COVID-19 has caused significant mortality and morbidity across the world. The most frequent cause of death is the severe acute respiratory syndrome which is sustained by a minority of patients. Acute respiratory infections are associated with elevated serum troponin levels, and linked to mortality even after recovery.
Troponin elevation, which occurs when the heart releases troponin (a protein) into the blood, can indicate a heart problem. High troponin levels are common in patients hospitalized with COVID-19, however, underlying causes are not yet clearly defined.
A team of researchers – including representatives from London’s Imperial College, University College London, and Royal Free London NHS Foundation Trust – used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. They set out to identify patterns of myocardial injury in patients who have been hospitalized with troponin-positive coronavirus disease 2019 (COVID-19), based on evaluation with CMR.
Study conducted across three NHS trusts
The study was conducted across six hospitals at three National Health Service (NHS) trusts:
- University College London Hospital (UCLH) NHS Foundation Trust
- Imperial College Healthcare NHS Trust (Hammersmith)
- Royal Free London NHS Foundation Trust
Every patient who was admitted with a COVID-19 diagnosis and had been discharged from hospitals in the trust up until 20th June, 2020, was reviewed. This time period represented the first wave of COVID-19. CMR scan appointments were offered to patients that had been discharged and who had abnormal high-sensitivity troponin (hsTnT >14 ng/L for Royal Free and UCLH; hsTnI >14 ng/L for females and >34 ng/L for males for Imperial). Exclusion criteria included patient refusal and acute coronary syndrome as the primary admitting diagnosis.
Historical and healthy control groups
A historical control group of 40 patients was taken from stable outpatients who had attended clinical CMR scans prior to 1st January, 2020. These patients were matched for age, gender, and presence or absence of diabetes, and hypertension. The purpose of this control group was to help assess whether COVID-19 infection is associated with diffuse elevation in native T1 or T2 mapping.
Another control group of 40 healthy volunteer scans, performed before 1st January, 2020, were analyzed to derive normal ranges for native T1 and T2. These volunteer participants had no symptoms, history of cardiovascular disease, or history of hypertension.
Clinical data, CMR study protocol, and statistical analysis
Clinical data reviewed included patients’ symptoms, medication histories, inpatient blood test results, chest radiographic imaging, electrocardiograms, and coronary angiography data.
The CMR protocol included standard long- and short-axis cine images and native T1 and T2 mapping of three long-axis and at least one mid-ventricular short-axis view. After 0.1 mmol/kg gadoterate meglumine (Royal Free and UCLH) or gadobutrol (Imperial), early gadolinium enhancement of a short-axis stack or three long-axis view images was performed to detect intracardiac thrombi. Patients with clinical indications and no contraindications to adenosine underwent quantitative stress perfusion mapping.
The study performed analyses using PSS Statistics, version 26 (IBM, Armonk, NY, USA), and data were examined for normality using the Shapiro–Wilk test.
148 recovered COVID-19 patients underwent CMR scans
From 820 troponin-positive patients who were discharged alive after being admitted to hospital with COVID-19, 148 recovered patients underwent CMR scans. This included 144 with gadolinium contrast and 76 with adenosine perfusion imaging. The mean age was 64 ± 12 years and the median length of inpatient hospital stay was nine days. Some 70% of patients were male, and 93% had typical early COVID-19 symptoms including at least one of fever, cough, dyspnoea, and myalgia. Some 32% needed an intensive care unit (ICU) for ventilatory support.
In terms of extracardiac findings, pleural effusions were present in 9% of patients and pericardial effusion in 5%. Cardiac structure and function findings included that the average left ventricular (LV) systolic function of the COVID-19 recovered group was normal and no different to matched and healthy volunteers. Left ventricular dysfunction was present in 11% of patients, with 9 cases due to myocardial infarction (of which 6 had a known history of ischemic heart disease).
Late gadolinium enhancement (LGE) was found in 49% of patients, with subendocardial or transmural LGE only in 16%, subepicardial LGE only in 19%, and mid-wall LGE only in 10%. A mixed pattern was found in 3% of patients, with LGE found in more than one distribution. The only type of LGE that was much more common in patients compared to matched controls was subepicardial LGE (5%, p = 0.018). In 6% of patients (nine individuals) inducible ischemia without LGE was present.
Myocarditis-pattern injury was seen to be present in 27% of patients, of whom 27 had healed myocarditis pattern. Four of these patients also had ischemia on stress imaging and three also had infarction. Regional wall motion abnormalities and LV dysfunction did not accompany myocarditis-pattern injury in any of the patients. No difference was found between mean native T1 in the remote myocardium in patients compared to matched controls, but compared to healthy controls, both had higher values.
The research showed that in approximately half of patients studied, myocardial injury during acute COVID-19 infection requiring acute hospital admission is associated with a CMR abnormality. Of these abnormalities, three patterns of injury were observed:
- Non-infarct, myocarditis-pattern injury in 27%
- Ischemic pathology in 22%
- Non-ischemic non-specific scar in 5%
The researchers believe that “the different patterns of abnormalities found suggest multiple possible underlying mechanisms including myocarditis (with limited extent and no functional consequence), MI (type 1 or type 2), and inducible myocardial ischemia”.
Bearing in mind that CMR is the most suitable non-invasive modality for the assessment of this type of unexplained troponin rise, the study concluded that results show that “ongoing localized myocardial inflammation, whilst less frequent than previously reported, remains present in a proportion” of patients who had survived severe COVID-19, and that this “may represent an emerging issue of clinical relevance”.