 ( p = 0.0302), APRI > 0.7 ( p < 0.0001), AST > 51 ( p = 0.0119) and ALT > 42 ( p < 0.0001). FIB-4 was also associated with high-flow oxygen use ( n = 255, HR 1.69, 95% CI 1.25–2.28, p = 0.001) and mechanical ventilation ( n = 39, HR 2.07, 95% CI 1.03–4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.
Objective
To evaluate the association of a prolonged corrected QT (QTc) interval in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its association with in-patient mortality.
Methods
A cohort of 745 patients were recruited from a single center between 1 March 2020 and 31 May 2020. We analyzed the factors associated with a prolonged QTc and mortality.
Results
A prolonged QTc interval >450 ms was found in 27% of patients admitted with SARS-CoV-2 infection. These patients were predominantly older, on a ventilator, and had hypertension, diabetes mellitus, or ischemic heart disease. They also had high troponin and D-dimer concentrations. A prolonged QTc interval had a significant association with the requirement of ventilator support and was associated with an increased odds of mortality. Patients who died were older than 55 years, and had high troponin, D-dimer, creatinine, procalcitonin, and ferritin concentrations, a high white blood cell count, and abnormal potassium concentrations (hypo- or hyperkalemia).
Conclusions
A prolonged QTc interval is common in patients with SARS-CoV-2 infection and it is associated with worse outcomes. Older individuals and those with comorbidities should have an electrocardiogram performed, which is noninvasive and easily available, on admission to hospital to identify high-risk patients.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection is the cause of the ongoing global pandemic. Mortality from COVID-19 infection is particularly high in patients with cardiovascular diseases. In addition, COVID-19 patients with preexisting cardiovascular comorbidities have a higher risk of death. Main cardiovascular complications of COVID-19 are myocardial infarction, myocarditis, acute myocardial injury, arrhythmias, heart failure, stroke, and venous thromboembolism. Therapeutic interventions in terms of drugs for COVID-19 have many cardiac adverse effects. Here, we review the relative therapeutic efficacy and adverse effects of anti-COVID-19 drugs.
Background:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has risen to the level of a global pandemic. Growing evidence has proven the cardiac involvement in SARS-CoV-2 infection. This study aims to evaluate the ability of cardiovascular complications determined by elevated troponin and electrocardiogram findings (e.g., corrected QT interval (QTc)) in predicting the severity of SARS-CoV-2 infection among hospitalized patients.
Methods:
This is a retrospective review of medical records of 800 patients, admitted to Richmond University Medical Center in Staten Island, NY, and tested positive for SARS-CoV-2 between March 1, 2020 and July 31, 2020. A total of 339 patients met the study inclusion and exclusion criteria and were included in statistical analysis.
Results:
Elevated serum troponin levels on admission statistically correlated with mortality in SARS-CoV-2 patients. Prolonged QTc was shown to have an independent statistically significant association with mortality among patients hospitalized with SARS-CoV-2.
Conclusions:
Growing concern for cardiovascular sequelae of coronavirus disease 2019 (COVID-19) has prompted many researchers to investigate the role of cardiovascular complications in mortality due to SARS-CoV-2. Obtaining a simple electrocardiogram for hospitalized patients with COVID-19 could provide an independent prognostic tool and prompt more coordinated treatment strategies to prevent mortality among patients hospitalized with COVID-19.
Aims:
Several studies have unveiled the great heterogeneity of COVID-19 pneumonia. Identification of the "vascular phenotype" (involving both pulmonary parenchyma and its circulation) has prognostic significance. Our aim was to explore the combined role of chest computed tomography (CT) scan and electrocardiogram (ECG) at hospital admission in predicting short-term prognosis and to draw pathophysiological insights.
Methods and results:
We analyzed the chest CT scan and ECG performed at admission in 151 consecutive COVID-19 patients admitted between 20 March and 4 April 2020. All-cause mortality within 30 days was the primary endpoint. Median age was 71 years (IQR: 62-76). Severe pneumonia was present in 25 (17%) patients, and 121 (80%) had abnormal ECG. During a median follow-up of 7 days (IQR: 4-13), 54 (36%) patients died. Deceased patients had more severe pneumonia than survivors did (80% vs. 64%, p = 0.044). ECG in deceased patients showed more frequently atrial fibrillation/flutter (17% vs. 6%, p = 0.039) and acute right ventricular (RV) strain (35% vs. 10%, p < 0.001), suggesting the "vascular phenotype". ECG signs of acute RV strain (HR 2.46, 95% CIs 1.36-4.45, p = 0.0028) were independently associated with all-cause mortality in multivariable analysis, and in the likelihood ratio test, showed incremental prognostic value over chest CT scan, age, and C-reactive protein.
Conclusions:
Combining chest CT scan and ECG data improves risk stratification in COVID-19 pneumonia by identifying a distinctive phenotype with both parenchymal and vascular damage of the lung. Patients with severe pneumonia at chest CT scan plus ECG signs of acute RV strain have an extremely poor short-term prognosis.
Background
COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients.
Methods
Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients.
Results
Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4⁺ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4⁺ T cell, and CD8⁺ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). For severe patients, the counts of T cell, CD4⁺ T cell, CD8⁺ T cell gradually decreased with the increased delayed hospitalization (p = 0.001, 0.03, and < 0.001, respectively). The proportions of T cell, CD8⁺ T cell gradually decreased with the increased delayed hospitalization (both p < 0.001), but the proportions of NK cell, B cell gradually increased with the increased delayed hospitalization (p = 0.007, and 0.002, respectively). For mild patients, only the NK cell count was gradually decreased with the increased delayed hospitalization (p = 0.012).
Conclusion
T lymphocyte and its subset negatively correlated with disease severity, CT manifestation and delayed hospitalization. The counts of lymphocyte subset were changed more profound than their proportions.
Importance:
Critical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc).
Objective:
To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19.
Design, setting, and participants:
This cohort study included 3050 patients aged 18 years and older who underwent SARS-CoV-2 testing and had ECGs at Columbia University Irving Medical Center from March 1 through May 1, 2020. Patients were analyzed by treatment group over 5 days, as follows: hydroxychloroquine with azithromycin, hydroxychloroquine alone, azithromycin alone, and neither hydroxychloroquine nor azithromycin. ECGs were manually analyzed by electrophysiologists masked to COVID-19 status. Multivariable modeling evaluated clinical associations with QTc prolongation from baseline.
Exposures:
COVID-19, hydroxychloroquine, azithromycin.
Main outcomes and measures:
Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater.
Results:
A total of 965 patients had more than 2 ECGs and were included in the study, with 561 (58.1%) men, 198 (26.2%) Black patients, and 191 (19.8%) aged 80 years and older. There were 733 patients (76.0%) with COVID-19 and 232 patients (24.0%) without COVID-19. COVID-19 infection was associated with significant mean QTc prolongation from baseline by both 5-day and 2-day multivariable models (5-day, patients with COVID-19: 20.81 [95% CI, 15.29 to 26.33] milliseconds; P < .001; patients without COVID-19: -2.01 [95% CI, -17.31 to 21.32] milliseconds; P = .93; 2-day, patients with COVID-19: 17.40 [95% CI, 12.65 to 22.16] milliseconds; P < .001; patients without COVID-19: 0.11 [95% CI, -12.60 to 12.81] milliseconds; P = .99). COVID-19 infection was independently associated with a modeled mean 27.32 (95% CI, 4.63-43.21) millisecond increase in QTc at 5 days compared with COVID-19-negative status (mean QTc, with COVID-19: 450.45 [95% CI, 441.6 to 459.3] milliseconds; without COVID-19: 423.13 [95% CI, 403.25 to 443.01] milliseconds; P = .01). More patients with COVID-19 not receiving hydroxychloroquine and azithromycin had QTc of 500 milliseconds or greater compared with patients without COVID-19 (34 of 136 [25.0%] vs 17 of 158 [10.8%], P = .002). Multivariable analysis revealed that age 80 years and older compared with those younger than 50 years (mean difference in QTc, 11.91 [SE, 4.69; 95% CI, 2.73 to 21.09]; P = .01), severe chronic kidney disease compared with no chronic kidney disease (mean difference in QTc, 12.20 [SE, 5.26; 95% CI, 1.89 to 22.51; P = .02]), elevated high-sensitivity troponin levels (mean difference in QTc, 5.05 [SE, 1.19; 95% CI, 2.72 to 7.38]; P < .001), and elevated lactate dehydrogenase levels (mean difference in QTc, 5.31 [SE, 2.68; 95% CI, 0.06 to 10.57]; P = .04) were associated with QTc prolongation. Torsades de pointes occurred in 1 patient (0.1%) with COVID-19.
Conclusions and relevance:
In this cohort study, COVID-19 infection was independently associated with significant mean QTc prolongation at days 5 and 2 of hospitalization compared with day 0. More patients with COVID-19 had QTc of 500 milliseconds or greater compared with patients without COVID-19.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021 report dawns with an update to the diagnostic, preventive and therapeutic strategies for Chronic obstructive pulmonary disease (COPD). Unlike the previous update, there are no major changes in diagnostic and treatment directives. There are however, numerous small updates which stem from over two hundred new references that have been added.
Background
There are some data showing that repurposed drugs used for the Coronavirus disease‐19 (COVID‐19) have potential to increase the risk of QTc prolongation and torsade de pointes (TdP), these arrhythmic side effects have not been adequately addressed in COVID‐19 patients treated with these repurposed medications.
Methods
This is the prospective study of 2,403 patients hospitalized at 13 hospitals within the COVID‐19 epicenters of the Iran. These patients were treated with chloroquine, hydroxychloroquine, lopinavir/ritonavir, atazanavir/ritonavir, oseltamivir, favipiravir, and remdesivir alone or in combination with azithromycin. The primary outcome of the study was incidence of critical QTc prolongation and secondary outcomes were incidences of TdP and death.
Results
Of the 2403 patients, 2365 met inclusion criteria. The primary outcome of QTc≥500 ms and ∆QTc≥60 ms was observed in 11.2% and 17.6% of the patients, respectively. The secondary outcomes of TdP and death were reported in in 0.38% and 9.8% of the patients, respectively. The risk of critical QT prolongation increased in the presence of female gender, history of heart failure, treatment with hydroxychloroquine, azithromycin combination therapy, simultaneous furosemide or betablocker therapy and acute renal or hepatic dysfunction. However, the risk of TdP predicted by treatment with lopinavir‐ritonavir, simultaneous amiodarone or furosemide administration and hypokalemia during treatment.
Conclusion
This cohort showed significant QTc prolongation with all COVID‐19 medications studied, however, life‐threatening arrhythmia of TdP occurred rarely. Among the repurposed drugs studied, hydroxychloroquine or lopinavir‐ritonavir alone or in combination with azithromycin clearly demonstrated to increase the risk of critical QT prolongation and/or TdP.
Background and Aims
Given gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance.
Methods
Human intestinal biopsy tissues were obtained from COVID-19 patients (n=19) and uninfected controls (n=10) for microscopic examination, CyTOF analyses and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in two large, independent cohorts of hospitalized patients in the United States (n=634) and Europe (n=287) using multivariate logistic regressions.
Results
COVID-19 cases and controls in the biopsy cohort were comparable for age, gender, rates of hospitalization and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy, in 14 of 16 patients studied. High dimensional analyses of GI tissues revealed low levels of inflammation, including downregulation of key inflammatory genes including IFNG, CXCL8, CXCL2 and IL1B and reduced frequencies of proinflammatory dendritic cells compared with controls. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of gender, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms.
Conclusion
These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in COVID-19 patients presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2 associated inflammation needs to be further examined.
Rationale:
The natural history of recovery from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) remains unknown. Since fibrosis with persistent physiological deficit is a previously-described feature of patients recovering from similar coronaviruses, treatment represents an early opportunity to modify the disease course, potentially preventing irreversible impairment.
Objectives:
Determine the incidence of and describe the progression of persistent inflammatory interstitial lung disease (ILD) following SARS-CoV2 when treated with prednisolone.
Methods:
A structured assessment protocol screened for sequelae of SARS-CoV2 pneumonitis. 837 patients were assessed by telephone four weeks after discharge. Those with ongoing symptoms had outpatient assessment at six weeks. Thirty patients diagnosed with persistent interstitial lung changes at multi-disciplinary team meeting were reviewed in the interstitial lung disease service and offered treatment. These patients had persistent, non-improving symptoms.
Results:
At four weeks post-discharge, 39% of patients reported ongoing symptoms (325/837), and were assessed. Interstitial lung disease, predominantly organising pneumonia, with significant functional deficit was observed in 35/837 survivors (4.8%). Thirty of these patients received steroid treatment, resulting in a mean relative increase in transfer factor following treatment of 31.6% (standard deviation ± 27.64, p <0.001), and FVC of 9.6% (standard deviation ± 13.01, p = 0.014), with significant symptomatic and radiological improvement.
Conclusion:
Following SARS-CoV-2 pneumonitis, a cohort of patients are left with both radiological inflammatory lung disease and persistent physiological and functional deficit. Early treatment with corticosteroids was well tolerated and associated with rapid and significant improvement. This preliminary data should inform further study into the natural history and potential treatment for patients with persistent inflammatory ILD following SARS-CoV2 infection.
The first cases of Coronavirus disease-2019 (COVID-19) were reported on 21 February in the small town of Vo’ near Padua in the Veneto region of Italy. This event led to 19,286 infected people in the region by 30 June 2020 (39.30 cases/10,000 inhabitants). Meanwhile, Rovigo Local Health Unit n. 5 (ULSS 5), bordering areas with high epidemic rates and having one of the world’s oldest populations, registered the lowest infection rates in the region (19.03 cases/10,000 inhabitants). The aim of this study was to describe timing and event management by ULSS 5 in preventing the propagation of infection within the timeframe spanning from 21 February to 30 June. Our analysis considered age, genetic clusters, sex, orography, the population density, pollution, and economic activities linked to the pandemic, according to the literature. The ULSS 5 Health Director General’s quick decision-making in the realm of public health, territorial assistance, and retirement homes were key to taking the right actions at the right time. Indeed, the number of isolated cases in the Veneto region was the highest among all the Italian regions at the beginning of the epidemic. Moreover, the implementation of molecular diagnostic tools, which were initially absent, enabled health care experts to make quick diagnoses. Quick decision-making, timely actions, and encouraging results were achieved thanks to a solid chain of command, despite a somewhat unclear legislative environment. In conclusion, we believe that the containment of the epidemic depends on the time factor, coupled with a strong sense of awareness and discretion in the Health Director General’s decision-making. Moreover, real-time communication with operating units and institutions goes hand in hand with the common goal of protecting public health.
Coronavirus disease 2019 (COVID-19) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events. A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury. This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications. Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure. Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19. Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation. Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction. Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19. Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients. Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19. Several clinical trials are currently underway to explore this concept.
SARS-CoV-2 induced the novel coronavirus disease (COVID-19) outbreak, the most significant medical challenge in the last century. COVID-19 is associated with notable increases in morbidity and death worldwide. Preexisting conditions, like cardiovascular disease (CVD), diabetes, hypertension, and obesity, are correlated with higher severity and a significant increase in the fatality rate of COVID-19. COVID-19 induces multiple cardiovascular complexities, such as cardiac arrest, myocarditis, acute myocardial injury, stress-induced cardiomyopathy, cardiogenic shock, arrhythmias and, subsequently, heart failure (HF). The precise mechanisms of how SARS-CoV-2 may cause myocardial complications are not clearly understood. The proposed mechanisms of myocardial injury based on current knowledge are the direct viral entry of the virus and damage to the myocardium, systemic inflammation, hypoxia, cytokine storm, interferon-mediated immune response, and plaque destabilization. The virus enters the cell through the angiotensin-converting enzyme-2 (ACE2) receptor and plays a central function in the virus’s pathogenesis. A systematic understanding of cardiovascular effects of SARS-CoV2 is needed to develop novel therapeutic tools to target the virus-induced cardiac damage as a potential strategy to minimize permanent damage to the cardiovascular system and reduce the morbidity. In this review, we discuss our current understanding of COVID-19 mediated damage to the cardiovascular system.
Coronavirus disease 2019 (COVID-19) is associated with adverse outcomes, including need for invasive mechanical ventilation and death in people with risk factors. Liver enzyme elevation is commonly seen in this group, but its clinical significance remains elusive. In this study, we calculated the Fibrosis-4 (FIB-4) score for a cohort of hospitalized patients with COVID-19 and assessed its association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, inflammatory cytokine levels, and clinical outcome. A total of 202 hospitalized participants who tested positive for SARS-CoV-2 by nasopharyngeal sampling were included in this analysis. FIB-4 was calculated for each participant using the alanine aminotransferase, aspartate aminotransferase, age, and platelet count. We evaluated the association between FIB-4 and mortality using both multivariate logistic regression and Cox proportional hazards model. Correlations between FIB-4 and SARS-CoV-2 RNA and cytokine levels were evaluated using the Spearman test. Among the 202 participants, 22 died. The median FIB-4 in participants who survived and died were 1.91 and 3.98 (P < 0.001 by Mann-Whitney U test), respectively. Each one-unit increment in FIB-4 was associated with an increased odds of death (odds ratio, 1.79; 95% confidence interval, 1.36, 2.35; P < 0.001) after adjusting for baseline characteristics including sex, body mass index, hypertension, diabetes, and history of liver diseases. During hospitalization, FIB-4 peaked and then normalized in the survival group but failed to normalize in the death group. FIB-4 was positively correlated with the level of SARS-CoV-2 viral load and monocyte-associated cytokines, especially interleukin-6 and interferon gamma-induced protein 10. Conclusion: FIB-4 is associated with mortality in COVID-19, independent of underlying conditions including liver diseases. FIB-4 may be a simple and inexpensive approach to risk-stratify individuals with COVID-19.
Since December 2019, coronavirus has gradually progressed to a pandemic with no efficacious treatment. Remdesivir is an antiviral medication and inhibitor of viral RNA dependent RNA polymerase with inhibitory action against SARS-CoV virus. Two patients diagnosed with coronavirus infection with worsening respiratory status were initiated with multimodality therapy with antibiotics, steroids and remdesivir. After initiation of remdesivir, the patients' developed bradycardia, with one of the two also showing signs of worsening QT interval. This reverted upon stopping remdesvir therapy. The prevalence of bradycardia with prolonged QT interval is not well-known yet with this medication.
Objectives
COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients’ outcomes is still poorly understood.
Design
Observational, prospective, multicentre study.
Setting
Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards.
Participants
Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded.
Interventions
Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101–200 mm Hg); mild (PaO2/FiO2 201–300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg).
Primary and secondary outcome measures
The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay.
Results
412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55–76) years with a PaO2/FiO2 at admission of 262 (140–343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04).
Conclusions
A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality.
Trial registration number
NCT04307459
Background:
SARS-CoV-2 infection has caused a global pandemic. Many of the medications identified to treat COVID-19 could be connected with QTc prolongation and its consequences.
Methods:
non-ICU hospitalized patients of the three centres involved in the study from the 19th of March to the 1st of May were included in this retrospective multicentre study. Relevant clinical data were digitally collected. The primary outcome was the incidence of QTc prolongation ≥ 500 ms, the main secondary outcomes were the Tisdale score ability to predict QTc prolongation and the incidence of ventricular arrhythmias and sudden deaths.
Results:
196 patients were analysed. 20 patients (10.2%) reached a QTc≥500 ms. Patients with QTc≥500 ms were significantly older (66.7±14.65 vs 76.6±8.77 years p: 0.004), with higher Tisdale score (low 56 (31.8%) vs 0; intermediate 95 (54.0%) vs 14 (70.0%); high 25 (14.2%) vs 6 (30.0%); p: 0.007) and with higher prognostic lab values (d-dimer 1819±2815 vs 11486±38554 ng/ml p: 0.010; BNP 212.5±288.4 vs 951.3±816.7 pg/ml p<0.001; procalcitonin 0.27±0.74 vs 1.33±4.04 ng/ml p: 0.003). After a multivariate analysis the Tisdale score was able to predict a QTc prolongation ≥500 ms (OR 1,358 95% CI 1,076 - 1,714 p: 0,010). 27 patients died because of COVID-19 (13.7%), none experienced ventricular arrhythmias, and 2 (1.02%) patients with concomitant cardiovascular condition died of sudden death.
Conclusions:
in our population, a QTc prolongation ≥500 ms was observed in a minority of patients, no suspected fatal arrhythmias have been observed. Tisdale score can help in predicting QTc prolongation.
Background:
The prognostic value of a prolonged QT interval in SARS-Cov2 infection is not well known.
Objective:
To determine whether the presence of a prolonged QT on admission is an independent factor for mortality in SARS-Cov2 hospitalized patients.
Methods:
Single-center cohort of 623 consecutive patients with positive polymerase-chain-reaction test (PCR) to SARS Cov2, recruited from 27 February to 7 April 2020. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval. A prolonged QT interval was defined as a corrected QT (QTc) interval >480 milliseconds. Patients were followed up with until 10 May 2020.
Results:
Sixty-one patients (9.8%) had prolonged QTc and only 3.2% had a baseline QTc > 500 milliseconds. Patients with prolonged QTc were older, had more comorbidities, and higher levels of immune-inflammatory markers. There were no episodes of ventricular tachycardia or ventricular fibrillation during hospitalization. All-cause death was higher in patients with prolonged QTc (41.0% vs. 8.7%, p < 0.001, multivariable HR 2.68 (1.58-4.55), p < 0.001).
Conclusions:
Almost 10% of patients with COVID-19 infection have a prolonged QTc interval on admission. A prolonged QTc was independently associated with a higher mortality even after adjustment for age, comorbidities, and treatment with hydroxychloroquine and azithromycin. An electrocardiogram should be included on admission to identify high-risk SARS-CoV-2 patients.
Men are consistently overrepresented in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and COVID (COrona- VIrus-Disease)-19 severe outcomes, including higher fatality rates. These differences are likely due to gender-specific behaviors, genetic and hormonal factors, and sex differences in biological pathways related to SARS-CoV-2 infection. Several social, behavioral and comorbid factors are implicated in the generally worse outcomes in men as compared with women. Underlying biological sex differences and their effects on COVID-19 outcomes, however, have received less attention. The present review summarizes the available literature regarding proposed molecular and cellular markers of COVID-19 infection, their associations with health outcomes, and any reported modification by sex. Biological sex differences characterized by such biomarkers exist within healthy populations and also differ with age- and sex-specific conditions, such as pregnancy and menopause. In the context of COVID-19, descriptive biomarker levels are often reported by sex, but data pertaining to the effect of patient sex on the relationship between biomarkers and COVID-19 disease severity/outcomes are scarce. Such biomarkers may offer plausible explanations for the worse COVID-19 outcomes seen in men. There is the need for larger studies with sex-specific reporting and robust analyses to elucidate how sex modifies cellular and molecular pathways associated with SARS-CoV-2. This will improve interpretation of biomarkers and clinical management of COVID-19 patients by facilitating a personalized medical approach to risk stratification, prevention, and treatment.
Coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly the world over. The disease was declared “pandemic” by the World Health Organization. An approved therapy for patients with COVID-19 has yet to emerge; however, there are some medications used in the treatment of SARS-CoV-2 infection globally including hydroxychloroquine, remdesivir, dexamethasone, protease inhibitors, and anti-inflammatory agents. Patients with underlying cardiovascular disease are at increased risk of mortality and morbidity from COVID-19. Moreover, patients with chronic stable states and even otherwise healthy individuals might sustain acute cardiovascular problems due to COVID-19 infection. This article seeks to review the latest evidence with a view to explaining possible pharmacotherapies for the cardiovascular complications of COVID-19 including acute coronary syndrome, heart failure, myocarditis, arrhythmias, and venous thromboembolism, as well as possible interactions between these medications and those currently administered (or under evaluation) in the treatment of COVID-19.
Background
Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. SARS-CoV-2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.
Objective
To evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.
Methods
We reviewed the characteristics of all COVID-19 patients admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias and in-patient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, kidney disease and ICU status as potential risk factors for each arrhythmia.
Results
Among 700 patients (mean age 50±18 years, 45% men, 71% African American, and 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred among patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (OR 4.68 [95% CI 1.66 – 13.18]) and NSVT (OR 8.92 [95% CI 1.73 – 46.06]) after multivariable adjustment. Also, age and incident AF (OR 1.05 [95% CI 1.02 – 1.09]); and prevalent heart failure and bradyarrhythmias (OR 9.75 [95% CI 1.95 – 48.65]) were independently associated. Only cardiac arrests were associated with acute, in-hospital mortality.
Conclusion
Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
Background and aims:
COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19.
Methods:
multicenter, retrospective study with prospective follow-up of 160 middle-aged (35 to 65 years) patients with COVID-19. FIB-4, clinical and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis. Through multivariate logistic regression and bootstrap analysis, independent predictors of intensive care unit admission for mechanical ventilation were identified.
Results:
risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 required more frequently mechanical ventilation (37.8% vs 18.3%; p= 0.009). In multivariate analysis, FIB-4 ≥2.67 (OR 3.41; 95% CI 1.30-8.92), cardiovascular risk factors (OR 5.05; 95% CI: 1.90-13.39), previous respiratory diseases (OR 4.54; 95% CI: 1.36-15.10) and C-reactive protein (OR 1.012; 95% CI: 1.006-1.017) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor.
Conclusions:
in middle-aged patients with COVID-19, FIB-4 may have a relevant prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies.
Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). COVID-19 significantly affects multiple systems including the cardiovascular system. Most importantly, in addition to the direct injury from the virus per se, the subsequent cytokine storm, an overproduction of immune cells and their activating compounds, causes devastating damage. To date, emerging anti-SARS-CoV-2 treatments are warranted to control epidemics. Several candidate drugs have been screened and are currently under investigation. These primarily include antiviral regimens and immunomodulatory regimens. However, beyond the anti-SARS-CoV-2 effects, these drugs may also have risks to the cardiovascular system, especially altering cardiac conduction. Herein, we review the cardiovascular risks of potential anti-COVID-19 drugs.
A reduced peripheral blood absolute lymphocyte count with an elevated neutrophil count has been a consistent observation in hospitalized COVID‐19 patients. In this brief meta‐analysis, the reduction of lymphocyte subset counts in COVID‐19 patients was investigated across 20 peer‐reviewed studies meeting criteria for reporting lymphocyte subset counts and COVID‐19 disease severity. CD4+ T cell, CD8+ T cell, B cell, NK cell and total lymphocyte cell counts all showed statistically significant reduction in patients with severe/critical COVID‐19 disease compared to mild/moderate disease. T cell subsets showed the largest standardized magnitude of change. In some studies, multivariate analysis has shown that CD4 and/or CD8 T cells counts are independently predictive of patient outcomes.
Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long-standing standard of care in anticoagulation, vitamin K antagonist. DOACs are indicated for prevention and treatment of several cardiovascular conditions. Since the first approval in 2010, DOACs have emerged as leading therapeutic alternatives that provide both clinicians and patients with more effective, safe, and convenient treatment options in thromboembolic settings. With the expanding role of DOACs, clinicians are faced with increasingly complex decisions relating to appropriate agent, duration of treatment, and use in special populations. This review will provide an overview of DOACs and act as a practical reference for clinicians to optimize DOAC use among common challenging scenarios. Topics addressed include (1) appropriate indications; (2) use in patients with specific comorbidities; (3) monitoring parameters; (4) transitioning between anticoagulant regimens; (5) major drug interactions; and (6) cost considerations.
Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus.
The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin–angotensin–aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.
Introduction: COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are known to foster cardiac adverse ADRs, notably QTc interval prolongation on the electrocardiogram and its arrhythmogenic consequences.
Methods: Since March 27th, 2020, the French Pharmacovigilance Network directed all cardiac adverse drug reactions associated with “off-label” use of hydroxychloroquine, azithromycin and lopinavir-ritonavir in COVID-19 to the Nice Regional Center of Pharmacovigilance. Each Regional Center of Pharmacovigilance first assessed causality of drugs. We performed a specific analysis of these cardiac adverse drug reactions amidst an array of risk factors, reassessed the electrocardiograms and estimated their incidence in coronavirus-disease-2019.
Results: In one month, 120 reports of cardiac adverse drug reactions have been notified, 102 of which associated with hydroxychloroquine alone (85%), or associated with azithromycin (60%). Their estimated incidence is 0.77% to 1.54% of all patients, notwithstanding strong underreporting. Lopinavir-ritonavir came third with 17 reports (14%) and chloroquine fourth with 3 reports (2.5%). There were 8 sudden, unexplained or aborted deaths (7%), 8 ventricular arrhythmias (7 %), 90 reports of prolonged QTc (75%) most of them “serious” (64%), 48 of which proved ≥ 500 ms, 20 reports of severe conduction disorders (17%) and 5 reports of other cardiac causes (4%). Six reports derived from automedication.
Discussion and conclusion: “Off-label” use of treatments in COVID-19 increases the risk of cardiac ADRs, some of them avoidable. Even if these drugs are perceived as familiar, they are used in patients with added risk factors caused by infection. Precautions should be taken to mitigate the risk, even if they will be proven efficacious.
Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.
At present, there is scarce information regarding the global prevalence of chronic liver disease in individuals with COVID‐19 disease, which is become a global pandemic early. Aim of this study was to assess the overall prevalence of chronic liver disease among patients with COVID‐19 disease by meta‐analyzing data in observational studies and to investigate the relationship between liver damage and COVID‐19 disease. We included 11 observational studies for a total of 2,034 adult individuals (median age 49 years [IQR 45‐54], 57.2% men). The overall prevalence of chronic liver disease at baseline was 3% (95% CI 2‐4%; I2=29.1%). Individuals with severe COVID‐19 disease had relevant alterations of liver enzymes and coagulative profile, probably due to the innate immune response against the virus. Further studies are needed to better investigate the causes of liver injury in patients with COVID‐19 disease and the effect of treatment for COVID‐19 on the liver.
Background and aims
Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients.
Methods
A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic.
Results
Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8-12% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients.
Conclusions
Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.
Description:
The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO).
Methods:
The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5).
Recommendations:
The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.
Background
Corona virus disease 2019 (COVID-19) is associated with coagulopathy (CAC) and venous thromboembolism (VTE). These are well-reported complications of COVID-19 infection. Earlier publications have shown that CAC and thromboembolism are predictors of mortality among COVID-19 patients with severe disease.
Material and Methods
A prospective study was conducted in the Intensive Care Unit (ICU) where all confirmed COVID-19 patients were enrolled and followed until death or ICU discharge. CAC, VTE, along with all comorbidities were recorded. Predictors of mortality were determined by univariate and multivariate regression.
Results
Among 261 patients with COVID-19, 48.3% survived and 51.7% died. CAC was present in 53.2% and 76.3% of the survivors and non-survivors, respectively (p<0.001); 89 patients (31.4%) had VTE (p=0.36) and 11 patients (4.2%) had arterial thrombosis (p=0.76) among survivors and non-survivors. Age between 71-80 years (p=0.009), male gender (p=0.045), CAC (p<0.001), comorbidities like chronic kidney disease (CKD, p=0.013), chronic obstructive pulmonary disease (COPD, p=0.001) and asthma (p=0.046), were significant predictors of mortality.
Conclusion
A severe complication of COVID-19 is CAC, such as sepsis-induced coagulopathy, overt disseminated-coagulopathy and VTE. Old age, various comorbidities (e.g. COPD, CKD or asthma), CAC, VTE (pulmonary embolism) and coagulation parameters with critical severity score (D-dimers, platelets, prothrombin time) and the SOFA (Sequential Organ Failure Assessment) score were significant predictors of mortality among COVID-19 patients.
Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.
The pandemic of Coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.
Purpose
Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID‐19) during the early pandemic period. It is well‐known that these agents can prolong the QTc interval and potentially induce Torsades de Pointes (TdP). We aim to assess the prevalence and risk of QTc prolongation and arrhythmic events in COVID‐19 patients treated with these drugs.
Methods
We searched electronic databases from inception to September 30, 2020 for studies reporting peak QTc ≥500ms, peak QTc change ≥60ms, peak QTc interval, peak change of QTc interval, ventricular arrhythmias, TdP, sudden cardiac death, or atrioventricular block (AVB). All meta‐analyses were conducted using a random‐effects model.
Results
Forty‐seven studies (three case series, 35 cohorts, and nine randomized controlled trials) involving 13087 patients were included. The pooled prevalence of peak QTc ≥500ms was 9% (95%CI [95% confidence interval], 3‐18%) and 8% (95%CI, 3‐14%) in patients who received hydroxychloroquine/chloroquine alone or in combination with azithromycin, respectively. Likewise, the use of hydroxychloroquine (risk ratio [RR], 2.68; 95%CI, 1.56‐4.60) and hydroxychloroquine + azithromycin (RR, 3.28; 95%CI, 1.16‐9.30) was associated with an increased risk of QTc prolongation compared to no treatment. Ventricular arrhythmias, TdP, sudden cardiac death, and AVB were reported in <1% of patients across treatment groups. The only two studies that reported individual data of lopinavir/ritonavir found no cases of QTc prolongation.
Conclusions
COVID‐19 patients treated with hydroxychloroquine/chloroquine with or without azithromycin had a relatively high prevalence and risk of QTc prolongation. However, the prevalence of arrhythmic events was very low probably due to underreporting. The limited information about lopinavir/ritonavir showed that it does not prolong the QTc interval.
Objectives
In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is associated with an increased risk of bradycardia.
Methods
Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23th of September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% Confident Intervals (95% CI).
Results
We found 302 cardiac effects including 94 bradycardia (31%) among the 2,603 reports with remdesivir prescribed in COVID-19 patients. Most of reports were serious (75, 80%) and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23, 2.22). Consistent results were observed in other sensitivity analyses.
Conclusions
This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with pharmacodynamic properties of the remdesivir.
Background
The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic. Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy. The incidence of torsade de pointes remains unknown. Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment.
Methods
Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study. A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest.
Results
The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin. Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5. There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced.
Conclusions
The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy.
Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug–disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.
Background:
During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K+ channel expression.
Methods:
We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K+ channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time.
Results:
In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K+ channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients.
Conclusions:
During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs. Graphic Abstract: A graphic abstract is available for this article.
Background
Hydroxychloroquine (HCQ) has been promoted as a potential treatment for COVID-19 but there are safety concerns.
Objectives
To determine the effect of HCQ treatment on QT interval
Methods
We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy.
Results
The patients were 64.0 (±10.9) years in age and 734 (90%) were men. The median dosage and duration of HCQ were 400mg daily and 1006 (471-2075) days, respectively. The mean on-treatment QTc was 430.9 (±31.8) msec. In total, 55 (7%) patients had QTc 470-500 msec and 12 (1.5%) had QTc >500msec. Chronic kidney disease (CKD), history of atrial fibrillation (AF) and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pre-treatment ECG, the mean QTc increased from 424.4 (±29.7) msec. to 432.0 (±32.3) msec (p<0.0001) during HCQ treatment. Of these, 23 (3.9%) patients had either prolongation of QTc >15% or an on-treatment QTc >500 msec. Over 5.97 (3.33-10.11) years of follow-up, 269 (33%) patients died. QTc >470 msec during HCQ treatment was associated with a greater mortality risk of (hazard ratio 1.78, 95% confidence interval 1.16-2.71; p=0.008) in univariable but not in multivariable analysis.
Conclusion
Hydroxychloroquine is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF and heart failure, who may benefit from greater scrutiny.
Background
The pandemic of coronavirus disease 2019 (COVID‐19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID‐19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non‐critically ill patients with COVID‐19.
Methods
In this multicenter, retrospective study, we collected data about 565 inpatients with COVID‐19. Data on LFTs were collected at admission and every 7±2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU).
Results
Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20vs8%; p<0.001), acute kidney injury (22vs13%, p=0.009), need for mechanical ventilation (14vs6%; p=0.005), and mortality (21vs11%; p=0.004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR=3.53; p<0.001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint.
Conclusions
LFTs abnormality is common at admission in patients with COVID‐19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.
Endothelial cell infection and endotheliitis in COVID-19
Importance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system.
Observations
Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality.
Conclusions and Relevance
Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.