Discussion
In post-mortem histopathology study, the incidence of myocarditis was 7.2% (among 277 cases of COVID-19) [5]. Although myocarditis seems not to be common among infected patients, its low prevalence could be due to the lack of cardiac MRI or biopsy in all patients. We presented eleven cases of clinically suspected myocarditis.
Sawalha et al. noted that the median age among fourteen COVID-19 patients was 50.4, and the male gender was predominance (58%) [6]. Moreover, in a meta-summary by Ho et al., the median age of patients with myocarditis was 55 years, and 69% of patients were male [7]. Craver et al. reported a 17-years-old male with COVID-19 manifestation who died due to cardiac arrest; the autopsy showed eosinophilic myocarditis, which there were no reasons for it except COVID-19 [8]. In our study, all patients were under 60-years-old, and the complications seem to be more severe in young patients. Six patients (50%) were under 30-years-old. Three cases died, and all of them were under 20-years-old. Therefore, cardiac monitoring in all age gradations is essential, not only in elderlies. In our study, the poor outcome in young patients could indicate that young age could be a risk factor for more severe cardiac involvement and myocarditis. Although, in contrast to the above studies, our results showed that the prevalence and disease severity were more in females (seven patients were female and two of them died), more studies with a bigger sample size are vital for finding the relation between gender and age with COVID-19 induced myocarditis.
Sawalha et al. noted reduced LVEF in 60% of patients with COVID-19 induced myocarditis [6]. Hypokinesis (global or regional; five patients), dilated vena cava (one patient), increased wall thickness (two patients), pericardial effusion (five patients), and tamponade (one patient) also were reported (among fourteen patients) [6]. Ho et al. reported (among nine myocarditis confirmed cases), six patients had abnormalities in echocardiography, including six cases of reduced LVEF (one severe reduced LVEF), two cases of pericardial effusion, three cases of left ventricle hypokinesia [7]. Overall, the most common finding was reduced left ventricle ejection fraction and LV dysfunction [6, 7, 9]. Right ventricle involvement seems not to be a common manifestation in COVID-19 induced myocarditis [6, 7]. The echocardiographic findings of our patients are consistent with the above findings. Findings include reduced LVEF (eleven patients), hypokinesia (four patients), pericardial effusion (three patients), increased wall thickness (two patients), and normal RV size and function (nine cases). Increased PAP (two patients), RV enlargement (three patients), and thrombosis (one patient) were found in lower incidence. As we can see through our results and previous studies, the most common findings could be reduced LVEF besides the normal RV size and function. RV involvement (case 2), indicating an underlying heart failure that decompensated due to COVID-19 infection. Furthermore, our results showed that the normal PAP indicates an acute event, leading to a better prognosis. It seems enhancing the LVEF within the first week of treatment could improve the prognosis. Moreover, the following up patients for three months showed improvement in LVEF.
Different studies and case-reports suggested several findings in the electrocardiogram; however, none of them was specific. The ECG findings could be without significant changes [10] or be associated with non-specific ST-segment (diffuse ST-segment elevation and depression) and T wave (T wave inversion) changes, and ventricular tachycardia [6, 7]. In our cases, the most common ECG findings include ST-segment changes (elevation and depression), T wave inversion, sinus tachycardia, and low voltage waves. Torsade de points (one patient) and ventricular tachycardia were other findings. So, it is important to pay attention to serial electrocardiograms. Although the ECG findings are not specific, they could inform the physicians of the impendent myocarditis in the case of any fluctuation.
Moreover, laboratory findings could be a cost-effective and easy way to predict the severity and outcome in patients with COVID-19. Gao et al. noted that the higher levels of pro-BNP could be associated with poor prognosis [11]. Sawalha et al. reported that the troponin was elevated in 91% of cases [6]. Ho et al. noted that the troponin and pro-BNP could be elevated or normal (few patients). However, they were elevated in most cases [7]. In our study, all patients had elevated levels of troponin and pro-BNP. High levels of pro-BNP were seen in patients who died. The increased inflammatory markers, including IL-6, CRP, ESR, and WBC were also observed. Moreover, significant and rapid (within a week) depression in levels of cardiac markers was observed in patients who were discharged in good condition. The results mentioned above emphasize the role of cardiac biomarkers as a good predictor factor for disease severity and outcome. The levels of markers got back to normal level during treatment and follow-up.
Patients with COVID-19 are at a higher risk for the hypercoagulable state in both arteries and veins. The thromboembolic disease could be a cause of sudden respiratory deterioration in these patients. The majority of patients have high levels of d-dimer that indicate sepsis-induced diffuse intravascular coagulation. Although the role of d-dimer as a predictive factor for thromboembolic diseases is unknown, it is proven that the elevated d-dimer is an independent risk factor for mortality [12]. Imaeda et al. reported a non-severe COVID-19 patient with ascending levels of d-dimer during admission, which echocardiography and contrast computed tomography revealed a clot in dilated left ventricle [13]. Rubartelli et al. reported a COVID-19 patient with multiple thromboses in the left ventricle; the patient had elevated d-dimer besides severe reduced LVEF (20%). Following up the patient for two months showed residual thrombosis in the left ventricle and LVEF of 16%. Moreover, the cardiac MRI showed the findings suggestive for previous recent myocarditis [14]. It seems that the occurring ventricular thrombosis due to COVID-19 is not a common finding. Our case with left ventricle thrombosis had elevated d-dimer and inflammatory markers beside the CMR suggestive for acute myocarditis. Also, echocardiography showed reduced LVEF (30-35%). Nevertheless, it is crucial to consider myocarditis in COVID-19 patients with ventricular thrombosis (especially left ventricle thrombosis).