Spectrum of myocardial involvement in patients with COVID-19 – An echocardiography study

Introduction: Covid-19 patients can have both regional and global ventricular dysfunction. We aim to study the spectrum of myocardial involvement in Covid-19 patients on echocardiography. Methods: This is a single center, observational study where wall motion abnormality patterns were studied in Covid-19 patients along with global and regional longitudinal strain analysis (GLS). Results: 30 Covid-19 patients were included in the study, with a mean age of 35.3±6.4 years. Echocardiography revealed characteristic wall motion abnormality involving hypokinesia of anterolateral and apical segments, which produced an operculum like appearance in all patients. Strain derived ejection fraction(EF) was lower in 4 chamber as compared to 2 chamber indicating regional myocardial dysfunction. Reduced GLS values in presence of normal EF indicates global systolic function impairment. Endocardial effacement was also noted in these segments along with stretching of interventricular septum. Conclusion: Specific myocardial involvement pattern can be detected on echocardiography, thus helping in diagnosis of Covid myocarditis.


Results
A total of 30 patients were included in this study.The mean age of the study population was 35.3 ± 6.4 years (range 14-50 years) and females comprised 45% of the study population.Fever and chest pain were the most common symptoms noted (35% and 30% respectively) (Table 1).All patients had elevated biomarkers in the study population which shows the prevalent proinflammatory state in these patients (Table 1).Half of the study group had rhythm abnormalities in the form of sinus tachycardia (n = 10), sinus bradycardia (n = 3) and atrial fibrillation (n = 2).
Echocardiography revealed normal sized left ventricle and preserved systolic function with a mean M-mode ejection fraction (EF) of 58.3 ± 6.7% in the study group.However, strain derived auto EF was significantly lower in 4 chamber (4C) as compared to 2 chamber(2C) (58.7 ± 4.7% vs 55.5 ± 4.1%, P = 0.002).This points towards the presence of regional myocardial dysfunction in these patients.All patients had myocardial involvement in the form of hypokinesia predominantly involving anterolateral, apicoseptal and apicolateral segments as compared to other segments (Figure 1 A, Table 2).This characteristics wall motion abnormality produces an "operculum" like appearance over the other segments in the short axis view in systole (Figure 1B, Supplementary Video 1).Endothelial involvement was characterized by predominant involvement of interventricular septum (IVS) producing a characteristic jerky motion and stretching of IVS.
Global longitudinal strain (GLS) was reduced in 45% of the study population (Table 3).The anterior and apicoseptal segments had maximum reduction in longitudinal strain values amongst all patients.Peak systolic index was elevated in the involved segments indicating contractile abnormalities.A high degree of correlation was seen between regional longitudinal strain and segmental PSI, demonstrating impaired systolic contraction in the affected segments (r = 0.702, P = 0.001).No gender difference in GLS values were noted in the study population (P = 0.237).

Discussion
The current study intended to evaluate the spectrum of myocardial involvement in Covid-19 patients using echocardiography.Echocardiography revealed reduced global ventricular function as demonstrated by reduced GLS in about half of the study population.All patients had a characteristic wall motion abnormality producing an operculum like appearance in systolic frames.There was predominant involvement of anterior and apical segments as compared to other segments leading to reduced strain derived 4C ejection fraction.Endothelial involvement was noted along with elevated PSI values.To our knowledge, this is the first study which aims to study myocardial involvement pattern noted in Covid-19 patients.
Echocardiography is an invaluable and easily accessible tool for diagnosis of Covid-19 associated myocarditis.Echocardiographic findings in Covid-19 patients were evaluated in a large study conducted by Dweck et al. 6 Left ventricular abnormalities were noted in 39% patients whereas myocarditis was seen in 3%.In our cohort, patients had global ventricular dysfunction as evidenced by reduced GLS as well as regional predilection as evidenced by characteristic motion abnormalities noted in anterolateral and apical segments.Regional involvement in Covid-19 patients has been documented, ranging from basal and mid ventricular involvement to limited hypokinesia of inferior/inferoseptal segment. 8A systematic review of cardiac MRI in 199 Covid-19 patients revealed that global hypokinesia was the most common myocardial involvement pattern in these patients. 9On the contrary, our study patients had hypokinesia involving anterolateral and apical segments, giving the appearance of an operculum.This was coupled with effacement of the endocardial lining in these segments and stretching of IVS.This characteristic pattern noted in our patients is a unique one, which has not been described before in Covid-19 patients.Global longitudinal strain is a sensitive marker for myocardial dysfunction.Echocardiographic evaluation of hospitalized Covid-19 patients revealed that global longitudinal strain was reduced in patients with preserved LV ejection fraction, as noted in our patients. 10PSI analysis is also a surrogate marker for evaluation of ventricular dysfunction.Longitudinal strain values were reduced in the involved segments whereas PSI values were elevated, signifying regional myocardial dysfunction.Covid-19 infection has been postulated to cause coronary   12 Follow up studies need to be undertaken to determine the long-term impact of Covid-19 on myocardium, regarding the reversibility of initial changes.
The current study has its inherent limitations.The small sample size prohibits us from generalizing the results to the entire spectrum of Covid-19 patients.CMR imaging could not be performed in these patients due to lack of availability and financial constraints.As this was a single center hospital-based study, selection bias could have influenced the results, with sicker patients being excluded from the analysis.

Conclusion
Covid-19 patients have global as well as regional myocardial dysfunction.Specific echocardiographic pattern can help identify myocardial involvement in Covid-19 patients.Echocardiography should be considered the modality of choice in such situations.

Figure 1 .
Figure 1.(A).Short axis view(SAX) at mid ventricular level showing hypokinesia of anterior and anterolateral segment (denoted by blue arrows).(B).The characteristic wall motion abnormality produces an appearance of an operculum resting on top of the heart

Table 1 .
Baseline demographics of Covid-19 patients Age, Spo2 and troponins are presented as mean ± SD whereas time duration post Covid-19 is presented as median.Rest all values are expressed in percentages.Spo2 -Room air saturation.

Table 3 .
Global longitudinal strain and PSI assessment in the study population