Infusion therapy for cardiovascular diseases: the allowed limits
Authors: Netiazhenko V.Z. 
Published: July 2021

Background. Analysis of the mortality structure of patients with coronavirus disease (COVID-19) had found that 69.2 % of non-survivors had hypertension. Comorbid diabetes mellitus (31.8 %) and coronary heart disease (28.2 %) were also common. During pandemic, it is necessary to maintain optimal cardiovascular therapy by continuing to administer its main drugs (acetylsalicylic acid, statins, β-blockers, angiotensin-converting enzyme inhibitors – ACEI).

Objective. To describe infusion therapy (IT) for cerebrovascular and cardiovascular diseases in settings of the COVID-19 pandemic.

Materials and methods. Analysis of the literature on this topic.

Results and discussion. Although the spike proteins of the new coronavirus have the tropism to ACE-2, discontinuation of ACEI is unwarranted and may worsen the course of cardiovascular disease (CVD). Particular attention should be paid to the diagnosis of acute coronary syndrome (ACS) in COVID-19. In myocardial infarction, myocarditis or cardiomyopathy on the background of COVID-19, there is a moderate increase in troponin, brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide. An increase in D-dimers is a prognostic marker of the unfavorable prognosis. The algorithm for the ACS diagnosis includes the detection of typical clinical symptoms, ECG analysis, detection of disorders of local contractility of the left ventricle. Determination of troponin in patients without clinical manifestations of ACS with nonspecific manifestations of COVID-19 is not recommended. As for reperfusion therapy strategies, it is indicated in patients with symptoms of ischemia lasting >12 hours and a persistent increase in ST in two adjacent leads. In the absence of prior testing for coronavirus infection, all patients should be managed according to the tactics for COVID-positive patients. In non-STEMI, patients should be stratified according to their risk level (very high, high, moderate, low). In case of high risk, the early (<24 hours) invasive strategy is reasonable, in case of intermediate risk it is reasonable to consider noninvasive treatment. It should be remembered that the use of certain drugs for the treatment of COVID-19 (azithromycin, chloroquine, hydroxychloroquine, lopinavir, ritonavir) is associated with a risk of cardiotoxicity and life-threatening arrhythmias. Cardiotoxicity monitoring (determination of the corrected QT interval) should be performed before the start of therapy and then once in 5 days, primarily in risk groups (men >55 years, women >65 years and people with the CVD history). Lopinavir and ritonavir may also decrease the levels of active metabolites of clopidogrel and increase – of ticagrelor, so prasugrel is the antiplatelet drug of choice for COVID-19. Amiodarone also interacts with a large number of antiviral drugs. In turn, statins have multiple immunomodulatory effects including increase of the innate antiviral immune response. It is recommended to continue taking those statins that were prescribed earlier. If co-administration with lopinavir and ritonavir is required, the minimum dose of rosuvastatin or atorvastatin should be started. These antivirals are able to interact with calcium channel blockers and increase their concentration, so the dose of amlodipine and diltiazem can be reduced by 50 %. Endothelial dysfunction (ED) caused by a viral infection leads to the excessive thrombin formation and inhibition of fibrinolysis, increasing the risk of thrombotic complications. Nitric oxide (NO) plays an important role in counteracting ED. NO also inhibits the replication of the acute severe respiratory syndrome coronavirus and improves the survival of infected cells. L-arginine (Tivortin, “Yuria-Pharm”) is the only substrate for NO synthase that catalyzes the formation of NO in endothelial cells. According to the results of the own study, Tivortin helped to reduce the content of fibrinogen and soluble fibrin-monomer complexes, as well as to increase the thromboplastin time. Endothelium-dependent vasodilation also improved after administration of Tivortin. Tivorel (“Yuria-Pharm”) contains L-arginine and L-carnitine, which allows this drug to increase the survival of cardiomyocytes and endothelial cells, to restore homeostasis in the affected areas of the myocardium, and to counteract the progression of atherogenesis and thrombosis. In case of COVID-19, it is also advisable to prescribe edaravone (Ksavron, “Yuria-Pharm”), which neutralizes the cytokine storm, inhibits lipid peroxidation, protects against endothelial damage and, penetrating the blood-brain barrier, counteracts cerebral edema. In case of the need in IT, it is advisable to choose Reosorbilact (“Yuria-Pharm”), which has anti-shock, rheological, detoxifying, alkalizing and osmodiuretic effects. In hypovolemic shock and intracranial hemorrhage, the use of isotonic low-molecular-weight gelatin preparations (Volutenz, “Yuria-Pharm”) has been shown.

Conclusions. 1. In the absence of prior testing for coronavirus infection, all patients should be managed following the tactics for COVID-positive patients. 2. The use of azithromycin, chloroquine, hydroxychloroquine, lopinavir, ritonavir is associated with a risk of cardiotoxicity and life-threatening arrhythmias. 3. ED, caused by a viral infection, increases the risk of thrombotic complications. 4. It is reasonable to include the required solutions (Tivortin, Tivorel, Ksavron, Reosorbilact, Volutenz) into the combined IT of COVID-19 patients.