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 myocarditis in the COVID era (part 2). Flutter Moment/Song by Drs. Matt (Internal Medicine) and Beth Faiman (Oncology).
- What is myocarditis? An inflammatory disease of the myocardium, classically as demonstrated on biopsy or autopsy specimen.
- How do we classify it? 4 ways: prognosis, time, etiology and histology.
- Prognosis: uncomplicated (no HF or ventricular arrhythmia, LVEF > 50) vs. complicated (fulminant with hemodynamic or electrical instability, HFrEF)
- Time: acute (no prior HF or cardiomyopathy, all symptoms w/in last month) versus chronic inflammatory myocarditis
- Etiology: viral-induced, autoimmune disorders, drugs (i.e. immune checkpoint inhibitors), allergic forms
- Histology based on biopsy and the inflammatory milieu: giant cell (worst prognosis), eosinophilic, lymphocytic (viral or immune checkpoint) or granulomatous (sarcoid)
- How do we diagnose myocarditis?
- Biopsy = Dallas criteria require inflammatory infiltrate and myocardial necrosis, updated with certain immunohistochemistry criteria.
- The syndrome = chest pain, new HF, dyspnea, fatigue, palpitations, heart block or unexplained cardiogenic shock. All pretty nonspecific.
- 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).
- Bottom line = use a MULTIPRONGED approach: syndrome + supporting criteria, rather than relying on only pathology or one technique.
- Why don’t we biopsy everyone?
- We only biopsy when it changes management.
- Inflammatory cell milieu on biopsy many not be specific enough to guide therapy.
- Yield can be low, not sensitive (especially if uncomplicated presentation), only getting a piece of the RV.
- There are risks (tricuspid valve trauma, RV perforationàtamponade).
- When do we think biopsy may change management?
- → When we find a treatable form in fulminant myocarditis: specific subtypes like giant cell or eosinophilic that are TREATABLE.
- → 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)
- 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!
- 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.
- Do we really understand the mechanism of myocardial injury in what we call myocarditis?
- Not really. In the classic sense of the definition of myocarditis there is infiltration of the myocyte with immune cells resulting in myocyte death.
- 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.
- How do we figure mechanisms out and why is this important?
- Only direct studies of the tissue can characterize these mechanisms of inflammation.
- This is hugely important because ultimately knowledge of what happens at the molecular level will inform the best therapeutic targets and dictate therapy.
Show notes prepared by Dr. Richa Gupta
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 by Barrie Stanton (RN).
The CardioNerds discuss a case of fulminant myocarditis, teaching a comprehensive approach to myocarditis with just 5 foundational principles. Review the myocarditis infographic on the myocarditis topic page. The episode ends with a special message from the true heroes of this episode, Chas and Julie Miller.
5 points of maximal impulse in approaching myocarditis
- Build the clinical suspicion for myocarditis: You need a high index of suspicion given the variable presentation, and definitely need to keep a differential so you don’t miss things like acute coronary syndromes.
- Decide if EMBx is necessary: Most often obtained in fulminant presentations to look for pathologic findings of giant cell myocarditis or eosinophilic myocarditis, because these findings will change management.
- Manage the acute cardiac injury, which can range from supportive care to treatment of shock, arrhythmias, and even tamponade.
- Manage the chronic cardiac sequelae: Recovering from the acute phase of myocarditis doesn’t necessarily mean smooth sailing — some develop chronic heart failure, warranting GDMT — or guideline directed management and therapy, as defined by Dr. Randall Starling in Ep 13.
- Treat the myocarditis: Immunosuppression is often started empirically in fulminant disease, but continuation depends on what you find on pathology.
What does it feel like to have fulminant myocarditis? How does it feel to see a loved one on ECMO? What impact do healthcare heroes have on their patients’ and their families’? Tune into this remarkable firsthand patient perspective as Chas and Julie Miller recount their experience with fulminant myocarditis. In Episode 31 we discussed the science & medicine of myocarditis. Now in Episode 32 we realize the emotions and human experience on the other side through the lens of a patient and his loving wife. Special messages from CCU nursing, Megan VanName, Alyssa Noonan, and Kelly Norsworthy, as well as Dr. Dan Choi, cardiac surgeon at Johns Hopkins Hospital.
The Cleveland Clinic Director of Cardiac MRI, Dr. Deborah Kwon, discusses the principles and clinical applications of cardiac MRI, taking us from the protons to the bedside with a series of illustrative cases. CardioNerds hosts Amit Goyal, Daniel Ambinder, and Carine Hamo are joined by Dr. Nicole Pristera (Cleveland Clinic cardiology fellow). Flutter moment by student doctor Arooma Shahid.
- What should we know about the common sequences for cardiac MRI?
- We all learn about the risks of NSF. How much of these risks are a reality and when should we truly avoid gadolinium exposure?
- What are some challenges to MRI:
- Time of scanning
- Patient tolerability: breath holding, claustrophobia, lying flat
- No patient monitor
- Ferromagnetic devices (especially CIEDs)
- Artifacts (lead)
- What types of information about the heart can we obtain with a CMR?
- Anatomic: 0.5 x 0.5 x 0.5mm spatial resolution
- Chamber dimensions, volumes, mass, anomalies (LV aneurysm, hypertrophy)
- Aortic Dissection
- Cardiac Tumors and Thrombi
- Congenital defects
- Cine images: EF, systolic wall thickening, wall motion
- Myocardial tagging → strain (infarct/scar)
- Measurement of blood flow velocity across the cardiac valves and the great vessels: regurg, stenosis, shunts, angio
- Tissue characterization: gadolinium enhancement
- Perfusion (stress, rest)
- Scar (LGE)
- Anatomic: 0.5 x 0.5 x 0.5mm spatial resolution
The role for Cardiac MRI in particular cases discussed with Dr. Kwon
- CAD: A 45 year old G1P1 woman with prior preeclampsia and anterior STEMI s/p LAD PCI 3 years ago is being seen for chest pain. TTE shows LVEF 45% with mid-apical anterior hypokinesis and apical aneurysm. How does CMR help delineate ischemic heart disease (perfusion, viability, chambers)
- Pericarditis: her stress MRI shows an anteroapical perfusion defect and apical aneurysm with mural thrombus, with corresponding LGE. On further review, her chest pain is sharp, pleuritic, and worsens with recumbency. EKG on follow-up shows diffuse ST elevations and PR depressions except for in aVR which shows ST depression and PR elevation. ESR and CRP are moderately elevated.
- ARVC: A 35 year old female athlete who is admitted after VF arrest that occurred during a tennis match. Thankfully she received immediate bystander CPR with early defibrillation and prompt ROSC. She has had prior syncope during training and an uncle died suddenly at age 40. Resting EKG shows an incomplete right bundle, right precordial TWIs, and epsilon waves in V1-V3. On tele she’s had multiple runs of NSVT of LBBB morphology. Echocardiogram shows RV dilation. A heart failure consult is considering EMBx but requests a CMR beforehand.
- Role in select other cardiomyopathies: HCM, Amyloid, hemochromatosis etc (if time)
- Valvular Heart Disease: A 28 year old man with no PMH who presents with progressive dyspnea during his routine morning runs. On exam he has a early diastolic decrescendo murmur best heard at end expiration while leaning forward. While concentrating on the murmur you notice a subtle rhythmic head bobbing. TTE shows eccentric AI and a dilated LV, but further characterization is limited. (CMR shows bicuspid aortic valve, TAA, LV dilation)
- Cardiac mass: a 55 year old woman with subacute fevers, chills, and night sweats now presents with acute ischemic left leg pain. Auscultation reveals a mid-diastolic plop. TTE is limited by poor sonographic windows, but there is a nondescript echodensity in the LA. What is the role of CMR in cardiac masses?
- Myocarditis: Chas Miller is our patient from episodes 31 & 32 who had presented with cardiogenic shock and heart block found to have fulminant myocarditis. Now unfortunately he was too sick to undergo a cardiac mri, but how would it have helped?
- Pollack A, Kontorovich AR, Fuster V, Dec GW. Viral myocarditis-diagnosis, treatment options, and current controversies. Nat Rev Cardiol. 2015;12(11):670-680.
- Sinagra G, Anzini M, Pereira NL, et al. Myocarditis in Clinical Practice. Mayo Clin Proc. 2016;91(9):1256-1266. doi:10.1016/j.mayocp.2016.05.013
- Kociol RD, Cooper LT, Fang JC, et al. Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement from the American Heart Association. Circulation. 2020:E69-E92.
- Leone O, Pieroni M, Rapezzi C, Olivotto I. The spectrum of myocarditis: from pathology to the clinics. Virchows Arch. 2019;475(3):279-301.
- Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019;139(18):E891-E908.
Myocarditis Youtube Lecture Series
Dr. Richa Gupta from Vanderbilt University Medical Center discusses what is known about myocardial injury in COVID-19 patients. Myocarditis diagnosis and treatment is reviewed and a paradigm for the clinical course of late presenting COVID-19 ARDS with systemic hyperimmune injury is described.
Dr. Richa Gupta from Vanderbilt University Medical Center discusses what is known about myocardial injury in COVID-19 patients. Treatment for COVID-19 related myocarditis is discussed including supportive management as well as a pharmacologic strategies under investigation that include antiviral agents, immune-modulators, statins, and convalescent plasma.
Meet our experts and guest hosts!
Richa Gupta, MD, MPH
Dr. Richa Gupta completed medical school at the Johns Hopkins School of Medicine and stayed on for internal medicine training in the Osler Residency Program at the Johns Hopkins Hospital. She is currently a third-year cardiology fellow at Vanderbilt University Medical Center where she will also be pursuing fellowship in advanced heart failure and transplant cardiology next year. Her current interests include post-transplant outcomes, the genetics of tachycardia-induced cardiomyopathy, the sequelae of mechanical circulatory support and applications of cardiac MRI. She also loves teaching the housestaff and medical students and getting them excited about all things heart failure. Outside of the hospital she loves horror movies, food, travel and good exercise.
JoAnn Lindenfeld, MD
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.
Javid Moslehi, MD
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.
Enrico Ammirati MD, PhD, FESC
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.
Deborah Kwon, MD
Dr. Debbie Kwon attended medical school at the University of Michigan and internal medicine residency at the University of Pennsylvania. She completed her general cardiology and cardiovascular imaging fellowships at the Cleveland Clinic. She is the Director of Cardiac MRI At the Cleveland Clinic and serves as the Core Lab MRI director for the Pulmonary Vascular Disease Phenomics (PVDOMICS) multicenter National institution of Health (NIH) Study.
Nicole Pristera, MD
Dr. Nicole Pristera is a cardiology fellow at the Cleveland Clinic. She earned her medical degree at Case Western Reserve University and completed her internal medicine residency training at Duke University. Her clinical interests include interventional cardiology and cardiac critical care. Outside of the hospital, she enjoys traveling, hiking, and learning foreign languages.
Meet our Flutter Stars!
Beth Faiman, PhD, CNP
Matthew Faiman, MD
Dr. Matthew Faiman is a physician in the department of Internal Medicine. His primary location is Lyndhurst Campus.
Arooma Tahir, MBBS