Author: Dr Matthew Durie
Peer reviewers: Dr Vinodh Nanjayya, Dr Rose Hadden
Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China [published online ahead of print, 2020 Mar 25]. JAMA Cardiol. 2020;e200950. doi:10.1001/jamacardio.2020.0950
In a single centre, retrospective cohort of 416 patients with COVID-19 from Wuhan, China, cardiac injury (defined as an elevation of high-sensitivity troponin I [hs-TnI] beyond the 99th centile) was associated with an increased risk of in-hospital mortality.
During the study period (Jan 20- Feb 10, 2020), the authors found 416/786 (53%) COVID-19 patients with cardiac biomarker (hs-TnI and CK-MB) results. Of these, 82 (19.7%) had evidence of cardiac injury. These patients were older (median age [range] 74 [34-95] vs 60 [21-90] years) and more likely to have pre-existing cardiovascular disease, diabetes, cerebrovascular disease or malignancy. Although chest pain on admission was more likely in patients with positive cardiac biomarkers, (13.4% vs 0.9%) it is worth noting that patients with chest pain remained a minority in both groups.
Mortality in the cohort with cardiac injury was 51.2% vs 4.5% (p<0.001) in those without and the patients with myocardial injury had a shorter time to event (death or data censored on Feb 15, 2020). The patients with myocardial injury were more likely to meet ARDS criteria (58.5 % vs. 14.7%, p < 0.001) and require invasive/non-invasive ventilation (68.3% vs 8.1% p < 0.001). In a multivariate Cox regression analysis, only cardiac biomarker level (hazard ratio [HR] 4.26, 95% CI 1.92 to 9.49) and the presence of ARDS (HR 7.89, 95% CI 3.73 to 16.66) were independently associated with mortality. Mortality rose with degree of cardiac injury (supplementary data).
The findings of this study are consistent with that of a smaller cohort of 187 patients in Wuhan (10.1001/jamacardio.2020.1017) published in the same issue of JAMA Cardiology. This study by Guo et al. reported a mortality rate of 59.6% in those with elevated troponin-T vs 8.9% in those without (p < 0.001). Mortality was highest in those with known cardiovascular disease and elevated troponin-T (69.4%), followed by those with elevated troponin but no known cardiac disease (37.5%). Mortality in those with known cardiovascular disease and normal troponin-T was only marginally higher than those without cardiovascular disease and normal troponin-T (13.3 vs 7.6%). This study also showed a significant positive linear correlation of troponin-T level with the C-reactive protein level and N-terminal pro-brain natriuretic peptide suggesting that infection severity may be associated with myocardial injury.
Limitations of both studies include a retrospective design. In Shi et al., data was missing in 47% of patients with COVID-19, and these were excluded from the cohort, leading to potential bias. Neither study reported the incidence of myocardial infarction, arrhythmia or cardiomyopathy, nor the proportion of patients requiring inotropic support. It may be that any biomarker rise is associated with increased mortality, or that there is a threshold effect, above which risk is greater. Finally, the applicability to cohorts outside of China, and outside of a disease epicentre is unknown.
Together, these studies raise several questions. Large-scale epidemiological data from China has identified that patients with cardiovascular disease have a higher mortality rate from COVID-19 (10.5% vs 0.9% for those without any comorbid conditions, [China CDC, 2020]). It is not clear whether increased demand placed on the myocardium due to COVID-19 in patients with chronic cardiovascular disease leads to myocardial injury or the myocardial injury is due to the direct myocardial insult from SARS-CoV-2 or both. SARS-CoV-2 has been reported to cause myocarditis (10.1001/jamacardio.2020.1096) and in one small case series, cardiomyopathy was seen in a third of critically ill patients with COVID-19 (10.1001/jama.2020.4326). Angiotensin-converting enzyme 2 is thought to be key to the pathogenesis of SARS-CoV-2, and some have hypothesised that altered regulation of this system in patients with cardiovascular disease, and/or the use of renin-angiotensin system modulators as ACE inhibitors (ACEI) or angiotensin receptor blockers (ARB) may influence the severity of disease (10.1093/cid/ciaa329).
A prospective study, in which all admitted patients with COVID-19 undergo biomarker assessment at pre-defined time points would reduce bias and improve understanding the correlation between biomarker level, degree of cardiac injury and risk of death. Further data regarding the nature of pre-existing cardiovascular disease (ie. coronary artery disease vs. cardiomyopathy), ACEI or ARB use, inotropic support, serial echocardiographic assessment and the reason for death (ie. respiratory failure vs. cardiovascular collapse, treatment failure vs. treatment limitation) would also aid clinicians in risk prediction and identify opportunities for intervention.
- Arentz M, Yim E, Klaff L, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. Published online March 19, 2020. doi:10.1001/jama.2020.4326
- Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1017
- Hanff TC, Harhay MO, Brown TS, Cohen JB, Mohareb AM. Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System-a Call for Epidemiologic Investigations [published online ahead of print, 2020 Mar 26]. Clin Infect Dis. 2020;ciaa329. doi:10.1093/cid/ciaa329
- Inciardi RM, Lupi L, Zaccone G, et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1096
- Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China [published online ahead of print, 2020 Mar 25]. JAMA Cardiol. 2020;e200950. doi:10.1001/jamacardio.2020.0950
- The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus disease (COVID-19) — China, 2020. China CDC Weekly 2020;2:1-10. [Accessed 2 April 2020]. Available at URL: https://newsus.cgtn.com/news/files/COVID-19.pdf