In December 2019, an increasing number of cases of patients with pneumonia of unknown origin was detected in the Hubei province in China,1,2 and SARS-CoV-2, a novel coronavirus capable of human infection and transmission, was found to be responsible. The virus led to a pandemic, with more than 53.1 million reported infections and 1.3 million deaths3 to date. However, numbers may be in fact higher due to the virus being highly infectious and asymptomatic patients being capable of transmission.4–6 COVID-19 disease presents with a wide range of symptoms but predominantly as an acute respiratory disease and fever7 leading to hospitalization in about 10-15% of patients and critical intensive care (ICU) in 3-14.2% of patients.7–11 With growing knowledge about the disease, other clinical symptoms are constantly being reported. Respiratory failure, cytokine storm, thromboembolic phenomena and acute fulminant myocarditis are the predominant known causes of death12–14 with a 1.2-7.7% case-fatality rate worldwide to date. However, it may in fact be lower if the presumed asymptomatic undetected cases are accounted for, or higher, as in the elderly or in people with known associated diseases.3,7,10,15,16 In the latter group, cardiovascular comorbidities account for a higher mortality risk (10.5%),11,17,18 as well as diabetes and chronic obstructive pulmonary disease. Cardiac arrhythmias have been reported as a frequent event in this population as the estimates account for 16.7% among hospitalized patients and 44% in ICU patients.19,20 In these patients, the effect of multiorgan damage and cardiac lesion on cardiac rhythm, as well as the effect of experimental therapies for treatment is yet unknown.

The aim of this research was to assess the real incidence of cardiac arrhythmias among COVID-19 patients admitted to Portuguese hospitals and to understand the underlying prognostic implications, in order to provide useful knowledge for the management of these patients.

As SARS-CoV-2 is a newly detected coronavirus capable of infecting humans and causing COVID-19 disease, there is a lot of uncertainty regarding risk factors for disease outcome, as well as the best therapeutic strategies. Although acute pneumonia is the hallmark of the disease, there are several reports of additional direct organ damage from COVID-19, including acute heart failure and cardiac arrhythmias.13,14,22 Whether naturally resulting from the disease or from the treatment, its true incidence is still unknown. Currently, remdesivir and dexamethasone appear to be the most promising therapeutic drugs for treating COVID-19 patients, as they demonstrated a reduction in disease duration and severity.23–27 At the time of data collection for this study, other experimental therapeutic targets for COVID-19 were in use and they have the additional potential of inducing arrhythmias, as is the case of chloroquine/hydroxychloroquine.4,22

In our registry, we aimed to assess the incidence of arrhythmic global events in COVID-19 patients as well as the potential harmful effects of experimental therapies on major cardiac adverse events. These results show that in a population of patients hospitalized for COVID-19 in Portuguese hospitals, with cardiac continuous monitoring and admitted to intermediate or intensive care, there was a preponderance of male patients and a prevalence of older age groups. Likewise, patients with associated comorbidities,8,10,28–31 especially arterial hypertension, dyslipidemia, type 2 diabetes and AF are prone to severe disease.

The majority of patients were on experimental therapy for COVID-19, although not yet proven to be efficacious.22,32 This is particularly dangerous33–38 because a high percentage of these patients were also on other concomitant QT prolonging drugs. In our survey, more than 10% of patients displayed QT prolongation, although there was no evidence of polymorphic ventricular tachycardia, Torsade de Pointes or ventricular fibrillation. The incidence of prolonged QT was high,39,40 when compared with the 6% reported incidence in the normal population but in line with QT prolongation in populations with comorbidities such as diabetes, hypertension and ischemic cardiac disease, as is the case of our population.41 Additionally, this higher QT prolongation was probably due to the extremely high percentage of concomitant drugs (Table 1) and not related to electrolyte disturbances (which were low). This corroborates other studies that report the incidence of QT prolongation in patients taking these drugs.21 Since chloroquine/hydroxychloroquine are drugs that are still in use in COVID-19 studies, there is an increased need for a standardized QT interval monitoring protocol. Overall, the global incidence of arrhythmic events was high (11.7%), characterized mostly by new onset arrhythmias. Most patients with arrhythmias were critically ill patients with respiratory and multiple organ failure. These patients pose a greater challenge in management and had a bad outcome. The most frequent arrhythmic events were paroxysmal supraventricular tachycardia and AF, which can be associated with severe pulmonary disease and multiorgan failure per se, rather than cardiac lesion due to SARS2-CoV-2 and were not responsible for death events. Although patients with ventricular arrythmias had an arrhythmic substrate (either a prolonged QT or severe left ventricle dysfunction) and the mortality rate was high, the cause of death was due to respiratory failure.

Regarding the impact of COVID-19 on other cardiovascular outcomes, in our study population, acute myocarditis had a low incidence, contrary to the previously reported information,8,13,42 as well as myocardial infarction. On the other hand, acute cardiac lesion occurred in more than half of the patients with severe disease with a non-despicable incidence (14.1% of patients) of left ventricle systolic dysfunction. Nevertheless, this did not lead to a significant impact on mortality since the leading cause of death was respiratory failure and septic shock. Direct cardiac causes of death in our population were low (cardiogenic shock or arrhythmias).

Our study has limitations. First, although most hospitals reported for the survey, we do not have full coverage across the country and there may be biases associated with differences between centers that report or do not report data to the survey. Second, as in all large-scale surveys, some data were missing and additionally, the complete information was not mandatory due to the high workload health care providers face due to the COVID-19 pandemic. Therefore, there was only information available on arrhythmias in the subgroup of monitored patients (56.8% of the population) and detailed information was limited to 79% of this subset.

In a population of COVID-19 patients admitted to Portuguese hospitals, the incidence of cardiac arrhythmias is high and occurred mostly in extremely ill patients, who were either ventilated or had multiple organ failure, but was not associated with increased cardiac mortality. Regardless of the widespread use of experimental drugs to target SARS2-CoV-2 with the potential for QT prolongation, the incidence of ventricular arrhythmias is low. Atrial fibrillation and other supraventricular arrhythmias were the most prevalent arrythmias in COVID-19 patients.

No funding was received for this study.

The authors have no conflicts of interest to declare.