CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 1, January–April 2023 AFRICA 19 19 could be mediated by ACE-2. Infection of the secretory cell population in the bronchial branches is not only affected by ACE-2 expression, potential co-factors such as proteases, TMPRSS2 and furin are also known to affect this process.7 However, it is not known how these proteases and SARS-CoV-2 affect heart cells and what kind of damage they cause. In a recent study in a patient with COVID-19, there were interstitial mononuclear inflammatory infiltrates in the heart tissue without significant myocardial injury. For this reason, they assumed that COVID-19 might not have directly harmed the heart.8 Due to the lack of sufficient data, the mechanism of cardiac injury in patients with COVID-19 remains unclear. In many studies, the high level of high-sensitivity troponin or the occurrence of new abnormalities in electrocardiography (ECG) or echocardiography have been defined as indicators of cardiac injury. Acute myocardial injury due to COVID-19 infection contributes to the development of cardiovascular complications such as acute coronary syndrome, myocarditis, cardiomyopathy, arrhythmia, cardiogenic shock or cardiac arrest. Ischaemic aetiologies of cardiac injury are acute coronary syndromes such as type I myocardial infarction (MI) resulting from plaque rupture or thrombosis, or type II MI developing as a result of supply–demand mismatch. Non-ischaemic conditions such as disseminated intravascular coagulopathy (DIC), myocarditis, stress-induced cardiomyopathy or cytokine storm may also be considered other causes of myocardial injury. Ischaemic increase in troponin levels in COVID-19 patients is caused by systemic and vascular inflammation with the development of prothrombotic endothelial dysfunction.9 Myocardial injury in COVID-19 patients may be caused by plaque rupture, coronary spasm, microthrombus or direct endothelial/vascular injury in addition to the mechanisms described.10 Increased troponin levels in COVID-19 patients may also be associated with deep-vein thrombosis caused by arterial or venous thrombosis, pulmonary thromboembolism, ischaemic stroke, MI and systemic arterial embolism.11-15 Mechanisms of cardiac injury are thought to be directly triggered and increased by viral action.14,15 In our study, the high daily troponin values in the 10-day follow up in COVID-19 patients were found to be associated with both mortality rate and the need for intensive care. It was observed that this value was higher in the group that died compared to the patients who needed intensive care. Similar to our study, COVID-19-related cardiac injury was reported to be between seven and 17% in hospitalised patients in China,6,16,17 remarkably, 22% of the patients in intensive care, and reaching 59% for the patients who died. When four studies of 374 patients were examined, it was seen that cardiac troponin I levels were significantly higher in patients with severe COVID-19 infection compared to a non-severe group.18 Mechanisms of cardiac injury can possibly be caused and amplified by direct viral action.14,15 In our study, a statistically significant relationship was shown between cardiac injury and mortality in patients with COVID19. This suggests that cardiac injury is related to the clinical consequences of COVID-19. Clinical deterioration occurs in patients developing cardiac injury. These patients were shown to have higher serum CRP, LDH and ferritin levels and more extensive pulmonary involvement, leading to a higher probability of the need for intensive care and a higher mortality rate in our study. One of the studies on acute COVID-19 infection found that reversible subclinical diastolic left ventricular disorder was common, even in those without underlying heart disease.19 It suggests that left ventricular dysfunction, seen in the acute phase of the infection, may be associated with cytokine storm syndrome. Systemic inflammation is at the forefront in COVID19 patients. This situation creates a serious life-threatening condition with the development of methaemoglobinaemia, haemodynamic instability and multiple organ failure. The distinctive feature of cytokine storm syndrome is an uncontrolled and dysfunctional immune response, involving the sustained activation and proliferation of lymphocytes and macrophages.19 It has been shown that COVID-19 patients admitted to the ICU had higher plasma cytokine levels [interleukins such as IL-2 IL-7 and IL-10, immunoglobulin G (IgG)-induced protein 10, granulocyte colony stimulating factor, tumour necrosis factoralpha, macrophage inflammatory protein 1-alpha, monocyte chemo-attractant protein-1].6 In our study, it was observed that CRP, ferritin and LDH values, which are indicators of inflammation, were higher in patients with cardiac injury. In comparison to the other parameters, remarkably high troponin I values during the cytokine storm were associated with statistically significant increases in the need for intensive care and higher mortality rates. Activation or increased release of these inflammatory cytokines can cause apoptosis or necrosis of myocardial cells. There is not sufficient evidence to establish a direct association between cardiac injury and cardiovascular co-morbidities. Table 6. Sensitivity, specificity, AUC, cut-off values of daily troponin I, D-dimer and other laboratory parameters and mortality rate Markers Sensitivity (%) Specificity (%) AUC Cut-off value p-value Troponin I 1 (pg/ml) 76.7 76.1 0.804 16.95 < 0.001 Troponin I 2 (pg/ml) 77.3 65.9 0.757 27.15 0.001 Troponin I 3 (pg/ml) 75 71.4 0.710 21.85 0.006 Troponin I 4 (pg/ml) 71.4 70.4 0.761 22.4 < 0.001 Troponin I 5 (pg/ml) 77.3 76 0.787 29.75 < 0.001 Troponin I 6 (pg/ml) 81 79.1 0.810 28.2 < 0.001 Troponin I 7 (pg/ml) 76.2 73.3 0.857 22.9 < 0.001 Troponin I 8 (pg/ml) 90.5 85.7 0.878 21.75 < 0.001 Troponin I 9 (pg/ml) 89.5 89.3 0.920 30.25 < 0.001 Troponin I 10 (pg/ml) 84.2 78.6 0.883 26.35 < 0.001 D-dimer 1 (ng/ml) 63.2 61.2 0.688 753 0.008 D-dimer 2 (ng/ml) 73.9 72.3 0.807 1172 < 0.001 D-dimer 3 (ng/ml) 68.4 67.2 0.742 1125 0.002 D-dimer 4 (ng/ml) 68.2 68.1 0.770 1012 < 0.001 D-dimer 5 (ng/ml) 69.6 68.9 0.740 949 0.001 D-dimer 6 (ng/ml) 69.6 65.9 0.718 997 0.004 D-dimer 7 (ng/ml) 65.2 63.9 0.707 938 0.008 D-dimer 8 (ng/ml) 71.4 69.7 0.710 1053 0.01 D-dimer 9 (ng/ml) 66.7 65.8 0.721 968 0.005 D-dimer 10 (ng/ml) 68.4 65.2 0.817 1106 < 0.001 CK (U/l) 61.8 59.7 0.668 79.5 0.003 CRP (mg/l) 62.9 62.3 0.676 51.55 0.01 Ferritin (ng/ml) 66.7 65.6 0.758 333 < 0.001 Urea (ng/ml) 67.6 66.3 0.693 39.5 0.001 Creatinine (mg/dl) 65.7 64.5 0.640 0.9 0.01 LDH (U/l) 76.3 75.3 0.823 317 < 0.001 AUC: area under the curve; CK: creatine kinase; CRP: C-reactive protein; LDH: lactate dehydrogenase.
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