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).