COVID-19
Despite not being particularly lethal, SARS-CoV-2 is very contagious. In
a published clinical cohort of COVID-19 patients, they observed that
acute cardiac injury, shock, and arrhythmias were present in 7.2%,
8.7%, and 16.7% of patients, respectively, with higher prevalence
amongst patients requiring intensive care2. In this
report, myocardial injury biomarkers levels were significantly higher in
patients requiring intensive care unit (ICU) admission than in those not
treated in the ICU [median creatine kinase (CK)-MB level 18 U/l vs. 14
U/l; p < 0.001; and high-sensitivity cardiac troponin I
(hs-cTnI) level 11.0 pg/ml vs. 5.1 pg/ml; p = 0.004],
suggesting that patients with severe symptoms often have complications
involving acute myocardial injury2. Overall,
arrhythmia rate was also more frequent in ICU patients (44.4% vs.
6.9%; p < 0.001). Despite the relevance of these
initial data, the authors did not provide any arrhythmia classification
or definition.
A study from Shi et al. evaluated a single-center cohort of 416 patients
hospitalized due to COVID-19. He observed that cardiac lesion, defined
by hs-cTnI >99th percentile of on
admission, was present in 19.7%, with median value of 0.19 (0.08-1.12)
μg/L in this group. Compared with those without cardiac injury, patients
with cardiac injury required more noninvasive ventilation (46.3% vs.
3.9%; p <0.001) and invasive mechanical ventilation
(22.0% vs. 4.2%; p < 0.001), and also had a higher
mortality (51.2% vs. 4.5%; p<0.001). It’s remarkable that
the elevated troponin group was older and significantly more ill, but
after adjustment for all the possible confounding factors, still the
cardiac injury was a predictor of mortality (HR 4.26 95% CI
1.92-9.49)¹.
In another small report, Huang C et al. demonstrated that SARS-CoV-2
associated myocardial injury occurred on 5 out of 41 patients, and was
manifested as an increase in hs-cTnI levels (>28 pg/ml).
Among these 5 patients, ICU management was required in 4, indicating the
severe nature of the myocardial injury in patients with
COVID-1920.
In a study by Guo et al., 187 SARS-CoV-2 positive patients were
analyzed, stratified by the level of troponin, which was elevated in
27.8%. During hospitalization, patients with elevated troponin T (TnT)
levels developed more frequently complications as acute respiratory
distress syndrome (57.7% vs. 11.9%), malignant ventricular arrhythmias
(11.5% vs. 5.2%), acute coagulopathy (65.8% vs. 20.0%), and acute
kidney injury (36.8% vs. 4.7%), compared with those with normal TnT
levels. But the most impressive observation is that mortality was
markedly higher in patients with elevated plasma TnT levels than in
patients with normal TnT levels (59.6% vs. 8.9%)21.
Contrary to the above mentioned studies Zhou et al. comparing survivors
and non-survivors in a cohort of 191 patients from 2 hospitals in Wuhan,
found that, despite more frequent in non survivors (46% vs. 1%,
p<0.001), hs-cTnI >28 pg/ml was not associated
with mortality in multivariate analysis. Even though, it is remarkable
that this study was unpowered to draw conclusions from this analysis due
to the excess of variable for only 54 events22.
Acute myocarditis, as well as ventricular arrhythmias might represent
the first clinical manifestation of SARS-CoV-2
infection3,44. In the epicenter of the current Italian
epidemic, sudden cardiac death (SCD) likely occurred in many
non-hospitalized patients with mild symptoms who were found dead home
while in quarantine. Myocardial biomarkers should be evaluated in all
COVID-19 patients for risk stratification and prompt intervention. Even
after hospital discharge, we should consider that myocardial injury
might result in atrial or ventricular fibrosis, the substrate for
subsequent cardiac arrhythmias. The extent of myocardial scar, as
assessed with cardiac magnetic resonance, might be a powerful tool to
better stratify the arrhythmic risk in patients recovered from COVID-19
who had evidence of myocardial injury at the time of infection.
Another relevant aspect of COVID-19 infection is that early diagnosis
can be confounded in patients with chronic cardiac conditions, once the
most frequent symptoms, like fatigue (51%, 95% CI 34-68%), dyspnea
(30%, 95% CI 21-40%) and cough (67%, 95% CI
59-76%)25 can also be manifestations of decompensated
heart failure or arrhythmic syndrome. Corroborating with this concern,
the National Health Commission of China (NHC) reported that among
SARS-CoV-2 infection confirmed cases, cardiovascular symptoms were the
first presentation in some patients. The problem behind these atypical
presentations is that patients suffering from heart palpitations and
chest tightness rather than respiratory symptoms, such as fever and
cough, had a delayed COVID-19 diagnosis26. Still
according to the NHC, among the people who died from COVID-19, 11.8%
had substantial heart damage, with elevated troponin I levels or cardiac
arrest during hospitalization26.
Explanatory theories regarding COVID-19 cardiovascular affection
postulate that chronic cardiovascular diseases may become unstable in
the setting of a viral infection as a consequence of the imbalance
between the infection-induced increase in metabolic demand and reduced
cardiac reserve2. This imbalance, concurrent with an
accentuated inflammatory response and myocardial damage, could raise the
risk of acute coronary syndromes, heart failure, and arrhythmias.
The deleterious SARS-CoV-2 infection myocardial effects could also be
perpetuated by the prompt and severe down-regulation of myocardial and
pulmonary ACE2 pathways, thereby mediating myocardial inflammation, lung
edema, and acute respiratory failure27. ACE2 is widely
expressed not only in the lungs but also in the cardiovascular system
and, therefore, ACE2-related signaling pathways might even have a role
in heart injury. Other proposed mechanisms of myocardial injury include
a cytokine storm triggered by an imbalanced response by type 1 and type
2 T-helper cells20,28, strong interferon-mediated
immunopathological events29, and respiratory
dysfunction and hypoxemia caused by COVID-19, resulting in damage to
myocardial cells. Therapeutic use of corticosteroids, in this context,
would further augment the possibility of adverse cardiovascular events.
Regarding hypoxemia caused by COVID-19, it is relevant to highlight that
this condition can trigger atrial fibrillation, which is the most common
arrhythmia among elderly individuals, and that atrial fibrillation can
become persistent even before pulmonary improvement. Furthermore, the
systemic inflammatory response would make anticoagulation therapy for
atrial fibrillation very complex30.