Myocarditis

The overall goal of the study is to investigate the characteristics and potential mechanisms responsible for myocardial injury and dysfunction in patients after COVID-19 vaccination. Cardiac damage will be assessed with cardiac MRI and endomyocardial biopsy (EmBx) histopathology. Myocardial gene expression will be measured in RNA extracted from EmBxs mRNA abundance compared to nonfailing and failing control hearts.

“Arrhythmogenic ventricular cardiomyopathy (AVC) is a genetic condition which affects the heart and can lead to heart failure and rhythm problems, of which, sudden cardiac arrest or death is the most tragic and dangerous. Diagnosis and screening of blood-relatives is very difficult as the disease process can be subtle, but sufficient enough, so that the first event is sudden death.
The Mayo Clinic AVC Registry is a collaboration between Mayo Clinic, Rochester, USA and Papworth Hospital, Cambridge University Hospitals, Cambridge, UK. The investigators aim to enroll patients with a history of AVC or sudden cardiac death which may be due to AVC, from the US and UK. Family members who are blood-relatives will also be invited, including those who do not have the condition. Data collected include symptoms, ECG, echocardiographic, MRI, Holter, loop recorder, biopsies, exercise stress testing, blood, buccal and saliva samples.
Objectives of the study:
Discover new genes or altered genes (variants) which cause AVC
Identify biomarkers which predict (2a) disease onset, (2b) disease progression, (2c) and the likelihood of arrhythmia (ventricular, supra-ventricular and atrial fibrillation)
Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally using clinical, electrocardiographic and imaging data.
Characterize desmosomal changes in buccal mucosal cells with genotype and validate with gold-standard endomyocardial biopsies”

The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.

This is a phase III, multi-center international, single blind randomized controlled trial to test the efficacy of pulsed intravenous (IV) methylprednisolone versus standard therapy on top of maximal support in patients with Acute myocarditis (AM).

“Multi-center, double-blind, placebo-controlled, parallel group design. Patients with myocarditis within 90 days of onset of symptoms will be screened and, if eligible, randomized to CardiolRx or placebo.
CardiolRx is pharmaceutically produced Cannabidiol and is free of tetrahydrocannabinol (THC<5 ppm). The treatment period is 12 weeks; a last follow-up visit is scheduled one week after the last treatment, 13 weeks after randomization. Study assessments include Cardiac Magnetic Resonance imaging (CMR), ECG monitoring, 24-hour Holter assessments, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as physical exams and laboratory tests. The primary outcome parameters are measured by CMR. Secondary outcomes include clinical endpoints and changes in inflammatory and biomarkers."

G-COR is the first Global Prospective Cardio-Oncology Registry. It is a multinational, multicenter prospective observational cohort registry, with the goal of collecting clinical, laboratory, imaging, demographic, and socioeconomic data to identify risk factors associated with increased incidence of cancer therapy related cardiovascular toxicity (CTR-CVT) in different settings and to derive and validate risk scores for cardio oncology patients treated in different geographic locations throughout the world.

“Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar.
The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage.
Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.”

The investigators will evaluate the detection of cardiac sarcoidosis or inflammation using 18F-FSPG PET/MRI.

A retrospective, observational study consisting of patients who presents with typical/atypical chest pain and have an ensuing negative ischemic evaluation

“The purpose of this clinical trial is to learn about the safety and effects of the study vaccine (called COMIRNATY) for the potential prevention of COVID-19. This study is seeking participants who:
Are age <21 years. Have presentation to participating medical center with evaluation in Emergency Room and/or hospitalization. Received either the 1st, 2nd, 3rd or booster dose(s) of COMIRNATY within 7 days of symptom onset. Meet criteria of Centers for Disease Control and Prevention case definition of probable or confirmed myocarditis/pericarditis Are capable of giving signed informed consent/assent (by parents/legal guardians of minors and/or patients), which includes compliance with the requirements and restrictions listed in the Informed Consent/Assent Document and in this protocol OR meets criteria for waiver of consent. This study will examine the potential long-term effects associated with myocarditis/pericarditis following vaccination with COMIRNATY. The association of myocarditis/pericarditis in participants who received the study vaccine (COMIRNATY) compared with those associated with COVID-19 will also be examined. This will help us determine if COMIRNATY is safe and effective, and if there is a myocarditis/pericarditis association that should be noted. Participants will take part in this study for up to 5 years. During this time, they will receive complete cardiac imaging tests, and have follow up visits per guidance stated in the study protocol."