COVID-19-associated cardiac arrest
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D. Ayesha Javid, MBBS[2]
Overview
Sudden cardiac death is defined as natural death from cardiac causes developed by abrupt loss of consciousness within one hour of onset of acute change in cardiovascular status. Preexisting heart disease may or may not be present at the time of the cardiac arrest. Sudden onset of chest pain, dyspnea or palpitations and other symptoms of arrhythmia may precede the onset of cardiac arrest. During the outbreak of COVID-19, the number of out-of-hospital cardiac arrests in Italy increased and prognosis of in-hospital cardiac arrest was generally poor. Factors related to medical services restriction, as well as the side effects of drugs and thrombotic complications related to COVID-19, increased the number of cardiac arrest during COVID-19 pandemic.
Historical Perspective
- In December 2019, the COVID-19 outbreak first appeared in China, Wuhan.[1]
- In January 2020, the first COVID-19 case was documented in the United States.[2]
- On February 20, 2020, the first case of COVID-19 was documented in the Province of Lodi in Italy.[3]
- In April 2020, an increase in out-of-hospital cardiac arrest was reported during the COVID-19 pandemic.
Classification
Cardiac arrest associated with COVID-19 may be classified into three subtypes:
- Pulseless electrical activity
- Bradyarrhythmia and asystolic arrest
- Fatal tachyarrhythmia
Causes
The potential causes of ventricular tachyarrhythmia and sudden cardiac death in COVID-19 include:[4]
- Hypercytokinemia
- Administration of drugs causing QT interval prolongation such as hydroxychloroquine ± azithromycin, lopinavir, and ritonavir[5]
- Concurrent use of drugs causing QT interval prolongation, such as antiemetics,floroquinolones,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
- Age ≥65
- Male gender
- 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)[6]
- Hypoxia
Pathophysiology
- The pathogenesis of cardiac arrest associated with COVID-19 is characterized by cytokine storm, especially elevation of IL-6.[7]
- 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.[8]
- Hydroxychloroquine and lopinavir/ritonavir inhibit HERG-K+ channel and increase both ventriculat repolarization and the level of other QTc prolongation drugs.[8]Hydroxychloroquine inhibits CYP2D6 (cytochrome P450 2D6) ,then the level of antipsychotics,antidepressants and antihistamins increase.[8]
- Ritonavir inhibits CYP3A4 (cytochrome P450 3A4), then the level of azols antifungals, macrolides (particulary azithromycin),antidepressants,antihistamines,fluoroquinolones increase.[8]
- Intrinsic genetic susceptibility (Ser1103Tyr-SCN5A) in African-Americans COVID-19 patients has been associated with increased risk of Torsade points arrhythmia.[9]
Differentiating inherited cardiac arrest from other causes of cardiac arrest.
- To view the differential diagnosis of COVID-19 click here.
- Inherited cardiac arrest associated COVID19 must be differentiated from other causes of cardiac arrest based on these characteristics:[10][11][12][13][14][15][16][17][18]
| Inherited causes of cardiac arrest and malignant arrhythmia associated covid-19 | long QT syndrome | Brugada syndrome | Short QT syndrome | Cathecolaminergic polymorphic ventricular tachaycardia |
|---|---|---|---|---|
| Gene mutation |
|
| ||
| EKG finding |
|
in lead V1 and/or V2 |
|
|
| Specific considerations in COVID19 patients |
|
|
|
|
| fatal arrhythmia |
|
Ventricular fibrillation |
- Corrected QT(QTc)=1000(QT/1000+0.154(1-RR)
- RR is measured in seconds and is the interval from the onset of one QRS complex to the onset of the next QRS complex.
Epidemiology and Demographics
Incidence
- During the COVID-19 pandemic, the incidence of out-of-hospital Sudden cardiac arrests (OHCA) has been 2 times greater compared to the non-pandemic time period.
- According to a study done in China, about 12% of patients with COVID-19 without a history of heart problems experience cardiac arrest during their hospitalization.[19]
- In a study done among 761 Chinese patients with severe COVID-19, about 20% patients developed in-hospital cardiac arrest within 40 days of their hospitalization course.[20]
Mortality
- There is a significant increase in the mortality rate of the OHCA in patients.[21]
Age
- The mean age observed among patients who experienced out-of-hospital Sudden cardiac arrest (OHCA) is 69.7 years.[21] .
Gender
- Studies showed that males have a slightly higher incidence of out-of-hospital sudden cardiac arrest (OHCA) as compared to the females.[21]
Race
- A higher incidence has been seen among African-Americans as compared to Caucasians.[22]
Risk Factors
- Common risk factors in the development of arrhythmia and cardiac arrest in COVID-19 are:[23]
- Fever
- Stress
- Electrolytes disturbances
- Use of some medications
Screening
- 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.[24][25]
- Prognosis of patients with severe COVID-19 pneumonia with in hospital cardiac arrest (IHCA) was poor in Wuhan, China.[26]
Diagnosis
Diagnostic Criteria
- 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
- Symptoms before cardiac arrest in COVID-19 may include the following:
Physical Examination
There is no specific finding associated with physical examination with cardiac arrest in COVID-19.
Laboratory Findings
- An elevated concentration of serum cardiac troponinI was detected in severe COVID-19 patients with cardiac complications. [28]
Imaging Findings
There are no imaging study findings associated with cardiac arrest in COVID-19.
Electrocardiogram
- Findings on EKG during in-hospital cardiac arrest (IHCA) with COVID-19 infection include:[26]
- Asystole (89.7%)
- Pulseless electrical activity (4.4%)
- Shockable rhythm (5.9%)
- Other abnormal EKG findings include QT prolongation. ECG shows corrected QT interval (QTc) more than 500 ms.
Treatment
- The mainstay of therapy for COVID-19-related cardiac arrest is cardiopulmonary resuscitation with attention to the following points:[29]
- 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
Prevention
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, redmisivir, lopinavir, ritonavir, include EKG and QTc measurement.[23]
- If QTc ≥500 ms, consult with 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:
- QTc≥500mse
- 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.
References
- ↑ 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.
- ↑ Giudicessi JR, Roden DM, Wilde A, Ackerman MJ (May 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
|pmc=value (help). PMID 32380288 Check|pmid=value (help). Vancouver style error: initials (help) - ↑ 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.
- ↑ Klok, F.A.; Kruip, M.J.H.A.; van der Meer, N.J.M.; Arbous, M.S.; Gommers, D.A.M.P.J.; Kant, K.M.; Kaptein, F.H.J.; van Paassen, J.; Stals, M.A.M.; Huisman, M.V.; Endeman, H. (2020). "Incidence of thrombotic complications in critically ill ICU patients with COVID-19". Thrombosis Research. 191: 145–147. doi:10.1016/j.thromres.2020.04.013. ISSN 0049-3848.
- ↑ 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.
- ↑ 8.0 8.1 8.2 8.3 Driggin, Elissa; Madhavan, Mahesh V.; Bikdeli, Behnood; Chuich, Taylor; Laracy, Justin; Biondi-Zoccai, Giuseppe; Brown, Tyler S.; Der Nigoghossian, Caroline; Zidar, David A.; Haythe, Jennifer; Brodie, Daniel; Beckman, Joshua A.; Kirtane, Ajay J.; Stone, Gregg W.; Krumholz, Harlan M.; Parikh, Sahil A. (2020). "Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic". Journal of the American College of Cardiology. 75 (18): 2352–2371. doi:10.1016/j.jacc.2020.03.031. ISSN 0735-1097.
- ↑ Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ (June 2020). "Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19)". Mayo Clin. Proc. 95 (6): 1213–1221. doi:10.1016/j.mayocp.2020.03.024. PMC 7141471 Check
|pmc=value (help). PMID 32359771 Check|pmid=value (help). - ↑ Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, Gussak I, Hasdemir C, Horie M, Huikuri H, Ma C, Morita H, Nam GB, Sacher F, Shimizu W, Viskin S, Wilde AA (October 2016). "J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge". Heart Rhythm. 13 (10): e295–324. doi:10.1016/j.hrthm.2016.05.024. PMC 5035208. PMID 27423412.
- ↑ van der Werf C, Wilde AA (April 2013). "Catecholaminergic polymorphic ventricular tachycardia: from bench to bedside". Heart. 99 (7): 497–504. doi:10.1136/heartjnl-2012-302033. PMID 23390049.
- ↑ van Noord C, Eijgelsheim M, Stricker BH (July 2010). "Drug- and non-drug-associated QT interval prolongation". Br J Clin Pharmacol. 70 (1): 16–23. doi:10.1111/j.1365-2125.2010.03660.x. PMC 2909803. PMID 20642543.
- ↑ Priori, Silvia G.; Wilde, Arthur A.; Horie, Minoru; Cho, Yongkeun; Behr, Elijah R.; Berul, Charles; Blom, Nico; Brugada, Josep; Chiang, Chern-En; Huikuri, Heikki; Kannankeril, Prince; Krahn, Andrew; Leenhardt, Antoine; Moss, Arthur; Schwartz, Peter J.; Shimizu, Wataru; Tomaselli, Gordon; Tracy, Cynthia (2013). "HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes". Heart Rhythm. 10 (12): 1932–1963. doi:10.1016/j.hrthm.2013.05.014. ISSN 1547-5271.
- ↑ White NJ (August 2007). "Cardiotoxicity of antimalarial drugs". Lancet Infect Dis. 7 (8): 549–58. doi:10.1016/S1473-3099(07)70187-1. PMID 17646028.
- ↑ Amin AS, Herfst LJ, Delisle BP, Klemens CA, Rook MB, Bezzina CR, Underkofler HA, Holzem KM, Ruijter JM, Tan HL, January CT, Wilde AA (July 2008). "Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome". J. Clin. Invest. 118 (7): 2552–61. doi:10.1172/JCI35337. PMC 2423868. PMID 18551196.
- ↑ Amin AS, Meregalli PG, Bardai A, Wilde AA, Tan HL (August 2008). "Fever increases the risk for cardiac arrest in the Brugada syndrome". Ann. Intern. Med. 149 (3): 216–8. doi:10.7326/0003-4819-149-3-200808050-00020. PMID 18678856.
- ↑ Michowitz Y, Milman A, Sarquella-Brugada G, Andorin A, Champagne J, Postema PG, Casado-Arroyo R, Leshem E, Juang J, Giustetto C, Tfelt-Hansen J, Wijeyeratne YD, Veltmann C, Corrado D, Kim SH, Delise P, Maeda S, Gourraud JB, Sacher F, Mabo P, Takahashi Y, Kamakura T, Aiba T, Conte G, Hochstadt A, Mizusawa Y, Rahkovich M, Arbelo E, Huang Z, Denjoy I, Napolitano C, Brugada R, Calo L, Priori SG, Takagi M, Behr ER, Gaita F, Yan GX, Brugada J, Leenhardt A, Wilde A, Brugada P, Kusano KF, Hirao K, Nam GB, Probst V, Belhassen B (September 2018). "Fever-related arrhythmic events in the multicenter Survey on Arrhythmic Events in Brugada Syndrome". Heart Rhythm. 15 (9): 1394–1401. doi:10.1016/j.hrthm.2018.04.007. PMID 29649615. Vancouver style error: initials (help)
- ↑ Luo C, Wang K, Liu T, Zhang H (July 2018). "Computational Analysis of the Action of Chloroquine on Short QT Syndrome Variant 1 and Variant 3 in Human Ventricles". Conf Proc IEEE Eng Med Biol Soc. 2018: 5462–5465. doi:10.1109/EMBC.2018.8513572. PMID 30441573.
- ↑ Zheng, Ying-Ying; Ma, Yi-Tong; Zhang, Jin-Ying; Xie, Xiang (2020). "COVID-19 and the cardiovascular system". Nature Reviews Cardiology. 17 (5): 259–260. doi:10.1038/s41569-020-0360-5. ISSN 1759-5002.
- ↑ Shao, Fei; Xu, Shuang; Ma, Xuedi; Xu, Zhouming; Lyu, Jiayou; Ng, Michael; Cui, Hao; Yu, Changxiao; Zhang, Qing; Sun, Peng; Tang, Ziren (2020). "In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China". Resuscitation. 151: 18–23. doi:10.1016/j.resuscitation.2020.04.005. ISSN 0300-9572.
- ↑ 21.0 21.1 21.2 Marijon E, Karam N, Jost D, Perrot D, Frattini B, Derkenne C; et al. (2020). "Out-of-hospital cardiac arrest during the COVID-19 pandemic in Paris, France: a population-based, observational study". Lancet Public Health. doi:10.1016/S2468-2667(20)30117-1. PMC 7255168 Check
|pmc=value (help). PMID 32473113 PMID: 32473113 Check|pmid=value (help). - ↑ 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
|pmc=value (help). PMID 32380288 PMID: 32380288 Check|pmid=value (help). - ↑ 23.0 23.1 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
|pmc=value (help). PMID 32244059 Check|pmid=value (help). Vancouver style error: initials (help) - ↑ Tam, Chor-Cheung Frankie; Cheung, Kent-Shek; Lam, Simon; Wong, Anthony; Yung, Arthur; Sze, Michael; Lam, Yui-Ming; Chan, Carmen; Tsang, Tat-Chi; Tsui, Matthew; Tse, Hung-Fat; Siu, Chung-Wah (2020). "Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment–Elevation Myocardial Infarction Care in Hong Kong, China". Circulation: Cardiovascular Quality and Outcomes. 13 (4). doi:10.1161/CIRCOUTCOMES.120.006631. ISSN 1941-7713.
- ↑ Scquizzato, Tommaso; Olasveengen, Theresa Mariero; Ristagno, Giuseppe; Semeraro, Federico (2020). "The other side of novel coronavirus outbreak: Fear of performing cardiopulmonary resuscitation". Resuscitation. 150: 92–93. doi:10.1016/j.resuscitation.2020.03.019. ISSN 0300-9572.
- ↑ 26.0 26.1 Shao F, Xu S, Ma X, Xu Z, Lyu J, Ng M, Cui H, Yu C, Zhang Q, Sun P, Tang Z (June 2020). "In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China". Resuscitation. 151: 18–23. doi:10.1016/j.resuscitation.2020.04.005. PMC 7151543 Check
|pmc=value (help). PMID 32283117 Check|pmid=value (help). - ↑ Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui D, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS (April 2020). "Clinical Characteristics of Coronavirus Disease 2019 in China". N. Engl. J. Med. 382 (18): 1708–1720. doi:10.1056/NEJMoa2002032. PMC 7092819 Check
|pmc=value (help). PMID 32109013 Check|pmid=value (help). Vancouver style error: initials (help) - ↑ Paul P (May 2020). "Cardiac Troponin-I may be a predictor of complications and mortality in COVID-19 patients". Curr Med Res Pract. doi:10.1016/j.cmrp.2020.05.001. PMC 7204698 Check
|pmc=value (help). PMID 32382587 Check|pmid=value (help). - ↑ Edelson, Dana P.; Sasson, Comilla; Chan, Paul S.; Atkins, Dianne L.; Aziz, Khalid; Becker, Lance B.; Berg, Robert A.; Bradley, Steven M.; Brooks, Steven C.; Cheng, Adam; Escobedo, Marilyn; Flores, Gustavo E.; Girotra, Saket; Hsu, Antony; Kamath-Rayne, Beena D.; Lee, Henry C.; Lehotsky, Rebecca E.; Mancini, Mary E.; Merchant, Raina M.; Nadkarni, Vinay M.; Panchal, Ashish R.; Peberdy, Mary Ann R.; Raymond, Tia T.; Walsh, Brian; Wang, David S.; Zelop, Carolyn M.; Topjian, Alexis A.; Starks, Monique Anderson; Bobrow, Bentley J.; Chan, Melissa; Berg, Katherine; Duff, Jonathan P.; Joyner, Benny L.; Lasa, Javier J.; Levy, Arielle; Mahgoub, Melissa; O’Connor, Michael F.; Hoover, Amber V.; Rodriguez, Amber J.; Meckler, Garth; Roberts, Kathryn; Mohr, Nicholas M.; Nassar, Boulos; Rubinson, Lewis; Sutton, Robert M.; Schexnayder, Stephen M.; Kleinman, Monica; de Caen, Allan; Morgan, Ryan; Bhanji, Farhan; Fuchs, Susan; Terry, Mark; McBride, Mary; Levy, Michael; Cabanas, Jose G.; Tan, David K.; Moitra, Vivek K.; Szokol, Joseph W. (2020). "Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19". Circulation. 141 (25). doi:10.1161/CIRCULATIONAHA.120.047463. ISSN 0009-7322.