Diagnosis Of Viral Myocarditis Research Articles

The Role of MicroRNA in the Pathophysiology and Diagnosis of Viral Myocarditis

Myocarditis is a non-ischemic condition with a heterogeneous etiology, clinical course and prognosis. The most common etiology of myocarditis are viral infections, whereas the most severe complications are acute and chronic heart failure and sudden cardiac death. The heterogeneous clinical course of the disease, as well as the availability and costs of diagnostic tools such as cardiac magnetic resonance and endomyocardial biopsy, hinder the diagnosis of myocarditis and its underlying cause. Non-coding RNAs such as micro-RNAs (miRNAs; miR) have been shown to be involved in the disease’s pathophysiology; however, their potential in disease diagnosis and treatment should also be considered. Non-coding RNAs are RNAs that are not translated into proteins, and they have the ability to regulate several intracellular pathways. MiRNAs regulate gene expression by binding with their targets and inhibiting protein synthesis by interfering with the translation of coding genes or causing the degradation of messenger RNA. Several miRNAs, such as miR-1, -133, -21, -15, -98, -126, -155, -148, -203, -208, -221, -222, -203 and -590, have been shown to be involved in the pathophysiology of viral myocarditis (VMC), and some of them have been shown to have diagnostic abilities. This article summarizes the available data on miRNAs and their associations with VMC.

Cardiovascular Involvement in Patients Recovered from COVID-19: Reality or Fantasy?

Background: COVID-19 infection has been associated with cardiovascular complications in 7-28% of hospitalized patients, with the diagnosis based on biomarkers elevation. Subclinical cardiac involvement in outpatients recovered from COVID-19 represents a growing concern, as well as mid- or long-term cardiovascular effects. Objective: The aim of the present study was to determine the usefulness of detecting cardiovascular involvement in outpatients recovered from COVID-19, and its association with symptoms and risk factors. Methods: Between September 2020 and March 2021, 668 patients >18 years were prospectively included. All the patients had to have COVID-19 confirmed diagnosis by a positive reverse transcription-polymerase chain reaction (RT-PCR) test in a respiratory tract sample COVID-19. They were evaluated with physical examination, electrocardiogram (ECG) and Doppler echocardiography. Patients with symptoms suggestive of risk or abnormal findings on ECG or echocardiogram underwent cardiac magnetic resonance imaging (CMRI) with gadolinium-based contrast agent. Results: Mean age was 42.9 ± 14.9 years and 56.9% were women; 12.9% were hypertensive, 4.3% were diabetic and 6.9% obese. Overall, 57.6% had no cardiovascular risk factors and only 4.2% had a history of cardiovascular disease. The disease was mild in 73.2%; 16.3% required hospitalization and 1.05% needed mechanical ventilation. Only 5 patients had myocarditis diagnosed by CMRI, and both pericardial effusion and abnormal repolarization were significantly associated with myocarditis (p < 0.0001). Conclusions: Abnormal ECG or echocardiographic findings were uncommon in our cohort. The diagnosis of viral myocarditis was made in 5 cases with clinical signs and symptoms, and was confirmed by CMRI.

Recurrent course of post-inflammatory cardiopathy: lessons from past epidemics

Viruses are the most common etiological agents of myocardium inflammation. Today the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) causes a high incidence of myocarditis and pericarditis. As a hypothetical scenario, we present a clinical case of a patient who underwent viral myocarditis on the background of SARS in 2004, with recurrent myocarditis in ARVI, the last of which was initiated by SARS-CoV-2. A 61-year-old male patient, in 2004 contacted a representative of the People's Republic of China and after 4 days felt the symptoms of ARVI. Before the viral disease, he had excellent health, the absence of cardiovascular diseases and pathological heredity. Fever 38–39 °C, myalgia, headache, general malaise, dry obsessive cough persisted for a week. After the addition of shortness of breath, he was hospitalized. According to the data of X-ray and computed tomography, infiltrates of the lungs of both of the "frosted glass" type were revealed. According to the clinic and laboratory data, a diagnosis of severe “atypical viral pneumonia” was made, and a diagnosis of viral myocarditis was suggested. Echocardiography showed a decrease in the left ventricular ejection fraction up to 50% for the first time, without signs of coronary heart disease based on the results of further examination. Dry cough disturbed in the next 4 months, LVEF 48–50% and 1 functional class of heart failure persisted for 10 years. The patient had a flu with mild respiratory symptoms in 2015, but it triggered a recurrence of myocarditis. The examination revealed a decrease in LVEF up to 35%, the progression of dilatation of the heart cavities also without signs of coronary heart disease according to the results of the treadmill test and coronary angiography. Post-inflammatory cardiopathy progressed relatively quickly during the year. The minimum LVEF was 23%; a cardioverter-defibrillator was implanted for secondary indications; radiofrequency ablation of fascicular tachycardia was performed. It was followed by another period of stabilization: 2 functional class of heart failure, ICD shocks did not occur. The patient underwent COVID-19 with minimal respiratory symptoms in March 2021. It provoked another recurrence of myocarditis, diagnosed with an increase in troponin, cerebral natriuretic peptide, CRP, ESR and increasing heart failure during 3 months. Persistent paroxysms of atrial fibrillation with a decrease of LVEF 15% and anasarсa. A successful radiofrequency isolation of the pulmonary vein was performed in 2021. By November 2021, in the absence of paroxysms, it was possible to achieve compensation for heart failure up to class 1 according to Vasilenko–Strazhesko and NYHA, LVEF 28%.In order to understand the recurrent nature of myocarditis against the background of various respiratory viral infections, an analysis of the literature was carried out, including the described cases of myocardial inflammation against the background of the predecessors of the SARS-CoV-2 strain: SARS-CoV-1 and MERS. We also reviewed the data on the diagnosis of viral myocarditis in the realities of this pandemic. It reveals a large heterogeneity of signs of inflammation of the heart muscle according to different diagnostic methods and large interobserver variability, and challenges us about the need to revise the criteria for myocarditis in the case of COVID-19.

МИОКАРДИТ НА ФОНЕ COVID-19: РАЗБОР КЛИНИЧЕСКОГО СЛУЧАЯ

Currently, the diagnosis of viral myocarditis against the background of a new coronavirus infection (COVID-19) is still controversial, since the clinical manifestations of this pathology are nonspecific, which creates certain difficulties for diagnosis and treatment

Review of COVID-19 Myocarditis in Competitive Athletes: Legitimate Concern or Fake News?

Since the first reported case of COVID-19 in December 2019, the global landscape has shifted toward an unrecognizable paradigm. The sports world has not been immune to these ramifications; all major sports leagues have had abbreviated seasons, fan attendance has been eradicated, and athletes have opted out of entire seasons. For these athletes, cardiovascular complications of COVID-19 are particularly concerning, as myocarditis has been implicated in a significant portion of sudden cardiac death (SCD) in athletes (up to 22%). Multiple studies have attempted to evaluate post-COVID myocarditis and develop consensus return-to-play (RTP) guidelines, which has led to conflicting information for internists and primary care doctors advising these athletes. We aim to review the pathophysiology and diagnosis of viral myocarditis, discuss the heterogeneity regarding incidence of COVID myocarditis among athletes, and summarize the current expert recommendations for RTP. The goal is to provide guidance for practitioners who will be managing and advising athletes in the COVID era.

Clinically Suspected Myocarditis in the Course of Severe Acute Respiratory Syndrome Novel Coronavirus-2 Infection: Fact or Fiction?

Cardiac complications, including clinically suspected myocarditis, have been described in novel coronavirus disease 2019. Here, we review current data on suspected myocarditis in the course of severe acute respiratory syndrome novel coronavirus-2 (SARS-CoV-2) infection. Hypothetical mechanisms to explain the pathogenesis of troponin release in patients with novel coronavirus disease 2019 include direct virus-induced myocardial injury (ie, viral myocarditis), systemic hyperinflammatory response (ie, cytokine storm), hypoxemia, downregulation of angiotensin-converting enzyme 2, systemic virus-induced endothelialitis, and type 1 and type 2 myocardial infarction. To date, despite the fact that millions of SARS-CoV-2 infections have been diagnosed worldwide, there is no definitive proof that SARS-CoV-2 is a novel cardiotropic virus causing direct cardiomyocyte damage. Diagnosis of viral myocarditis should be based on the molecular assessment of endomyocardial biopsy or autopsy by polymerase chain reaction or in-situ hybridization. Blood, sputum, or nasal and throat swab virology testing are insufficient and do not correlate with the myocardial involvement of a given pathogen. Data from endomyocardial biopsies and autopsies in clinically suspected SARS-CoV-2 myocarditis are scarce. Overall, current clinical epidemiologic data do not support the hypothesis that viral myocarditis is caused by SARS-CoV-2, or that it is common. More endomyocardial biopsy and autopsy data are also needed for a better understanding of pathogenesis of clinically suspected myocarditis in the course of SARS-CoV-2 infection, which may include virus-negative immune-mediated or already established subclinical autoimmune forms, triggered or accelerated by the hyperinflammatory state of severe novel coronavirus disease 2019.

Myocarditis Associated With COVID-19.

Coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic, with affecting to-date over 23 million people and causing over 800,000 deaths around the globe. The major pathogenetic mechanisms include inflammation, vasoconstriction and thrombogenesis. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically manifests as fever, cough, shortness of breath, and exhibits radiographic evidence of bilateral pneumonic infiltrates. Recent meta-analyses have shown that myocardial injury, including viral myocarditis, is prevalent among infected patients, especially in patients requiring ICU level care. Diagnosis of viral myocarditis is multifactorial and involves detection of elevated cardiac biomarkers and echocardiographic evidence of cardiomyopathy, in the absence of diseased coronary arteries. Endomyocardial biopsy with histopathologic examination provides definitive confirmation. We present a case of a previously healthy 52-year-old male who presented clinically with suspected myocarditis with new-onset dilated cardiomyopathy (DCM) and systolic dysfunction as a sequela of infection with SARS-CoV-2. In this report we highlight the clinical presentation of echocardiographic findings and proposed pathogenetic mechanisms of myocarditis associated with COVID-19 which has a varied presentation, ranging from clinically silent to life-threatening arrhythmias with hemodynamic compromise.

Parvovirus B19-induced vascular damage in the heart is associated with elevated circulating endothelial microparticles

BackgroundDiagnosis of viral myocarditis is difficult by clinical criteria but facilitated by detection of inflammation and viral genomes in endomyocardial biopsies. Parvovirus B19 (B19V) targets endothelial cells where viral nucleic acid is exclusively detected in the heart. Microparticles (MPs) are released after cell damage or activation of specific cells. We aimed to investigate whether circulating endothelial MPs (EMPs) in human and experimental models of myocarditis are associated with B19V myocarditis.MethodsMPs were investigated in patients with myocarditis (n = 54), divided into two groups: B19V+ (n = 23) and B19V- (n = 31) and compared with healthy controls (HCTR, n = 25). MPs were also investigated in B19V transgenic mice (B19V-NS1+) and mice infected with coxsackievirus B3 (CVB3). MPs were analyzed with fluorescent activated cell sorting (FACS).ResultsIn human samples, EMP subpopulation patterns were significantly different in B19V+ compared to B19V- and HCTR (p<0.001), with an increase of apoptotic but not activated EMPs. Other MPs such as platelet- (PMPs) leukocyte-(LMPs) and monocyte-derived MPs (MMPs) showed less specific patterns. Significantly different levels of EMPs were observed in transgenic B19V-NS1+ mice compared with CVB3-infected mice (p<0.001).ConclusionEMP subpopulations are different in B19V+ myocarditis in humans and transgenic B19V mice reflecting vascular damage. EMP profiles might permit differentiation between endothelial-cell-mediated diseases like myocardial B19V infection and other causes of myocarditis.

Acute myocarditis mimicking ST-elevation myocardial infarction: A case report and review of the literature.

The present study describes the case of a young man aged 22 who had acute retrosternal pain, elevated cardiac markers and electrocardiographic ST-T changes, which led to an original misdiagnosis of acute myocardial infarction. The patient underwent immediate coronary angiography, which revealed normal coronary arteries. Finally, the diagnosis of viral myocarditis was made on consideration of his fever, scattered red dots on his arms and legs and other auxiliary examination results obtained in the following days, which were supportive of the diagnosis. The patient improved on antiviral and myocardial protection therapy and was discharged 2 weeks later. Viral myocarditis is a common disease with a variable natural history. It remains challenging for doctors to differentiate between acute myocarditis and myocardial infarction, particularly in the early stages. A diagnosis of myocarditis should be made on the basis of synthetic evaluation of the evidence, including medical history, clinical presentation and results of the available auxiliary tests, in order to provide guidelines for treatment.

Abstract O.37: Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings In Kawasaki Disease

Background: Coronary artery dilatations are almost always secondary to Kawasaki disease in the pediatric population. The presence of CA involvement is used as a criterion to diagnose incomplete KD disease, which may be challenging. It has been recently demonstrated that febrile patients had larger CA size than non-febrile children in a pilot study. As there is almost always a myocarditis in the acute phase of KD disease we sought to investigate whether viral myocarditis may cause CA dilatations. Method: This retrospective study reviewed 14 consecutive patients with a diagnosis of viral myocarditis at Saint-Justine Hospital, Montreal, from April 2000 trough December 2010. Kawasaki disease was excluded in all patients. All echocardiogram studies were reviewed by an independent experienced technician for CA size and function parameters. Patients were classified in three categories: definite CA dilatation (Z-score ≥ 2.5 in one or more CA), occult CA dilatation (Z score variation ≥ 2 for the same CA on 2 different echogrardiograms, but absolute Z score always &lt; 2.5) and normal coronary artery. Demographics, laboratory values, microbial etiology testing, diagnostic studies were also collected. Results: Mean age at presentation was 1.67 ± 3.22 years, the majority &lt; 2 years old, and 11 (78%) were girls. Of the 14 patients 8 (57.1%) had normal CA, 3 (21.4%) had occult CA dilatation and 3 (21.4%) had definite CA dilatation. When present, CA dilatation was detected within the first 8 days of presentation. Eleven (78%) patients presented with acute onset features and the remaining 3 presented with subacute characteristics. There was no correlation between CA involvement and the intensity of LV dysfunction however (p = 0.84). Conclusion: Patients with viral myocarditis can present CA dilatation during the acute phase of the illness. This finding should be taken into account when diagnosing patients with incomplete KD on the basis of the CA involvement as the two illnesses may present with similar features.

Diagnostic value of high sensitive cardiac troponin T in pediatric viral myocarditis

Objective To evaluate the clinical application value of the hs-cTnT in the diagnosis of pediatric viral myocarditis.Methods 72 viral myocarditis (VMC) children patients' hs-cTnT,cTnT,creatine kinase-myocardial band (CK-MB) were measured and statistically analyzed.Results The hs-cTnT,cTnT,CK-MB of blood samples instantly collected in VMC group after hospitalizing were significantly higher than those of control group,the difference had statistical significance (P ＜ 0.01).The dynamic detection of VMC group' s abnormal rate in each period showed that hs-cTnT was higher than those of cTnT and CKMB.Conclusion The hs-cTnT is sensitive index for diagnosis of VMC,and it may reduce the misdiagnosis or missed diagnosis for VMC patients. Key words: Viral myocarditis (VMC); High sensitive cardiac troponin T; Troponin T; Creatine kinase-myocardial band

Detection of myocardial inflammation in Chagas' disease by cardiac magnetic resonance

Methods Fifty-four patients with CD were analyzed, 16 patients in the indeterminate form (IND), 17 patients with the cardiac form without systolic dysfunction (CF), and 21 patients with the cardiac form with systolic dysfunction (CFSD). All patients underwent 1.5-T cardiac magnetic resonance (CMR) using three pulse sequences, previously described as useful for the diagnosis of viral myocarditis: the myocardial delayed enhancement (MDE) technique, Triple-IR FSE T2-weighted sequence and the T1 weighted global enhancement acquired before and after contrast injection, to identify fibrosis, edema and hyperemia of the myocardium, respectively. The parameters for all sequences followed precisely the recommendations for acute myocarditis published on JACC White Paper (Friedrich et al. J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87).

The value of cardiovascular magnetic resonance for diagnosis of viral myocarditis

Endocardial myocardial biopsy is the gold standard in the diagnosis of viral myocarditis.However,the limitations of sampling to the low sensitivity,and invasive inspection methods limit its clinical application.The traditional diagnostic tool electrocardiography,laboratory values and echocardiography are lack of specificity.Thus,a non-invasive diagnostic approach with high sensitivity is in need.Cardiovascular magnetic resonance(CMR) can evaluate the function of the heart parameters,such as left ventricular function and regional wall motion,and various CMR imagings including T2-weighted imaging,and early- and late-contrast enhanced T1-weighted imaging can evaluate the hyperemia,oedema and necrosis of myocardial inflammation histological character.CMR provides a scientific basis for the diagnosis of viral myocarditis in clinical. Key words: Viral myocarditis; Diagnosis; Endomyocardial biopsy; Cardiovascular magnetic resonance

Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood

In patients with acute myocarditis, viral genome can be detected in plasma and peripheral leukocytes. Its relationship with active myocardial inflammation, however, is not well understood. Myocardial edema as a feature of inflammation and myocardial necrosis or fibrosis can be frequently observed in patients with acute myocarditis by cardiovascular magnetic resonance (CMR). We assessed the association of viral genome presence in peripheral blood samples with myocardial edema and irreversible injury. We examined consecutive patients with clinically suspected myocarditis after an episode of viral illness. State-of-the-art methods were used for detecting myocardial edema and irreversible injury using CMR and viral genome applying reverse transcribed, nested polymerase chain reaction in peripheral blood samples. The specificity of viral amplification products was confirmed by automatic DNA sequencing. Of a total of 55 patients (53.5 ± 15.6 years), 21 were positive for viral genome in peripheral leukocytes. Interestingly, 18 (86%) of these patients also showed global myocardial edema, as compared to only 7/34 (21%) without PCR evidence for viral genome. The overall agreement between CMR criteria for edema and viral PCR was 84%. In contrast, there was no significant relationship of viral genome presence with myocardial necrosis or scars. In patients with clinically suspected myocarditis, myocardial edema but not irreversible myocardial injury is associated with the presence of viral genome in peripheral blood.

Inclusion of electric disturbance type cardiomyopathy in the classification of cardiomyopathy: A current review

There are cases of cardiomyopathy which are not easily classifiable into hypertrophic, dilated or restrictive type. They often show ventricular arrhythmia, right or left bundle branch block, intraventricular conduction disturbance, atrioventricular conduction disturbance, and sinus node dysfunction (sick sinus syndrome). Endomyocardial biopsy in such cases reveals advanced myocardial disease, for which we propose the simpler term "electric disturbance type cardiomyopathy (ECM)". In our consecutive series of studies of cardiomyopathy employing endomyocardial biopsy in 573 cases, 264 (46%) were hypertrophic, 224 (39%) were dilated, and 85 (14.8%) were classified into the ECM.

Extensive tyrosine nitration in human myocardial inflammation

Production of nitric oxide via the cytokine-mediated activation of myocardial inducible nitric oxide synthase decreases myocardial contractility. Whether myocardial dysfunction is mediated directly by nitric oxide or indirectly through the formation of secondary reaction products, such as peroxynitrite, has not been established. Peroxynitrite, but not nitric oxide, reacts with the phenolic ring of tyrosine to form the stable product 3-nitro-L-tyrosine. Demonstration of tissue nitrotyrosine residues, therefore, infers the presence of peroxynitrite or related nitrogen-centered oxidants. Retrospective analysis of human autopsy specimens. University pathology and basic science laboratories. Formalin-fixed, paraffin-embedded myocardial tissue samples were obtained from 11 patients with a diagnosis of sepsis, seven patients with a diagnosis of viral myocarditis, and five control patients without clinical or pathologic cardiac disease. None. Specific antibodies to nitrotyrosine were utilized to detect nitrotyrosine residues in human autopsy specimens. Cardiac tissue obtained from patients with myocarditis or sepsis demonstrated intense nitrotyrosine immunoreactivity in the endocardium, myocardium, and coronary vascular endothelium and smooth muscle. In contrast, connective tissue elements were without appreciable immunohistochemical staining. Nitrotyrosine antibody binding was blocked by coincubation with nitrotyrosine or nitrated bovine serum albumin, but not by aminotyrosine, phosphotyrosine, or bovine serum albumin. In situ reduction of tissue nitrotyrosine to aminotyrosine by sodium hydrosulfite also blocked antibody binding. Densitometric analysis of nitrotyrosine immunoreactivity demonstrated significantly higher values for specimens from myocarditis and sepsis patients when compared with control tissue specimens. These results demonstrate the formation of peroxynitrite within the myocardium during inflammatory disease states, suggesting a role for peroxynitrite in inflammation-associated myocardial dysfunction.

Detection of enteroviral genome and its significance in cardiomyopathy.

Myocarditis is an important disease that can lead to dilated cardiomyopathy (DCM). Using the polymerase chain reaction (PCR), we examined whether viral genomes were present specifically in the hearts of viral myocarditis or DCM patients in our autopsy series and compared the results with their clinicopathological features. We applied three different criteria of myocarditis to fully describe the histological features. The presence of a viral genome was detected by PCR but was not specific in DCM or myocarditis. PCR might be helpful in the diagnosis of viral myocarditis, when combined with other clinical information.

Coxsackie virus heart disease: 15 years after.

From 1969 to 1973, 68 patients were admitted to the 4th Division of Medicine of the Brescia Civil Hospital with the diagnosis of viral myocarditis. The patients were divided into two groups according to the results of the Coxsackie virus complement fixing antibodies test: Group 1 (42 patients) with a fourfold or greater rising antibody titre; Group 2 (26 patients) with a negative serum test. Both groups were examined after a follow-up period of 15 years. Ten patients from Group 1 died. The diagnoses were chronic myocarditis (three cases); chronic cardiomyopathy-pulmonary embolism (one case); chronic cardiomyopathy-liver cirrhosis (one case); dilated cardiomyopathy-sudden death (two cases); congestive cardiomyopathy (three cases). No Group 2 patients died. The 15-year mortality rate of Group 1 was significantly higher than that of Group 2 (Fisher Test: p less than 0.005). In conclusion, the natural history of Coxsackie virus heart disease is characterized by two possibilities: a complete recovery from a clinical point of view, in some cases with only minor T wave abnormalities, or evolution into a chronic disease (dilated cardiomyopathy) having a high mortality rate within 10 years of the onset of the acute disease.

A Severe Case of Viral Myocarditis

For almost anyone, the diagnosis of viral myocarditis-inflammation of the myocardium caused by a virus-could be a threatening experience. When this disease occurs in its most serious form, however, and in a vigorous young man on the threshold of his professional career, the consequences, both physical and psychological, could be devastating. Bill, the young man in question, was admitted to our hospital in mid-October with a diagnosis of viral myocarditis complicated by atrial fibrillation (AF) and congestive heart failure (CHF); he was not discharged until shortly before Christmas. That he survived at all was almost a miracle; that he coped so well was probably due to his own inner resources, the support of his family and friends, and the quality of his medical and nursing care. During the course of his hospitalization he was on several different units, where his care demanded superb technical skills and was characterized by the holistic, integrated approach of primary nursing.