Cardiovascular magnetic resonance imaging and spectroscopy in clinical long-COVID-19 syndrome: a prospective case-control study

Abstract

Background: The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (³¹P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism.

Methods: Prospective case-control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent ³¹P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission.

Results: Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T₁ mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics.

Conclusions: In this prospective case-control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Keywords: 31-phosphorus magnetic resonance spectroscopy; COVID-19; Cardiovascular magnetic resonance imaging; LONG COVID; Post-COVID-19 syndrome.

Fig. 1

Study flow chart of participant recruitment

Fig. 2

Study CMR protocol. Multi-parametric cardiovascular magnetic resonance included ³¹P-CMR spectroscopy (CMRS) (20 min). This was followed by CMR, which included cine imaging to assess left ventricular (LV) volumes, mass and ejection fraction and strain parameters; native pre-contrast and native post contrast T1 mapping for measuring T1 values and extracellular volume fraction; adenosine stress perfusion imaging for assessment of myocardial rest and stress blood flow and myocardial perfusion reserve; late gadolinium enhancement (LGE) imaging for measuring myocardial scar percentage

Fig. 3

Timeline and investigations undertaken in the long COVID-19 patient with evidence of myocarditis on CMR. This patient presented first to the emergency department 36 days after diagnosis of COVID-19 with chest pain. 12-lead electrocardiogram (ECG) and cardiac biomarkers were all normal. On second presentation to the emergency department at 125 days post diagnosis, ECG and cardiac biomarkers were again normal. CMR during the study visit remonstrated evidence of prior myocarditis with subepicardial late gadolinium hyperenhancement (LGE) in the lateral wall at basal to mid-ventricular level (red arrows) in the short-axis (SAx) view (left) and 4 chamber (4Ch) view (right). 31^P-CMRS demonstrated PCR/ATP ratio of 1.87. Other parameters were as follows: LV end-diastolic volume (LVEDV) 146 ml, LV ejection fraction (LVEF) 64%, right ventricular (RV) end diastolic volume (RVEDV) 151 ml, RV ejection fraction (RVEF) 68%, native T1 1221 ms, extracellular volume fraction (ECV) 21%, T2 43 ms, global longitudinal strain (GLS) -11.3 and myocardial perfusion reserve (MPR) 3.9