DISCUSSION:
To our knowledge this is the first study demonstrating the incidence and
outcome of new onset atrial fibrillation in patients with severe
COVID-19 treated in ICU. There is increased evidence that the systemic
inflammatory response per se is a predominant trigger of NOAF in
critically ill patients [13]. In the literatures available on
cardiovascular complications related to critically ill patients with
COVID-19, the nature and classification of the arrhythmogenic events and
their mechanisms have not yet well described. Our retrospective
multicentre study assessing NOAF, showed an incidence of 14.6% amongst
patients with COVID-19 treated in ICU and this is comparatively lower
than the occurrence of NOAF reported in studies relating to severe
sepsis in ICU in general [9-11]. This raises the question of whether
the mechanism triggering AF in COVID-19 differ from other forms of
sepsis despite high systemic inflammatory milieu by pro-inflammatory
cytokine storm and possible direct viral invasion into cardiomyocytes
through angiotensin-converting enzyme 2 (ACE2) receptors [15].
A systematic review by Kuipers et al, described that advanced age, male
gender, obesity, organ failure were associated with development of AF
during sepsis. In contrast to reported associations in the general
population, diabetes and hypertension were not identified as risk
factors in sepsis [16,17]. In our study advanced age, chronic heart
failure and chronic kidney disease have shown to be a risk factor for
development of NOAF among severely ill patients with COVID-19. Presence
of diabetes, obesity or hypertension has not been identified as trigger
for NOAF in our cohort (Table 1).
Patients with and without NOAF did not have any significant difference
in the trend of inflammatory markers or troponin, however AKI was a risk
for NOAF in patient with severe form of COVID-19 infection.
Just over 90% of our study population showed raised troponin T level
above the normal range, but there was no significant association with
NOAF or indeed left ventricular systolic function. Further detailed
studies with cardiac MRI may help to assess the degree of myocardial
involvement through tissue characteristics. There is compelling evidence
that LA size is an independent predictor for atrial fibrillation in
general population [18-20] and likewise in our cohort with severe
COVID-19, enlarged LA size certainly remained a risk factor for NOAF.
Uncontrolled activation of coagulation cascade following lung injury
contributes to lung inflammation in ARDS [21]. In general,
significantly higher D-Dimer levels are found in patients with severe
pneumonia/ARDS and also shown to be a predictor of poor clinical outcome
and mortality [22]. COVID-19 data from recent studies described
similar findings [14, 23] and our data reveal very high levels of
D-Dimer in our cohort with more than one-third having levels
>50mg/L. This indicates the severity of COVID-19 infection
and the thrombosis risk in our study population, however did not achieve
statistical significance when considering the in-hospital death.
The manifestation of even a single episode of AF is associated with
increased mortality and poor outcome in critically ill patients with
sepsis [10,11,16]. In this study the occurrence of NOAF was strongly
associated with poor outcome. Patients who develop NOAF earlier during
the course of COVID-19 illness had worse outcome and this may be a
useful marker for physicians to predict prognosis.
Patients with severe sepsis who developed NOAF have a greater risk of
in-hospital stroke than patients with pre-existing AF or individuals
without history of AF [15,24]. We have reported one case of
ischaemic stroke amongst the group developed NOAF with poor outcome.
However, it was difficult to ascertain the contribution by AF, as
COVID-19 infection per se has risk of arterial thromboembolism due to
hypercoagulable state.
Anticoagulation significantly reduces the risk of stroke amongst
patients with high risk factors, based on
CHA2DS2 VASc score (congestive heart
failure, hypertension, age, diabetes mellitus, stroke, vascular disease
and sex). However there is not much evidence to support anticoagulating
critically ill patients in ICU which may expose them to risk of bleeding
during sepsis [25,26] or invasive intensive care management. Virally
driven hyper-inflammation with cytokine release will lead to
hypercoagulable state and propensity for disseminated intravascular
coagulation (DIC) in severe COVID-19 [27]. This is increasingly
evident as substantial proportion of patients develop venous and
arterial thromboembolic complications which was seen in our cohort. This
may in turn could increase the risk of stroke in patients who develop
NOAF with severe COVID-19, and careful assessment regarding decision on
anticoagulation is warranted in these patients irrespective of
CHA2DS2 VASc score. However further
studies are needed to determine the value of anticoagulation in treating
NOAF in severe COVID-19 patients.