key: cord-328307-378cfb23 authors: Shirazi, Samira; Mami, Sanaz; Mohtadi, Negar; Ghaysouri, Abas; Tavan, Hamed; Nazari, Ali; Kokhazadeh, Taleb; Mollazadeh, Reza title: Sudden cardiac death in COVID-19 patients, a report of three cases date: 2020-07-03 journal: Future cardiology DOI: 10.2217/fca-2020-0082 sha: doc_id: 328307 cord_uid: 378cfb23 The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1–6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19. Recently, an Italian group reported that during the COVID-19 outbreak in 2020 a 58% increase in out-ofhospital cardiac arrest cases occurred when compared with the same period in 2019. Notably, the cumulative incidence of out-of-hospital cardiac arrest in 2020 strongly associated with the cumulative incidence of COVID-19. Moreover, they estimated that patients receiving a COVID-19 diagnosis accounted for most of such an increase of events, close to 80% of cases [10] . In the present study, we reported sudden cardiac death, which is not the dominant mode of death, in three patients with COVID-19 infection admitted to Shahid Mostafa Khomeini Hospital of Ilam in March and April 2020. A 50-year-old woman without known history of specific diseases or using specific drugs, complaining of fever, chills and dry cough was hospitalized in our center. On admission, her condition was as blood pressure (BP) = 130/80 mmHg, pulse rate (PR) = 80/min, body temperature (BT) = 37.2 • C and O 2 saturation (in room air) = 95%. She had no abnormal findings at the initial examination. Baseline ECG was within normal limits ( Figure 1A ). Due to pulmonary involvement evidenced in chest CT scan (Figure 2A) , she was treated with levofloxacin, vancomycin, hydroxychloroquine, lopinavir/ritonavir, as well as heparin for prophylaxis of deep venous thrombosis at standard doses. There was no electrolyte abnormality during hospitalization. On the fifth day of hospitalization, the treating physician decided to discharge the patient and continue the rest of treatment at home. While being discharged; the patient developed a sudden cardiac arrest and died as resuscitation was ineffective. The patient's laboratory information has been shown in Table 1 . saturation (in room air) = 87%. Crackles were heard in both lungs while other examinations were normal. Due to pulmonary involvement and dyspnea, the patient was treated with oseltamivir, hydroxychloroquine, lopinavir/ritonavir, meropenem, dexamethasone and enoxaparin adjusted based on serum creatinine level. The patient was consulted with a cardiologist and an endocrinologist. ECG ( Figure 1B ) and echocardiography revealed no abnormality and the blood glucose level was closely monitored. According to recommendations, the patients was treated with corticosteroids as well. The result of troponin I test was negative and creatinine level was reported as 1.5 mg/dl. There were no electrolyte abnormalities during hospitalization. After 7 days and with the improvement of symptoms and reaching O 2 saturation >95% within the last 48 h, the patient was decided to continue quarantine in a recovery center. The next day, after being transferred while having good general condition and normal vital signs, she suddenly developed cardiac arrest and died due to lack of response to resuscitation. Table 1 shows the patient's laboratory information and Figure 2B demonstrates the results of the patient's chest CT scan. A 60-year-old man without any history of specific diseases was referred to our hospital due to fever and dyspnea. He was diagnosed with COVID-19 and hospitalized. On admission, the patient's vital signs were as BP = 110/70, PR = 105/min, BT = 38.7 • C and O 2 saturation (in room air) = 82% which increased to >94% after applying O 2 masks. During a clinical examination, crackle was heard in the patient's left lung. He was treated with oseltamivir, hydroxychloroquine, lopinavir/ritonavir and azithromycin. The patient had no specific problems and the vital signs were normal with no evidence of electrolyte disturbances. The troponin I test was negative. Baseline ECG was normal ( Figure 1C ). On day 2 of hospitalization, he suffered from cardiac arrest and unfortunately died as resuscitation was unsuccessful. Table 1 shows the patient's laboratory information; and the results of the patient's chest CT scan is shown in Figure 2C . During the past 18 years, coronaviruses have caused three major crises in human societies [4] . For the first time, in November 2002, SARS emerged due to SARS-CoV and spread across China. Then in September 2012, Middle East respiratory syndrome caused by the MERS-CoV spread in many parts of the world causing many deaths. And now, there has been a new pneumonia related to COVID-19 virus identified in December 2019 turning to a global pandemic since March 2020 [5] . Because of being highly contagious, as well as having high mortality rate in the elderly and people with pre-existing medical conditions [11] , many concerns have been raised worldwide regarding the pandemic global outcomes. Many studies have reported pneumonia and acute respiratory distress as the main causes of death in COVID-19 patients. Underlying diseases that increase the risk of mortality due to COVID-19 include high BP, cardiovascular and cerebral disease, diabetes, hyperlipidemia, peripheral vascular diseases and chronic renal failure [11] . Numerous studies have highlighted an association between cardiovascular conditions and risk of mortality in COVID-19 patients [7] . Cardiac troponin I is one of the laboratory parameters predicting cardiac ischemia in patients with COVID-19. In fact, this laboratory parameter indicates cardiac damage in the patients [12] . Although most studies have noted that cardiac damage as a risk factor of mortality, Inciardi et al. reported death due to cardiac failure in a patient with COVID-19 who had no history of cardiovascular problems. However, there was no indication of possible mechanisms of cardiac failure in this recent report [13] . 10 .2217/fca-2020-0082 Future Cardiol. (Epub ahead of print) future science group Viral infection is an important cause of myocarditis. The most well-known viruses of this type include influenza and parvovirus B-19. Nevertheless, it is not clear whether SARS-CoV-2 also induces cardiac damage. Possible mechanisms by which COVID-19 may cause cardiac damage include inflammatory responses and cytokine storm, direct attack to cardiomyocytes and inducing severe hypoxia. Another potential cause is the proarrhythmic effects of hydroxychloroquine. This is the standard of treatment for COVID-19 in our country, Iran. QT prolongation and torsades de pointes (TdP) are a known adverse effect of this drug. Besides hydroxychloroquine, other risky drugs include lopinavir/ritonavir (administered in all 3 cases), azithromycin (case 3) and levofloxacin (case 1) may lead to (TdP) [14] . Although we did not have the ECG of the patients prior to their death to prove this theory. Another potentially important factor involved in QT C prolongation in COVID-19 is the high-grade systemic inflammation which characterize the diseases, frequently a real 'cytokine storm' in which IL-6 seems to play a pivotal role. As recently pointed out by PE et al., IL-6 could promote QT C prolongation in COVID-19 patients by different mechanisms [15] . Another very rare cause could be transient bradycardia in these patients. We have reported this complication before [16] . In compliance with our national guidelines, all patients admitted with the diagnosis of COVID-19, should be treated with hydroxychloroquine and ECG is obtained for patients >40 years old or with known cardiovascular disease. It is recommended to repeat the ECG on the third to fifth day of therapy. Prolongation of QT C intervals in the first and second case (480 and 500 msec, respectively) could be due to inflammatory activation (besides pre-existing risk factors, specifically diabetes and chronic heart failure in patient 2). Thus, it is plausible that a further QT C increase occurred after starting drug assumption, possibly reaching critical levels to favor TdP and SCD. According to the official reports by the Shahid Mostafa Khomeini Hospital of Ilam, 353 patients have been confirmed with COVID-19 infection until 10 April 2020 in Ilam Province. Of these, 35 deaths have been reported giving a mortality rate of 9.91%. From the 35 deceased cases, sudden cardiac arrest had been observed in three patients rendering an uncommon condition (0.84%). These patients had no symptoms or recognizable predictors requiring more examinations to timely identify them. ECG of the patients prior to their death are not available and in that case we could discuss more precisely about the QT and QT C . Death due to sudden cardiac arrest is not common, but possible, in COVID-19 patients. It is recommended to examine and monitor COVID-19 patients' cardiac condition to identify at risk individuals. • COVID-19 pandemic is growing day by day. • Although the cardinal manifestations are pulmonary, cardiovascular involvements are illustrated in the literature. • Sudden cardiac arrest and death may happen in COVID-19. • Herein we reported three sudden cardiac deaths among 353 proved COVID-19 patients in our institution. • Interestingly, death occurred despite improvement of general condition and constitutional symptoms. • Sudden death could be due direct involvement of myocardium by virus and arrhythmic events, cytokine storm or adverse drug effects (hydroxychloroquine and antivirals). Clinical features of patients infected with 2019 novel coronavirus in Wuhan • First report of COVID-19 in Lancet Clinical characteristics of coronavirus disease 2019 in China Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China • First report of COVID-19 in JAMA From SARS to MERS, thrusting coronaviruses into the spotlight Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study • First report of complete heart block from our institution New clinical experiences and evaluation of clinical and paraclinical features of deceased patients with COVID-19 infection referred to Shahid Mostafa Khomeini Hospital of Ilam • Introduces a hypothesis that cytokine storm may induce QT prolongation and torsades de pointes Association of cardiovascular manifestations with in-hospital outcomes in patients with COVID-19: a hospital staff data. medRxiv Hypertension and its severity or mortality in coronavirus disease 2019 (COVID-19): a pooled analysis End-stage heart failure with COVID-19: strong evidence of myocardial injury by 2019-nCoV Out-of-hospital cardiac arrest during the COVID-19 outbreak in Italy Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19) Considerations for drug interactions on QT C interval in exploratory COVID-19 treatment COVID-19, arrhythmic risk and inflammation: mind the gap! Circulation Transient complete heart block in a patient with critical COVID-19 The authors thank the staff of Shahid Mostafa Khomeini Hospital of Ilam for their kind cooperation. This research was financially supported by the Deputy of Research and Technology of the University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript. future science group 10 .2217/fca-2020-0082Case Series Shirazi, Mami, Mohtadi et al. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. This research was approved by ethical department of Ilam University of Medical Sciences (IR.MEDILAM.REC.1399.098).