1348594 - Ex vivo CMR for myocardial tissue characterization in COVID-19 patient autopsies

COVID-19 elicits hyperinflammatory responses and has now been established to be a multisystem disease. Risk factors such as prior comorbidities, age and sex have been linked to cardiac involvement with unfavorable prognosis in patients with COVID-19. While prior viral epidemics (e.g. HIV) suggest that fibrotic processes are driving substrates for arrhythmogenesis, there is currently a paucity of autopsy studies to understand the pathogenesis of long-term sequalae including sudden cardiac death of severe COVID-19. In this study, we investigated the value of ex vivo CMR to identify and characterize changes in myocardial tissue composition in COVID-19 patient autopsies.

Methods:

Hearts were extracted from nine (6m/3f; age=59±13 y.o.) consecutive autopsied patients who died due to COVID-19 complications. Duration between death and CMR was 229±15 days, during which the patients’ hearts were kept in formalin. Myocardial specimens (3-12 samples/heart; 1-2 inches in each dimension) were extracted from different regions of the heart and placed in compartments of a plastic ice-cube tray covered with lid (Fig 1). The tissues were scanned on a GE 3T MRI scanner using T1 and T2 mapping sequences. The resulting images were analyzed to measure average T1 and T2 times for each subject. Medical and autopsy reports were accessed to retrieve relevant information.

Results:

The results are summarized in Table 1. The main cause of death in the subjects was acute bronchopneumonia that led to respiratory failure. Seven of the subjects had cardiovascular diseases and six of them had risk factors. The autopsy reports revealed the existence of myocardial fibrosis in 6 subjects and that one subject had necrotic cardiac myofibers and acute inflammation. Average T1 and T2 values in these seven subjects were higher than those in the rest of the subjects: 328±95ms and 52±5ms vs 271±34ms and 50±1ms, respectively, despite large variability in serum biomarkers (Table 1). The subject with acute inflammation had the highest T1 value of 533ms. It should be noted that the measured myocardium T1 values were significantly less than the range of values seen in in vivo scans due to the formalin effect on myocardium, as previously reported. However, as the hearts from all subjects were kept in formalin for almost the same duration, relative differences in T1 and T2 values could be adequately used to reflect changes in tissue composition, reflecting increased diffuse fibrosis and edema.

Conclusion:

In this study, we demonstrated the value of CMR for noninvasive myocardial tissue characterization in COVID-19 patients and compared the CMR results to findings from autopsy reports. This approach would allow for better understanding of COVID-19 pathophysiological effect on the heart, allow for longitudinal studies without the need for invasive endomyocardial biopsy, and allow for prompt medical intervention to save lives through risk stratification and prophylaxis from fatal cardiac complications.