Discussion
There are growing links between COVID-19 and cardiovascular morbidity (6). Although cardiac biomarkers such as high-sensitivity troponin appear as good predictors of prognosis in COVID-19 patients, data on echocardiographic abnormalities in these individuals are scarce (10). To the best of our knowledge, this is the first prospective health care workers cohort with a long-term follow-up about the impact of COVID-19 and its severity on echocardiographic indices. In this cohort follow-up report, we demonstrated that although LV and RV function did not change substantially over time in our cohort, various patterns of change were seen based on the early echocardiogram.
In both severe and non-severe COVID-19 severity groups, among systolic indices, 4DLVEDVI increased significantly, and in turn, 4DLVSVI and LVEF increased significantly in the follow-up echocardiogram which may indicate that in the early-time echocardiogram, patients had a higher pulse rate in order to improve oxygenation in response to diseased lung and after the lung recovery phase the heart rate slowed down and the stroke volume increased naturally in response. An echocardiographic study by Szekely et al. proved that patients with more COVID-19 clinical severity had significantly higher heart rates, and the stroke volume was reported non-significantly lower in the group with more severe COVID-19(6).
In the severe COVID-19 group, 4DLVGLS increased significantly, presenting that LV function is improved during the time, and the fall in the 4DLVGLS in the early echocardiogram might have been a consequence of the compensatory tachycardia mentioned above. It was expressed previously in the ECHOVID study that LVGLS was lower in patients hospitalized for COVID-19 compared to the healthy population (11). Moreover, it was shown in Croft et al. study that the LVGLS in hospitalized COVID-19 patients were lower than the assumed lower limit of the normal range. They hypothesized that the decrease in LVGLS associated with COVID-19 infection might be attributable to a combination of causes. Direct and indirect processes may cause myocardial damage. Viral invasion of the myocardium directly results in cardiomyocyte death and inflammation. Indirect mechanisms include cardiac stress caused by insults such as respiratory failure and hypoxemia, as well as cardiac inflammation in the presence of substantial systemic hyper inflammation (12-14).
In the non-severe COVID-19 group, of the diastolic indices, lateral E’ decreased significantly in the normal range, indicating the hyperactivity of LV in the early phase and relaxation of LV far after COVID-19 relief.
Global RV function indicators demonstrate hyperactivity of RV during the early COVID-19 recovery phase, as the 4DRVFAC in both non-severe and severe COVID-19 groups decreased significantly in the follow-up echocardiogram in comparison with the early echocardiogram while it still lies within normal range. Furthermore, RVFWGLS decreased significantly in the non-severe COVID-19 group. Among COVID-19 patients, a cytokine storm is prevalent. Cardiac myofibroblasts and cardiomyocytes are the major generators of various proinflammatory cytokines (15). As a result of systemic inflammation in COVID-19, the afterload increases (16); thus, the rise in RVFWGLS in early echocardiogram among the non-severe COVID-19 group demonstrates hyperactivity of the RV in order to overcome the risen afterload.
A study of the right ventricle in COVID-19 proved that Interleukin 6 (IL-6) serum levels are associated with respiratory dysfunction, ARDS, and poor clinical outcomes. The proinflammatory cytokine cascade may lead to RV dysfunction through adverse inotropic effects on the myocardium. Taken together, reduced RV contractility and abruptly high pulmonary vascular resistance due to ARDS and pulmonary embolism in COVID-19 may be fatal (15). The present study’s findings showed no RV failure amongst patients as it was the study of non-critically ill patients. It seems that in non-severe cases of COVID-19, in the absence of a cytokine storm healthy heart will increase its contractility during the acute phase. Although the higher afterload is previously suggested to fail RV, in this circumstance was not to an extent capable of failing the RV.
In a study of the prognostic value of RV strain, Li et al. stated that non-survivors had RV enlargement and dysfunction. The SARS-CoV-2 infection has been shown to generate both pulmonary and systemic inflammation, which may lead to RV failure via RV overload and direct cardiomyocyte injury. This research reveals that RVLS is an independent predictor of clinical outcomes in COVID-19 patients. Significantly, this index may have more predictive value than other echocardiographic markers. Therefore, individuals with COVID-19 should undergo an examination of RV function by investigating RVLS for risk stratification (17). In agreement with our findings, the WASE-COVID study, which provided participants with a follow-up echocardiogram, revealed an improvement in RVGLS in patients with impaired RV function, which may be solid evidence of advancement in lung function between the time of the baseline echocardiogram and the time of the follow-up study (18).
Although TAPSE altered non-significantly in none of the COVID-19 severity groups, 4DRVFAC decreased significantly on the follow-up echocardiogram in both severe and non-severe COVID-19 groups, suggesting the RV hyperactivity to improve oxygenation against the COVID-19 affected lung in the early phase recovery period. Paternoster et al., in a systematic review and meta-analysis, defined the RV dysfunction in COVID-19 patients based on the recommended cut-offs of echocardiographic guidelines that the cut-offs for RV failure determinants also assessed in this study were FAC <35%, TAPSE < 17 mm and, (PAP) > 25 mmHg. Thereafter, in line with the present study, none of the mentioned indices in either severe or non-severe groups had a significant alternation toward RV failure (7, 19, 20).