SUMMARY

Severe Acute Respiratory Syndrome Coronavirus 2 is part of the Cononaviridae family and is the causative agent of the 2019 (Covid-19) Coronavirus pandemic declared by the World Health Organization in March, 2020. This virus has a high rate of transmission, affecting several individuals, and has caused thousands of deaths. The clinical manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 infection are not restricted only to the respiratory tract, and there is an express involvement of the cardiovascular system with a higher risk of death in this group. In such patients there is an overactivation of renin-angiotensin-aldosterone system, which promotes an increase in the expression of angiotensin-converting enzyme – 2 that acts as a receptor for the SPIKE protein expressed by the virus and enables the interaction between the host cell and Severe Acute Respiratory Syndrome Coronavirus 2. This process of infection causes a hyperinflammatory state that increases the inflammatory markers of cardiac injury. Hence, an adequate understanding and clinical guidance regarding the monitoring, and controlling the damage in these patients is essential to avoid worsening of their clinical condition and to prevent death.

Keywords:
SARS-CoV-2; Inflammation mediators; Shock, cardiogenic; Heart failure; Heart decompensation

INTRODUCTION

At the end of December, 2019, a series of cases of pneumonia caused by a new virus was reported in the Chinese city of Wuhan¹1. Costa IBSDS, Bittar CS, Rizk SI, Flho AEA, Santos KAQ, Machado TIV, et al. The heart and COVID-19: what cardiologists need to know. Arq Bras Cardiol. 2020;114(5):805-16. https://doi.org/10.36660/abc.20200279
https://doi.org/10.36660/abc.20200279... ^,22. Zu ZY, Jiang MD, Xu PP, Chen W, Ni QQ, Lu GM, et al. Coronavirus Disease 2019 (COVID-19): a perspective from China. Radiology. 2020;296(2):E15-25. https://doi.org/10.1148/radiol.2020200490
https://doi.org/10.1148/radiol.202020049... . The coronavirus 2 acute severe respiratory syndrome virus (SARS-CoV-2) has been identified as the etiological agent of coronavirus disease, officially named Covid-19 by the World Health Organization (WHO)¹1. Costa IBSDS, Bittar CS, Rizk SI, Flho AEA, Santos KAQ, Machado TIV, et al. The heart and COVID-19: what cardiologists need to know. Arq Bras Cardiol. 2020;114(5):805-16. https://doi.org/10.36660/abc.20200279
https://doi.org/10.36660/abc.20200279... . This virus is part of the Coronaviridae family, and SARS-CoV-2 was the seventh identified member of this family.

The new coronavirus has a high dissemination potential, since it is transmitted from person to person through saliva and through the nasopharyngeal route by direct transmission. It can also infect people indirectly due to its ability to survive on different types of surfaces, which increases the infectious potential of the virus³3. Ganatra SHS, Hammond SP, Nohria. A. The novel coronavirus disease (COVID-19) threat for patients with cardiovascular disease and cancer. JACC CardioOncol. 2020;2(2):350-355. https://doi.org/10.1016/j.jaccao.2020.03.001
https://doi.org/10.1016/j.jaccao.2020.03... ^,44. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Bondi-zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-71. https://doi.org/10.1016/j.jacc.2020.03.031
https://doi.org/10.1016/j.jacc.2020.03.0... .

In the beginning, Covid-19 was known only for its high potential to infect the respiratory system. However, as it spread throughout Asia and Europe, turning into a pandemic, it was observed that the disease goes beyond the manifestations of the respiratory tract. Reports emerged about its effects of variable severity on the cardiovascular system including cardiac dysfunction, acute cardiac injury, tachycardia, arrhythmias, and heart failure, which were further aggravated in individuals with a previous history of heart disease⁵5. Chan KW, Wong VT, Tang SCW. COVID-19: an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative chinese-western medicine for the management of 2019 novel coronavirus disease. Am J Chin Med. 2020;48(3):737-62. https://doi.org/10.1142/S0192415X20500378
https://doi.org/10.1142/S0192415X2050037... .

Hence, we conducted a literature review to understand how the cardiovascular system is affected by the SARS-CoV-2 infection, and to identify the main phenomena and biochemical markers associated with the inflammatory response and cardiovascular damage. We also focused on the interaction between the angiotensin-converting enzymes with ACE inhibitors (ACE ACE) and angiotensin II receptor blockers (ARB) in the individuals infected by SARS-CoV-2.

METHODS

Literature search for studies published between 2019 and 2020 involving patients affected by SARS-CoV-2 treated for cardiovascular complications.

In all, six studies were selected, two of which were case reports, three were retrospective cohort studies, and one was a case series. The data extraction was determined after analyzing the information available in the selected studies to understand the pathophysiological, clinical, and laboratory aspects of SARS-CoV-2. Additionally, we have grouped a series of clinical findings in Table 1, to provide information about the possible cardiovascular damage resulting from the clinical repercussions caused by Covid-19,

DISCUSSION

Relationship between Sars-Cov-2 and angiotensin 2 converting enzyme (ACE2)

The angiotensin-2 converting enzyme (ACE2) is mainly expressed in the lungs, more precisely in the alveolar epithelial cells of type II⁶6. Zhao Y, Zhao Z, Wang Y., Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ECA2, the putative receptor of Wuhan 2019-nCov. bioRxiv. 2020. https://doi.org/10.1101/2020.01.26.919985
https://doi.org/10.1101/2020.01.26.91998... . In patients with cardiovascular comorbidities such as hypertension, atherosclerosis, and congestive heart failure (CHF) that hyperactivate the renin-angiotensin system (RAS), overexpression of ACE2 occurs in the cardiac muscles⁷7. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90. https://doi.org/10.1007/s00134-020-05985-9
https://doi.org/10.1007/s00134-020-05985... .

This is crucial because SARS-CoV-2 has surface proteins with high affinity for ACE2 receptors, which are expressed in high rate in the cardiac muscle and lung tissue, making these organs more susceptible to infection. This phenomenon is exacerbated in individuals with a pre-existing cardiac disease because they have a higher concentration of ACE2 compared to that in healthy individuals⁷7. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90. https://doi.org/10.1007/s00134-020-05985-9
https://doi.org/10.1007/s00134-020-05985... , as shown in Figure 1. Thus, it is assumed that the cardiac and lung injury is more severe due to the high concentration of ACE2 in these organs⁷7. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90. https://doi.org/10.1007/s00134-020-05985-9
https://doi.org/10.1007/s00134-020-05985... ^,88. Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020;41(19):1798-1800. https://doi.org/10.1093/eurheartj/ehaa231
https://doi.org/10.1093/eurheartj/ehaa23... ^,99. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol. 2020;5(7):831-40. https://doi.org/10.1001/jamacardio.2020.1286
https://doi.org/10.1001/jamacardio.2020.... .

Some studies indicate that SARS-CoV-2 binds to ACE2 through one of its four structural proteins: spike protein (S), nucleocapsid protein (N), membrane protein (M), and the protein envelope⁷7. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90. https://doi.org/10.1007/s00134-020-05985-9
https://doi.org/10.1007/s00134-020-05985... , as shown in Figure 1. The viral protein that promotes interaction with the receptor of ACE2 is the S protein, and through this interaction it is able to infect the cells, and inactivate ACE2 causing lung injury, since the protective function provided by ACE2 is inhibited by the viral action. Thus, there is a displacement of angiotensin I to ACE type 1, causing an increase in the levels of angiotensin II and III. These have a harmful effect on the tissues, especially the cardiac tissue, because they have pro-apoptotic, pro-fibrotic, pro-inflammatory, and pro-oxidant activity, resulting in severe impairment of the cardiovascular function.

Cardiovascular diseases and SARS-CoV-2 infection

Individuals with cardiovascular diseases (CVD) are more susceptible to infection due to the presence of proteins that act as viral receptors; in addition, CVD itself makes the individual more likely to develop clinical upsetting due to the hyperinflammatory state¹⁰10. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457-60. https://doi.org/10.1007/s11427-020-1637-5
https://doi.org/10.1007/s11427-020-1637-... ^,1111. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020;92(6):595-601. https://doi.org/10.1002/jmv.25726
https://doi.org/10.1002/jmv.25726... ^,1212. Liu Y, Yang, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-74. https://doi.org/10.1007/s11427-020-1643-8
https://doi.org/10.1007/s11427-020-1643-... ^,1313. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. https://doi.org/10.1016/S2213-2600(20)30076-X
https://doi.org/10.1016/S2213-2600(20)30... as shown in Table 1. In individuals with hypertension with long-term intake of antihypertensives of the angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARB) class, the susceptibility to infection can increase and it can develop into a more aggressive form that leads to death⁴4. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Bondi-zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-71. https://doi.org/10.1016/j.jacc.2020.03.031
https://doi.org/10.1016/j.jacc.2020.03.0... .

Several clinical presentations resulting from cardiovascular damage in patients with Covid-19 have been observed. In a study that evaluated 138 individuals admitted for Covid-19, 16.7% presented arrhythmia and 7.2% presented acute cardiac injury¹²12. Liu Y, Yang, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-74. https://doi.org/10.1007/s11427-020-1643-8
https://doi.org/10.1007/s11427-020-1643-... . The study could not identify a single cause for these changes, and the clinical and laboratory phenomena were interpreted as multifactorial causes resulting from the hyperinflammatory state caused by SARS-CoV-2, as shown in Figure 2.

In the case report by Rente et al. (2020)¹⁵15. Rente A, Uezato Junior D, Uezato KMK. Coronavirus and the Heart. A case report on the evolution of COVID-19 associated with cardiological evolution. Coronavírus e o coração. Um relato de caso sobre a evolução da COVID-19 associado à evolução cardiológica. Arq Bras Cardiol. 2020;114(5):839-42. https://doi.org/10.36660/abc.20200263
https://doi.org/10.36660/abc.20200263... , a diabetic patient with Covid-19 presented with a severe cardiovascular involvement secondary to the inflammatory process. Computed Tomography (CT) revealed thickening of the myocardial wall with a slight increase in the cardiac area.

The study by Puntmann et al., (2020)¹⁶16. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73. https://doi.org/10.1001/jamacardio.2020.3557
https://doi.org/10.1001/jamacardio.2020.... , assessed the presence of myocardial injury in patients who had recently recovered from Covid-19, with a mean interval of 71 (64 - 92) days between diagnosis and cardiac magnetic resonance imaging (CMRI). Compared to individuals from a healthy control group, with patients presenting compatible risk factors with recently recovered patients from COVID-19, this last one had low left ventricular ejection fraction, high left ventricular volume, and left ventricular mass on native T1 and T2 MRI images. Of the 100 individuals in the study, 78 presented abnormal findings on CMRI, including 73 patients with myocardial elevation on native T1 and 60 on T2, in addition to delayed myocardial enhancement on gadolinium imaging in 32 and pericardial enhancement in 22 patients.

Increased native T1 values indicate the presence of diffuse myocardial fibrosis and/or edema, while native T2-weighted images are specific for edema. Thus, individuals with increased T1 and native T2-weighted sequences correspond to those with an active inflammatory process, while those with increased native T1 and normal native T2-weighted sequences no longer present with a hyperinflammatory state, but only diffuse residual damage to the myocardium¹⁶16. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73. https://doi.org/10.1001/jamacardio.2020.3557
https://doi.org/10.1001/jamacardio.2020.... . However, native T1-weighted images might be increased in a variety of diseases involving different pathways leading to diffuse fibrosis, such as SAH or genetic cardiomyopathies¹⁶16. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73. https://doi.org/10.1001/jamacardio.2020.3557
https://doi.org/10.1001/jamacardio.2020.... .

In a study conducted and published by the Chinese Center for Disease Prevention and Control, involving data from 44,672 individuals who were positive for SARS-CoV-2, the mortality rate was 2.3%. The majority of deaths was seen among individuals above 70 years of age or those who had some comorbidity that compromised the cardiac function, such as CVD, SAH, and diabetes mellitus (DM)¹⁷17. CDC, Centers for Disease Control and Prevention. Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145-51. https://doi.org/10.3760/cma.j.issn.0254-6450.2020.02.003
https://doi.org/10.3760/cma.j.issn.0254-... .

Other authors⁴4. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Bondi-zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-71. https://doi.org/10.1016/j.jacc.2020.03.031
https://doi.org/10.1016/j.jacc.2020.03.0... ^,1010. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457-60. https://doi.org/10.1007/s11427-020-1637-5
https://doi.org/10.1007/s11427-020-1637-... ^–1111. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020;92(6):595-601. https://doi.org/10.1002/jmv.25726
https://doi.org/10.1002/jmv.25726... reported venous thromboembolism in individuals infected by SARS-CoV-2, which is related to vascular inflammation, hypercoagulability, and endothelial dysfunction. In addition, cases of fulminant myocarditis and heart failure (HF) associated with SARS-CoV-2 infection were found¹⁸18 Ruan Q, Yang K, Wang W, Jiang L, Song J. Correction to: clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(6):1294-7. https://doi.org/10.1007/s00134-020-06028-z
https://doi.org/10.1007/s00134-020-06028... .

However, in a study conducted in Germany involving the autopsy of 39 individuals infected with SARS-CoV-2, it was demonstrated that the virus does not necessarily infect the cardiomyocytes, but the interstitial cells or macrophages that end up invading the myocardium. The inflammatory response with increased cytokines was seen in cases with a viral load greater than 1,000 copies²⁰20. Lindner D, Fitzek A, Bräuninger H, Aleshcheva G, Edler C, Meissner K, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol. 2020;5(11):1281-5. https://doi.org/10.1001/jamacardio.2020.3551
https://doi.org/10.1001/jamacardio.2020.... .

This indicates that the clinical manifestations of Covid-19 are not restricted to the lower and upper respiratory tract, and might have repercussions on other systems, such as the cardiovascular system. In some cases, it might not affect the respiratory system and compromise only the cardiac function, in which the patient with SARS-CoV-2 presents with myopericarditis with significant ventricular dysfunction, and absence of pulmonary manifestations¹⁹19. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):819-24. https://doi.org/10.1001/jamacardio.2020.1096
https://doi.org/10.1001/jamacardio.2020.... .

Severe cases of rapid evolution can still occur in patients infected by SARS-CoV-2 in which 20% evolved to severe cases with shock¹³13. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. https://doi.org/10.1016/S2213-2600(20)30076-X
https://doi.org/10.1016/S2213-2600(20)30... ^,2121. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. https://doi.org/10.1016/S0140-6736(20)30566-3
https://doi.org/10.1016/S0140-6736(20)30... .

Main biochemical markers of the impairment of cardiovascular function in patients infected with SARS-CoV-2

Direct injury to the heart occurs due to a systemic inflammatory response resulting from SARS-CoV-2 infection, in which high levels of cytokines involved with injury to the cardiovascular system are observed. Thus, there is an elevation of troponin I concomitant with the increase in other inflammatory markers such as D dimer, ferritin, IL-6, lactate dehydrogenase (LDH), C-reactive protein, procalcitonin, and lymphocyte count²²22. Strabelli TMV, Uip DE. COVID-19 and the heart. Arq Bras Cardiol. 2020;114(4):598-600. https://doi.org/10.36660/abc.20200209.
https://doi.org/10.36660/abc.20200209... ^,2323. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and cardiovascular disease. Circulation. 2020;141(20):1648-55. https://doi.org/10.1161/CIRCULATIONAHA.120.046941
https://doi.org/10.1161/CIRCULATIONAHA.1... ^,2424. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020 Jul 1;5(7):802-10. https://doi.org/10.1001/jamacardio.2020.0950
https://doi.org/10.1001/jamacardio.2020.... .

The increase in troponin I was indicated as a marker of severe Covid-19 infection compared to the non-serious form, in a meta-analysis of four studies including 341 patients. Malignant arrhythmias (ventricular tachycardia with degeneration to ventricular fibrillation or hemodynamic instability) were most frequent in individuals with high troponin I at 11.5% versus 5.2% in individuals in which it was not elevated²⁵25. Gho T, Fan Y, Chen M, Wu X, Zhang L, He T. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. https://doi.org/10.1001/jamacardio.2020.1017
https://doi.org/10.1001/jamacardio.2020.... .

In a study by SHI et al., (2020) which involved 416 patients admitted with Covid-19, the presence of myocardial injury was verified by increasing troponin I levels higher than the 99th percentile. This was associated with increased mortality and adult respiratory distress syndrome (ARDS), wherein the group of patients without cardiac injury had an average troponin I level of <0.006 μg/L (<0.006–0.009), while the group with cardiac injury had an average level of 0.19 μg/L (0.08–1.12)²⁵25. Gho T, Fan Y, Chen M, Wu X, Zhang L, He T. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. https://doi.org/10.1001/jamacardio.2020.1017
https://doi.org/10.1001/jamacardio.2020.... .

The mortality rate for individuals who developed Covid-19 without CVD involvement and with normal troponin levels was 7.6%²⁵25. Gho T, Fan Y, Chen M, Wu X, Zhang L, He T. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. https://doi.org/10.1001/jamacardio.2020.1017
https://doi.org/10.1001/jamacardio.2020.... . However, the mortality rate for patients affected by Covid-19 with CVD and troponin normal levels was 13.3%, and in those infected by SARS-CoV-2 without prior CVD and with high troponin levels, the mortality rate was 37%²⁵25. Gho T, Fan Y, Chen M, Wu X, Zhang L, He T. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. https://doi.org/10.1001/jamacardio.2020.1017
https://doi.org/10.1001/jamacardio.2020.... . In those who had prior CVD and were infected with SARS-CoV-2 with high troponin levels, the mortality rate was 69.4%²⁶26. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382(17):1653-9. https://doi.org/10.1056/NEJMsr2005760
https://doi.org/10.1056/NEJMsr2005760... . Furthermore, patients who presented with increased troponin needed more mechanical ventilation and had a higher incidence of ventricular arrhythmias²⁵25. Gho T, Fan Y, Chen M, Wu X, Zhang L, He T. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811-8. https://doi.org/10.1001/jamacardio.2020.1017
https://doi.org/10.1001/jamacardio.2020.... .

In a study by Puntmann et al. (2020)¹⁶16. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73. https://doi.org/10.1001/jamacardio.2020.3557
https://doi.org/10.1001/jamacardio.2020.... , high-sensitivity troponin T was correlated with native T1 (r=0.35; p<0.001) and native T2 mapping (r=0.22; p=0.03), showing significant results, which illustrates that during the active inflammatory process, troponin T levels are higher, being concordant with the findings of CMRI that reveals the presence of myocardial fibrosis and edema.

In another study, it was reported that patients who presented with D-dimer values higher than 1 μg/mL at admission had a higher risk of death, regardless of other laboratory parameters, as well as advanced age and high q-SOFA score¹⁹19. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):819-24. https://doi.org/10.1001/jamacardio.2020.1096
https://doi.org/10.1001/jamacardio.2020.... .

In addition to the inflammatory markers, there is a concomitant increase in the levels of BNP (cerebral natriuretic peptide) or NT-proBNP (cerebral N-terminal natriuretic propeptide). These proteins have biological effects such as diuresis, decreased peripheral vascular resistance, inhibition of SARS, and sympathetic activity. However, when there is an impairment of the cardiac function, the values of these markers of myocardial dysfunction are quite high in patients of Covid-19 with previous cardiac dysfunction, which makes them more likely to develop a severe impairment.

Do patients who use ACE inhibitors have a greater risk of death than those who do not?

It should be noted that although ACE2 and ACE have homologous structures, the activation sites are different; hence, inhibition of ACE would theoretically have no effect on the activity of ACE2. The function of ACE2 is to promote recovery of the ventricular activity in patients with harmful damage to the cardiomyocytes, through the inhibition of angiotensin II activity²⁶26. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382(17):1653-9. https://doi.org/10.1056/NEJMsr2005760
https://doi.org/10.1056/NEJMsr2005760... . However, some researchers cite that cardiac damage during infection by SARS-CoV-2 is due to angiotensin II, and one way to reduce this damage would be to administer recombinant ACE2 to stabilize the angiotensin II levels²⁶26. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382(17):1653-9. https://doi.org/10.1056/NEJMsr2005760
https://doi.org/10.1056/NEJMsr2005760... .

Given the fact there are few published studies, and numerous studies that are currently ongoing, the current recommendation of the Brazilian Society of Cardiology (2020)²⁷27. SBC, Sociedade Brasileira de Cardiologia. Informa: Infecção pelo Coronavírus 2019 (COVID-19); 2020. [cited on Mar 18, 2020]. Available from: http://www.cardiol.br/sbcinforma/2020/20200315-comunicado-coronavirus.html.
http://www.cardiol.br/sbcinforma/2020/20... , the European Society of Cardiology, and the American College of Cardiology (2020)²⁸28. ACC, American College of Cardiology. COVID-19 clinical guidance for the cardiovascular care team. Acc Clinical Bulletin; 2020 [cited on Jun, 10, 2020]. Available from https://www.acc.org/~/media/665AFA1E710B4B3293138D14BE8D1213.pdf
https://www.acc.org/~/media/665AFA1E710B... is that ACE inhibitors and ARB should not be discontinued in patients who are stable and have been taking these medications regularly, given the proven efficacy of these drugs for the treatment of SAH and HF. However, in specific cases in which the patient presents with Covid-19 in its severe form, it is necessary to evaluate the hemodynamic stability and renal function, to make a decision about continuation or discontinuation of antihypertensive therapy.

CONCLUSION

The SARS-CoV-2 virus has a potential to cause several clinical repercussions in the body of an infected individual. Patients with pre-existing cardiac diseases need special attention, since they are at a high risk of complications and death. A possible increase in the chronic repercussions due to the cardiac lesions caused by an hyperinflammatory process triggered by the infection that alters the cardiovascular homeostasis should be considered. It is still recommended that users of ACE inhibitor or ARB should not discontinue their antihypertensive treatment, unless they develop hemodynamic or renal instability, and the decision to change the antihypertensive drugs should be taken by the specialist. In view of these findings, it is essential to maintain measures of social distancing, hands hygiene, protecting the mouth and nose when coughing or sneezing, and continued use of masks.

REFERENCES

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