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.