Myocarditis in Clinical Practice

doi:10.1016/j.mayocp.2016.05.013

Mayo Clinic Proceedings

Volume 91, Issue 9, September 2016, Pages 1256-1266

https://doi.org/10.1016/j.mayocp.2016.05.013 Get rights and content

Abstract

Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class.

Section snippets

Etiology and Epidemiology

Myocarditis can be triggered by different causes: infections (ie, viruses, bacteria, parasites), autoimmune diseases, hypersensitivity, high catecholamine states, drugs, toxic substances, or physical agents.⁵ Once other specific causes are ruled out, most cases of myocarditis observed in clinical practice are attributable to viral infections and/or immune reactions. In particular, even when no viruses are detected by serologic and polymerase chain reaction (PCR) analyses, an unrecognized viral

Clinical Presentation and Diagnosis

The heterogeneity of clinical presentation of myocarditis ranges from subclinical, or benign, forms to major clinical syndromes, such as severe heart failure or life-threatening ventricular arrhythmias.⁴ In most cases, the clinical expression of myocarditis can be exemplified by 3 main patterns of presentation4, 10: (1) recent-onset heart failure (<6 months), (2) arrhythmias, and (3) chest pain. According to the position statement on the diagnosis and management of myocarditis from the European

Role of Noninvasive and Invasive Diagnostic Testing

The diagnostic work-up of myocardial inflammatory syndromes should be tailored to the severity of clinical/instrumental presentation and the short-term response to medical therapy (Figure 2).

Natural History and Prognostic Stratification

Myocarditis is characterized by a highly variable natural history, ranging from quick resolution, to relapse, to the development of dilated cardiomyopathy and heart failure or unexpected sudden cardiac death.⁴ Thus, the identification of reliable early predictors of long-term prognosis is crucial for clinical management. A concise summary of the results of the main clinical trials and prospective studies reporting data on the outcome of myocarditis are reported in the Supplemental Table

Conventional and Supportive Therapy

The therapeutic management of myocarditis should be based on the pattern and severity of the clinical presentation, the short-term response to conventional treatments, and spontaneous or therapeutically induced improvement. The main pattern of presentation, ie, heart failure, arrhythmias, and myopericardial inflammatory syndromes, should be treated with standard therapeutic regimens.

In the context of active myocarditis associated with severe left ventricular dysfunction, major clinical

Conclusions and Key Points

Myocarditis is an underdiagnosed polymorphic disease with variable clinical presentation, evolution, and prognosis. The diagnostic approach and clinical management should be tailored to the clinical phenotype of the individual patient.

Patients presenting with chest pain and preserved left ventricular function typically have an excellent long-term prognosis and consequently should be managed conservatively. Once all ECG and echocardiographic abnormalities have disappeared during the short-term

Acknowledgments

We thank Professor Raffale De Caterina, MD, PhD (Institute of Cardiology, G. d'Annunzio University, Chieti, Italy), for his support and motivation.

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Myocarditis is a serious condition that carries with it a high rate of morbidity and mortality.
This review highlights the pearls and pitfalls of myocarditis, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence.
Myocarditis is an inflammatory syndrome of myocardium, most often resulting from a viral infection, that can cause life-threatening cardiovascular collapse. It has a highly variable presentation and no widely available specific diagnostic test, making it a challenging diagnosis. Emergency clinicians should obtain an electrocardiogram and perform bedside ultrasound to assess cardiac function. Treatment in the ED is largely supportive, focusing on resuscitation, cardiovascular support, cardiology specialist consultation, and appropriate disposition.
An understanding of myocarditis can assist emergency clinicians in diagnosing and managing this potentially deadly disease.
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In recent years, important advances have been made in the field of Cardio-Oncology. The 2022 ESC Guidelines on Cardio-Oncology proposed a baseline cardiovascular risk stratification for cancer patients and preventive strategies in patients at high and very-high risk of cardiotoxicity.
Cardiovascular toxic effects of anti-cancer drugs are being extensively studied; surveillance programs have been proposed, based on the baseline cardiovascular risk.
On the other hand, there is little data on Cardio-Oncological management of patients at high and very-high cardiovascular risk with previous cardiovascular diseases.
For example, little is known about management of cancer patients with heart failure with reduced ejection fraction (HFrEF), patients with a recent myocardial infarction or other cardiovascular diseases; when to resume anti-cancer drugs after a cardiovascular toxic event.
Collaboration between Cardiologists and Oncologists and multidisciplinary team evaluations are certainly essential to decide the best therapeutic strategy for cancer patients, to treat cancer while saving the heart.
Therefore, in the present review, we attempt to provide a useful guide to clinicians in treating patients with high and very-high risk of cardiotoxicity by enucleating main questions and answering them based on the evidence available as well as expert opinion and our clinical experience.
Sudden Cardiac Death in Young Athletes: JACC State-of-the-Art Review
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Athletes epitomize the healthiest segment of society. Despite this premise, sudden cardiac death may occur in apparently healthy athletes, attracting significant attention not only in the medical community but also in laypersons and media. The incidence of sudden cardiac death is variably reported, and epidemiological burden differs among cohorts. Athletes appear to be at risk of developing fatal arrhythmias when harboring a quiescent cardiac disorder. Primary cardiomyopathies, ion channelopathies, and coronary artery anomalies are prevalent causes in young individuals. Cardiac assessment of athletes can be challenging because these individuals exhibit a plethora of electrical, structural, and functional physiological changes that overlap with cardiac pathology. A diagnosis of cardiac disease in a young athlete is not necessarily an indication to terminate competition and sports participation. International guidelines, traditionally focused on disqualification of individuals with cardiac disease, have recently adopted a more liberal attitude, based on a careful assessment of the risk and on a shared-decision making approach.
Commentary on why implementing and standardizing histologic diagnosis of myocarditis is crucial for the clinical setting and patient care
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Histological examination of endomyocardial biopsy or myocardium at autopsy is key to the diagnosis of myocarditis. Among pathologists there is currently extensive variability in routine practice and criteria used to define, diagnose, and report myocarditis as well as to achieve consensus on cases. Two manuscripts emphasizing the need to standardize and implement histopathological diagnostic criteria for myocarditis are reviewed.
Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study
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Citation Excerpt :
Viral myocarditis unrelated to mRNA COVID-19 vaccination can lead to heart failure, cardiac transplantation, or death.6 Conversely, case descriptions suggest that clinical outcomes following a diagnosis of myocarditis after mRNA COVID-19 vaccination are more favourable than those associated with viral myocarditis, with resolution of symptoms often described at or soon after discharge from a short hospital stay for myocarditis after mRNA COVID-19 vaccination.5,7–9 However, data on follow-up prognoses for adolescents and young adults diagnosed with myocarditis after mRNA COVID-19 vaccination are scarce.10–12
Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults.
In this follow-up surveillance study, we conducted surveys in US individuals aged 12–29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18–24 years) from before and early on in the COVID-19 pandemic.
Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15–22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p<0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients).
After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered.
US Centers for Disease Control and Prevention.
Mechanism of the combination of KuShen and XiYangShen on myocarditis based on network pharmacology and animal experiments
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Myocarditis is an inflammatory disease of the myocardium and one of the leading causes of sudden death in young people. Its treatment remains challenging. Sophorae Flavescentis Radix (KuShen) and Panacis Quinquefolii Radix (XiYangShen) (the combination of KuShen and XiYangShen is referred to as KX) are the main drugs used to treat myocarditis; however, their active components and mechanisms of action remain unclear. The present study used network pharmacology and animal experiments to analyze the main targets and mechanisms of KX for the treatment of myocarditis. In total, 32 active ingredients, 258 drug targets, 1076 disease targets, and 151 common drug-disease targets were obtained from the initial screening. The drug component–target–myocarditis network, protein-protein interaction (PPI) network and enrichment analysis indicated that ginsenoside Rb1, ginsenoside Re, ginsenoside Rg, oxymatrine, and matrine may be the main active substances of KX. The main effector genes were TNFα, IL-1β, IL-6, IL-17, JAK2, and STAT. The enrichment results indicated that the enriched genes were mainly involved in the IL-17, TNF, and T helper 17 (Th17) cell differentiation signaling pathways. The results from the animal experiments showed evident myocardial damage in the experimental autoimmune myocarditis (EAM) group. In addition, the TNFα, IL-1β, IL-6, and IL-17 levels were significantly increased in the EAM group, while KX ameliorated myocardial injury and inhibited the secretion of inflammatory factors in a dose-dependent manner. Moreover, KX dose-dependently activated the Th17 cell differentiation pathway. Overall, our findings explained the multicomponent, multitarget and multibiological effects of KX for the treatment of myocarditis.

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ReviewMyocarditis in Clinical Practice

Abstract

Section snippets

Etiology and Epidemiology

Clinical Presentation and Diagnosis

Role of Noninvasive and Invasive Diagnostic Testing

Natural History and Prognostic Stratification

Conventional and Supportive Therapy

Conclusions and Key Points

Acknowledgments

JACC Cardiovasc Imaging

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

JACC Cardiovasc Imaging

Int J Cardiol

Cardiovasc Pathol

Am Heart J

J Am Coll Cardiol

Int J Cardiol

J Am Coll Cardiol

Heart Lung Circ

Am J Cardiol

Myocarditis: a histopathologic definition and classification

Am J Cardiovasc Pathol

Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies

Circulation

Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases

Eur Heart J

Long-term evolution and prognostic stratification of biopsy-proven active myocarditis

Circulation

Acute viral myocarditis

Eur Heart J

The effects of gender and age on occurrence of clinically suspected myocarditis in adulthood

Heart

Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy

N Engl J Med

The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID): first epidemiological results

Herz

Fatal myocarditis: morphologic and clinical features

Ital Heart J

A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis

Eur Heart J

Clinical presentation and long-term follow-up of perimyocarditis

J Cardiovasc Med (Hagerstown)

Good prognosis for pericarditis with and without myocardial involvement: results from a multicenter, prospective cohort study

Circulation

Review
Myocarditis in Clinical Practice