**8. Biomarker evidence of myocardial injury in COVID-19**

A significant proportion of patients requiring hospitalisation, intensive therapy and the need for mechanical ventilation demonstrate elevation of biomarkers of cardiac injury [42–44, 50–55], namely cardiac troponin T (cTnT); cardiac troponin I (cTnI) and the natriuretic peptides N-terminal pro-B-type natriuretic peptide (NTproBNP) and the active hormone b-type natriuretic peptide (BNP).

The evidence of cardiac injury in COVID-19 is wide ranging and its association with mortality differs between studies. Li and collages performed a metaanalysis of 28 studies involving 4,189 individuals with COVID-19. Elevated cardiac biomarkers (cTn, creatine kinase-MB, myoglobin and NTproBNP were associated with the severe forms of infection compared to subjects with mild forms of the disease (**Figure 10**). In addition, those with evidence of COVID-19


#### **Figure 10.**

*Forest plot of cardiac biomarker standard mean difference between severe and less severe cases [source, Li et al. [53]].*

**137**

**Figure 11.**

*Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement…*

related cardiac injury was more likely to die than those without (summary risk

With the emergence of cTn elevation in severe COVID-19 disease, attention turned to its prognostic value. A study of 416 COVID-19 patients by Shi and colleagues found elevated cTnI in 1 in 5 presenting patients, and positive cTn patients were more likely to require non-invasive ventilation and develop acute respiratory distress syndrome or acute kidney injury. In addition, the mortality rate was 10-fold higher in those patients with evidence of myocardial injury [43]. This is consistent

Guo and colleagues reported 28% myocardial injury demonstrated by an elevated cTnT in 187 COVID-19 patients; with an in-hospital mortality of 60% and a higher incidence of mortality (69%) in those cTnT positive patients with underlying cardiovascular disease compared to 38% mortality in those without a cardiac

*Kaplan–Meier survival analysis of survival by (a) dichotomised cTnI over 40 days and by (b) cTnT quartiles* 

*over 30 days. [sources: Adapted from Cinar, et al. [61] and Almeida Jr. et al. [62] respectively].*

*DOI: http://dx.doi.org/10.5772/intechopen.98210*

with other studies.

history [55].

ratio 3.85 (95%CI 2.13 to 6.96, p = <0.001) [53].

*Coronavirus Disease: Epidemiology, Aetiology, Pathophysiology and Involvement… DOI: http://dx.doi.org/10.5772/intechopen.98210*

related cardiac injury was more likely to die than those without (summary risk ratio 3.85 (95%CI 2.13 to 6.96, p = <0.001) [53].

With the emergence of cTn elevation in severe COVID-19 disease, attention turned to its prognostic value. A study of 416 COVID-19 patients by Shi and colleagues found elevated cTnI in 1 in 5 presenting patients, and positive cTn patients were more likely to require non-invasive ventilation and develop acute respiratory distress syndrome or acute kidney injury. In addition, the mortality rate was 10-fold higher in those patients with evidence of myocardial injury [43]. This is consistent with other studies.

Guo and colleagues reported 28% myocardial injury demonstrated by an elevated cTnT in 187 COVID-19 patients; with an in-hospital mortality of 60% and a higher incidence of mortality (69%) in those cTnT positive patients with underlying cardiovascular disease compared to 38% mortality in those without a cardiac history [55].

#### **Figure 11.**

*Kaplan–Meier survival analysis of survival by (a) dichotomised cTnI over 40 days and by (b) cTnT quartiles over 30 days. [sources: Adapted from Cinar, et al. [61] and Almeida Jr. et al. [62] respectively].*

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

A significant proportion of patients requiring hospitalisation, intensive therapy and the need for mechanical ventilation demonstrate elevation of biomarkers of cardiac injury [42–44, 50–55], namely cardiac troponin T (cTnT); cardiac troponin I (cTnI) and the natriuretic peptides N-terminal pro-B-type natriuretic peptide

The evidence of cardiac injury in COVID-19 is wide ranging and its association with mortality differs between studies. Li and collages performed a metaanalysis of 28 studies involving 4,189 individuals with COVID-19. Elevated cardiac biomarkers (cTn, creatine kinase-MB, myoglobin and NTproBNP were associated with the severe forms of infection compared to subjects with mild forms of the disease (**Figure 10**). In addition, those with evidence of COVID-19

Haematological differentials along with abnormal clotting factors and elevated D-dimer result in haemostasis and thrombosis as evident of coronary microvascular disease. (3) Endothelial injury causing diffuse disruption to the vasculature in several organs including the heart. (4) Down regulation of ACE2 expression in cardiomyocytes and loss of the protective signalling pathway (5) Inflammatory and stress response causing plaque rupture in those subjects with active coronary artery disease (**Figure 9**).

**8. Biomarker evidence of myocardial injury in COVID-19**

(NTproBNP) and the active hormone b-type natriuretic peptide (BNP).

*Forest plot of cardiac biomarker standard mean difference between severe and less severe cases [source,* 

**136**

**Figure 10.**

*Li et al. [53]].*

Giustino and colleagues investigated 305 COVID-19 patients in 7 hospitals in New York City, USA and Milan, Italy. Patients exhibiting myocardial injury has elevated inflammatory markers, electrocardiographic abnormalities as well as transthoracic echocardiographic (TTE) evidence of left ventricular wall motion abnormalities, global left ventricular dysfunction, grade II or III left ventricular diastolic dysfunction, right ventricular dysfunction and pericardial effusion. In-hospital mortality was 32% in patients with myocardial damage and TT abnormalities, 19% with cTn positive myocardial injury only and 5% in those without evidence of cardiac involvement [56].

Lala and colleagues investigated the degree of myocardial injury in laboratoryconfirmed cases of COVID-19 and correlated findings with outcome [57]. 36% of 2,736 patients had an elevated cTnI (>0.03 ng/mL).

Seven studies have investigated the prognostic value of elevated cTn in COVID-19. Five utilised cTnI [57–61], one cTnT [62] and one with combined cTnT and cTnI from different institutions [63]. In all cases, an elevated cTn (cTnI, **Figure 11a**; cTnT **Figure 11b**) was associated with poor outcome; be it in-hospital mortality, or combined endpoints of all-cause mortality and need for mechanical ventilation. Lala and colleagues [57] identified even minor elevations in cTnI (0.03 to 0.09 ng/ml) were associated with mortality (Hazard ratio 1.75; 95%CI = 1.37 to 2.24, p < 0.001). Those with greater cTnI concentrations above 0.09 ng/L conferred greater risk (Hazard ratio 3.03, 95% CI 2.42 to 3.80).

The underlying pathological mechanisms resulting in elevation in cTn in patients with COVID-19 have not been fully elucidated. The vast majority of reported cardiovascular complications in COVID-19 refer to acute cardiac injury, with an incidence of 8–22%. Other mechanisms (% incidence) include pulmonary thrombosis and arterial/venous thromboembolism (16–49%); chronic heart failure (52% in non-survivors, 12% in survivors); Acute coronary syndromes (44% with ST segment elevation myocardial infarction [STEMI]); arrhythmia (17% overall; 44% vs. 9% in severe and mild cases respectively). A few case reports have demonstrated myocarditis and pericardial disease [64].
