Persistent heart symptoms in people with mild initial COVID-19

In a recent study published in the journal natural medicine, researchers performed serial cardiac assessments in people with mild onset coronavirus disease 2019 (COVID-19) who had no history of heart disease and significant comorbidities. They measured blood biomarkers of heart damage or dysfunction and performed cardiac magnetic resonance (CMR) imaging.

Studies have identified cardiac symptoms, including exercise intolerance, tachycardia, and atypical chest pain, as late-stage complications of COVID-19. In addition, studies have also documented subtle myocardial inflammatory changes, non-ischemic myocardial scarring, and pericarditis in young athletes soon after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). . However, the underlying pathophysiology leading to long-term cardiac symptoms in people with mild initial COVID-19 and no history of heart disease remains unclear.

​​​​​​​Study: Long-term heart disease in people with mild initial COVID-19 disease. Image Credit: Kateryna Kon / Shutterstock

About the study

In the current study, researchers evaluated individuals infected with SARS-CoV-2 and possible subclinical cardiac involvement, but no clinical indication for CMR imaging. They hypothesized that people with persistent heart symptoms after COVID-19 have different imaging and biomarker parameters than those without symptoms or controls without previous infection. The control group had a similar distribution in terms of age, sex and cardiovascular risk factors. Additionally, these biomarker parameters improved upon follow-up and were predictable from baseline parameters.

Trained clinical research staff used a standardized questionnaire to systematically screen all participants prior to enrollment, after which they underwent a baseline CMR imaging study.

Each eligible study participant completed a baseline visit between April 2020 and October 2021, i.e. four weeks after diagnosis of acute COVID-19 illness. Of these, only 346 participants completed a follow-up visit scheduled four months after the baseline visit. Researchers ensured that all participants were assessed at each visit to provide demographic data and undergo CMR imaging. Additionally, they assessed their heart symptoms, risk factors, resting blood pressure, heart rate, and blood parameters.

During the baseline visit, the researchers performed the acquisition of cardiac function, volumes, mass, myocardial mapping and scar imaging. Follow-up examinations included cardiac function, volumes, mass, and myocardial mapping.

Study results

The average age of the study cohort was 43.3 years and the average time from diagnosis of COVID-19 to baseline analysis was 109 days. At baseline, 73% of participants reported new onset of heart symptoms, but these symptoms were mild in 38% of them. The most common cardiac symptom in all study participants was dyspnea on exertion (62%), followed by palpitations (28%), chest pain (27%) and syncope (3%).

(a f) Late gadolinium imaging (A, DF) and native T1 (B) and T2 (C) mapping measurements of a 57-year-old woman assessed 201 days after COVID-19 infection. This person reported dyspnea, palpitations, and chest pain, worsening with minimal exertion. Late gadolinium-enhancement imaging visualizes regional accumulation of gadolinium-based contrast agent along the outer edge of the myocardial free wall (red arrows), as well as in the thickened pericardial layers, separated by small amounts of pericardial effusion (blue arrows).

At follow-up visits, 198 participants had heart symptoms, which persisted in 182 participants. Of the previously asymptomatic participants, 16 developed new symptoms, 78 remained asymptomatic, and 70 became asymptomatic. More women than men (67% vs. 46%) continued to experience heart symptoms.

CMR imaging techniques can detect diffuse inflammatory myocardial involvement (a non-specific measure of abnormal myocardium) by T1 mapping and myocardial water content by T2 mapping. Late gadolinium enhancement (LGE) indicated regional myocardial damage. On the other hand, the accumulation of gadolinium contrast agents made it possible to visualize thickened pericardial layers.

Participants with cardiac symptoms also had significantly higher myocardial native T1 mapping values. However, they had similar blood biomarkers, including C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Additionally, the authors noted that 64% of participants had detectable troponin. Only a few participants had structural heart disease. Overall, CMR imaging indicated inflammatory cardiac involvement after COVID-19 as a pathophysiological commonality, regardless of the expression of cardiac symptoms. However, since overall troponin levels were low and unrelated to the presence of cardiac symptoms, this suggested that cardiac symptoms manifested as increased myocardial wall stress and not necrosis.


Because the authors excluded people hospitalized after COVID-19 and those with abnormal lung function tests, they did not confuse the effects of severe illness and its increasing pathophysiology. Therefore, the present study provided direct insight into post-SARS-CoV-2 sequelae, its spectrum, and the subsequent course of cardiac symptoms after COVID-19.

Dyspnea on exertion appeared to be the most frequently experienced cardiac symptom. Participants who experienced it struggled to return to a previous level of fitness, limiting the physical aspects of their daily lives. More importantly, the study results challenged conventional definitions of viral myocarditis and established that deep myocardial injury or structural heart disease is not a prerequisite for the presence of cardiac symptoms. However, since subclinical cardiovascular inflammation is considered a risk factor in chronic autoimmune diseases, more research is needed to establish the long-term sequelae of post-COVID-19.​​​​​​​

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