key: cord-333121-kt6t41ff authors: Kwenandar, Felix; Valeriani Japar, Karunia; Damay, Vika; Ivan Hariyanto, Timotius; Tanaka, Michael; Pratama Hardjito Lugito, Nata; Kurniawan, Andree title: Coronavirus Disease 2019 and Cardiovascular System: A Narrative Review date: 2020-06-03 journal: Int J Cardiol Heart Vasc DOI: 10.1016/j.ijcha.2020.100557 sha: doc_id: 333121 cord_uid: kt6t41ff At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management. The first cases of COVID-19 were reported in December 2019, originating in Wuhan, China, [1] and with its rapid spread, COVID-19 has now become a pandemic affecting 972,303 people across more than 170 countries around the world. [2] With the increasing number of confirmed cases and the accumulating clinical data, in addition to the common clinical presentation of respiratory failure caused by COVID-19, the cardiovascular manifestations induced by this viral infection has generated considerable concern. Huang et al. reported that 12% of patients with COVID-19 were diagnosed as having acute myocardial injury, showed by elevated levels of high-sensitive troponin I. [3] From other recent data, among 138 hospitalized patients with COVID-19, 16.7% had arrhythmias and 7.2% had acute myocardial injury. [4] These reports provides evidences of cardiac involvement as a possible late phenomenon of the viral respiratory infection. This process can be subclinical with few interstitial inflammatory cells, as reported by an autopsy study, [5] or can present with overt manifestations even without respiratory symptoms. [6] Not only has its number increased, cardiovascular manifestations were also associated with increased mortality among COVID-19 patients. Tao Guo et al. conducted a study on 187 patients with COVID-19, a total of 52 (27.8%) exhibited myocardial injury as demonstrated by elevation of TnT levels, and mortality was markedly higher in patients with elevated Troponin T (TnT)levels than in patients with normal TnT levels (59.6% vs 8.9%). Patients with underlying cardiovascular disease (CVD) and escalation of TnT levels had the highest mortality (69.44%) and the shortest survival term. [7] All of these data suggest that we must also put concern on cardiovascular manifestations in patients with COVID-19 infections. Therefore, here we review the cardiovascular system involvement in the course of COVID-19 infection. Current data from China and Italy as well in the US show that COVID-19 can present in relatively mild symptoms in affected individuals. However, some patients can suffer from very severe or even deadly conditions which require intensive care. Patients with more severe illness also at greater risk of mortality, particularly older individuals with underlying comorbidities including cardiovascular disease. [8, 9] Table 1 shows various risk factors from several studies that increases the likelihood of patients developing cardiovascular involvement of COVID-19, both with or without prior cardiovascular disease history. 8, 9, 10, 11, 12, 13 Risk Factors Author Results Hypertension Diabetes Shaw et al. 8 Kwong et These are the most common risk factors for developing cardiovascular involvement in COVID- Failure Cancer al. 9 Shi et al. 12 Oudit et al. 13 Troponin I or Troponin T. These factors increase risk of developing acute coronary syndrome during acute infections as seen on previous studies of influenza and other acute inflammatory conditions. Although the exact pathophysiological mechanism underlying myocardial injury caused by COVID-19 is not fully understood, a previous report showed that in 35% of the patients infected, the SARS-CoV genome was positively detected in the heart. [13] As shown in figure 1 , SARS-CoV binds to cells expressing appropriate viral receptors, particularly ACE2, which is abundant in the heart. [14] Murine models and human autopsy samples demonstrate that SARS-CoV can down-regulate myocardial and pulmonary ACE2 pathways, thereby mediating myocardial inflammation, lung edema, and acute respiratory failure. [8] This raises the possibility of direct damage of cardiomyocytes by the virus. SARS-CoV-2 may share the same mechanism with SARS-CoV because the 2 viruses are highly homologous in genome. [1, 15] Some recent studies from China address the unique marked affinity of SARS-CoV-2 for the host angiotensin-converting enzyme 2 (ACE2) receptor, raising the possibility of direct viral infection of vascular endothelium and myocardium. [12, 16] Furthermore, two experimental studies proved that SARS-CoV-2 uses ACE2, which is also expressed in the heart, as their receptor for entry into the cell. [17, 18] All of this data further suggested that SARS-CoV-2 can have a direct invasion mechanism to the heart. in oxygen supply, destabilization of coronary plaque, and micro thrombogenesis. [3] Chronic cardiovascular disease also may become unstable as a consequence of imbalance between infection-induce increased metabolic demand and reduced cardiac reserve. Acute coronary events in patients with COVID-19 may result from the significant increase in myocardial demand triggered by infections that precipitate myocardial injury or infarct, similar to type 2 myocardial infarction. [11] Patients with coronary artery disease and heart failure may be at particular risk as a result of coronary plaque rupture secondary to virally induced systemic inflammation, therefore, rigorous use of plaque stabilizing agents (aspirin and statins) has been suggested as a possible therapeutic strategy. [20] Coagulation abnormalities and arrhythmias are also seen in patients but the mechanism has yet to be known. Table 2 shows the potential mechanism of each cardiovascular manifestation in COVID-19 patients. Coronary heart disease (8%), Heart failure (23%), coagulopathy (19%) Significantly higher mortality rate The mainstay treatment of COVID-19 is generally symptomatic supportive treatment and intervention. Although currently no specific guidelines regarding the prevention and treatment of cardiovascular complications of COVID-19 have yet to be established, some things have to be taken into consideration when treating these patients. It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury. This measure is to provide prioritized treatment and more aggressive treatment strategies compared to those without such conditions. Other cardiac biomarkers such as NT-proBNP and electrocardiograms should be closely monitored for early warning and intervention. Many drugs used to treat COVID-19 patients may cause and exacerbate cardiac insufficiency, arrhythmia or other cardiovascular disorders. antivirals, this the possibility of these side effect must be taken into consideration. Close monitoring using ECG is to be done in patients treated with these drugs. With the likelihood of critically ill COVID-19 patients to develop thromboembolic disease, thrombo phylactic utilization is recommended. It is still unknown which drug is optimal for this purpose. While there is drug-drug interaction between some antiviral therapy and direct oral anticoagulant, low molecular heparins or unfractionated heparin with or without mechanical prophylaxis are suggested and preferred in acutely ill patients. [33] 5.4. Reperfusion therapy In this pandemic settings, the trend of reperfusion therapy intended for STEMI patients has shifted. Fibrinolytic therapy is more preferred than percutaneous coronary intervention (PCI) whenever the facilities and the infrastructure are compatible to deliver the procedure. Each institution should also develop protocols for appropriate triage, isolation, and treatment of COVID-19 patients who may need such interventions. [34] Harm associated with pursuing reperfusion therapy may exceed the anticipated gain in some COVID-19 patients, particularly if the primary competing illness portends a poor outcome. Underlying medical comorbidities appear to significantly impact COVID-19 severity and mortality Acknowledging the lack of data we have, it is therefore highly desirable that the mechanisms, the clinical presentation, the outcomes of various CV manifestations and the proper treatment in these patients be studied further. Finally, it is concluded that SARS-CoV-2 has a devastating impact on the cardiovascular system. 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Ahmanson/UCLA Adult Congenital Heart Center, 100 UCLA Medical Plaza Characteristics of and Important Lessons From the COVID-19) Outbreak in China: Summary of a Cases From the Chinese Center for Disease Control and Prevention No consent from patients was needed regarding this type of study because this study did not involve the process of collecting data from patients. No ethical approval was needed regarding this type of study because this study did not involve animal projects.