Acute changes in myocardial tissue characteristics during hospitalization in patients with COVID-19.

Background: Patients with a history of COVID-19 infection are reported to have cardiac abnormalities on cardiovascular magnetic resonance (CMR) during convalescence. However, it is unclear whether these abnormalities were present during the acute COVID-19 illness and how they may evolve over time. Methods: We prospectively recruited unvaccinated patients hospitalized with acute COVID-19 (n = 23), and compared them with matched outpatient controls without COVID-19 (n = 19) between May 2020 and May 2021. Only those without a past history of cardiac disease were recruited. We performed in-hospital CMR at a median of 3 days (IQR 1-7 days) after admission, and assessed cardiac function, edema and necrosis/fibrosis, using left and right ventricular ejection fraction (LVEF, RVEF), T1-mapping, T2 signal intensity ratio (T2SI), late gadolinium enhancement (LGE) and extracellular volume (ECV). Acute COVID-19 patients were invited for follow-up CMR and blood tests at 6 months. Results: The two cohorts were well matched in baseline clinical characteristics. Both had normal LVEF (62 ± 7 vs. 65 ± 6%), RVEF (60 ± 6 vs. 58 ± 6%), ECV (31 ± 3 vs. 31 ± 4%), and similar frequency of LGE abnormalities (16 vs. 14%; all p > 0.05). However, measures of acute myocardial edema (T1 and T2SI) were significantly higher in patients with acute COVID-19 when compared to controls (T1 = 1,217 ± 41 ms vs. 1,183 ± 22 ms; p = 0.002; T2SI = 1.48 ± 0.36 vs. 1.13 ± 0.09; p < 0.001). All COVID-19 patients who returned for follow up (n = 12) at 6 months had normal biventricular function, T1 and T2SI. Conclusion: Unvaccinated patients hospitalized for acute COVID-19 demonstrated CMR imaging evidence of acute myocardial edema, which normalized at 6 months, while biventricular function and scar burden were similar when compared to controls. Acute COVID-19 appears to induce acute myocardial edema in some patients, which resolves in convalescence, without significant impact on biventricular structure and function in the acute and short-term. Further studies with larger numbers are needed to confirm these findings.

Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study.

BACKGROUND: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. METHODS: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. RESULTS: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02). CONCLUSIONS: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: 58667920.

Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19.

BACKGROUND: The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. METHODS: Fifty-eight patients and thirty matched controls (single visit), recruited between 14th March - 25th May 2020, underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. FINDINGS: At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m2, P=0·005) decreased and RV ejection fraction (+3·2%, P=0·0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O2, although better, were abnormal in patients versus controls. 31% had reduced pV̇O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. INTERPRETATION: In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. FUNDING: The authors' work was supported by the NIHR Oxford Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE/18/3/34214), United Kingdom Research Innovation and Wellcome Trust. This project is part of a tier 3 study (C-MORE) within the collaborative research programme entitled PHOSP-COVID Post-hospitalization COVID-19 study: a national consortium to understand and improve long-term health outcomes, funded by the Medical Research Council and Department of Health and Social Care/National Institute for Health Research Grant (MR/V027859/1) ISRCTN number 10980107.

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

Adverse cardiovascular magnetic resonance phenotypes are associated with greater likelihood of incident coronavirus disease 2019: findings from the UK Biobank.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes. AIMS: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19. METHODS: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction. RESULTS: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity. DISCUSSION: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors. CONCLUSIONS: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.