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.