Discussion
In this study, critically ill COVID+ and COVID- individuals with new onset ATA had increased in-hospital mortality when compared to those who were COVID- without ATA, although the magnitude of this association was greater for those who were COVID+ . In addition, we observed a temporal relationship between new onset ATA and HC 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 ATA who subsequently died, 12 (75%) had HC immediately after developing the ATA.
ATA 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.20-23 The occurrence of ATA 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 ATA in COVID-19 related critical illness have not been previously reported.
We found that the short-term effect of ATA on COVID+ participants was distinct from that seen in those who were COVID- , with a marked temporal correlation between onset of ATA and HC seen uniquely among a group of COVID+ individuals who were mechanically ventilated and requiring significant levels of ventilator support. COVID+ participants who developed ATA with concurrent respiratory failure appeared much more vulnerable to HC just after ATA onset, suggesting an increased hemodynamic sensitivity of mechanically ventilated COVID+ individuals to loss of sinus rhythm relative to COVID-critically ill participants. Despite the known association of severe COVID-19 infection with cardiovascular comorbid diseases, COVID+ participants actually had a lower burden of chronic cardiac disease and valvular disease, and a higher ejection fraction compared to the COVID-group, arguing that structural heart disease is not the reason for their apparent hemodynamic sensitivity to the loss of sinus rhythm. Rather, our data suggest that the striking relationship of hemodynamic deterioration to new onset ATA in COVID+individuals may be related to cardiopulmonary interactions in severe acute respiratory distress syndrome (ARDS) and/or to the high degree of ventilator support that they require, including high PEEP support.
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 ATA. 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 ATA 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 ATA associated HC did have worsened survival in our study. We hypothesize that vigilance to optimize factors that may increase the risk of ATA, 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 hemodynamically impactful ventilatory strategies, such as a low PEEP strategy, could improve hemodynamic stability in COVID+ individuals or ARDS individuals with ATA, this study does not directly address this question. It is conceivable that increased attention to a rhythm control strategy in COVID-19 individuals may have greater benefit than that seen in general critical illness, and prospective studies of this question may be justified. As our COVID- comparative cohort did not have a high incidence of ARDS, it is unclear if the observed hemodynamic changes related to ATA are unique to COVID infection and may represent a phenomenon seen in all individuals with severe ARDS. Studies have shown that prone positioning in individuals with ARDS improves ventilation and improves right ventricular ejection fraction,28 left ventricular preload28, 29 and cardiac output.30, 31 Thus, prone positioning may represent another potential approach to attenuate the hemodynamic effects of ATA in COVID-19, an effect which could conceivably contribute to the survival benefit shown with this agent in ARDS.
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 ATA in these individuals will mitigate the severe clinical course of the disease.