Lesson from previous epidemics
Much of our present knowledge of SARS-CoV-2 comes from previous
historical epidemics that preceded the current outbreak, as SARS-CoV,
MERS-CoV, and H1N1 influenza syndromes. It was observed, during these
outbreaks, a significant association between underlying cardiovascular
disease, myocardial injury, and worse outcomes4.
The first human infection by a new strain of coronavirus, the SARS-CoV,
was reported in 2002. At that time it was known that, at least in
rabbits, coronavirus infections could induce cardiomyopathy resulting in
cardiac chambers dilatation and systolic function impairment, simulating
other dilated cardiomyopathies5.
In humans, hypotension, cardiac arrhythmias, and even sudden cardiac
death were described as possible SARS-CoV
manifestations6. In a cohort of 121 patients, Yu CM et
al. demonstrated that sinus tachycardia was the commonest cardiovascular
SARS-CoV finding with an overall incidence of 72%. Persistent
tachycardia mean duration was 12.7 days with a mean heart rate of 117
beats/min (range: 102-150 beats/min) and the tachycardia remained
persistent in nearly 40% of patients within 30 days after hospital
discharge. The incidence of tachycardia during the third hospitalization
week, when most patients were afebrile, could be related to drug
treatment, such corticosteroid and ribavirin. However, corticosteroid
therapy was not associated with persistent tachycardia during follow-up.
Hence, longstanding tachycardia could eventually be due to autonomic
tone changing. Or, alternatively, sinus tachycardia secondary to
cardiopulmonary or peripheral deconditioning since this disease resulted
in prolonged bed rest7.
Besides these findings, significant sinus bradycardia was seen in 18
(14.9%) patients. Unlike tachycardia, which was persistent, bradycardia
was somewhat transient with a mean heart rate of 43 beats/min (range:
38-49 beats/min) and a mean duration of 2.6 days. Reversible
cardiomegaly was also reported in 13 (10.7%), with no clinical evidence
of heart failure. Transient atrial fibrillation was observed in one
patient7.
Lau
ST et al. additionally described that palpitation, in the form of
tachycardia at rest or mild exertion, was noted amongst patients
recovering from SARS. Possible causes, according to them, were
deconditioning, impaired pulmonary function, impaired cardiac function,
cardiac arrhythmia, thyroid dysfunction, anemia, autonomic dysfunction,
and anxiety state8.
Trying to explain the occurrence of cardiac arrest in 15 SARS patients,
Pan
SF et al. suggested some possible mechanisms: (1) lung injury caused by
SARS virus leading to hypoxemia and an unsteady state in myocardial
electricity; (2) SARS direct causing new myocardial cells and/or
conduction system damage; (3) SARS infection aggravating pre-existing
myocardial conditions, or conduction disturbances; (4) extreme anxiety
leading to further endogenous catecholamine release, causing myocardial
electrical instability (see figure 1)9.
In the setting of the 2012 MERS-CoV syndrome, despite some similarities
with SARS-CoV, the early mortality rate for the former achieved
60%10, remaining higher than 35% during the overall
outbreak period, while for SARS-CoV the mortality rate was about
10%11. A meta-analysis suggested that MERS-CoV
infection was more likely to occur in patients with underlying
cardiovascular diseases12. In terms of overall
complications, renal failure (40.9%), cardiac arrhythmias (15.7%),
hepatic dysfunction (31.4%)13, besides pericarditis,
and hypotension were the most commonly reported14. In
a case report published by Alhogbani, he describes an acute myocarditis
caused by MERS-CoV; a 60-year-old presenting with respiratory symptoms,
chest pain, and persistent tachycardia (120bpm). Echocardiogram
demonstrated severe LV function impairment, cardiac magnetic resonance
showed typical findings of acute myocarditis, and sputum was positive
for MERS-CoV. The patient was intubated and required hemodialysis, after
6 weeks of ICU and 1 month of ward hospitalization, he was discharged in
stable condition15.
Last but not least, influenza virus infection is well-known to aggravate
a plenty of cardiovascular disorders, being associated with myocarditis,
myocardial infarction, and heart failure
exacerbation16.
An interesting survey conducted by Madjid M et al. tested the possible
effect of seasonal influenza on the occurrence of ventricular
arrhythmias (VA) requiring shock or antitachycardia pacing (ATP)
treatment in patients with implantable cardiac defibrillator (ICD) or
cardiac resynchronization therapy defibrillator (CRT-D). The results
indicated that more shocks were delivered during influenza season than
during other periods of the year, suggesting a correlation between
higher arrhythmia burden and influenza season. The multivariate
generalized linear model showed that during high influenza activity,
patients were more likely to have a VA treated with shock [odds ratio
(OR) 1.06; p <0.001] or ATP (OR 1.06;p <0.0001)17.
Multiple mechanisms have been proposed to explain influenza triggering
arrhythmias, among them severe systemic, arterial, and myocardial
inflammatory reaction seems to be one of the most plausible. Moreover,
influenza is known to exacerbate congestive heart failure (CHF) and
increase CHF-related hospital admissions18.
Decompensated CHF, besides leading to hospitalization, is related to
electrical myocardial homeostasis impairment, causing VTs treated with
shock or ATP therapy. In patients with underlying ischemic
cardiomyopathy, the worsening of ischemia by increased oxygen demand and
potential acute coronary syndromes led by influenza can also have a role
in the increase of arrhythmic events17.
These concepts were strengthened by a nationwide Denmark studied, which
showed a strong relationship between yearly influenza vaccination and
mortality in heart failure patients. In this study, annual influenza
vaccination was associated with 18% reduction in the adjusted risk of
all-cause death and 18% reduction in the adjusted risk of
cardiovascular death (p <0.001, for both). Remarkably,
those who received more than one seasonal vaccination also had a more
pronounced reduction in atrial fibrillation incidence [hazard ratio
(HR) 0.94; p =0.009]. According to this study, influenza
infection may result in increased metabolic demand, hypoxia, and
adrenergic surges, which may lead to acute decompensation or
exacerbation of heart failure. Additionally, the infection may induce a
hypercoagulable state and trigger acute coronary syndromes, resulting in
further left ventricular function deterioration, or it could cause
direct myocardial depression. Based on these results, the authors
advocated that influenza vaccination may be a valuable treatment
strategy to improve survival in heart failure
patients19.