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.