Discussion:
The present prospective study evaluated the presence of myocardial injury and subclinical myocardial dysfunction using CMR in COVID-19 recovered subjects. The major findings of our study were the presence of abnormal CMR in 16 (53.3%) patients who had recently recovered from COVID-19. A significant proportion of patients had either raised T2 (40%) and/or LGE (33.3%). These findings persisted even on follow-up (13.3% of patients had abnormal CMR scan at six months). These findings are important as myocardial injury and subclinical cardiac involvement is not well elucidated and is often overlooked in patients who have recovered from COVID-19 infection. The authors have earlier reported sub-clinical left ventricular dysfunction in one-third of COVID-19 recovered subjects using speckle tracking echocardiography.
There is a limited data regarding the role of CMR in COVID-19 recovered patients. Previous studies have reported the prevalence of abnormal CMR findings in COVID-19 recovered subjects to be ranging between 1.4% and 78%.8-12 This marked degree of heterogeneity can be explained based on the differences in population studied (asymptomatic to severe COVID) and varying methods for detection of myocardial injury (conventional CMR sequences such as LGE and T2WI versus native T1 and T2 measurements). In a study from China, among 26 COVID-19 recovered subjects, myocardial edema was reported in 14 (54%) while 8 (31%) patients had LGE.9 However, the authors had included patients recovering from moderate or severe COVID-19 illness and utilized only conventional MR sequences such as LGE and T2WI for detection of myocardial damage. Previous small studies have reported variable myocardial inflammation in heterogenous group of patients10,11. Major limitation was either the absence of a control group or inclusion of large number of patients with various comorbidities such as diabetes mellitus, hypertension, coronary artery disease that may have otherwise contributed to the ongoing inflammation.10,11Our study addresses all the previous limitations including incorporation of both the conventional parameters such as LGE and T2WI as well as T1 and T2 mapping.
Findings on CMR in our study included the presence of myocardial edema and or LGE in more than 50% of the patients recovering from COVID-19 infection. Additionally, our results showed that the myocardial T1 and T2 values were higher in COVID-19 patients as compared to healthy controls. In our study, elevated T1 was reported in 53.3% while raised T2 was reported in 40% subjects. These findings are concurrent to those in previous studies 9-12. Prior studies have documented that elevated T2 values corresponds to areas of myocardial edema while elevated T1 values reflect development of myocardial interstitial fibrosis.16,17 These findings often reflect the inflammatory damage to the myocardium during active COVID-19 infection or an ongoing low-grade localized inflammation during the convalescent phase. Additionally, myocardial edema could be due to increased vascular permeability which is mediated by the endothelial angiotensin converting enzyme (ACE-2).18 In subjects with viral myocarditis, edema and LGE commonly occurs in the inferior and inferior-lateral wall with most of the lesions being patchy sub-epicardial in nature.19 Similar findings were observed in our study too where the predominant distribution of LGE was sub-epicardial involving inferior and infero-septal segments at base and mid-LV cavity level. Severity of the initial COVID-19 infection has an important bearing on findings on CMR. Severe COVID-19 patients with higher levels of inflammatory markers and greater immune mediated myocardial damage often have significantly higher T1 and T2 values as compared to those with mild and moderate COVID-19 infection.11
In our study, COVID-19 recovered patients had evidence of right ventricular (RV) dysfunction on CMR as compared to healthy controls. Previous studies using CMR and echocardiogram have reported RV dysfunction among COVID-19 survivors.4,9,20 Most of this has been attributed to development of pulmonary fibrosis following lung injury and ARDS in COVID-19 recovered subjects. This often results in increased pulmonary vascular
resistance, raised systolic pulmonary arterial pressure with an increased RV afterload along with hypoxia and oxidative stress.21,22
Though use of CMR as a routine investigation in COVID-19 recovered patients is not possible, but it did provide some important insights and serves as an important tool in detection of viral myocarditis and sub-clinical left ventricular dysfunction. Since, inflammation, LGE and fibrosis plays an important role in the development of dilated cardiomyopathy, it becomes all the more prudent to follow-up these patients with an abnormal baseline CMR. There is limited data regarding follow-up CMR imaging in recovered COVID-19 patients. The present study reported abnormal follow-up CMR in 4/16 (25%) with LGE persisting in 3 while one had a raised myocardial T2 value. Earlier reports showed complete resolution of both T2 abnormalities and LGE in 11/27 athletes (40.7%) while 16 athletes (59.3%) still had persistent LGE.23