Combined Cardiac Fluorodeoxyglucose–Positron Emission Tomography/Magnetic Resonance Imaging Assessment of Myocardial Injury in Patients Who Recently Recovered From COVID-19

Abstract

IMPORTANCEAlthough myocardial injury can occur with acute COVID-19, there is limited understanding of changes with myocardial metabolism in recovered patients.OBJECTIVE To examine myocardial metabolic changes early after recovery from COVID-19 using fluorodeoxyglucose-positron emission tomography (PET) and associate these changes to abnormalities in cardiac magnetic resonance imaging (MRI)-based function and tissue characterization measures and inflammatory blood markers. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study took place at a single-center tertiary referral hospital system. A volunteer sample of adult patients within 3 months of a diagnosis of COVID-19 who responded to a mail invitation were recruited for cardiac PET/MRI and blood biomarker evaluation between November 2020 and June 2021.EXPOSURES Myocardial inflammation as determined by focal fluorodeoxyglucose (FDG) uptake on PET.MAIN OUTCOMES AND MEASURES Demographic characteristics, cardiac and inflammatory blood markers, and fasting combined cardiac 18 F-FDG PET/MRI imaging were obtained. All patients with focal FDG uptake at baseline returned for repeated PET/MRI and blood marker assessment 2 months later. RESULTSOf 47 included patients, 24 (51%) were female, and the mean (SD) age was 43 (13) years. The mean (SD) interval between COVID-19 diagnosis and PET/MRI was 67 (16) days. Most patients recovered at home during the acute infection (40 [85%]). Eight patients (17%) had focal FDG uptake on PET consistent with myocardial inflammation. Compared with those without FDG uptake, patients with focal FDG uptake had higher regional T2, T1, and extracellular volume (colocalizing with focal FDG uptake), higher prevalence of late gadolinium enhancement (6 of 8 [75%] vs 9 of 39 [23%], P = .009), lower left ventricular ejection fraction (mean [SD], 55% [4%] vs 62% [5%], P < .001), worse global longitudinal and circumferential strain (mean [SD], −16% [2%] vs −17% [2%], P = .02 and −18% [2%] vs −20% [2%], P = .047, respectively), and higher systemic inflammatory blood markers including interleukin 6, interleukin 8, and high-sensitivity C-reactive protein. Among patients with focal FDG uptake, PET/MRI, and inflammatory blood markers resolved or improved at follow-up performed a mean (SD) of 52 (17) days after baseline PET/MRI. CONCLUSIONS AND RELEVANCEIn this study of patients recently recovered from COVID-19, myocardial inflammation was identified on PET in a small proportion of patients, was associated with cardiac MRI abnormalities and elevated inflammatory blood markers at baseline, and improved at follow-up.

2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play

“… 160 In a separate study of 47 patients convalescing from COVID-19 (an average of 67 days after diagnosis), CMR and FDG-PET were performed. 19 Nineteen patients (40%) had ongoing cardiac symptoms, and 8 (17%) were noted to have myocardial inflammation by FDG-PET that correlated with CMR abnormalities and laboratory markers of inflammation. Although cardiac symptoms were approximately twice as common in individuals with abnormalities on FDG-PET, this was not statistically significant.…”

“… 18 At the same time, various abnormalities on CMR (and positron emission tomography [PET]) have been reported in those with COVID-19, even in the absence of cardiac symptoms. 11 , 19 Collectively, these findings challenge our understanding of viral-mediated myocardial (and pericardial) involvement 20 , 21 , 22 , 23 , 24 , 25 and raise questions about the pandemic’s long-term cardiovascular consequences.…”

“… 11 Similar findings have been observed in other CMR studies, with variable degrees of LGE and mapping abnormalities in those convalescing from COVID-19. 19 , 63 , 64 , 65 , 66 , 67 When performed in athletes as part of a RTP screening protocol, various abnormalities have been noted, with 0.6%-3% of subjects meeting modified Lake Louise criteria for clinical myocarditis. 43 , 68 , 69 Variability in observed findings with CMR likely reflect differences in the populations studied, timing relative to infection onset, and the specific imaging protocols and interpretations used.…”

Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

“…In one study of 47 non-hospitalized COVID-19 patients examined 67 ± 16 days after recovery, 40% of whom had cardiopulmonary PASC symptoms, focal fluorodeoxyglucose uptake by the heart on PET, consistent with myocardial inflammation, was found in only 17% ( 72 ). Initially elevated systemic inflammatory biomarkers, including IL-6, IL-8, and CRP, resolved a mean 52 ± 17 days after baseline testing ( 72 ). But evidence is accumulating for microvascular involvement in the setting of cardiopulmonary PASC.…”

Cardiovascular signatures of COVID-19 predict mortality and identify barrier stabilizing therapies

“…14 In this regard, while standard metrics including measures of cardiac damage (e.g., troponin values above the 99 th percentile), the extent of inflammatory activation (e.g., C-reactive protein expression), and cardiovascular imaging have elucidated the spectrum of COVID-19 complications, they have only modestly elucidated the risk of adverse in-hospital outcomes and often provide limited insight into disease mechanisms. 15 , 16 , 17 , 18 Current COVID-19 therapeutics focus on stemming aberrant immune responses and controlling viral reproduction (e.g., tocilizumab, dexamethasone, and remdesevir), which may neglect other key elements of the host response contributing to severe outcomes. 19 , 20 From this perspective, clinical data and autopsy studies revealing endotheliitis and thrombosis have raised the possibility that endothelial dysfunction, particularly alterations in vascular integrity and coagulative capacity, could be a driver of clinical outcomes.…”