29. Myocarditis with Drs. JoAnn Lindenfeld, Javid Moslehi and Dr. Enrico Ammirati: Part 1

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Cardiovascular experts, Drs. JoAnn Lindenfeld, Javid Moslehi and Richa Gupta from Vanderbilt University Medical Center and Dr. Enrico Ammirati from Milan, Italy join Amit and Dan for a two part discussion about all things to consider for myocarditis in general (part 1) and COVID-19 myocarditis and heart transplantation in the COVID-19 era (part 2). Flutter Moment/Song by Drs. Matt (Internal Medicine) and Beth Faiman (Oncology).

On the CardioNerds Myocarditis page you will find podcast episodes, infographic, youtube videos, references, tweetorials and guest experts & contributors, flutter stars and so much more.

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Show notes prepared by Dr. Richa Gupta

  1. What is myocarditis? An inflammatory disease of the myocardium, classically as demonstrated on biopsy or autopsy specimen.
  2. How do we classify it? 4 ways: prognosis, time, etiology and histology.
    1. Prognosis: uncomplicated (no HF or ventricular arrhythmia, LVEF > 50) vs. complicated (fulminant with hemodynamic or electrical instability, HFrEF)
    2. Time: acute (no prior HF or cardiomyopathy, all symptoms w/in last month) versus chronic inflammatory myocarditis
    3. Etiology: viral-induced, autoimmune disorders, drugs (i.e. immune checkpoint inhibitors), allergic forms
    4. Histology based on biopsy and the inflammatory milieu: giant cell (worst prognosis), eosinophilic, lymphocytic (viral or immune checkpoint) or granulomatous (sarcoid)
  3. How do we diagnose myocarditis?
    1. Biopsy = Dallas criteria require inflammatory infiltrate and myocardial necrosis, updated with certain immunohistochemistry criteria.
    2. The syndrome = chest pain, new HF, dyspnea, fatigue, palpitations, heart block or unexplained cardiogenic shock. All pretty nonspecific.
    3. What if you don’t have biopsy? Use supporting criteria: = Abnormal EKG, arrhythmia, Tn elevation, wall motion abnormality on TTE, tissue characterization on CMR (T2 weighting for edema or LGE).
    4. Bottom line = use a MULTIPRONGED approach: syndrome + supporting criteria, rather than relying on only pathology or one technique.
  4. Why don’t we biopsy everyone?
    1. We only biopsy when it changes management.
    2. Inflammatory cell milieu on biopsy many not be specific enough to guide therapy.
    3. Yield can be low, not sensitive (especially if uncomplicated presentation), only getting a piece of the RV.
    4. There are risks (tricuspid valve trauma, RV perforationàtamponade).
  5. When do we think biopsy may change management?
    1. → When we find a treatable form in fulminant myocarditis: specific subtypes like giant cell or eosinophilic that are TREATABLE.
    2. → When it informs prognosis and tells us the patient is unlikely to recover: for example, giant cell carries BAD prognosis (> 60% will die or need transplant at 60 days)
    3. BUT—giant cell and eosinophilic will only comprise ~ 10% of all fulminant myocarditis—the rest may be all lymphocytic myocarditis (LM) for which there is no strong evidence for therapy!
      1. Many experts still use histology here to decide whether to immunosuppress based on cell milieu. We still need updated clinical trials to know if steroids are useful in fulminant LM.
  6. Do we really understand the mechanism of myocardial injury in what we call myocarditis?
    1. Not really. In the classic sense of the definition of myocarditis there is infiltration of the myocyte with immune cells resulting in myocyte death.
    2. However, there can also be direct cardiotoxicity as seen in injury caused by CAR-T cells accompanied by cytokine release syndrome and it is UNCLEAR if this is truly a myocarditis.
  7. How do we figure mechanisms out and why is this important?
    1. Only direct studies of the tissue can characterize these mechanisms of inflammation.
    2. This is hugely important because ultimately knowledge of what happens at the molecular level will inform the best therapeutic targets and dictate therapy.

Dr. JoAnn Lindenfeld, is a Professor of Medicine and the Director of Heart Failure and Heart Transplantation Section at Vanderbilt Heart and Vascular Institute.  She is the past president of the Heart Failure Society of America and serves on editorial boards of numerous journals including JACC, JACC Heart Failure and JHLT.  She is also a member of the AHA/ACC/HFSA heart failure guideline writing committee and was previously chair of the HFSA practice guidelines for the 2006 and 2010 guidelines. In addition to this she’s been an investigator in multiple large-scale clinical trials including the COAPT trial and has served on numerous steering committees, end point committees and data and safety monitoring committees. She is the author of a more than 300 original papers, reviews, and book chapters in the field of heart failure and heart transplantation.

Dr. Javid Moslehi is an associate professor of medicine at Vanderbilt University Medical Center where he is the director of the cardio-oncology program.  He is a clinical cardiologist and basic/translational biologist interested in cardiovascular complications associated with novel molecular targeted cancer therapies and the implications of these on our knowledge of basic cardiovascular biology. At Vanderbilt he runs an independent basic and translational research laboratory and program with a focus on signal transduction in the myocardium and vasculature as well as establishing pre-clinical models of cardiotoxicity involving novel targeted oncologic therapies.

Dr. Enrico Ammirati is an assistant professor of cardiology and advanced heart failure and transplant cardiologist in Milan, Italy at the Niguarda Hospital with a special research interest and expertise in acute myocarditis and acute heart failure.  He is a fellow of the European Society of Cardiology and has won numerous awards, he has also published incredibly important work on the distinction between fulminant and nonfulminant myocarditis and the prognostic implication of histologic subtypes.  His research interests also include the role of adaptive immunity in heart transplantation and atherosclerosis and he is the author of well over 100+ peer reviewed publications.

Myocarditis by Carine Hamo, MD