Myocardial Tissue Characterization in Cardiac Magnetic Resonance Studies of Patients Recovering From COVID‐19: A Meta‐Analysis

Figures

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  Figure 1. Forest plot for ratio of means of native T1 (COVID‐19/controls) for studies in adults, athletes, and children. The point estimate of the ratio of means for each study are shown as a squares with a horizontal line that indicates the extent of the study confidence interval. The gray, diamond‐shaped polygons summarize the random‐effects estimate for each subgroup, and for all studies at the bottom (corresponding to dashed vertical line). The horizontal length of each diamond denotes the confidence interval of the pooled result. The ratio of means estimates for T1 in the subgroups of middle‐aged to older adults, athletes, and children were significantly different (P=0.03). Numbers in superscript next to the “Study” column identify the corresponding published references. ROM indicates ratio of means.

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  Figure 2. Moderating effects of the time from diagnosis to cardiac magnetic resonance study. The duration of recovery from COVID‐19 infection was a moderator for the mean percent differences of T1 (%ΔT1) (A) and of T2 (%ΔT2) between patients with COVID‐19 and controls (B). For %ΔT1, age was an important additional moderator. There was a significant interaction effect between duration of recovery and age when both were included in a meta‐regression model for %ΔT1. The continuous line in (A) represents the predicted mean of %ΔT1 for the median age of 48 years in the adult cohorts. The dashed lines correspond to the confidence intervals. The size of the data points is proportional to the weights given in the meta‐regression analysis. The study by Bartoszek involved children with pediatric inflammatory multisystem syndrome, which may have contributed to a more abnormal native T1, compared with the other studies of children. CMR indicates cardiac magnetic resonance; %ΔT1, percent difference of the study‐level means of myocardial T1 in patients with COVID‐19 and controls; and %ΔT2, percent difference of the study‐level means of myocardial T2 in patients with COVID‐19 and controls.

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  Figure 3. Mean percent differences of native T1 (%ΔT1 in A) and T2 (%ΔT2 in B) were moderated by serum levels of cardiac troponin (log‐transformed) contemporaneous with the cardiac magnetic resonance imaging studies. The moderating effect of cardiac troponin blood serum levels was larger for %ΔT2 than %ΔT1, suggesting that T2 may be a more sensitive biomarker for acute myocardial injury in COVID‐19 than T1. cTnI indicates cardiac troponin I; cTnT, cardiac troponin T; %ΔT1, percent difference of the study‐level means of myocardial T1 in patients with COVID‐19 and controls; and %ΔT2, percent difference of the study‐level means of myocardial T2 in patients with COVID‐19 and controls.

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  Figure 4. In a meta‐regression model, the heterogeneity of the myocardial extracellular volume between studies was significantly moderated by the duration of recovery from COVID‐19 (log‐transformed; P=0.005) and the age at time of cardiac magnetic resonance study (P<0.001). The continuous line and dashed lines correspond to the predicted mean and its confidence interval with the age‐covariate in the meta‐regression model set to its median of 42.5 years. Without simultaneous adjustment by age, ECV did not decrease significantly with the duration of recovery. CMR indicates cardiac magnetic resonance; and ECV, myocardial extracellular volume.

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  Figure 5. Proportion of patients with late gadolinium enhancement in each study increased with median age. The proportion of patients with hypertension also had a significant moderating effect on LGE (P=0.008). If both age and the proportion of hypertension were simultaneously included in a meta‐regression model, only the moderating effect of hypertension remained significant (P=0.016). The duration of recovery had no significant moderating effect on the proportion of LGE. LGE proportions were logit‐transformed for fitting with an inverse‐normal linear regression model, illustrated by the solid line with 95% prediction limits as dashed lines. CMR indicates cardiac magnetic resonance; and LGE, late gadolinium enhancement.

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  Figure 6. Putative links between cardiac magnetic resonance myocardial tissue biomarkers and serum biomarkers in patients infected with COVID‐19 include C‐reactive protein and cardiac troponin, markers of systemic inflammation and myocardial injury, respectively. Diffuse inflammatory edema is expected to increase native myocardial T2 and T1 relaxation times. Myocardial injury leads to interstitial fibrosis, which can be detected by increases of ECV and native T1. Replacement fibrosis from myocardial necrosis is detected by focal late‐gadolinium enhancement. The expected increases of CMR biomarkers above the normal range are marked with a “+” sign. CKMB indicates creatine kinase myocardial band; CMR, cardiac magnetic resonance; ECV, myocardial extracellular volume; and LGE, late gadolinium enhancement.