A Case of COVID-19-Induced Delayed-Onset Myocarditis

Background

In December 2019, many instances of influenza-like disease were reported in Wuhan (China), prompting the designation of COVID-19 as the next pandemic (Siripanthong, Nazarian, Muser [1]). SARS-CoV-2 was the designation given to the newly discovered coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2). The majority of deaths occur as a result of acute respiratory distress or multiorgan failure, which combined account for up to 1% of all deaths [1]. According to a recent analysis, patients with COVID-19 had a nearly 16-fold increased risk of myocarditis compared to those without COVID-19 [2]. At least 47.8% of COVID-19 patients exhibited myocardial damage, and around 2% had confirmed myocarditis, according to autopsy findings [3]. Additionally, myocardial injury can result in irregular heartbeats and, in severe cases, cardiac shock. As a result, acute myocarditis must be recognized and treated appropriately in this situation.

We describe a patient with SARS-CoV-2 who developed myocarditis and acute heart failure at University Medical Center Ho Chi Minh City. A consent form for publication was signed by the patient.

Case Report

A 38-year-old woman with no known cardiac abnormalities presented with dyspnea after a 15-day fever, a 5-day dry cough course, and a positive fast COVID-19 test. Three days before admission, she began having breathing problems while walking and developed paroxysmal nocturnal dyspnea later in the day. She was then admitted to a nearby hospital and treated with vasopressor medicines for severe dyspnea and hypotension. The admission ECG indicated a sinus rhythm of 158 beats per minute, a QS wave in the inferior, V1, and V2 leads, with a ST elevated segment in the V1, V2, and V3 leads (Figure 1). The echocardiogram indicated a 40% ejection fraction and hypokinesis of the septal wall. Chest computed tomography showed ground-glass opacification lesions in both lungs with no signs of pulmonary artery embolism. The laboratory test results revealed elevated hs-troponin T concentration at 30 670 ng/L, D-dimer was 7103 ng/mL, CRP was 91 mg/L, LDH was 677 U/L, and a negative fast COVID-19 test. Treatment began with a 15 L/min oxygen supplement, noradrenaline (0.04 mcg/kg/min) and dobutaminee (5 mcg/kg/min). The diagnosis of acute anterior ST elevation myocardial infarction was made and the patient was then transferred to University Medical Center Ho Chi Minh City for primary PCI.

At the Emergency Department, the patient was conscious, with cold extremities, a weak 130 bpm pulse, 110/60 mmHg blood pressure, and a 96% oxygen saturation with a 15 L/m mask. The examination revealed moist coarse rales on both lungs. A routine chest radiograph showed evidence of peri-bronchial cuffing and an elevated cardiothoracic ratio (Figure 2). The ECG indicated a 120-bpm sinus rhythm, QS in V1–V3, D3, and aVF leads, elevated ST segment in V1–V4 leads, and a negative T wave in V2–V6 leads. The laboratory test results showed elevated hs-troponin T at 1716 ng/L, D-dimer was 10880 ng/mL, LDH was 782.80 U/L, ferritin was 7861 ng/mL, and IL-6 was 66.71 pg/mL. Her PCR SARS-CoV-2 test result was positive. We kept her on a 15 L/m oxygen mask, as well as noradrena-line, dobutamine, and intravenous furosemide. She was subsequently moved to the Interventional Cardiology Department, where she was diagnosed with COVID-19-related acute heart failure and severe pneumonia.

The patient remained conscious for the next 72 h, with a blood pressure ranging between 85/50 and 120/70 mmHg. Oxygen supplementation was continued nasally with a 5 L/m flow. A new chest X-ray was taken, and the indicators of congestion were considerably reduced. She was kept on dobutamine for a few days after that, with concomitant oral digoxin, and intravenous furosemide and spironolactone. We ordered a cardiac MRI (Figure 3), which revealed a mildly dilated left ventricle, a severe reduction in left ventricular ejection fraction (18%), hypokinesis of the septal region and left free ventricular wall, myocardial hyperintensity in the left free ventricular wall on T2W, and late gadolinium enhancement (LGE) of cardiac muscles with non-ischemic pattern. An angiography of the coronary arteries indicated no major stenoses in the main arteries. The final diagnosis was COVID-19-associated myocarditis aggravating severe acute heart failure.

We then started her on 100 mg sacubitril/valsartan and 2.5 mg bisoprolol every day. There was no fever or dyspnea, and her appetite was normal. Other laboratory test results, such as NT-proBNP, were within normal limits. Another echocardiogram was performed after dobutamine was terminated, which indicated no dilated chambers, no dyskinesis, a 57% left ventricular ejection fraction, and no significant abnormalities. Her rehabilitation was satisfactory, and a 2-week checkup found no irregularities.

Discussion

We describe the case of a 38-year-old woman who experienced myocarditis following COVID-19. Although the predominant clinical manifestation of COVID-19 is in the respiratory system, some patients experience cardiac symptoms [4]. COVID-19’s cardiac involvement in other coronavirus disorders is hypothesized to be caused by the direct viral impact on myocardial cells or indirect toxicity via systemic infection, inflammatory arteries, and the host’s hypersensitive reactivity [5].

Symptoms of COVID-19-associated myocarditis include tiredness, dyspnea, chest discomfort, tachycardia, sudden cardiac failure, and cardiac shock [1]. Ventricular failure can be utilized to diagnose acute myocarditis patients 2–3 weeks after viral infection, and this has been shown by 22 studies on COVID-19 myocarditis. Symptoms included fever, fatigue, and myalgia in 77% of articles (18%) [6]. In 12 instances, chest discomfort (50%), tachycardia (25%), and hypotension (50%) were recorded. Troponin, CRP, CK-MB, and NT-proBNP were also high in most cases. T wave inversion, tachycardia, and ST abnormalities were identified in 47% of patients (18%). In this research, 77% of patients exhibited worsened left ventricular function.

Endocardial biopsy should be used to confirm the diagnosis of definite myocarditis. In the absence of diagnostic instruments and experienced physicians to perform the biopsy, there are alternative approaches to increase the likelihood of correctly diagnosing myocarditis, such as cardiac MRI or echocardiography [1]. Myocarditis is characterized by ischemia-reperfusion injury (IRI) (MRI). With regard to the left ventricle of our patient, an MRI indicated slight dilatation, a low left ventricular ejection fraction (18%), hypokinesis in the septum and left free wall, late enhancement of cardiac muscles, and hyperintensity in the left free wall on T2W. All of these signs point to myocarditis. The Lake Louise criteria, which is typically used to diagnose suspected myocarditis, states that if at least 1 of the following criteria is positive in a patient with a high clinical suspicion of myocarditis, a CMR scan gives strong evidence for acute myocardial inflammation: T2-based marker for myocardial edema and T1-based marker for associated myocar-dial injury [7]. As previously described, our patient displayed myocardial edema on T2-turbo inversion recovery magnitude imaging (Figure 4) and a non-ischemic pattern on ventricular septum imaging (Figure 5), both of which are consistent with a high suspicion of myocarditis.

Myocarditis often manifests within a few hours or days after exposure to risk factors. In the case of novel, non-experimental agents such as the SARS-CoV-2 virus, case reports and series would provide a new perspective on the virus’s effect on cardiac cells in addition to other organs. Cytokine storm is the hallmark of the condition, resulting in endothelial inflammation and micro- and macrovascular thrombosis [8]. The term “delayed-onset myocarditis” was coined in a recent study [9]. The authors found 12 cases of myocarditis associated with COVID-19, with onset times ranging from several days to weeks and the longest period since SARS-CoV-2 infection being 1 month. Numerous factors can contribute to a delayed diagnosis or realization, spanning from the rarity of severe myocardial injuries to the limited diagnostic value of antibody tests, systolic dysfunction secondary to previous cardiac conditions, and the difficulty of conducting several investigations during the COVID-19 period. Although consensus has not been reached on the definition of “delayed-onset myocarditis”, recent findings indicate that COVID-19-related myocarditis that manifests several days to weeks later, as in our case, 13 days later, should be called “delayed-onset myocarditis”.

Throughout the diagnostic process for viral myocarditis, it is important to rule out the presence of bacteria. Aside from culture specimens, supporting variables for distinguishing between the 2 illnesses include the symptoms of presentation and laboratory test results. Throughout the course of treatment, our patient showed no indicators of acute infection, and procalcitonin levels and blood cultures were all negative throughout the process. The diagnosis for viral myocarditis became more likely when the SARS-CoV-2 PCR test revealed a positive result.

Using cardiac MRI, Inciardi et al identified COVID-19-related myocarditis by elevated troponin and impaired left ventricular function [5]. After 1 week of inotropic therapy, this patient fully recovered. Hu et al found a similar pattern in their investigation [10]. Due to hyperacute myocarditis and severe left ventricular failure, the 37-year-old patient required immediate surgery. After 3 weeks of corticosteroid and immunoglobulin treatments, he recovered completely. COVID-19-related myocarditis requires ICU care, oxygen, vasoconstrictor medications, and other bridging therapy [11]. In some cases, ECMO, intraaortic balloon pumps, and ventricular assist devices have been employed. Despite this, the European Society of Cardiology does not recommend immunoglobulins or corticosteroids for advanced myocarditis [1]. COVID-19 patients with early signs of hypoxia can be effectively managed with Remdesivir 200 mg on day 1 and 100 mg on the next 9 days [12]. Dexamethasone is also used in this group of COVID-19 patients, with a dose of 6 mg per day for up to 10 days [13]. COVID-19-related myocarditis can be successfully treated with inotropic medications, renin-angiotensin system inhibitors, and diuretics.

Conclusions

Myocarditis is a serious cardiac consequence of SARS-CoV-2 infection, made even more problematic by the virus’s proclivity for delayed onset. Although its incidence is unknown, it is one of the causes of cardiac mortality in patients with COVID-19. As a result, early discovery and comprehensive treatment, including cardiac support, are crucial. Due to the difficulty of performing endocardial biopsy during the COVID-19 pandemic, cardiac magnetic resonance imaging is a noninvasive approach that can be utilized to identify myocarditis.