key: cord-1032985-1v7lr8kd authors: Colon, Chad M.; Barrios, James G.; Chiles, Joe W.; Brown, Todd M.; Pogwizd, Steven M.; McElwee, Samuel K.; Gandotra, Sheetal; Russell, Derek W.; McElderry, H. Tom; Maddox, William R. title: Atrial arrhythmia related outcomes in critically ill COVID‐19 patients date: 2021-03-31 journal: Pacing Clin Electrophysiol DOI: 10.1111/pace.14221 sha: 8303177b81b7e18c9b91e35a153fa6a7c955c02e doc_id: 1032985 cord_uid: 1v7lr8kd RATIONALE: Coronavirus disease 2019 (COVID‐19) is associated with many clinical manifestations including respiratory failure and cardiovascular compromise. OBJECTIVES: We examine outcomes in critically ill individuals with COVID‐19 who develop atrial tachyarrhythmias. METHODS: We collected data from electrocardiograms and the electronic medical record of COVID‐19 positive (COVID(+)) and negative (COVID(−)) individuals admitted to our medical intensive care unit between February 29 and June 28, 2020. We compared clinical and demographic characteristics, new onset atrial tachyarrhythmia, hemodynamic compromise following atrial tachyarrhythmia, and in‐hospital mortality in COVID(+) versus COVID(−). Hemodynamic compromise was defined as having a new or increased vasopressor requirement or the need for direct current cardioversion for hemodynamic instability within 1 hour of atrial tachyarrhythmia onset. RESULTS: Of 300 individuals included, 200 were COVID(+) and 100 were COVID(−). Mean age was 60 ± 16 years, 180 (60%) were males, and 170 (57%) were African American. New onset atrial tachyarrhythmia occurred in 16% of COVID(+) and 19% of COVID(−) individuals (P = .51). When compared to COVID(−) participants without atrial tachyarrhythmia, COVID(+) individuals with new onset atrial tachyarrhythmia had higher mortality after multivariable adjustment (OR 5.0, 95% CI 1.9–13.5). New onset atrial tachyarrhythmia was followed by hemodynamic compromise in 18 COVID(+) but no COVID(−) participants (P = .0001). COVID(+) individuals with hemodynamic compromise after atrial tachyarrhythmia required increased ventilatory support at the time of atrial tachyarrhythmia onset. CONCLUSIONS: Atrial tachyarrhythmia is associated with increased mortality in critically ill individuals with COVID‐19, especially those mechanically ventilated. Recognition of this could assist with clinical care for individuals with COVID‐19. Coronavirus disease 2019 , the disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2, can present with a wide range of clinical manifestations but most commonly with severe respiratory failure. 1 A significant incidence of cardiovascular morbidity and mortality related to COVID-19 infection is now also recognized. [2] [3] [4] [5] We previously published an analysis showing a high incidence of atrial tachyarrhythmia in critically ill COVID-19 individuals. 6 This is similar to the incidence published in prior cohorts of critically ill patients without COVID-19. 7 The development of new onset atrial tachyarrhythmia has been associated with increased incidence of heart failure, stroke, and death in critically ill patients. [8] [9] [10] [11] In this study, we report an analysis of consecutive critically ill participants that required intensive care unit (ICU) admission at a single center with a high degree of suspicion for COVID-19 infection. We describe the incidence of new-onset atrial tachyarrhythmia and the association of atrial tachyarrhythmia with short-term hemodynamic sequelae. We initially included 215 consecutive individuals age >18 years who Board with waiver of informed consent. Participant demographic information, past medical history, comorbidities, inflammatory markers, high-sensitivity (hs) troponin levels, outpatient medications, and inpatient therapies were collected from the electronic medical record. In addition, data on the need for mechanical ventilation, duration of mechanical ventilation, ICU and hospital lengths of stay (LOS), and in-hospital mortality was obtained. To standardize vasopressor dosing across participants receiving different agents, the cumulative dose of norepinephrine equivalents (NE Eq) was calculated as has been described previously 12, 13 with a conversion factor for angiotensin II of 1 ng per 0.1 µg of norepinephrine based upon the ATHOS-3 trial (Table S1 ). 13 All patients admitted to the ICU were monitored with continuous, centrally monitored telemetry. Any change in clinical rhythm was confirmed with 12-lead electrocardiograms (ECGs). All 12-lead ECGs recorded were reviewed by a board-certified cardiologist to determine the development of atrial arrhythmias. Participants with ECG documentation of a new-onset atrial fibrillation, atrial flutter, or atrial tachycardia were labeled as having an atrial tachyarrhythmia. We collected data on in-hospital mortality as well the development of Continuous variables are presented as mean ± standard deviation and compared using independent samples t-tests. Categorical variables were expressed as frequencies and compared using chi-square tests. To examine mortality, we divided our study population into four groups: (1) COVID + with atrial tachyarrhythmia, (2) COVID + without atrial tachyarrhythmia, (3) COVID − with atrial tachyarrhythmia, and (4) COVID − without atrial tachyarrhythmia. Individual logistic regression models were constructed using the COVID − without atrial tachyarrhythmia group as the referent. Models were adjusted for age, sex, race, body mass index, and clinical characteristics that varied by COVID status (systolic heart failure, diastolic heart failure, atrial fibrillation, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, cirrhosis, and tobacco use). All tests were two-tailed, and a P value < .05 (set a priori) was considered statistically signif- The baseline characteristics of those with and without COVID-19 are shown in Table 1 The demographic and clinical characteristics and inpatient therapies for individuals with atrial tachyarrhythmias are shown in Table 3 . Those who were COVID + and developed an atrial tachyarrhythmia were more likely to require vasopressors (91% vs. 47%, P = .001), had a longer duration on vasopressors (9 ± 6 days vs. In this study, critically ill COVID + and COVID − individuals with new onset atrial tachyarrhythmia had increased in-hospital mortality when Values are mean ± SD or n (%). Abbreviations: ATA, atrial tachyarrhythmia; BMI, body mass index; COPD, chronic obstructive pulmonary disease; COVID, coronavirus disease; CRRT, continuous renal replacement therapy; FiO 2 , fraction of inspired oxygen; LA dilation, left atrial dilation; LVEF, left ventricular ejection fraction; LVIDd, left ventricular internal diameter end diastole; MAP, mean arterial pressure; PEEP, positive end expiratory pressure; TAPSE, tricuspid annular plane systolic excursion. a P value comparing COVID + hemodynamic collapse group versus COVID + stable group. b P value comparing COVID + hemodynamic collapse group versus COVID − stable group. c Individuals who were on room air at the time of analysis were given a PEEP value of 0 and an FiO 2 value of 0.21 + Oxygen in L/min × 0.03. No plateau pressure was recorded for patients not ventilated. compared to those without atrial tachyarrhythmia, although the magnitude of this association was greater for those who were COVID + . In addition, we observed a temporal relationship between new onset atrial tachyarrhythmia and hemodynamic compromise in individuals who were COVID + which might explain their increased in-hospital mortality. In fact, of the 16 individuals with COVID-19 and a new onset atrial tachyarrhythmia who subsequently died, 12 (75%) had hemodynamic compromise immediately after developing the atrial tachyarrhythmia. Atrial tachyarrhythmia in critically ill individuals is thought to be driven by both individual factors such as myocardial dysfunction due to infection, drugs, and cytokine levels 19 as well as by critical care interventions such as vasopressor use and mechanical ventilation. [20] [21] [22] [23] The occurrence of atrial tachyarrhythmia during critical illness has been associated with poor outcomes, including increased hospital mortality, 9 increased duration of ICU admission, and 1-year adjusted survival. 7 However, to our knowledge, the consequences of atrial tachyarrhythmia in COVID-19 related critical illness have not been previously reported. We found that the short-term effect of atrial tachyarrhythmia on COVID + participants was distinct from that seen in those who were Previous studies have shown that increasing PEEP is associated with decreased cardiac output and mean blood pressure. 24 We speculate that the loss of atrial contractility in individuals with COVID-19 ARDS may further decrease preload and cause hemodynamic decompensation. This is further supported by the high prevalence of mechanical ventilation and subsequent temporal decompensation observed at onset of atrial tachyarrhythmia. Moreover, recent studies have highlighted the importance of right ventricular longitudinal strain in individuals with ARDS as a predictor of mortality highlighting the importance of right heart function and clinical outcomes. 25, 26 These findings carry several important implications. This study suggests a potential causal relationship between atrial tachyarrhythmia onset and hemodynamic instability in COVID + individuals. Importantly, the high mortality associated with ARDS appears to be driven more strongly by hemodynamic instability and degree of shock than by hypoxemia, 27 therefore a complication so closely associated with marked hemodynamic deterioration may significantly influence outcomes. Indeed, participants with atrial tachyarrhythmia associated hemodynamic compromise did have worsened survival in our study. We hypothesize that vigilance to optimize factors that may increase the risk of atrial tachyarrhythmia, such as electrolyte imbalances and volume overload, may be beneficial not only for heart rhythm, but also for blood pressure stability and downstream outcomes including survival. Although these findings may suggest that less hemodynam- While the specific mechanism of myocardial injury in COVID infection remains to be defined, individuals susceptible to atrial arrhythmias and myocardial injury may be more likely to develop severe manifestations of viral infection. 32 It remains to be seen whether early intervention of atrial tachyarrhythmia in these individuals will mitigate the severe clinical course of the disease. There are several significant limitations of our study. First, this is a retrospective study from a single tertiary referral center that likely over represents individuals with severe manifestations of COVID-19 infection. Secondly, our study has a small sample size with a comparative group that does not perfectly match our COVID + population. However, our COVID + population had decreased incidence of comorbid conditions and structural heart abnormalities offering less potential for confounding than our standard intensive care population. Individuals with COVID-19 who are admitted to the ICU have a high incidence of new onset atrial tachyarrhythmia that is associated with hemodynamic compromise and death. Special attention should be paid to new onset atrial tachyarrhythmia in COVID + patients as it appears to be associated with worse outcomes. The work was not supported by industry. This study received internal funding from the Departments of Cardiovascular Disease and Pulmonary, Allergy and Critical Care at the University of Alabama at Birmingham. The authors have no conflict of interest to disclose relevant to the content matter being studied or discussed. There are no other grants, contracts, or other forms of financial support to disclose. Each author contributed via data collection, analysis, and manuscript writing or editing. Each author has reviewed the final manuscript and has approved it. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Chad M. 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