The important findings of this study are:
1. Patients recovered from COVID-19 with cardiovascular comorbidities have significantly reduced echocardiographic LV-GLS values three months after initial infection, compared to those with cardiovascular comorbidities but without a history of COVID-19 and healthy individuals.
2. In patients with cardiovascular comorbidities and prior COVID-19, coronary artery disease history upon admission is associated with reduced LV-GLS values three months after initial infection.
3. No significant differences were observed in RV-FWS values between patients with cardiovascular comorbidities regardless of prior COVID-19 infection, albeit their RV-FWS values are significantly lower than healthy individuals.
4. No admission factors were associated with differences in RV-FWS values in recovered COVID-19 patients with cardiovascular comorbidities.
To our knowledge, this is the first study to study the long implications of COVID-19 infection in patients with cardiovascular comorbidities utilizing echocardiographic strain measurement. Previous studies have acknowledged the effects of COVID-19 on the cardiovascular system through various mechanisms such as endothelial inflammation, microvascular thrombosis, and initiation of organ failure.[2]
GLS measurement was reported to be a sensitive modality to detect subclinical myocardial dysfunction and potentially detect endomyocardial fibrosis. This is in line with findings reported by Baycan et al., whose investigation revealed that LV-GLS values were significantly reduced in severe COVID-19 patients compared to those with less severity. Of note, this study also reported no changes in left ventricular ejection fraction and FEVK patterns regardless of reduced LV-GLS.[7] This further proved the superiority of LV-GLS values in detecting subendocardial fibrosis. Myocardial fibrosis, one of the cardiac manifestations of long COVID-19 syndrome, is thought to be the result of aberrant immune responses that release systemic inflammatory cytokines such as IL-6 and TNF-a.3,36 Increased levels of angiotensin II in COVID-19 also further contribute to an increased inflammatory reaction, hypertension, and thrombosis.[8] Direct viral invasion into the myocardium could cause myocarditis leading to cardiac sequelae long after the acute period of infection. [9]
Contrary to the previous finding, this study found no significant differences in RV-FWS values in patients with cardiovascular comorbidities regardless of a history of COVID-19 infection. This shows that COVID-19 exerts no chronic effect on right ventricle function. It has been postulated that SARS-CoV-2 receptor distributions between two ventricles are not equivalent, with the lateral segment of the left cardiac ventricle having the most viral receptors.[10] However, our findings contrast with a study by Tryfou et al. which reported a significant decrease in RV-FWS values in severe COVID-19 subjects compared to the healthy population (− 18.17 ± − 3.32 vs. − 26.03 ± − 4.55%, p < 0.0001).[11] Nevertheless, it is important to note that the echocardiograph measurement in the study as mentioned above was conducted 30 days after admission, while our study conducted the measurement after 12 weeks. Another study by Lassen et al. reported that right ventricle function repair occurred two months after the initial COVID-19 infection, depicted by returned RV-FWS values to baseline; meanwhile, LV-GLS values remained the same.[12]
This study also found an association between having CAD as a comorbidity on admission and decreased LV-GLS values three months after COVID-19 admission. No previous evidence regarding this matter. However, a study by Xie et al. linked having ischemic heart disease during the acute period of COVID-19 infection with an increased risk of cardiovascular sequelae observed within a year.[13] Endothelial dysfunction plays a major role in the pathophysiology of COVID-19 and CAD. It may activate an inflammation cascade, which chronically may contribute to long COVID-19 syndrome. Moreover, conditions such as thromboembolism, systemic vasculitis, endothelial apoptosis, and multi-organ inflammation as part of long COVID-19 syndrome have been linked with endothelial dysfunction.[14] Other admission factors including DM, hypertension, dyslipidemia, obesity, smoking, levels of SpO2, PaO2, lactate, and CT values, were not associated with changes in GLS values. This is in line with several previous studies which reported no association between admission factors and changes in echocardiography parameters.[15,16] Minhas et al. found a relationship between DM and hypertension with abnormal GLS values.[17] This warrants further elucidation.
Our study has several limitations. Firstly, this is a single-center study with a relatively small sample size. Secondly, no baseline data regarding echocardiography strain values before COVID-19 infection. To minimize bias, a comparison was made with other demographic and risk-factors-matched cohorts of patients. Lastly, some admission factor variables data were significantly missing (e.g., CRP, d-dimer, NT-proBNP, troponin). Hence these could not be included in the multivariate analysis.