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The Journal of Clinical Investigation Mar 2021Immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers, including malignancies once considered untreatable. These agents, however, are... (Review)
Review
Immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers, including malignancies once considered untreatable. These agents, however, are associated with inflammation and tissue damage in multiple organs. Myocarditis has emerged as a serious ICI-associated toxicity, because, while seemingly infrequent, it is often fulminant and lethal. The underlying basis of ICI-associated myocarditis is not completely understood. While the importance of T cells is clear, the inciting antigens, why they are recognized, and the mechanisms leading to cardiac cell injury remain poorly characterized. These issues underscore the need for basic and clinical studies to define pathogenesis, identify predictive biomarkers, improve diagnostic strategies, and develop effective treatments. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems.
Topics: Biomarkers; Humans; Immune Checkpoint Inhibitors; Myocarditis
PubMed: 33645548
DOI: 10.1172/JCI145186 -
Circulation Research May 2023Viral infections are a leading cause of myocarditis and pericarditis worldwide, conditions that frequently coexist. Myocarditis and pericarditis were some of the early... (Review)
Review
Viral infections are a leading cause of myocarditis and pericarditis worldwide, conditions that frequently coexist. Myocarditis and pericarditis were some of the early comorbidities associated with SARS-CoV-2 infection and COVID-19. Many epidemiologic studies have been conducted since that time concluding that SARS-CoV-2 increased the incidence of myocarditis/pericarditis at least 15× over pre-COVID levels although the condition remains rare. The incidence of myocarditis pre-COVID was reported at 1 to 10 cases/100 000 individuals and with COVID ranging from 150 to 4000 cases/100 000 individuals. Before COVID-19, some vaccines were reported to cause myocarditis and pericarditis in rare cases, but the use of novel mRNA platforms led to a higher number of reported cases than with previous platforms providing new insight into potential pathogenic mechanisms. The incidence of COVID-19 vaccine-associated myocarditis/pericarditis covers a large range depending on the vaccine platform, age, and sex examined. Importantly, the findings highlight that myocarditis occurs predominantly in male patients aged 12 to 40 years regardless of whether the cause was due to a virus-like SARS-CoV-2 or associated with a vaccine-a demographic that has been reported before COVID-19. This review discusses findings from COVID-19 and COVID-19 vaccine-associated myocarditis and pericarditis considering the known symptoms, diagnosis, management, treatment, and pathogenesis of disease that has been gleaned from clinical research and animal models. Sex differences in the immune response to COVID-19 are discussed, and theories for how mRNA vaccines could lead to myocarditis/pericarditis are proposed. Additionally, gaps in our understanding that need further research are raised.
Topics: Female; Humans; Male; COVID-19; COVID-19 Vaccines; Myocarditis; Pericarditis; SARS-CoV-2
PubMed: 37167363
DOI: 10.1161/CIRCRESAHA.123.321878 -
Clinical Medicine (London, England) Sep 2021Acute myocarditis is a serious, likely underdiagnosed condition affecting people of all ages and for which the number of UK hospital admissions is rising. A primary... (Review)
Review
Acute myocarditis is a serious, likely underdiagnosed condition affecting people of all ages and for which the number of UK hospital admissions is rising. A primary diagnosis of myocarditis accounted for 0.04% (36.5 per 100,000) of all hospital admissions in England between 1998 and 2017, although this is likely to be an underestimate of the true burden of myocarditis. The aetiology is broad, including infective and inflammatory conditions as well as exposure to toxic agents. Clinical features are varied and overlap with other acute cardiac conditions making diagnosis a challenge. Cardiovascular magnetic resonance imaging currently serves as the gold standard non-invasive diagnostic modality. If an underlying aetiological process is identified, then therapy may be directed at the cause; however, for most, treatment is supportive and aimed at managing any complications such as heart failure or arrhythmias. There is emerging evidence for immunosuppressive therapy in certain cases. Prognosis is generally good with recovery in most; however, up to 30% with biopsy-proven myocarditis progress to develop a dilated cardiomyopathy and its potential associated complications. All-cause mortality in the UK for patients presenting to hospital with acute myocarditis is approximately 4%.
Topics: Acute Disease; Biopsy; Cardiomyopathy, Dilated; Heart; Humans; Myocarditis; Prognosis
PubMed: 34507935
DOI: 10.7861/clinmed.2021-0121 -
Circulation. Heart Failure Nov 2020Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis... (Review)
Review
Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.
Topics: Acute Disease; Cardiology; Chronic Disease; Consensus; Humans; Myocarditis; Predictive Value of Tests; Risk Factors; Terminology as Topic; Treatment Outcome
PubMed: 33176455
DOI: 10.1161/CIRCHEARTFAILURE.120.007405 -
Circulation Aug 2021Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a... (Review)
Review
Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.
Topics: Animals; Biopsy; Child; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Multimodal Imaging; Myocarditis; Prognosis; Symptom Assessment; Treatment Outcome
PubMed: 34229446
DOI: 10.1161/CIR.0000000000001001 -
Cardiovascular Journal of AfricaDengue is a neglected viral arthropod-borne tropical disease transmitted by the bite of infected spp. mosquitoes. It is responsible for a significant global burden of... (Review)
Review
Dengue is a neglected viral arthropod-borne tropical disease transmitted by the bite of infected spp. mosquitoes. It is responsible for a significant global burden of disease and corresponding socio-economic implications. There are four different virus serotypes, all of which are found predominantly in countries with tropical climates. Patients with dengue may present with cardiovascular (CV) manifestations, contributing to associated death and disability. A systematic review was conducted to identify CV manifestations of dengue, wherein 30 relevant studies were identified in the MEDLINE and PubMed databases. CV complications of dengue include rhythm abnormalities, hypotension, myocarditis, pericarditis and deterioration in myocardial function. Prompt recognition and treatment of CV complications of dengue are essential to reduce morbidity and mortality in these patients, who are at risk of progressing to cardiogenic shock and heart failure.
Topics: Animals; Dengue; Heart; Humans; Myocarditis; Neglected Diseases
PubMed: 34292294
DOI: 10.5830/CVJA-2021-033 -
Journal of the American College of... Apr 2018Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized.
BACKGROUND
Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized.
OBJECTIVES
The authors sought to understand the presentation and clinical course of ICI-associated myocarditis.
METHODS
After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block.
RESULTS
The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates.
CONCLUSIONS
Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
Topics: Aged; Antineoplastic Agents, Immunological; Case-Control Studies; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Middle Aged; Myocarditis; Neoplasms; Registries; Troponin T
PubMed: 29567210
DOI: 10.1016/j.jacc.2018.02.037 -
Circulation Research May 2019Myocarditis is generally a mild and self-limited consequence of systemic infection of cardiotropic viruses. However, patients can develop a temporary or permanent... (Review)
Review
Myocarditis is generally a mild and self-limited consequence of systemic infection of cardiotropic viruses. However, patients can develop a temporary or permanent impairment of cardiac function including acute cardiomyopathy with hemodynamic compromise or severe arrhythmias. In this setting, specific causes of inflammation are associated with variable risks of death and transplantation. Recent translational studies suggest that treatments tailored to specific causes of myocarditis may impact clinical outcomes when added to guideline-directed medical care. This review summarizes recent advances in translational research that influence the utility of endomyocardial biopsy for the management of inflammatory cardiomyopathies. Emerging therapies for myocarditis based on these mechanistic hypotheses are entering clinical trials and may add to the benefits of established heart failure treatment.
Topics: Animals; Cardiomyopathies; Disease Progression; Heart Failure; Humans; Myocarditis; Recovery of Function; Risk Factors; Treatment Outcome
PubMed: 31120823
DOI: 10.1161/CIRCRESAHA.118.313578 -
Cardiology Clinics Feb 2023Myocarditis is an inflammatory disease of the myocardium secondary to infectious and noninfectious insults. The most feared consequence of myocarditis is sudden cardiac... (Review)
Review
Myocarditis is an inflammatory disease of the myocardium secondary to infectious and noninfectious insults. The most feared consequence of myocarditis is sudden cardiac death owing to electrical instability and arrhythmia. Typical presenting symptoms include chest pain, dyspnea, palpitations and/or heart failure. Diagnosis is usually made with history, electrocardiogram, biomarkers, echocardiogram, and cardiac MRI (CMR). Application of the Lake Louise criteria to CMR results can help identify cases of myocarditis. Treatment is usually supportive with medical therapy, and patients are recommended to abstain from exercise for 3 to 6 months. Exercise restrictions may be lifted after normalization on follow-up testing.
Topics: Humans; Myocarditis; Return to Sport; Myocardium; Magnetic Resonance Imaging; Electrocardiography
PubMed: 36368807
DOI: 10.1016/j.ccl.2022.08.009 -
Trends in Cardiovascular Medicine Aug 2021Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions... (Review)
Review
Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.
Topics: Acute Disease; Cardiotonic Agents; Decision Support Techniques; Heart-Assist Devices; Humans; Immune Checkpoint Inhibitors; Immunosuppressive Agents; Magnetic Resonance Imaging; Myocarditis; Prosthesis Implantation; Risk Assessment; Risk Factors; Treatment Outcome; Virus Diseases
PubMed: 32497572
DOI: 10.1016/j.tcm.2020.05.008