The novel corona virus, severe acute respiratory syndrome coronavirus 2 has spread worldwide since late 2019, with clinical manifestations of coronavirus disease 2019 (COVID-19) ranging from asymptomatic to respiratory impairment to multiorgan dysfunction with life-threatening cardiovascular complications. The mechanism of cardiovascular involvement is likely multifactorial, hypothesized to include direct myocardial injury, secondary injury due to the inflammatory response, and macro- and microthrombotic complications due to hypercoagulability. Acute cor pulmonale and pulmonary embolism are cardiovascular causes of serious morbidity and mortality, and myocarditis and Takotsubo syndrome have also been reported. It is not clear if arrhythmias represent a primary viral effect or a secondary effect of disease severity, though certain pharmacotherapies such as hydroxychloroquine may increase this risk. Point-of-care ultrasound and echocardiography are important tools for the screening and monitoring of these potential complications. Cardiovascular decompensation must be managed supportively with the escalation of vasoactive support, inhaled vasodilators, and consideration of mechanical circulatory support. Many questions remain and ongoing study is required to optimize care of the patient with cardiovascular complications of COVID-19.
World Health Organization. Available from: https://covid19.who. int/. [Last accessed on 2020 Sep 16].
Deng G, Yin M, Chen X, Zeng F. Clinical determinants for fatality of 44,672 patients with COVID-19. Crit Care 2020;24:179.
Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020;323:1775-6.
Gémes K, Talbäck M, Modig K, Ahlbom A, Berglund A, Feychting M, et al. Burden and prevalence of prognostic factors for severe COVID-19 in Sweden. Eur J Epidemiol 2020;35:401-9.
Li X, Pan X, Li Y, An N, Xing Y, Yang F, et al. Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: A meta-analysis and systematic review. Crit Care 2020;24:468.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.
Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med 2020;202:756-9.
Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res 2020;116:1097-100.
Bradley BT, Maioli H, Johnston R, Chaudhry I, Fink SL, Xu H, et al. Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: A case series. Lancet 2020;396:320-32.
Liu F, Li L, Xu M, Wu J, Luo D, Zhu YS, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol 2020;127:104370.
Prabhu SD. Cytokine-induced modulation of cardiac function. Circ Res 2004;95:1140-53.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31.
Levi M, van der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004;109:2698-704.
Ryan D, Frohlich S, McLoughlin P. Pulmonary vascular dysfunction in ARDS. Ann Intensive Care 2014;4:28.
Crystal GJ, Pagel PS. Right ventricular perfusion: Physiology and clinical implications. Anesthesiology 2018;128:202-18.
Park JF, Banerjee S, Umar S. In the eye of the storm: The right ventricle in COVID-19. Pulm Circ 2020;10:1-7.
Zochios V, Parhar K, Tunnicliffe W, Roscoe A, Gao F. The right ventricle in ARDS. Chest 2017;152:181-93.
Li Y, Li H, Zhu S, Xie Y, Wang B, He L, et al. Prognostic value of right ventricular longitudinal strain in patients With COVID-19. JACC Cardiovasc Imaging 2020;13:2287-99.
Whittenberger JL, McGregor M, Berglund E, Borst HG. Influence of state of inflation of the lung on pulmonary vascular resistance. J Appl Physiol 1960;15:878-82.
Niden AH. The acute effects of atelectasis on the pulmonary circulation. J Clin Invest 1964;43:810-24.
Jardin F, Brun-Ney D, Hardy A, Aegerter P, Beauchet A, Bourdarias JP. Combined thermodilution and two-dimensional echocardiographic evaluation of right ventricular function during respiratory support with PEEP. Chest 1991;99:162-8.
Dambrosio M, Fiore G, Brienza N, Cinnella G, Marucci M, Ranieri VM, et al. Right ventricular myocardial function in ARF patients. PEEP as a challenge for the right heart. Intensive Care Med 1996;22:772-80.
Luecke T, Pelosi P. Clinical review: Positive end-expiratory pressure and cardiac output. Crit Care 2005;9:607-21.
Jardin F, Vieillard-Baron A. Is there a safe plateau pressure in ARDS? The right heart only knows. Intensive Care Med 2007;33:444-7.
Mekontso Dessap A, Boissier F, Charron C, Bégot E, Repessé X, Legras A, et al. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact. Intensive Care Med 2016;42:862-70.
Potus F, Mai V, Lebret M, Malenfant S, Breton-Gagnon E, Lajoie AC, et al. Novel insights on the pulmonary vascular consequences of COVID-19. Am J Physiol Lung Cell Mol Physiol 2020;319:L277-L288.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;383:120-8.
Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145-7.
Becattini C, Casazza F, Forgione C, Porro F, Fadin BM, Stucchi A, et al. Acute pulmonary embolism: External validation of an integrated risk stratification model. Chest 2013;144:1539-45.
Creel-Bulos C, Hockstein M, Amin N, Melhem S, Truong A, Sharifpour M. Acute Cor Pulmonale in Critically Ill Patients with Covid-19. N Engl J Med 2020;382:e70.
Benzakoun J, Hmeydia G, Delabarde T, Hamza L, Meder JF, Ludes B, et al. Excess out-of-hospital deaths during the COVID-19 outbreak: Evidence of pulmonary embolism as a main determinant. Eur J Heart Fail 2020;22:1046-7.
Ali S, Mathew S, Pappachan JM. Acute cor pulmonale from saddle pulmonary embolism in a patient with previous COVID-19: Should we prolong prophylactic anticoagulation? Int J Infect Dis 2020;97:299-302.
Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Eur Heart J 2020;42:206.
Kim IC, Kim JK, Kim HA, San H. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J 2020;41:1859.
Sala S, Peretto G, Gramegna M, Palmisano A, Villatore A, Vignale D, et al. Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection. Eur Heart J 2020;41:1861-2.
Kariyanna PT, Sutarjono B, Grewal E, Singh KP, Aurora L, Smith L, et al. A systematic review of COVID-19 and myocarditis. Am J Med Case Rep 2020;8:299-305.
Siripanthong B, Nazarian S, Muser D, Deo R, Santangeli P, Khanji MY, et al. Recognizing COVID-19-related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm 2020;17:1463-71.
Pirzada A, Mokhtar AT, Moeller AD. COVID-19 and myocarditis: What do we know so far? CJC Open 2020;2:278-85.
Cheng P, Zhu H, Witteles RM, Wu JC, Quertermous T, Wu SM, et al. Cardiovascular risks in patients with COVID-19: Potential mechanisms and areas of uncertainty. Curr Cardiol Rep 2020;22:34.
Minhas AS, Scheel P, Garibaldi B, Liu G, Horton M, Jennings M, et al. Takotsubo syndrome in the setting of COVID-19. JACC Case Rep 2020;2:1321-5.
Pasqualetto MC, Secco E, Nizzetto M, Scevola M, Altafini L, Cester A, et al. Stress cardiomyopathy in COVID-19 disease. Eur J Case Rep Intern Med 2020;7:001718.
Giustino G, Croft LB, Oates CP, Rahman K, Lerakis S, Reddy VY, et al. Takotsubo cardiomyopathy in COVID-19. J Am Coll Cardiol 2020;76:628-9.
Desai HD, Jadeja DM, Sharma K. Takotsubo syndrome a rare entity in patients with COVID-19: An updated review of case-reports and case-series. Int J Cardiol Heart Vasc 2020;29:100604.
Jabri A, Kalra A, Kumar A, Alameh A, Adroja S, Bashir H, et al. Incidence of stress cardiomyopathy during the coronavirus disease 2019 pandemic. JAMA Netw Open 2020;3:e2014780.
Delmas C, Bouisset F, Lairez O. COVID-19 pandemic: No increase of takotsubo syndrome occurrence despite high-stress conditions. ESC Heart Fail 2020;7:2143-5.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
Sala S, Peretto G, De Luca G, Farina N, Campochiaro C, Tresoldi M, et al. Low prevalence of arrhythmias in clinically stable COVID-19 patients. Pacing Clin Electrophysiol 2020;43:891-3.
Bhatla A, Mayer MM, Adusumalli S, Hyman MC, Oh E, Tierney A, et al. COVID-19 and cardiac arrhythmias. Heart Rhythm 2020;17:1439-44.
Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai MC. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm 2020;17:1472-9.
Mercuro NJ, Yen CF, Shim DJ, Maher TR, McCoy CM, Zimetbaum PJ, et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:1036-41.
Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: Open label, randomised controlled trial. BMJ 2020;369:m1849.
Magagnoli J, Narendran S, Periera F, Cummings TH, Hardin JW, Sutton SS, et al. Outcomes of hydroxychloroquine usage in united states veterans hospitalized with COVID-19. Med (N Y) 2020;1:114-27.e3.
Misra S, Nath M, Hadda V, Vibha D. Efficacy of various treatment modalities for nCOV-2019: A systematic review and meta-analysis. Eur J Clin Invest 2020;50:e13383.
Hall DP, Jordan H, Alam S, Gillies MA. The impact of focused echocardiography using the Focused Intensive Care Echo protocol on the management of critically ill patients, and comparison with full echocardiographic studies by BSE-accredited sonographers. J Intensive Care Soc 2017;18:206-11.
Jain SS, Liu Q, Raikhelkar J, Fried J, Elias P, Poterucha TJ, et al. Indications for and Findings on Transthoracic Echocardiography in COVID-19. J Am Soc Echocardiogr 2020;33:1278-84.
Huang G, Vengerovsky A, Morris A, Town J, Carlbom D, Kwon Y. Development of a COVID-19 point-of-care ultrasound protocol. J Am Soc Echocardiogr 2020;33:903-5.
Anile A, Castiglione G, Zangara C, Calabro C, Vaccaro M, Sorbello M. COVID: The new ultrasound alphabet in SARS-CoV-2 era. Anesth Analg 2020;131:e232-e234.
Johri AM, Galen B, Kirkpatrick JN, Lanspa M, Mulvagh S, Thamman R. ASE statement on point-of-care ultrasound during the 2019 novel coronavirus pandemic. J Am Soc Echocardiogr 2020;33:670-3.
Kirkpatrick JN, Mitchell C, Taub C, Kort S, Hung J, Swaminathan M. ASE statement on protection of patients and echocardiography service providers during the 2019 novel coronavirus outbreak: Endorsed by the American College of Cardiology. J Am Soc Echocardiogr 2020;33:648-53.
Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-8.
Vieillard-Baron A, Charron C, Caille V, Belliard G, Page B, Jardin F. Prone positioning unloads the right ventricle in severe ARDS. Chest 2007;132:1440-6.
Bloomfield R, Noble DW, Sudlow A. Prone position for acute respiratory failure in adults. Cochrane Database Syst Rev 2015:CD008095.
Keyaerts E, Vijgen L, Chen L, Maes P, Hedenstierna G, Van Ranst M. Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. Int J Infect Dis 2004;8:223-6.
Gebisstorf F, Karam O, Wetterslev J, Afshari A. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev 2016:CD002787.
Fuller BM, Mohr NM, Skrupky L, Fowler S, Kollef MH, Carpenter CR. The use of inhaled prostaglandins in patients with ARDS: A systematic review and meta-analysis. Chest 2015;147:1510-22.
Chen L, Liu P, Gao H, Chao D, Wang F, Zhu Y, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: A rescue trial in Beijing. Clin Infect Dis 2004;39:1531-5.
Parikh R, Wilson C, Weinberg J, Gavin D, Murphy J, Reardon CC. Inhaled nitric oxide treatment in spontaneously breathing COVID-19 patients. Ther Adv Respir Dis. 2020;14:1753466620933510. doi:10.1177/1753466620933510.
Cardinale M, Esnault P, Cotte J, Cungi PJ, Goutorbe P. Effect of almitrine bismesylate and inhaled nitric oxide on oxygenation in COVID-19 acute respiratory distress syndrome. Anaesth Crit Care Pain Med 2020;39:471-2.
Tavazzi G, Marco P, Mongodi S, Dammassa V, Romito G, Mojoli F. Inhaled nitric oxide in patients admitted to intensive care unit with COVID-19 pneumonia. Crit Care 2020;24:508.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Hu Y, Sun J, Dai Z, Deng H, Li X, Huang Q, et al. Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis. J Clin Virol 2020;127:104371.
Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: A prospective cohort study. Lancet 2020;395:1763-70.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020;8:475-81.
Phua J, Weng L, Ling L, Egi M, Lim CM, Divatia JV, et al. Intensive care management of coronavirus disease 2019 (COVID-19): Challenges and recommendations. Lancet Respir Med 2020;8:506-17.
Alhazzani W, Moller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving sepsis campaign: Guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med 2020;46:854-87.
Michard F, Malbrain ML, Martin GS, Fumeaux T, Lobo S, Gonzalez F, et al. Haemodynamic monitoring and management in COVID-19 intensive care patients: An International survey. Anaesth Crit Care Pain Med 2020;39:563-9.
Peek GJ, Mugford M, Tiruvoopati R, Wilson A, Allen E, Thalanany MM et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): A multicenter randomized controlled trial. Lancet 2009;374:1351-63.
Extracorporeal Life Support Organization, International Summary. Available from: https://www.elso.org/Registry/Statistics/International Summary.aspx. [Last accessed on 2020 Sep 16].
Extracorporeal Life Support Organization, COVID-19 Registry. Available from: https://www.elso.org/Registry/FullCOVID19RegistryDashboard. aspx. [Last accessed on 2020 Sep 16].
De Piero ME, Lo Coco V, Taccone FS, Belliato M, Broman LM, Malfertheiner MV, et al. Has venoarterial ECMO been underutilized in COVID-19 patients? Innovations (Phila) 2020;15:317-21.
Haiduc AA, Alom S, Melamed N, Harky A. Role of extracorporeal membrane oxygenation in COVID-19: A systematic review. J Card Surg 2020;35:2679-87.
Kaushal M, Schwartz J, Gupta N, Im J, Leff J, Jakobleff WA, et al. Patient demographics and extracorporeal membranous oxygenation (ECMO)-related complications associated with survival to discharge or 30-day survival in adult patients receiving venoarterial (VA) and venovenous (VV) ECMO in a Quaternary Care Urban Center. J Cardiothorac Vasc Anesth 2019;33:910-7.
Prekker ME, Brunsvold ME, Bohman JK, Fischer G, Gram KL, Litell JM, et al. Regional planning for extracorporeal membrane oxygenation allocation during coronavirus disease 2019. Chest 2020;158:603-7.
Rajagopal K, Keller SP, Akkanti B, Bime C, Loyalka P, Cheema FH, et al. Advanced pulmonary and cardiac support of COVID-19 patients: Emerging recommendations from ASAIO - A “Living Working Document”. ASAIO J 2020;66:588-98.
Schmidt M, Burrell A, Roberts L, Bailey M, Sheldrake J, Rycus PT, et al. Predicting survival after ECMO for refractory cardiogenic shock: The survival after veno-arterial-ECMO (SAVE)-score. Eur Heart J 2015;36:2246-56.