LitCovid-sentences  

PMC:7796041 / 2016-33632 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T24 0-2 Sentence denotes 1.
T25 3-15 Sentence denotes Introduction
T26 16-153 Sentence denotes The global pandemic caused by coronavirus disease 2019 (COVID-19) continues to evolve and exerts tremendous strain on healthcare systems.
T27 154-325 Sentence denotes Pathomechanisms differentiating patients at high risk for adverse outcomes from those displaying minor symptoms and a mild course of disease are insufficiently understood.
T28 326-483 Sentence denotes Cardiovascular involvement and myocardial injury are commonly observed and associated prognostic implications have been suggested by early reports [1,2,3,4].
T29 484-603 Sentence denotes Impairment of ventricular function and inflammatory myocardial processes have been detected in COVID-19 patients [5,6].
T30 604-760 Sentence denotes However, evidence regarding prevalence and prognostic effects of cardiac arrhythmias in COVID-19 is sparse and mainly limited to single center observations.
T31 761-933 Sentence denotes Early studies among the first patient cohorts analyzed in China reported an incidence of cardiac arrhythmia of 17%, with rates of up to 44% in patients admitted to ICU [7].
T32 934-1016 Sentence denotes However, there was no information on the respective types of arrhythmia diagnosed.
T33 1017-1205 Sentence denotes Another monocentric study from Pennsylvania reported similar rates of arrhythmia events during hospitalization for COVID-19, in particular in patients treated in an intensive care setting.
T34 1206-1264 Sentence denotes AF was identified as the most common arrhythmic event [8].
T35 1265-1513 Sentence denotes In a cohort of 30 patients from Italy, a possible association of cardiac arrhythmias and increased inflammatory markers as well as mortality in COVID-19 was pointed out, however, with limited reliability of results due to the small sample size [9].
T36 1514-1727 Sentence denotes Insight into the role of arrhythmias in COVID-19 is of particular importance as widely used pharmacological therapies attempting to mitigate the course of disease may be associated with proarrhythmic effects [10].
T37 1728-2012 Sentence denotes This study aims to systematically investigate the prevalence of cardiac arrhythmias in patients hospitalized for COVID-19 at multiple centers, to identify risk factors for the occurrence of cardiac arrhythmias, and to assess their role regarding clinical course and patient prognosis.
T38 2014-2016 Sentence denotes 2.
T39 2017-2024 Sentence denotes Methods
T40 2026-2030 Sentence denotes 2.1.
T41 2031-2048 Sentence denotes Patient Selection
T42 2049-2191 Sentence denotes All patients with COVID-19 who had been hospitalized at the participating centers were included in this registry from 5 March to 17 June 2020.
T43 2192-2331 Sentence denotes Only patients with a complete documentation of the clinical stay (i.e., discharged from the respective center or deceased) were considered.
T44 2332-2510 Sentence denotes Further inclusion criteria were a confirmation of SARS-CoV-2 infection by polymerase chain reaction testing of a nasopharyngeal sample and a duration of hospital stay for ≥ 24 h.
T45 2511-2570 Sentence denotes In total, 166 patients with were included in this registry.
T46 2571-2644 Sentence denotes In the majority of patients, COVID-19 was the reason for hospitalization.
T47 2645-2803 Sentence denotes A subgroup of nine patients had been admitted for different indications and SARS-CoV-2-infection was diagnosed and treated in the course of the hospital stay.
T48 2804-3008 Sentence denotes The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the University of Heidelberg (study registration number at the ethics committee: S-281/2020).
T49 3009-3264 Sentence denotes Due to the retrospective, non-interventional nature of the study based solely on data generated and documented during clinical routine processes, informed and written consent was not required in accordance with the statement of the local ethics committee.
T50 3266-3270 Sentence denotes 2.2.
T51 3271-3286 Sentence denotes Data Collection
T52 3287-3479 Sentence denotes All available clinical records including physicians’ and nurses’ written reports, diagnostic test results, telemetry logs and electronic patient files were used for systematic data collection.
T53 3480-3661 Sentence denotes Demographic and clinical baseline parameters, comorbidities, biomarkers, medical therapy as well as information on endpoints regarding the clinical course of disease were extracted.
T54 3662-3813 Sentence denotes Clinically relevant arrhythmias previously diagnosed or incident during hospitalization were recorded and classified according to arrhythmia diagnosis.
T55 3814-3935 Sentence denotes Electrocardiograms (ECGs) conducted at admission to hospital were evaluated regarding QRS and QTc duration, if available.
T56 3936-4086 Sentence denotes If ECG documentation of the arrhythmia was available in the patient file, the diagnosis was confirmed by electrophysiology experts of the study group.
T57 4087-4356 Sentence denotes With respect to biomarker analyses, peak values of high-sensitive troponin T (hsTnT), N-terminal pro-B-type natriuretic peptide (NTproBNP), lactate dehydrogenase (LDH), C-reactive protein (CRP) and interleukin-6 (IL-6) were recorded, if assessed during hospitalization.
T58 4357-4441 Sentence denotes Data on body mass index (BMI) or presence of obesity were available in 138 patients.
T59 4442-4510 Sentence denotes Obesity was defined as BMI > 25 kg/m2 for the purpose of this study.
T60 4512-4516 Sentence denotes 2.3.
T61 4517-4536 Sentence denotes Statistical Methods
T62 4537-4623 Sentence denotes The patient cohort was described using summary measures of the empirical distribution.
T63 4624-4776 Sentence denotes Continuous variables are reported as median (with inter-quartile range, 25th percentile = P25; 75th percentile = P75) or mean ± standard deviation (SD).
T64 4777-4861 Sentence denotes The t-test or Mann-Whitney-Wilcoxon-test were applied for between-group comparisons.
T65 4862-5019 Sentence denotes Dichotomous variables are presented as absolute and relative frequencies and were compared applying the Fisher Boschloo-test from the R package “Exact” [11].
T66 5020-5315 Sentence denotes For the purpose of selecting variables with predictive impact on the incidence of arrhythmia, the variables sex, age, hypertension, cardiovascular disease, hydroxychloroquine, and combined therapy with hydroxychloroquine and azithromycin were initially considered in terms of variable selection.
T67 5316-5442 Sentence denotes First, regularized logistic regression using the elastic net penalty implemented in the package “glmnet” was computed [12,13].
T68 5443-5593 Sentence denotes The hyperparameters α (elastic net mixing parameter) and β (shrinkage parameter) were tuned conducting 5-fold cross-validation (CV) and a grid search.
T69 5594-5777 Sentence denotes Subsequently, multiple logistic regression modeling was conducted only incorporating the selected variables, to estimate the odds ratios (ORs) and their 95% confidence intervals (CI).
T70 5778-5940 Sentence denotes The area under the curve (AUC) value was computed applying the receiver operating characteristics (ROC) curve to evaluate the model using the package “pROC” [14].
T71 5941-6051 Sentence denotes To prevent overestimation of the model’s performance measure, the AUC-value was calculated applying 5-fold CV.
T72 6052-6174 Sentence denotes During 5-fold CV, each patient is part of the training set for four times and is assigned exactly once to the testing set.
T73 6175-6354 Sentence denotes Hence, in each step a model is fitted based on 80% of the data whereas a probability of the remaining 20% of the patients is estimated with respect to the incidence of arrhythmia.
T74 6355-6446 Sentence denotes Information on left ventricular ejection fraction (LVEF) was only available in 44 patients.
T75 6447-6609 Sentence denotes To account for a potential influence of LVEF on the development of cardiac arrhythmia, we performed attempts to impute the missing data (Supplementary Materials).
T76 6610-6723 Sentence denotes Due to a high number of missing values, LVEF was omitted from further analyses to ensure reliability of the data.
T77 6724-6847 Sentence denotes To evaluate the impact of biomarkers on the incidence of arrhythmia, univariate logistic regression modeling was performed.
T78 6848-6978 Sentence denotes The AUC-values und the Youden index for identifying the optimal cut-off value were computed for each biomarker, respectively [15].
T79 6979-7059 Sentence denotes Confidence intervals of the AUC-values were calculated according to DeLong [16].
T80 7060-7185 Sentence denotes To assess the prognostic impact of arrhythmia on clinical outcomes univariate and multiple regression modeling was performed.
T81 7186-7359 Sentence denotes To preserve the validity of multiple regression modeling in the light of the limited number of patients, the models were adjusted for a maximum of two additional covariates.
T82 7360-7501 Sentence denotes Age and cardiovascular disease were chosen due to their clinical significance regarding outcome in COVID-19 shown by previous studies [2,17].
T83 7502-7741 Sentence denotes Due to the high proportion of newly diagnosed atrial fibrillation (AF), we conducted a subgroup analysis comparing patients with incident AF to patients who neither had a history of AF nor displayed AF in the course of the hospitalization.
T84 7742-7858 Sentence denotes Due to the small sample size in the subgroup of patients with incident AF, only descriptive analyses were performed.
T85 7859-8082 Sentence denotes Due to the exploratory character of this analysis, the p-values are interpreted only in a descriptive sense and no adjustment for multiple testing was applied [18]. p-values < 0.05 were denoted as statistically significant.
T86 8083-8170 Sentence denotes The statistical analysis was performed using R version 4.0.2. [19] and SPSS version 25.
T87 8172-8174 Sentence denotes 3.
T88 8175-8182 Sentence denotes Results
T89 8184-8188 Sentence denotes 3.1.
T90 8189-8244 Sentence denotes Baseline Characteristics and Outcomes in Overall Cohort
T91 8245-8335 Sentence denotes Median age was 64.1 ± 16.7 years, and the majority of patients were male (n = 108, 65.1%).
T92 8336-8414 Sentence denotes Arterial hypertension constituted the most common risk factor (n = 83, 50.0%).
T93 8415-8568 Sentence denotes Cardiovascular disease was present in 18.1% (n = 30), cardiomyopathy in 3.0% (n = 5), diabetes mellitus in 17.5% (n = 29), and obesity in 21.7% (n = 36).
T94 8569-8930 Sentence denotes Other relevant comorbidities comprised pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary fibrosis) in 14.5% (n = 24), previous or active cancer disease in 8.4% (n = 14), and conditions associated with immunodeficiency (e.g., due to chronic immunosuppression therapy after organ transplantation or hematological disease) in 8.4% (n = 14).
T95 8931-9025 Sentence denotes Information on left ventricular ejection fraction (LVEF) was available in 44 patients (26.5%).
T96 9026-9070 Sentence denotes Mean LVEF in this subgroup was 53.0 ± 12.3%.
T97 9071-9135 Sentence denotes In three patients a cardiac pacemaker had been implanted (1.8%).
T98 9136-9217 Sentence denotes Implanted cardioverter-defibrillators (ICDs) were present in two patients (1.2%).
T99 9218-9320 Sentence denotes Seven patients (4.2%) presented with syncope in association with COVID-19 prior to hospital admission.
T100 9321-9375 Sentence denotes Median duration of hospitalization was 10.5 days (P25:
T101 9376-9388 Sentence denotes 5 days; P75:
T102 9389-9407 Sentence denotes 22 days, n = 154).
T103 9408-9552 Sentence denotes In 12 patients, data on duration of hospitalization could not be assessed due to transfer to a different center not participating in this study.
T104 9553-9748 Sentence denotes The majority of patients required oxygen therapy in the course of hospital stay, and over a third of all patients was admitted to intensive care (ICU) or intermediate care units (IMC) (Figure 1).
T105 9749-9800 Sentence denotes Median duration of ICU/IMC-therapy was 8 days (P25:
T106 9801-9813 Sentence denotes 4 days; P75:
T107 9814-9825 Sentence denotes 22.5 days).
T108 9826-10065 Sentence denotes High-flow oxygen therapy and/or non-invasive ventilation (NIV) by continuous positive airway pressure (CPAP) was necessary in 39 patients (23.5%), and pharmacological circulatory support by vasopressors was provided in 30 patients (18.1%).
T109 10066-10167 Sentence denotes Thirty-seven patients (22.3%) received mechanical ventilation with a median duration of 17 days (P25:
T110 10168-10182 Sentence denotes 7.5 days; P75:
T111 10183-10192 Sentence denotes 26 days).
T112 10193-10285 Sentence denotes Of these, six patients had to be re-intubated after initially successful weaning (Figure 1).
T113 10286-10423 Sentence denotes Only a minority of patients underwent extracorporeal membrane oxygenation (ECMO) or in-hospital cardiopulmonary resuscitation (Figure 1).
T114 10424-10584 Sentence denotes With respect to cardiovascular events, myocarditis was suspected in one patient based on cardiac biomarker-kinetics and mildly reduced LVEF in echocardiography.
T115 10585-10655 Sentence denotes This patient died due to respiratory failure during the hospital stay.
T116 10656-10730 Sentence denotes However, the diagnosis of myocarditis could not be confirmed upon autopsy.
T117 10731-10817 Sentence denotes Four patients were diagnosed with myocardial infarction (2.4%) during hospitalization.
T118 10818-11051 Sentence denotes Percutaneous coronary intervention (PCI) was performed in two cases, of which one patient presented with ST segment elevation myocardial infarction (STEMI) and one patient with non-ST segment elevation myocardial infarction (NSTEMI).
T119 11052-11246 Sentence denotes In the other two cases diagnosed with NSTEMI, medical therapy alone was preferred due to clinical instability with predominant respiratory symptoms and stable echocardiographic and ECG findings.
T120 11247-11344 Sentence denotes One patient with NSTEMI and PCI died in the course of hospitalization due to mesenteric ischemia.
T121 11345-11421 Sentence denotes Stroke or transient ischemic attack (TIA) was seen in three patients (1.8%).
T122 11422-11572 Sentence denotes Twenty-six patients died during hospitalization, predominantly due to respiratory failure (n = 20, 76.9%) or other non-cardiac reasons (n = 5, 19.2%).
T123 11573-11748 Sentence denotes Only one death was attributed to cardiac causes (3.8%), i.e., cardiac circulatory failure in a mechanically ventilated patient with pre-existent severe cardiovascular disease.
T124 11750-11754 Sentence denotes 3.2.
T125 11755-11802 Sentence denotes Arrhythmias During Hospitalization for COVID-19
T126 11803-11882 Sentence denotes In our cohort 34 patients (20.5%) displayed arrhythmias during hospitalization.
T127 11883-12050 Sentence denotes In 17 cases (10.2%), the arrhythmia type occurring during hospital stay had already been previously diagnosed in the respective patients prior to SARS-CoV-2 infection.
T128 12051-12174 Sentence denotes Specifically, in 16 patients previously diagnosed AF occurred, in one patient previously observed bradycardia was recorded.
T129 12175-12372 Sentence denotes Twenty-two patients (13.3%) displayed new-onset arrhythmia that had not been diagnosed before-either without any previous arrhythmia history or in addition to other previously diagnosed arrhythmia.
T130 12373-12493 Sentence denotes Of these, 16 patients (9.6%) had never been diagnosed with any type of arrhythmia prior to hospitalization for COVID-19.
T131 12494-12630 Sentence denotes With regard to arrhythmia diagnosis during hospitalization for COVID-19, AF was the most common type of arrhythmia recorded (Figure 2A).
T132 12631-12873 Sentence denotes Similarly, in patients diagnosed with a new arrhythmia type during hospitalization (Figure 2B) and in patients without any previous arrhythmia diagnosis prior to hospitalization (Figure 2C), AF constituted the most common incident arrhythmia.
T133 12874-12994 Sentence denotes Bradycardia was recorded in four cases, of which one patient already had previously documented asymptomatic bradycardia.
T134 12995-13052 Sentence denotes No pacemaker implantation was necessary in this subgroup.
T135 13053-13158 Sentence denotes In addition, patients with frequent PVCs and ventricular tachycardia (VT) constituted relevant subgroups.
T136 13159-13203 Sentence denotes All recorded VT-episodes were non-sustained.
T137 13204-13347 Sentence denotes Ventricular fibrillation occurred in one patient with cardiovascular disease who had previously received an ICD due to ventricular tachycardia.
T138 13348-13463 Sentence denotes In three patients (1.8%) electrical cardioversion was performed for termination of hemodynamically compromising AF.
T139 13464-13633 Sentence denotes Amiodarone for pharmacological cardioversion was administered in four patients (2.4%), and chronic antiarrhythmic medical therapy was initiated in three patients (1.8%).
T140 13634-13802 Sentence denotes Patients with arrhythmias more often received therapeutic anticoagulation therapy (Table 1) in accordance with the high proportion of patients with AF in this subgroup.
T141 13803-13949 Sentence denotes Reasons for therapeutic anticoagulation in patients without arrhythmias were previous or new diagnosis of venous thrombosis or pulmonary embolism.
T142 13951-13955 Sentence denotes 3.3.
T143 13956-14001 Sentence denotes Clinical Predictors for New-Onset Arrhythmias
T144 14002-14240 Sentence denotes We analyzed predisposing factors associated with arrhythmias during hospitalization for COVID-19 comparing baseline characteristics of patients with arrhythmia and patients without arrhythmia during hospitalization for COVID-19 (Table 1).
T145 14241-14367 Sentence denotes Patients with arrhythmias were older and more often had been diagnosed with hypertension and cardiovascular disease (Table 1).
T146 14368-14517 Sentence denotes QTc duration at baseline was longer in patients with arrhythmia, however, median values were within the physiological range in both groups (Table 1).
T147 14518-14638 Sentence denotes Furthermore, we analyzed the prevalence of potentially proarrhythmic medication administered in the context of COVID-19.
T148 14639-14741 Sentence denotes In both subgroups, hydroxychloroquine was used in 44.1% and 44.6% of patients, respectively (Table 1).
T149 14742-14823 Sentence denotes A smaller fraction of patients in both groups additionally received azithromycin.
T150 14824-14938 Sentence denotes There was no statistically significant difference in the use of QT-prolonging drugs between both groups (Table 1).
T151 14939-15060 Sentence denotes Median QTc-duration at baseline was within normal range in patients who later received hydroxychloroquine (409.0 ms; P25:
T152 15061-15075 Sentence denotes 390.5 ms, P75:
T153 15076-15086 Sentence denotes 421.5 ms).
T154 15087-15257 Sentence denotes Regularized logistic regression led to the selection of the variables age, cardiovascular disease and hypertension with respect to the prediction of arrhythmia incidence.
T155 15258-15601 Sentence denotes The subsequently fitted multiple logistic regression model revealed significant association of age (OR 1.036; 95% CI 1.004–1.074; p = 0.036) and cardiovascular disease (OR 3.307; 95% CI 1.329–8.232; p = 0.01) with incident arrhythmia in COVID-19, whereas the effect of hypertension was not significant (OR 2.08; 95% CI 0.794–5.796; p = 0.144).
T156 15602-15692 Sentence denotes As measure of the model’s performance an area under the curve (AUC) value of 0.74 (95% CI:
T157 15693-15781 Sentence denotes 0.65; 0.84) was estimated by applying 5-fold cross-validation (Supplementary Figure S1).
T158 15782-15944 Sentence denotes Left ventricular ejection fraction was documented in 47.1% of patients with incident arrhythmia and only 21.2% of cases without arrhythmia during hospitalization.
T159 15945-16142 Sentence denotes Attempts at imputing LVEF and including the imputed dataset in the final logistic regression model hinted at a potential role of LVEF as an additional predictor for arrhythmia incidence (Table S1).
T160 16143-16298 Sentence denotes However, due to the high number of missing values, LVEF was omitted from the final logistic regression model to ensure reliability of statistical analyses.
T161 16299-16484 Sentence denotes With regard to peak levels of cardiac and inflammatory biomarkers assessed during hospitalization, patients with arrhythmia displayed higher levels of hsTnT and NTproBNP (Figure 3A, B).
T162 16485-16707 Sentence denotes Additionally, a more pronounced increase in IL-6 and LDH could be detected in the arrhythmia subgroup, whereas there was no statistically significant difference in peak levels of CRP between groups (Table 2, Figure 3C, D).
T163 16709-16713 Sentence denotes 3.4.
T164 16714-16771 Sentence denotes Prognostic Implications of Arrhythmia on Clinical Outcome
T165 16772-16882 Sentence denotes Overall duration of hospitalization was longer in patients with arrhythmia associated with COVID-19 (Table 3).
T166 16883-17038 Sentence denotes Univariate analysis showed an increase of hospitalization duration of 11.4 days with the presence of incident arrhythmia (95% CI 6.05–16.7 days; p <0.001).
T167 17039-17270 Sentence denotes Additionally, patients with arrhythmia were more often admitted to ICU or IMC wards (OR 2.37; 95% CI 1.10–5.09; p = 0.03), and incident arrhythmia was associated with a longer duration of hospitalization on ICU/IMC wards (Table 3).
T168 17271-17429 Sentence denotes Patients with incident arrhythmia more often received vasopressors for circulatory support and non-invasive ventilation or high-flow oxygen-therapy (Table 3).
T169 17430-17594 Sentence denotes Importantly, patients with arrhythmia more often presented with severe respiratory failure requiring mechanical ventilation (OR 6.69; 95% CI 2.92–15.35; p < 0.001).
T170 17595-17717 Sentence denotes Duration of mechanical ventilation was not significantly different between patients with and without arrhythmia (Table 3).
T171 17718-17880 Sentence denotes With regard to cardiac events, myocardial infarction was more common in the patient group with arrhythmia, however, with a low overall number of events (Table 3).
T172 17881-18071 Sentence denotes Stroke or transient ischemic attack (TIA) occurred in one case in the patient group with arrhythmia who had a prior diagnosis of AF and frequent PVCs, and in two patients without arrhythmia.
T173 18072-18313 Sentence denotes All patients with myocardial infarction or stroke/TIA had received anticoagulation therapy with low-molecular-weight-heparin, however, in one patient heparin-therapy was paused after coronary angiography due to severe bleeding complications.
T174 18314-18470 Sentence denotes In-hospital mortality was significantly elevated in COVID-19 patients with incident arrhythmia during hospitalization (OR 3.02; 95% CI 1.22–7.46; p = 0.02).
T175 18471-18772 Sentence denotes Multiple regression analyses adjusting for differences in baseline parameters revealed that the incidence of arrhythmia constitutes a more powerful prognostic factor regarding hospitalization duration and the need for mechanical ventilation than age and prevalence of cardiovascular disease (Table 4).
T176 18773-18903 Sentence denotes Finally, previous diagnosis of cardiovascular disease in our cohort was significantly associated with mortality in these analyses.
T177 18905-18909 Sentence denotes 3.5.
T178 18910-18964 Sentence denotes Subgroup Analysis of Patients with Atrial Fibrillation
T179 18965-19069 Sentence denotes Atrial fibrillation constituted the most common incident arrhythmia during hospitalization for COVID-19.
T180 19070-19229 Sentence denotes In the subgroup analysis of patients with incident AF, age, hypertension and cardiovascular disease were associated with incidence of the arrhythmia (Table 5).
T181 19230-19315 Sentence denotes Both cardiac and inflammatory markers showed a stronger increase in patients with AF.
T182 19316-19488 Sentence denotes Similar to the effects of incident arrhythmia in the overall cohort, AF itself was associated with longer overall hospitalization times and longer duration of ICU/IMC care.
T183 19489-19673 Sentence denotes Additionally, an increased need for high-flow oxygen therapy or non-invasive ventilation, mechanical ventilation and pharmacological circulatory support could be seen in this subgroup.
T184 19674-19807 Sentence denotes Information regarding initiation of anticoagulation therapy was available in 10 patients with AF during hospitalization for COVID-19.
T185 19808-19926 Sentence denotes In six cases, low-molecular-weight heparin (LMWH) in therapeutic doses was applied, two other patients received NOACs.
T186 19927-20106 Sentence denotes Two patients only received prophylactic doses of LMWH, in one case due to a low CHA2DS2-Vasc-Score of 1 and a self-limiting AF-episode, in one case due to delayed diagnosis of AF.
T187 20107-20181 Sentence denotes Two patients in the AF-subgroup were diagnosed with myocardial infarction.
T188 20182-20250 Sentence denotes In both cases, anticoagulation therapy had been initiated with LMWH.
T189 20251-20356 Sentence denotes One patient underwent PCI and died in the later course of the hospitalization due to mesenteric ischemia.
T190 20357-20519 Sentence denotes In this patient anticoagulation therapy had been paused for 22 days after coronary angiography due to severe bleeding complications requiring transfusion therapy.
T191 20520-20662 Sentence denotes The other patient received medical treatment as a type-II myocardial infarction was suspected due to stable echocardiography und ECG-findings.
T192 20663-20835 Sentence denotes All cases of death in patients with AF were attributed to non-cardiac causes: in addition to the patient described above three patients deceased due to respiratory failure.
T193 20837-20839 Sentence denotes 4.
T194 20840-20850 Sentence denotes Discussion
T195 20851-20951 Sentence denotes Cardiac arrhythmias were the most common cardiac event associated with hospitalization for COVID-19.
T196 20952-21048 Sentence denotes Age and cardiovascular disease were identified as risk factors for the incidence of arrhythmias.
T197 21049-21315 Sentence denotes Arrhythmia was associated with elevated cardiac biomarkers suggesting myocardial injury, need for ICU/IMC care and mechanical ventilation as well as mortality, and constituted an independent predictor of prolonged hospitalization and need for mechanical ventilation.
T198 21316-21530 Sentence denotes This is the first multicenter study including both tertiary care centers and regional hospitals focusing on the role of arrhythmias in hospitalization for COVID-19, considering both clinical and biomarker profiles.
T199 21531-21702 Sentence denotes With respect to age, baseline parameters and the overall incidence of arrhythmias, our cohort corresponds to previously described COVID-19 patient populations [7,8,17,20].
T200 21703-21881 Sentence denotes In accordance with prior results, AF was the most common incident arrhythmia both in the entire cohort and in the subgroup of patients without any previous history of arrhythmia.
T201 21882-22092 Sentence denotes An elevated risk for AF has been described in association with other respiratory virus infections, in particular influenza [21], however, with a lower incidence compared to our cohort of COVID-19-patients [22].
T202 22093-22307 Sentence denotes The present analyses of the patient subgroup with newly diagnosed AF revealed not only a relevant increase in cardiac biomarkers hinting at myocardial injury but also significantly elevated inflammatory biomarkers.
T203 22308-22555 Sentence denotes This may point to an association between the degree of inflammatory state caused by COVID-19 and susceptibility to AF, which is in line with previous findings regarding inflammatory mechanisms promoting the development of atrial fibrillation [23].
T204 22556-22756 Sentence denotes With respect to risk factors for arrhythmia incidence during hospitalization for COVID-19, we could identify age and previous cardiovascular disease as predictors for the occurrence of any arrhythmia.
T205 22757-22939 Sentence denotes These baseline characteristics have previously been shown to predispose for the development of arrhythmia in the general population without association with infectious diseases [24].
T206 22940-23044 Sentence denotes Thus, they may reflect a subgroup of greater general susceptibility to additional proarrhythmic effects.
T207 23045-23181 Sentence denotes In patients with arrhythmia in our cohort, QTc duration was longer at admission, albeit within normal range in the majority of patients.
T208 23182-23381 Sentence denotes Dynamic changes of the QTc interval under therapy with hydroxychloroquine and azithromycin cannot be evaluated as repeated ECGs during hospital stay were not systematically available in all patients.
T209 23382-23459 Sentence denotes Thus, proarrhythmic effects of these drugs cannot be excluded in this cohort.
T210 23460-23647 Sentence denotes Previous reports point towards significant prolongation of the QTc interval by hydroxychloroquine in COVID-19 which is even more enhanced in combination with azithromycin therapy [25,26].
T211 23648-23733 Sentence denotes However, the rate of associated ventricular arrhythmia has been low in these studies.
T212 23734-23986 Sentence denotes Similarly, no typical “torsades des pointes” were seen in our cohort: in three of five patients with ventricular arrhythmias pre-existent cardiovascular disease was present, and only one of the remaining two patients received QTc-prolonging medication.
T213 23987-24150 Sentence denotes Thus, rather than induced by direct effects of administered medication, ventricular arrhythmias may have been due to other predisposing risk factors in our cohort.
T214 24151-24263 Sentence denotes Patients with arrhythmias during hospitalization showed elevated cardiac biomarkers and elevated levels of IL-6.
T215 24264-24400 Sentence denotes Myocardial injury in COVID-19 has been reported by multiple studies, however, the underlying mechanisms have yet to be elucidated [2,4].
T216 24401-24638 Sentence denotes In our cohort, arrhythmia itself may have promoted a more pronounced increase in hsTNT and NTproBNP by an additional shift in myocardial oxygen demand under a restricted respiratory function and by increasing atrial and ventricular load.
T217 24639-24794 Sentence denotes In particular, among patients with pre-existent cardiovascular disease a myocardial supply-demand-imbalance of oxygen may become evident during arrhythmia.
T218 24795-25011 Sentence denotes On the other hand, myocardial injury or ischemia-especially in the light of a higher prevalence of cardiovascular disease in this subgroup-may have exerted proarrhythmic effects in addition to the inflammatory state.
T219 25012-25145 Sentence denotes Such additional inflammatory influences are implicated by the pronounced increase in IL-6 in patients with arrhythmias in our cohort.
T220 25146-25280 Sentence denotes In COVID-19 a state of hyperinflammation is commonly observed and correlates with both respiratory failure and myocardial injury [27].
T221 25281-25511 Sentence denotes Based on our observations, it may additionally constitute a risk factor for the incidence of arrhythmia but distinct molecular mechanisms have yet to be investigated in experimental studies and larger, prospective patient cohorts.
T222 25512-25617 Sentence denotes Estimating optimal cut-off values is associated with uncertainty and is affected by the study population.
T223 25618-25721 Sentence denotes Therefore, the calculated cut-offs for the biomarkers in this study should be interpreted with caution.
T224 25722-25911 Sentence denotes With respect to clinical outcome, an association of incident arrhythmia with the need for ICU/IMC-care was identified, which is in line with the previous observations from Pennsylvania [8].
T225 25912-26042 Sentence denotes However, age and cardiac co-morbidities have been identified as potential confounders in our analyses regarding ICU/IMC admission.
T226 26043-26153 Sentence denotes Furthermore, rates of NIV- or high-flow oxygen-therapy and need for vasopressors were increased in this group.
T227 26154-26329 Sentence denotes These observations, together with the results from biomarker analyses, reflect an association of the severity of disease with the incidence of cardia arrhythmia in our cohort.
T228 26330-26516 Sentence denotes More specifically, we show that mechanical ventilation is associated with the occurrence of arrhythmias, even when correcting for age and cardiovascular disease as potential confounders.
T229 26517-26713 Sentence denotes Additionally, overall duration of hospitalization was significantly increased in patients with incident arrhythmia in multiple regression analyses, which has not been reported by previous studies.
T230 26714-26809 Sentence denotes This result points towards a potentially independent prognostic role of arrhythmia in COVID-19.
T231 26810-26953 Sentence denotes In light of limited ventilator- and hospital-capacity during peak episodes of the COVID-19-pandemic, these aspects are of particular relevance.
T232 26954-27212 Sentence denotes In this context, our exploratory univariate analysis of patients with atrial fibrillation shows that not only ventricular arrhythmias but also supraventricular arrhythmias may have implications on the clinical course during hospitalization COVID-19 patients.
T233 27213-27339 Sentence denotes Arrhythmia during hospitalization for COVID-19 was associated with increased in-hospital mortality in the univariate analysis.
T234 27340-27584 Sentence denotes However, in multiple regression analyses, pre-existent cardiovascular disease had a stronger prognostic implication than incident cardiac arrhythmia regarding this aspect, even though the majority of fatal cases were due to respiratory failure.
T235 27585-27714 Sentence denotes This is in line with observations from large multicenter cohorts identifying risk factors for in-hospital death in COVID-19 [28].
T236 27715-27899 Sentence denotes With respect to a wide range of symptoms and prognostic severity associated with an infection with SARS-CoV-2, further studies aiming at individualized risk stratification are crucial.
T237 27901-27912 Sentence denotes Limitations
T238 27913-27986 Sentence denotes Due to its retrospective design, this study carries inherent limitations.
T239 27987-28197 Sentence denotes Despite thorough analysis of clinical records and use of different source documents (e.g., discharge notes, nurses’ reports, daily doctors’ documentation) underreporting of arrhythmia events cannot be excluded.
T240 28198-28295 Sentence denotes Not all arrhythmic events during the clinical course may have been documented in written reports.
T241 28296-28393 Sentence denotes Asymptomatic arrhythmias in patients without continuous ECG-monitoring may also have been missed.
T242 28394-28531 Sentence denotes However, clinically relevant arrhythmias leading to medical interventions are documented as part of the participating centers’ standards.
T243 28532-28652 Sentence denotes Baseline and outcome data recorded in this study were prespecified and screened for in the available clinical documents.
T244 28653-28730 Sentence denotes Missing parameters were specifically inquired from the participating centers.
T245 28731-28898 Sentence denotes Due to different admission protocols and diagnostic standards, there are remaining missing values with regard to certain baseline parameters or biomarker measurements.
T246 28899-29035 Sentence denotes However, we clearly indicate this limitation in the respective tables whenever information was available only in a subgroup of patients.
T247 29036-29295 Sentence denotes QTc-duration was available at baseline in the majority of patients, however, due to different standards of ECG-based follow-up, QTc-duration in the course of hospitalization, e.g., during therapy with QT-prolonging drugs, could not be systematically analyzed.
T248 29296-29439 Sentence denotes Inclusion of both tertiary and secondary-level hospitals may lead to treatment bias due to different standards of care or available facilities.
T249 29440-29601 Sentence denotes Importantly, in our study, all contributing centers provide intermediate and intensive care units and operate according to national and international guidelines.
T250 29602-29741 Sentence denotes Cardiorespiratory monitoring, non-invasive and mechanical ventilation are carried out according to guidelines in all participating centers.
T251 29742-29805 Sentence denotes All centers treated both moderate and severe cases of COVID-19.
T252 29806-29956 Sentence denotes Patients requiring extracorporeal life support were primarily treated at tertiary centers but constituted a minority of subjects in this study cohort.
T253 29957-30036 Sentence denotes Therefore, we do not expect significant bias due to differences in center size.
T254 30037-30169 Sentence denotes However, due to the limited number of patients in the respective subgroups a comprehensive analysis of this aspect was not feasible.
T255 30170-30309 Sentence denotes In order to provide further insight, we present an overview into the types and individual contribution of participating centers (Table S1).
T256 30310-30452 Sentence denotes Additionally, individual specific therapy attemps with respect to COVID-19, e.g., hydroxochloroquine administration, were specified (Table 1).
T257 30453-30641 Sentence denotes Left ventricular ejection fraction (LVEF) may have constituted an additional predictor for arrhythmia, however, the value was not provided in a relevant number of patients in this cohorts.
T258 30642-30861 Sentence denotes In order to account for this limitation, we attempted imputation of these values (Supplementary Materials) hinting at a potential role of reduced LVEF as a risk factor for arrhythmia during hospitalization for COVID-19.
T259 30862-30982 Sentence denotes However, these results are exploratory and have to be interpreted with caution due to the high number of missing values.
T260 30983-31065 Sentence denotes Further efforts should be made to study this specific aspect in COVID-19 patients.
T261 31067-31069 Sentence denotes 5.
T262 31070-31081 Sentence denotes Conclusions
T263 31082-31279 Sentence denotes The present multicenter study identifies patients with cardiac arrhythmia during hospitalization for COVID-19 as a high-risk subgroup characterized by severe course of disease and adverse outcomes.
T264 31280-31426 Sentence denotes Underlying pathomechanisms may be related to a hyperinflammatory state and myocardial injury, particularly in patients with cardiac comorbidities.
T265 31427-31616 Sentence denotes Due to the high incidence of arrhythmic events in COVID-19 and their potential prognostic implications, arrhythmias should be screened for in affected patients with respective risk factors.