ABC | Volume 114, Nº5, May 2020

Review Article Askin et al. COVID-19 and cardiovascular diseases Arq Bras Cardiol. 2020; 114(5):817-822 cardiogenic shock. However, the rate of recovery and treatment is not yet at a systematic level. The exact mechanism of COVID-19’s cardiac involvement is still under investigation. Apotential mechanism is ACE2‑mediated direct myocardial involvement. It was observed that a myocardial infection due toACE2was also triggered by SARS-CoVpulmonary infection developed by in murine model.²² During the Toronto SARS epidemic, SARS-CoV viral RNA was detected in 35% of autopsies.²³ Other possible mechanisms of cardiac involvement related to 21 COVID-19 are cytokine storm induced by an imbalanced response between T helper cell subtypes and excess intracellular calcium inducing hypoxic cardiomyocyte apoptosis.¹² The role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers ACE2 is an ACE homolog that converts angiotensin II to angiotensin 1-7, thereby reducing vasoconstriction mediated by the renin-angiotensin system. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) use is common in CVD (HT, coronary artery disease [CAD], CHF, and DM). There are conflicting data from studies showing that these drugs increase ACE2 levels. 24,25 SARS-CoV-2 binds to ACE2 in order to gain entry into cells. However, ACE2 has a protective role against acute lung injury. In a murine model, binding of the SARS-CoV spike protein to ACE2 is the reason for ACE2 downregulation, increased angiotensin II levels, pulmonary vascular permeability, pulmonary edema, and impaired lung function. However, treatment with recombinant ACE2 26 and losartan 27 reduced the degree of lung injury. Studies are currently underway in patients with COVID-19 due to the potential to reduce lung damage with losartan. 28 Currently, no recommendations have been reported on the continuation or discontinuation of ACEi, ARB or other renin- angiotensin-aldosterone system (RAAS) antagonists. Due to the lack of evidence about the harms of RAAS antagonists, RAAS therapy will continue in COVID-19. 29 Peng et al. 30 reported that patients with COVID-19 and CVD had a higher risk of mortality. Critical patients also had low lymphocyte counts and high body mass index (BMI). ACEI/ARB usage does not affect morbidity and mortality in COVID-19 patients with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation, and thrombotic events. COVID-19 has caused great damage to the health and economic situation of China. How to deal with aortic diseases has become a serious problem in this situation. Rapid diagnosis, safe and effective transportation, implementation of the interventional procedure, protection of the vascular surgery team, postoperative management, and follow-up of such patients are urgent problems for patients. More studies are needed tominimize complications in vascular diseases, critical emergencies in vascular surgery and even manage routine vascular diseases with COVID-19. ³¹ Drug Therapy and COVID-19: Cardiovascular Effects Antiviral Therapy Ribavirin and remdesivir are two agents that bind to the active site on RNA-dependent RNA polymerases on SARS- CoV2.³² However, lopinavir/ritonavir inhibits the replication of the RNA virus and proves to have a synergistic effect with ribavirin.³³ Clinical trials are currently researching ribavirin and lopinavir/ritonavir for COVID19, and these antivirals were used as components of hepatitis C and HIV treatment for years. 34,35 Ribavirin does not characteristically have direct cardiovascular toxicity. However, lopinavir/ritonavir may cause QT prolongation in patients with long QT. 35 Both ribavirin and lopinavir/ritonavir have the potential to affect the anticoagulant dose. 36 Ribavirin affects warfarin doses. It may be necessary to avoid CYP3A-mediated drugs such as rivaroxaban and apixaban with lopinavir/ritonavir treatment. 37,38 Lopinavir/ritonavir may also influence the activity of P2P12 inhibitors through CYP3A4 inhibition, lead to decreased serum concentrations of clopidogrel and prasugrel active metabolites, and increase serum concentrations of ticagrelor. In the United States and Canada, it is not recommended to use such drugs with ticagrelor due to the excessive risk of bleeding. 39,40 On the contrary, clopidogrel may not always provide adequate platelet inhibition in the simultaneous administration of lopinavir/ritonavir. 41,42 Prasugrel may be preferable to other P2Y12 inhibitors during lopinavir/ritonavir therapy. However, it is contraindicated in cases such as a history of stroke or TIA, low BMI, or active pathological bleeding. A test- guided approach with alternative antiplatelet agents may be considered. Details about switching P2Y12 inhibitors have already been determined. 43 cangrelor metabolism is independent of hepatic function, so drug interaction is not expected. 44 HMG-CoA reductase inhibitors (statins) also have the potential to interact with the lopinavir/ritonavir combination. Co-administration may cause myopathy due to high statin levels. Lovastatin and simvastatin are contraindicated for co-administration with lopinavir/ritonavir due to the risk of rhabdomyolysis. Other statins, including atorvastatin and rosuvastatin, should be administered in the lowest possible dose, and they should not exceed the maximum dose indicated with lopinavir/ritonavir. 35 Remdesivir is a research drug previously evaluated during the Ebola epidemic and currently studied in patients with COVID-19. Although extensive cardiovascular toxicities and drug interactions have not yet been reported, preliminary assessment of this drug during the Ebola epidemic noted the development of hypotension and subsequent cardiac arrest in one patient (out of a total of 175 patients). 45 Other therapies In addition to antiviral drugs, a large number of immunomodulators and secondary drugs are being investigated to prevent complications from COVID-19. Chloroquine, used as an antimalarial agent, blocks virus infection by increasing the endosomal pH required for virus/cell fusion and stops SARS- CoV2 activity in vitro. 46,47 Chloroquine and hydroxychloroquine act toxic to cardiac myocytes. Risk factors include prolonged exposure (> 3 months), higher weight‑based dose, pre-existing heart disease, and kidney failure. Chloroquine cardiac toxicity occurs as restrictive or dilated cardiomyopathy or conduction abnormalities that are thought to be due to intracellular 819