COVID-19: an unprecedented pandemia with a potential arrhythmic undertone

ABSTRACT

Data has shown that intense impact events such as large magnitude earthquakes and the US terrorist attacks of 11 September 2001 have shown us that unforeseen catastrophic events are followed by a significant increase of ventricular arrhythmias (VA) and sudden cardiac death (SCD).

We are concerned that similarly, the recent COVID-19 pandemia that not only has dismantled our way of living, in a matter of weeks, but also has challenged all of us beyond our abilities might be also related to an increase in prevalence of VA and SCD.

In addition to such provocative suggestions raise in this article we want to convey the message that we must remain vigilant long after we have silenced COVID-19.

KEYWORDS:

• Pandemia
• covid19
• arrhythmia
• sudden cardiac death

Intense impact events such as large magnitude earthquakes have shown us that unforeseen catastrophic events are followed by a significant increase of ventricular arrhythmias (VA) and sudden cardiac death (SCD) [1–3].

Even when some controversy might still exist between cause and effect regarding the mechanism(s) of increased cardiac mortality, in the Northridge earthquake in the San Fernando Valley region of the County of Los Angeles, a large-scale natural disaster, there was a significant increase in the number of SCD [1]. Careful data analysis of these events did not show any significant association between SCD and unusual physical exertion, but rather pointed to emotional stress as a more likely trigger, particularly in individuals already predisposed with an adverse cardiac risk profile [1]. This conclusion was driven not only by an increased number of hospital admissions for acute myocardial infarction [1], but also, by an increased number of VA among patients with implantable defibrillators in the weeks following the earthquake [1]. A similar increase in out-of-hospital cardiac arrests occurred following the Great East Japan earthquake [2] and similarly there were increased hemodynamically unstable VA events among hospitalized patients with known heart disease after the Wenchuan earthquake and its aftershocks [3]. In sharp contrast, data from Chan and associates failed to show any significant association between cardiac arrhythmias following the Christchurch earthquakes, in New Zealand [4]. Though a clear explanation was never given to explain differences concerning cardiac events and earthquake magnitude; we wonder if the latter occurred over a less populated area.

It is our belief that the continuing unprecedented COVID-19 pandemia with widespread mandatory social isolation, dramatic economic collapse, and social instability, associated with intense and continued health anxiety has provided us with a unique and ongoing opportunity to examine the potential relationship that could exist between this prolonged global scale catastrophe and VA as well as SCD.

Though initially not recognized as a potential threat, last 31 December 2019 Chinese Health officials first notified the World Health Organization (WHO) of a cluster of 41 patients who had developed a mysterious pneumonia connected to Huanan Seafood Wholesale Market [5]. On 11 January 2020 the first of these patients died, only 4 dayss after we first heard the news of a new coronavirus [6]. In February 2010, the WHO identified this new coronavirus as COVID-19 with the virus causing severe acute respiratory syndrome as SARS-CoV-2 [6].

What followed since has not only mystified the scientific community but also has continued to challenge our conventional understanding and any prediction model. By 12 February 2020 an outbreak erupted in Iran, followed by Italy on 21 February 2020, Spain on 3 March 2020, and on 4 March 2020, the first COVID-19 cases were reported in the US west coast [5]. By March 11, the COVID-19 outbreak had spread uncontrolled to at least 120,000 people across 114 nations, prompting the WHO to refer COVID-19 as a pandemic which at that time had already claimed 4,000 lives [5]. In a matter of 11 days, on 22 March 2020, New York City had 21,000 confirmed infected cases becoming the biggest epicenter outbreak in the US [5].

As of 6 April 2020, the Johns Hopkins Resource Center reported 1,346,299 confirmed cases with 74,679 deaths worldwide as a result of COVID-19 [7]. Though staggering, these numbers were at the time; the unfortunate reality is that as of 14 May 2020 these numbers have skyrocket to 4,442,163 confirmed global cases with 302,376 deaths [7].

Early in the pandemia, the WHO issued a warning with regards to potential mental health and psychological consequences of the pandemia, factors that would certainly be aggravated by the institution of much needed mitigation strategies. Isolation and effective lockdown mandates have had adverse social and economic consequences. Such disruption has also adversely impacted healthcare practices by which outpatient doctor visits are either performed by phone or video and patients with cardiac devices are not routinely interrogated.

This unprecedented pandemia has brought to the forefront two opposing realities. On the one hand, everyone faces the prospect of getting sick with the possibility of dying from COVID-19. On the other hand, prolonged quarantine, particularly when inundated with sensationalist negative news further aggravate an already frail confidence by fostering an overarching pervasive depression, anger, and anxiety. It is therefore expected that the longer this quarantine continues, the more devastating consequences it might have. From a physiological point of view, these extreme mitigating strategies have already been linked to systemic inflammation, endothelial dysfunction, and sympathetic nervous system activation [8]. Consequently, as a direct consequence of these metabolic interactions, faster heart rates, higher blood pressure, increased ventricular contractility as well as irritability, greater propensity for thrombus formation, atherosclerotic plaque rupture, and coronary vasoconstriction are expected [9]. These place patients at risk, particularly those with underlying cardiovascular conditions or risk profiles.

The whole paradigm seems to fold into place as new data emerges from Europe’s experience with the pandemic. Specifically, Baldi and associates corroborate our fears of an increased number of out of hospital cardiac arrests in northern Italy that matched the same geographical areas most harshly affected by the pandemia [10]. A significant increase in SCD events (58%) was reported in this region and these investigators attribute this spike to pulmonary embolisms and late complications of myocardial infract or ischemia, as patients were more likely to stay home away from hospitals for fear of COVID-19 infection [10].

As a testament to this supposition, data reported from both DeFilippo O, et al. and Metzler B, et al. have shown significant reductions in the overall number of hospital admissions attributed to patients presenting with acute coronary syndromes (ACS) [11,12].

Perhaps, both fear from becoming infected and inability to reach a nearby hospital could have been plausible explanations that limited cardiac care for residents of Lombardy, Italy as they centralized care of ACS [13]. A similar measure was certainly adopted in many places; however, we are still waiting for data to emerge to assess the impact that this reassigning of hospitals has had on global health in trying to maximize resources to respond to a COVID surge.

Our institution following similar guidelines was assigned as COVID-19 hospital and saw a significant decrease in the number of cardiac patients early on during the pandemic. However, in the weeks that follow we have seen a spike in the number of out-of-hospital cardiac arrest survivors from 1 to 3 per week.

Aside from all tangible concerns unique to this pandemia, but in keeping with our concerns about VA and SCD, was the initial indiscriminate, and yet of unproven efficacy at the time, use of chloroquine, hydroxychloroquine, and azithromycin for treating COVID-19 patients. The sudden use of these drugs was based on results from 26 patients treated showing either a significant reduction or disappearance of viral load [14]. However, The American College of Cardiology promptly issued warnings regarding the use of these medications due to the potential of QT interval prolongation, raising concerns about the potential risk of arrhythmic death on these individuals [15].

Subsequently, QTc prolongation was indeed demonstrated from data analysis of 84 patients receiving hydroxychloroquine and azithromycin [16]. These investigators from New York showed that even when the QTc interval prolonged from a baseline average of 435 ± 24 ms to a value of 463 ± 32 ms (P < 0.001), occurring approximately 3.6 ± 1.6 days after therapy was initiated [16]. Most importantly, no torsades de pointes were reported in any of these patients, even in those with the most prolonged QTc [16]. It is quite poignant to reconcile what might appear as a discrepancy between known data regarding QTc interval and hydroxychloroquine and azithromycin use. Surely, these drugs can result in just mild QTc prolongation when used in young healthy volunteers [17]. However, more significant QTc interval prolongation should be expected in COVID-19 patients based on the number of their co-morbidities and the extent of their respiratory and/or systemic inflammation severity [18]. Important clinical profiles that might increase the proarrhythmic potential include very high fever, profound electrolyte disturbances, that are further aggravated by vomiting and diarrhea, as well as hypoxia, concomitant use of antiviral drugs, underlying elevation in troponin levels and severe systemic inflammation [18,19,20].

Though we are just beginning to realize that we have more questions than answers and at best most is still speculative, data will eventually emerge that could give us a better indication of the overall social, economic, health, and clinical impact of this pandemia; we raise concerns for plausible and still unrecognized VA and SCD consequences either as a direct result from COVID-19 or its treatment. Perhaps, we would never be able to truly know the exact number of nursing home residents, individuals that stayed home either asymptomatic or with presumed infections, or how many hospitalized patients might have experienced VA or SCD. In fact, we would never know whether or not patients have died from cardiac complications or how many deaths have been improperly attributed as simply COVID-19 deaths. However, our message is clear, remain vigilant, particularly as the number of VA and SCD events might continue to emerge long after we have silenced COVID-19.

Declaration of interest

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.