COVID-19-associated cardiac arrest
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief: Sara Zand, M.D. Ayesha Javid, MBBS
Synonyms and keywords: Cardiac arrest, In-hospital cardiac arrest, IHCA, Out-of-hospital cardiac arrest, OHCA, Covid-19, SARS-COV-2, Ventricular arrhythmia, pulseless electrical activity, Asystole, Return Of Spontaneouse Circulation, ROSC
SARS-COV2 which causes coronavirus disease 2019 (covid-19) led to global pandemic on March 11, 2020, is an enveloped B-coronavirus transmitted via respiratory droplets, attached via viral spike protein to angiotensin-converting enzyme 2 receptor (ACE2 receptor) causing clinical asyndrome of coronavirus disease 2019. Severe covid-19 may progress to develope acute respiratory distress syndrome, cardiovascular complications, shock, and death. Cardiac arrest is often unexpected and acute event may present in every hospitalized patient. Abnormal vital signs can be the predictos of in-hospital cardiac arrest. During the outbreak of covid-19, there were increase reports of in-hospital cardiac arrest (IHCA), out-of hospital cardiac arrest (OHCA), lower rate of successful cardiopulmonary resuscitation (CPR), and increased mortality. 30-days mortality in covid-19 patients was increased 3.4 fold in OHCA and 2.3 fold in IHCA compared with pre-pandemic period. survival of in-hospital cardiac arrest was poor. Factors related to restricted or delay access to emergency care, late presentation of ACS or heart failure in hospital, avoidance of witness CPR in public due to fear contracting covid-19, as well as the side effects of drugs and thrombotic complications related to covid-19 led to higher incidence of cardiac arrest during covid-19 pandemic.
- In December 2019, the COVID-19 outbreak first appeared in China, Wuhan.
- In January 2020, the first COVID-19 case was documented in the United States.
- On February 20, 2020, the first case of COVID-19 was documented in the Province of Lodi in Italy.
- In April 2020, an increase of out-of-hospital cardiac arrest was reported during the COVID-19 pandemic in Italy by Dr.Enrico Baldi.
Cardiac arrest associated with COVID-19 may be classified into three subtypes:
- Pulseless electrical activity (49.8%)
- Bradyarrhythmia and asystolic arrest (23.8%)
- Ventricular tachycardia(8.3%)
- Ventricular fibrillation(3.8%)
The potential causes of ventricular tachyarrhythmia and sudden cardiac death in COVID-19 include:
- Administration of drugs causing QT interval prolongation such as hydroxychloroquine ± azithromycin, lopinavir, and ritonavir
- Concurrent use of drugs causing QT interval prolongation, such as antiemetics,fluoroquinolones,SSRIs
- Electrolyte abnormalities such as hypokalemia and hypomagnesemia
- High-risk comorbidity condition such as Congestive heart failure, chronic kidney disease, diabetes mellitus, and chronic obstructive pulmonary disease
- Inherited arrhythmia syndromes
- Increased sympathetic activity
- Inhibition of CYP450
- Direct myocardial injury or SARS-COV-2 myocarditis
- Acute cardiac events (acute coronary syndrome, decompensated heart failure, arrhythmia)
- Thromboembolic events related to COVID-19 (pulmonary embolism, acute coronary syndrome)
- The pathogenesis of cardiac arrest associated with COVID-19 is characterized by cytokine storm, especially elevation of IL-6.
- IL-6 directly blocks hERG/Kv11.1 potassium channels and causes action potential depolarization(APD) prolongation and ventricular repolarization.
- IL-6 induces hyperactivity of cardiac sympathetic nerve.
- Hypoxia causes myocardial injury and ventricular repolarization.
- IL-6 inhibits cytochrome P450 enzyme involved in metabolism of some QTc prolongation drugs.
- Hydroxychloroquine and lopinavir/ritonavir inhibit HERG-K+ channel and increase both ventriculat repolarization and the level of other QTc prolongation drugs.
- Hydroxychloroquine inhibits CYP2D6 (cytochrome P450 2D6) ,then the level of antipsychotics,antidepressants and antihistamins increase.
- Ritonavir inhibits CYP3A4 (cytochrome P450 3A4), then the level of azols antifungals, macrolides (particulary azithromycin), antidepressants,antihistamines, fluoroquinolones increase.
- Intrinsic genetic susceptibility (Ser1103Tyr-SCN5A) in African-Americans COVID-19 patients has been associated with increased risk of Torsades de pointes arrhythmia.
Differentiating inherited cardiac arrest from other causes of cardiac arrest
- To view the differential diagnosis of COVID-19-associated cardiac arrest click here.
- To view the differential diagnosis of COVID-19 click here.
Epidemiology and Demographics
- The incidence of out-of hospital cardiac arrest was estimated to be 10,000 cases per 100,000 covid-19 patients.
- The incidence of in-hospital cardiac arrest was estimated to be 16,000 per 100,000 covid-19 patients.
- There is a significant increase in the mortality rate of the OHCA in covid-19 patients.
- The mean age observed among patients who experienced out-of-hospital Sudden cardiac arrest (OHCA) is 69.7 years. .
- Studies showed that males have a slightly higher incidence of out-of-hospital sudden cardiac arrest (OHCA) as compared to the females.
- A higher incidence has been seen among African-Americans as compared to Caucasians.
- Common risk factors in the development of arrhythmia and cardiac arrest in COVID-19 are:
- Electrolytes disturbances
- Side effect of medications
- Age ≥65
- Male gender
- Factors associated with increased out of hospital cardiac arrest during covid-19 pandemic include: 
- Increased non-shockable rhythm at home
- Restricted or delay access to emergency care
- Longer response time by EMS due to increased workload
- Delay seeking medical care due to fear contracting covid-19 in hospital
- Decrease hospitalization of ACS and heart failure due to fear contracting covid-19 in hospital leading to increased severity of acute coronary syndrome and heart failure and cardiac arrest
- To view screening for COVID-19, click here.
Natural History, Complications, and Prognosis
- The proportion of patients who developed out-of-hospital cardiac arrest (OHCA) increased during the COVID-19 pandemic and was affected by aggravation of underlying comorbidities, late presentation of acute STEMI (ST elevation myocardial infarction) due to fear of being infected in hospital, and avoidance of bystander cardiopulmonary resuscitation in public due to fear of infection.
- In the setting of in-hospital cardiac arrest, Only 12% of patients survived to hospital discharged after cardiopulmonary resuscitation and only 7% of patients discharged with normal or mildly impaired neurologic status.
- 30-days mortality in covid-19 patients was increased 3.4 fold in OHCA and 2.3 fold in IHCA, compared with prepandemic period.
- Prognosis was poor in critically ill Covid-19 patients with pulseless electrical activity or asystole, patients older than 80 years with comorbidities.'.
- Survival rate after out-of-hospital cardiac arrest during the pandemic was 8.8%.
- Mortality rate of patients with COVID-19 is approximately 1-2%
- The diagnosis of sudden cardiac death is made when the following diagnostic criteria are met:
- Prodromes phase occurring weeks or months before an event includes: new or worsening cardiovascular symptoms(chest pain, dyspnea, palpitations, fatigability)
- Onset of terminal event occurring one hour before cardiac arrest includes: abrupt change in clinical status(arrhythmia, hypotension, chest pain, dyspnea, lightheadness)
- Cardiac arrest includes: sudden collapse, loss of effective circulation, loss of consciousness
- Biologic death: failure of resuscitation or failure of electrical, mechanical, or CNS function after initial resuscitation
- Symptoms before cardiac arrest in COVID-19 may include the following:
There is no specific finding associated with physical examination with cardiac arrest in COVID-19.
- An elevated concentration of serum cardiac troponinI was detected in severe COVID-19 patients with cardiac complications. 
There are no imaging study findings associated with cardiac arrest in COVID-19.
- Findings on EKG during in-hospital cardiac arrest (IHCA) with COVID-19 infection include:
- Asystole (89.7%)
- Pulseless electrical activity (4.4%)
- Shockable rhythm (5.9%)
- Another study showed the most common EKG findings during inhospital cardiac arrest was pulseless electrical activity(49.8%), asystole(23.8%), shockable rhthm(12.6%).
- Other abnormal EKG findings include QT prolongation. ECG shows corrected QT interval (QTc) more than 500 ms.
- The mainstay of therapy for COVID-19-related cardiac arrest is cardiopulmonary resuscitation with attention to the following points:
- Wearing personal protective equipment (PPE) before entering the room or on the scene.
- Limiting the personnel in the room or on the scene
- Using high-efficacy particulate air filter for ventilator
- Intubating with a cuffed tube
- Stopping chest compression for intubation
- Using bag-mask device before intubation
- Using non-rebreathing face mask instead of bag-mask for short term oxygenation
Effective measures for the primary prevention of ventricular arrhythmia during using hydroxychloroquine in the setting of long QT syndrome or aquired LQTS or heart rate <50/min or receiving azithromycin, remdesivir, lopinavir, ritonavir, include EKG and QTc measurement.
- If QTc ≥500 ms, consult with a cardiologist.
- If QTc<500ms, start hydroxychloroquine and repeat EKG after 1-3 days.
- After starting the first dose of hydroxychloroquine, If any of the following factors were present repeat EKG after 4 hours:
- Increased QTc>60ms
- Ventricular ectopy
- Treatment of hypokalemia due to diarrhea associated COVID-19 ,which prolonges QT interval is another measurement to be considered.
- Effective measures for the primary prevention of ventricular arrhythmia in brugada syndrome is starting acetaminophen or parastamol immediately if there is sign of fever and also self-isolation.
- ↑ Liu, Yen-Chin; Kuo, Rei-Lin; Shih, Shin-Ru (2020). "COVID-19: The first documented coronavirus pandemic in history". Biomedical Journal. doi:10.1016/j.bj.2020.04.007. ISSN 2319-4170.
- ↑ Sayre, Michael R.; Barnard, Leslie M.; Counts, Catherine R.; Drucker, Christopher J.; Kudenchuk, Peter J.; Rea, Thomas D.; Eisenberg, Mickey S. (2020). "Prevalence of COVID-19 in Out-of-Hospital Cardiac Arrest: Implications for Bystander CPR". Circulation. doi:10.1161/CIRCULATIONAHA.120.048951. ISSN 0009-7322.
- ↑ Baldi, Enrico; Sechi, Giuseppe M.; Mare, Claudio; Canevari, Fabrizio; Brancaglione, Antonella; Primi, Roberto; Klersy, Catherine; Palo, Alessandra; Contri, Enrico; Ronchi, Vincenza; Beretta, Giorgio; Reali, Francesca; Parogni, Pierpaolo; Facchin, Fabio; Bua, Davide; Rizzi, Ugo; Bussi, Daniele; Ruggeri, Simone; Oltrona Visconti, Luigi; Savastano, Simone (2020). "Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy". New England Journal of Medicine. doi:10.1056/NEJMc2010418. ISSN 0028-4793.
- ↑ Baldi E, Sechi GM, Mare C, Canevari F, Brancaglione A, Primi R, Klersy C, Palo A, Contri E, Ronchi V, Beretta G, Reali F, Parogni P, Facchin F, Bua D, Rizzi U, Bussi D, Ruggeri S, Oltrona Visconti L, Savastano S (July 2020). "Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy". N Engl J Med. 383 (5): 496–498. doi:10.1056/NEJMc2010418. PMC 7204428 Check
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- ↑ Mehra, Mandeep R; Desai, Sapan S; Ruschitzka, Frank; Patel, Amit N (2020). "RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis". The Lancet. doi:10.1016/S0140-6736(20)31180-6. ISSN 0140-6736.
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- ↑ Lazzerini, Pietro Enea; Laghi-Pasini, Franco; Boutjdir, Mohamed; Capecchi, Pier Leopoldo (2018). "Cardioimmunology of arrhythmias: the role of autoimmune and inflammatory cardiac channelopathies". Nature Reviews Immunology. 19 (1): 63–64. doi:10.1038/s41577-018-0098-z. ISSN 1474-1733.
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- ↑ 12.0 12.1 Sandroni C, Skrifvars MB, Nolan JP (2021). "The impact of COVID-19 on the epidemiology, outcome and management of cardiac arrest". Intensive Care Med. 47 (5): 602–604. doi:10.1007/s00134-021-06369-3. PMC 7904033 Check
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- ↑ Giudicessi JR, Roden DM, Wilde AAM, Ackerman MJ (2020). "Genetic susceptibility for COVID-19-associated sudden cardiac death in African Americans". Heart Rhythm. doi:10.1016/j.hrthm.2020.04.045. PMC 7198426 Check
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- ↑ 15.0 15.1 Wu CI, Postema PG, Arbelo E, Behr ER, Bezzina CR, Napolitano C, Robyns T, Probst V, Schulze-Bahr E, Remme CA, Wilde A (March 2020). "SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes". Heart Rhythm. doi:10.1016/j.hrthm.2020.03.024. PMC 7156157 Check
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