Acute symptomatic COVID-19 myocarditis: Case series

Abstract

Background

Coronavirus disease 2019 COVID-19 still remains a major cause of morbidity and mortality worldwide, mainly due to Acute Respiratory Distress Syndrome (ARDS). Nevertheless, other extra-pulmonary pathological aspects of COVID-19, notably cardiovascular, were disclosed as the global understanding of the pathogen agent advanced.

Objectives

To detect and evaluate acute myocarditis in patients with active and symptomatic COVID-19 infection.

Materials and methods

In this prospective analysis, patients presented with active COVID-19 illness and meeting the inclusion criteria were identified at the University Hospital Complex of Rabat between January and September 2021.

Results

Fifteen patients (8 males and 7 females) aged from 17 to 52 were included during the analysis period, the average delay between the confirmation of COVID-19 and the onset of myocarditis symptomatology was 17 days. The symptomatology was dominated by chest pain, unexplained cardiogenic shock and palpitations. The ECG showed essentially diffuse repolarization disorders. The inflammatory markers were significantly disturbed with an elevation of ultra-sensitive cardiac troponin I in all patients. Cardiac MRI showed impaired global longitudinal strain (GLS) myocardial edema, early and late subepicardial Gadolinium enhancement, compared to the control group (p < 0,01).

Conclusion

Cardiac involvement was detected in a proportion of patients with active COVID-19. Age, gender, clinical and electrical presentations didn't seem to influence the diagnosis. Cardiac MRI played an essential role for detecting and evaluating active myocarditis. Patients who presented myocardial injury had to have a longer follow-up as current understanding of long-term prognosis is still lacking.

1. Introduction

Since the beginning of 2020, the world has been ravaged by a Coronavirus disease 2019 pandemic. COVID-19 is an emerging infectious disease that appeared in central China, caused by the new strain of coronavirus SARS-CoV-2.¹ To date, COVID-19 has been responsible for more than 600 million confirmed cases and more than six million deaths, mostly by acute respiratory distress syndrome.²

With the perpetuation of the current epidemiological situation of COVID-19, several extra-pulmonary aspects of this disease, especially cardiovascular, were revealed over time.³ Yet current information about acute myocarditis occurring in the course of SARS-CoV-2 infection remains limited.

To better understand the clinical presentations, type of cardiovascular sequelae, evolving and therapeutic aspects of acute myocarditis occurring in the course on SARS-CoV-2 infection, we proactively examined patients with a confirmed recent COVID-19 infection using serological markers of cardiac injury and cardiac magnetic resonance (CMR).

2. Materials and methods

2.1. Study design and participants

A prospective audit of consecutive patients at Hospital Ibn Sina, Rabat, Morocco was performed. Participants with confirmed COVID-19 by reverse transcription polymerase chain reaction (PCR) on swab test and of the upper respiratory tract and CT scans, without any modifiable risk factors for cardiovascular disease, structural heart disease, and mechanical ventilatory support were included during the recruitment period from January 2021 to September 2021. Comparisons were made with age-matched, sex-matched control group of normotensive adults, with no anterior medical history or cardiac medications. The institutional ethics commission approved the study and all participants gave their consent to participate and share the results of this study.

Patients had a clinical suspicion for COVID-19 myocarditis with signs of acute myocardial injury (compatible clinical presentation, elevated troponin levels and electrocardiographic modifications). Acute coronary syndromes (ACS) were excluded with cardiac catheterization. Cardiac MRI was performed at 1.5 T in all patients, the protocols included multiplanar cine images, T2-weighted imaging and late gadolinium enhancement (LGE) imaging.

2.2. Statistical analysis

all data were processed by EPI INFO 7 software. The results were expressed as mean ± standard deviation for the quantitative variables and in percentage for the qualitative variables. Continuous variables between the two groups were compared with the Student t-test. The value of P < 0.05 was considered statistically significant.

3. Results

A total of fifteen patients were enrolled in this study based on the inclusion and exclusion criteria. There were 8 men and 7 women (median age 37 [IQR: 28 to 45] years). All patients had respiratory symptoms, positive reverse-transcription polymerase chain reaction (PCR) test result and pneumonic infiltrates on chest CT scans. The control group consisted of fifteen participants of similar age and gender distributions (median age 39 [IQR: 27 to 48] years, 9 males).

The delay between the confirmation of SARS-CoV-2 infection and the onset of symptomatology suggestive of myocardial injury ranged from 5 to 25 days, with a mean delay of 17 days. Precordial chest pain, unexplained cardiogenic shock and palpitation were reported in 6 (40%), 6 (40%), and 3 (20%) patients, respectively.

ECG alterations were observed in the majority of patients. Sinus tachycardia was observed in 6 patients (40%). ST-segment elevation, T waves inversion, diffuse low ECG voltage and premature ventricular contractions (PVC) were found in 5 (33,33%), 3 (20%), 2 (13,33%) and 1 (6,67%) patients, respectively.

Increased concentrations of inflammatory markers, namely C-reactive protein concentration (125 mg/L ± 89,90) and ferritin concentration (508 ng/mL ± 236,58) were observed in all patients. Similarly, High Sensitivity cardiac Troponin T was elevated in all patients (Hs cTnT 2470ng/L [IQR: 469–4010 ng/L], normal value, n. v.<30ng/L), yet it decreased to normal value in all patients within five days.

The echocardiographic findings of our patients were essentially LVEF reduction associated with global wall motion abnormalities in 6 patients (40%), while pericardial effusion and increased septal thickness were reported in 3 (20%) and 1 (6,67%) patients respectively. Clinical, electrocardiographic, echocardiographic results and outcomes of the fifteen patients are presented in Table 1 .

Table 1.

Summary of clinical, electrocardiographic, echocardiographic findings and outcomes of COVID-19 myocarditis patients.

Cases	Clinical presentation	ECG findings	Echocardiographic findings	Outcomes
Case 1	Acute chest pain, fever and diarrhea	Sinus tachycardia, inverted T waves in anterior leads	LVEF = 55% Increased septal thickness	Survived
Case 2	Altered consciousness, paleness, myalgias	Sinus tachycardia, diffuse anterior ST-segment elevation Fig. 1	LVEF = 25–30% Global hypokinesia	Died due to cardiogenic shock
Case 3	Palpitations, fever, cough	Sinus rhythm with detected PVCs	LVEF = 65%	Survived
Case 4	Abdominal pain, peripheral cyanosis, dizziness	ST-segment elevation in precordial leads	LVEF = 30% Global hypokinesia	Died due to cardiogenic shock
Case 5	Stabbing chest pain, dyspnea, fever	Diffuse Low voltage waves	LVEF = 50% moderate pericardial effusion	Survived
Case 6	Chest pain, cough, tachypnea	Sinus rhythm, No changes in ST-segment	LVEF = 45–50% Normal RV and LV sizes	Survived
Case 7	Dizziness, headache, asthenia	Sinus tachycardia	LVEF = 35–40% Moderate LV dysfunction	Survived
Case 8	Acute chest pain, fever, arthralgias, headache	ST-segment elevation in lateral and inferior leads	FEVG = 55–60%	Survived
Case 9	Palpitations, anxiety and fever	Sinus rhythm	LVEF = 50% Normal cardiac cavities size	Survived
Case 10	Loss of consciousness, peripheral cyanosis, tachypnea	Sinus tachycardia, ST-segment elevation in precordial and limb leads	LVEF = 20–25% Global hypokinesia Enlarged RV	Died due to cardiogenic shock
Case 11	Chest pain, fever,	Inverted T waves in V4–V6 leads	LVEF = 60% Normal LV size	Survived
Case 12	Altered consciousness, tachypnea, oliguria	Sinus tachycardia Inverted T waves in anterior leads	LVEF = 40% Global hypokinesia	Survived
Case 13	Positional chest pain, fever, tachypnea	Low-voltage waves in precordial leads	LVEF = 45–50% Diffuse precordial effusion	Survived
Case 14	Palpitations, asthenia, fever, cough	ST-segment elevation in V3–V6 leads	LVEF = 60% Mild effusion regarding free LV wall	Survived
Case 15	Asthenia, diffuse abdominal pain, confusion	Sinus tachycardia	LVEF = 30–35% Global hypokinesia RV dysfunction	Died due to cardiogenic shock

Patients underwent cardiac MRI within the first week from troponin rise and cardiac symptoms onset (median 7 days [IQR: 4–9 days]). CMR showed a diffuse intense myocardial edema, with raised myocardial native T1 (26,6%), raised myocardial native T2 (66,67%), non-ischemic type pattern of myocardial LGE (100%) (Fig. 2 ), LVEF was in the normal range for eleven patients (73,33%), however, average global longitudinal strain (GLS) was significantly altered when compared with the control group (-18.1% vs 21,3%, p < 0.01). In addition, 20% of patients had pericardial effusions and/or pericardial enhancement (Table 2 ).

Fig. 1.

ECG of a 30-year-old male patient, with no previous medical history nor cardiovascular risk factors, presented with acute chest pain with flu-like symptoms one week before, note the concave ST-segment elevation in lateral and inferior leads.

Fig. 2.

CMR Imaging findings in adult female with active COVID-19 presenting chest pain after 10 days.

Upper panel: (A) short axis and (B) four chamber view. T2-weithed images visualizing areas of myocardial edema in the lateral wall (yellow arrows) concordant to regional late gadolinium enhancement with subepicardial distribution (white arrows). Lower panel: late gadolinium enhancement imaging. (C) short axis (D) four chamber view.

Table 2.

Clinical and cardiac MRI characteristics of control group participants and patients with COVID-19 myocarditis.

Variable	Control group (n = 15)	COVID-19 myocarditis (n = 15)	P value
Clinical characteristics
Age	35,13 ± 8.87	37,93 ± 10,37	0,43
No. of men	9 (60%)	8 (53,33%)	0,72
Heart rate	77,86 ± 9.73	84,13 ± 8,55	0,07
Cardiac MRI
LVEF	59,13% ± 4,49	54,11,26% ± 11,26	0,15
Average GLS	−21,3% ± 2,15	−18,1% ± 2,65	<0,01
Visual Myocardial edema	0 (0%)	10 (66,67%)	<0,01
Visual LGE	0 (0%)	15 (100%)	<0,01

Cardiac magnetic resonance imaging revealed enlarged volumes in myocardial mapping acquisitions, including significantly raised native T1 and native T2. E and F, Pericardial effusion and enhancement (yellow arrowheads) and epicardial and intramyocardial enhancement (white arrowheads) were seen on late gadolinium enhancement (LGE) acquisition.

The therapeutic management of the patients was based on symptomatic treatment, according to the treatment protocol for COVID-19 infection, including oxygen titration if needed, vitamin therapy, injectable glucocorticoids, antibiotic therapy in case of bacterial superinfection. Betablockers (bisoprolol 2,5–10 mg) were administered to all patients, None of our patients received an angiotensin-converting enzyme (ACE) inhibitor or other heart failure medication.

4. Discussion

In this study, we present 15 patients who had reported cardiac symptoms in the course of COVID-19 infection, None of them had known previous cardiovascular risk factors, myocarditis or any other structural heart diseases before SARS-CoV-2 infection. Patients showed myocardial edema and/or foci late gadolinium enhancement lesion. The current literature concerning acute COVID-19 myocarditis is still scarce, yet the major CMR findings were diffuse edema and frequent LGE.4, 5, 6 Moreover, our findings reveal that significant cardiac involvement occurs, irrespective of preexisting cardiovascular risk factors or conditions, and the severity of the original presentation.

Cardiovascular involvement of COVID-19 was suspected since the beginning of this pandemic, as arrhythmias and myocardial injury induced by COVID-19 were reported, associated with a high inflammatory burden and mortality.⁷ While acute myocarditis seems to be a less common complication of COVID-19, its low prevalence could be explained by the preponderance of asymptomatic forms and the non-feasibility of cardiac MRI or endomyocardial biopsy. Halushka et al. histopathological analysis dealing with COVID-19 myocarditis found an incidence of around 7.2%.⁸

Different studies found that the average age of patient presented with COVID-19 was around 50 years, with a male predominance. The main presenting symptom, a part of infectious and respiratory ones, was chest pain.^{9 , 10} In our study, all patients were under 50 years old, with chest pain and palpitations as major complaints.

In the cases of our analysis, the most common ECG findings were repolarization changes (ST-segment depression, T-wave inversion), sinus tachycardia, premature ventricular contractions and low voltage waves. Several case reports suggested similar findings on the ECG, but none of them is specific to this condition.^{9 , 10}

During acute myocarditis in the course of COVID-19 infection, myocardial edema affects cardiac functioning and might be the expression of two major pathological mechanisms: Firstly, direct myocardial damage, as SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) is responsible for direct viral infection¹¹ Secondly, indirect myocardial injury may be the result of an inflammatory storm, known also as cytokine storm, caused by the excessive immune response.^{3 , 12}

In our cohort, left ventricular ejection fraction was altered in patients presenting a cardiogenic shock, Wong et al. studied this topic detailing the differences in fulminant and non-fulminant COVID-19 myocarditis; data showed that all cases of fulminant myocarditis have a significant systolic dysfunction.¹² Huang et al. concluded the same results with only one patient showing impaired left ventricular ejection faction.¹³ Echocardiographic findings of other series and case reports were consistent with the above results, mainly LVEF reduction, pericardial effusion, increased wall thickness and segmental hypokinesia.^{9 , 10 , 12} The conservation of LV systolic function in the majority of cases may be explained that they were in an early phase of cardiac involvement, preceding functional remodeling in the left ventricle.³ In our study, the global longitudinal strain among COVID-19 patients with acute myocarditis was significantly altered in comparison with the control group (-18,1% vs −23,1%, p < 0,01). Luetkens et al. found a similar result.⁶ Notable GLS impairment could be considered as an objective indicator of altered systolic function despite normal left ventricular ejection fraction.¹⁴

Taking into consideration the lack of sufficient data and evidence-based management of COVID-19 induced acute myocarditis, therapeutic approaches should be similar as those of viral myocarditis, including the use of inotropes, circulatory and ventilatory support for fulminant forms, diuretics and fluid management for congestive decompensations, while administration of betablockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers could be discussed according to the case^{15 , 16}

5. Conclusion

In conclusion, we present cardiac involvement in the form of acute myocarditis in 15 patients with active SARS-CoV-2 infection, as confirmed by CMR imaging, independently of preexisting medical conditions, cardiovascular history and the severity of the initial COVID-19 illness. COVID-19 induced myocarditis tends to be a rare but fatal complication, which affects a young population, thus highlighting the key role of early diagnosis and adapted management of this disease. Further investigations are needed to identify etiopathogenic mecanisms, therapeutic options and long term consequences of COVID-19 induced myocarditis.

Informed consent

All patients gave their informed consent to participate and share the results of this study.

Author contributions

Drs Bouchaala and Alilou had full access to all of the data in this study and assume responsibility for the integrity of the data and the accurateness of the data analysis.

Concept and design: Dr. Bouchaala, Dr. Alilou.

Acquisition, analysis, or interpretation of data: Dr. Bouchaala.

Statistical analysis: Dr. Bouchaala, Dr. Kerrouani Oualid, Dr. Yassini Yassine.

Drafting of the manuscript: Dr. Bouchaala.

Study supervision: Dr. Tadili Sidi Jawad, Dr. Tachinante Rajae, Dr. Oukerraj Latifa, Dr. Cherti Mohamed, Dr. Alilou Mustapha.

Declaration of competing interest

The authors declare they have no conflicts of interests.

Handling Editor: Dr Yadav Rakesh