107. Case Report: A Rare Cause of Cardiogenic Shock – More than Meets the Eye – Thomas Jefferson University Hospital

CardioNerds (Daniel Ambinder & Karan Desai) join Thomas Jefferson University FITs, Drs. Sean Dikdan, Rachel Debenham and Harsh Doshi. They discuss a profound story about a young man who presented with ventricular arrhythmias and cardiogenic shock that was ultimately found to be due to giant cell myocarditis. From the evaluation of cardiogenic shock to the role of endomyocardial biopsy to facing inequities in organ allocation, there are learning pearls for every listener! Dr. Enrico Ammirati, an advanced heart failure and transplant cardiologist in Milan, Italy, provides the E-CPR segment. For more insights from Dr. Ammirati, check out episodes 29 and 30 which feature an in-depth discussion on myocarditis with Dr. Ammirati, along with Drs. JoAnn Lindenfeld and Javid Moslehi. Audio editing by CardioNerds Academy intern, Gurleen Kaur.

CME is unavailable for this episode.

Jump to: Patient summaryCase mediaCase teachingReferences


Patient Summary

A 35 year old healthy male presents with cardiogenic shock and new heart failure with reduced ejection fraction. He has ventricular instability and is diagnosed with giant cell myocarditis by endomyocardial biopsy. His course over several years includes LVAD bridge to heart transplantation. He then has a recurrence of giant cell myocarditis in the transplanted heart which is successfully treated with high dose immunosuppression. 


Case Media

A. ECG, B. CXR


Episode Schematics & Teaching

Giant Cell Myocarditis Pearls

  1. Giant cell myocarditis (GCM is a rare – and often fatal – cause of acute myocarditis. A hallmark of GCM is the presence of multinucleated giant cells; however, these may take 1-2 weeks to appear and can also be seen in sarcoidosis.
  2. Most etiologies of fulminant myocarditis do not have bradyarrhythmias as a prominent feature, and their presence should increase the suspicion for sarcoidosis, Chagas disease, or GCM.
  3. While non-specific, a clue to the diagnosis of GCM amongst other causes of myocarditis could be rapid clinical deterioration with minimal response to guideline directed therapy, including a lack of spontaneous recovery on mechanical support which more commonly occurs in fulminant lymphocytic myocarditis.
  4. Mechanical support is typically needed in the management of GCM, either as a bridge to transplantation or recovery.
  5. GCM can recur in the transplanted heart. This happens in up to 25% of transplant patients and warrants aggressive immunosuppression which usually is sufficient to ensure disease remission.

Notes – Giant Cell Myocarditis

  1. What is Giant Cell myocarditis (GCM)?
    • Giant cell myocarditis (GCM) is an extremely rare – and often fatal – cause of acute non-infectious myocarditis. The pathophysiology of GCM is poorly understood, but thought to be a T-cell mediated autoimmune process leading to diffuse or multifocal inflammatory infiltrate, including lymphocytes with multinucleated giant cells (note multinucleated giant cells are not exclusive to GCM and can be seen in sarcoidosis as well). It has been estimated to occur at a rate of 0.13 cases per 100,000 people (one in a million).
    • It typically affects the myocardium in isolation and may not have any extracardiac manifestations, presenting with rapid hemodynamic deterioration, ventricular arrhythmias, and at times bradyarrhythmias.  The rate of death or cardiac transplantation has been estimated at 89%, with a median survival of 5.5 months from the onset of symptoms to the time of death or transplantation.
  2. When should you be suspicious of GCM?
    • The classic presentation is in a middle-aged Caucasian male who develops acute or subacute nonischemic cardiomyopathy (NICM) with clinical heart failure that progressively worsens. These patients often develop cardiogenic shock or arrhythmic instability – including both ventricular arrhythmia and conduction delays/heart block. See our prior episodes on the basics of building a clinical suspicion for myocarditis and the differential diagnosis (Episodes 29-33).
    • While non-specific, a clue to the diagnosis of GCM amongst other causes of myocarditis should be rapid clinical deterioration with minimal response to guideline directed therapy, including a lack of spontaneous recovery on mechanical support which more commonly occurs in fulminant lymphocytic myocarditis. Furthermore, bradyarrhythmias are less common in myocarditis and should raise the suspicion for GCM, sarcoidosis or Chagas disease.
  3. How is GCM diagnosed?
    • Definitive diagnosis of GCM requires endomyocardial biopsy (EMB). Similar to other rare forms of myocarditis like sarcoidosis or eosinophilic myocarditis, GCM requires pathology for diagnosis. Typically, a Class I indication (based on a joint statement 2007 statement from the AHA/ACC/ESC) for performing an EMB are (1) unexplained acute cardiomyopathywith < 2 weeks duration that is associated with hemodynamic compromise or  (2) unexplained cardiomyopathy between 2 weeks’ to 3 months’ duration associated with a dilated LV and new bradyarrhythmia, new ventricular arrhythmias or lack of response to GDMT within 1 to 2 weeks of initial diagnosis. 
    • The specific pathology will naturally include multinucleated Giant cells, but it will also include a high count of CD3 cells and usually a higher CD8 to CD4 ratio. The characteristic giant cells make typically take 1-2 weeks to appear and thus EMB in the first few days of the illness may render a false negative. Furthermore, because myocardial involvement in GCM can be patchy, repeat biopsy may be needed if the clinical suspicion remains high. Finally, multinucleated cells can also be seen in sarcoidosis; however, granulomas and fibrosis tend to be more striking features in cardiac sarcoid.
    • MRI can aid the diagnosis of GCM, however, many of these patients are too unstable to undergo MRI. When an MRI is able to be obtained, it will generally show diffuse abnormalities in T1 and T2 imaging and mapping.
  4. How is GCM treated?
    • In addition to GDMT as tolerated, treatment includes multi-drug immunosuppression that typically involve some combination of cyclosporine, azathioprine, and high dose steroids. Antithymocyte immunoglobulin and the T-cell specific monoclonal antibody, muromonab, have been used as well. Even after treating the underlying myocarditis with aggressive immunosuppression, ventricular arrhythmias may persist.
    • Mechanical circulatory support (MCS) is often needed as a bridge to heart transplantation or recovery. Options typically include intra-aortic balloon pump (IABP), IMPELLA (both RV and/or LV support devices), LVAD, RVAD, and ECMO. In patients with fulminant myocarditis, our goal is to maintain tissue perfusion while ensuring that we reduce LV workload and LVEDP. For this reason, peripheral VA ECMO alone is generally not used as it can increase afterload.
    • IABP is typically not useful in a patient with a rapid and severe decrease in cardiac output, as it offers an additional 0.5L to 1 L/min of support. In this patient, LVAD and RVAD support were pursued. Surgical RVAD implantation involves cannulation of the right atrium or RV as well as pulmonary artery and is connected to an extracorporeal centrifugal flow pump. Another option for percutaneous RV support is a novel axial-flow pump. This device utilizes a catheter-mounted microaxial flow pump with the inflow just below the right atrium-inferior vena cava junction and the outflow into the pulmonary artery after insertion via the femoral vein due to the design of the system, internal jugular placement and ambulation are not possible.
  5. What are the expected outcomes in patients with GCM?
    • Outcomes are generally poor without a heart transplant. With transplantation, however, 5-year survival is estimated at around 71%, which is similar to transplant survival rates in patients of other disease. Of note, GCM can recur in the transplanted heart. This happens in up to 25% of transplant patients. Recurrence warrants aggressive immunosuppression which is typically sufficient for disease remission.

References

1. Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Cirò A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319. PMID: 29764898.

2. Heymans S, Eriksson U, Lehtonen J, Cooper LT Jr. The quest for new approaches in myocarditis and inflammatory cardiomyopathy. J Am Coll Cardiol. 2016;68:2348-2364.

3. Rosenstein ED, Zucker MJ, Kramer N. Giant cell myocarditis: most fatal of autoimmune diseases. Semin Arthritis Rheum. 2000 Aug;30(1):1-16.

4. Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis–natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. 1997 Jun 26;336(26):1860-6.

5. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R; American Heart Association; American College of Cardiology; European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007 Nov 6;116(19):2216-33.

6. Kociol, R. D. et al. (2020). Recognition and Initial Management of Fulminant Myocarditis. Circulation, 141, E69-E92.

7. Kandolin R, Lehtonen J, Salmenkivi K, Räisänen-Sokolowski A, Lommi J, Kupari M. Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression. Circ Heart Fail. 2013 Jan;6(1):15-22.

8. Tschöpe C, Van Linthout S, Klein O, et al. Mechanical Unloading by Fulminant Myocarditis: LV-IMPELLA, ECMELLA, BI-PELLA, and PROPELLA Concepts. J Cardiovasc Transl Res. 2019;12(2):116-123.

9. Kirklin JK, Naftel DC. Mechanical circulatory support: registering a therapy in evolution. Circ Heart Fail. 2008;1(3):200-205.

10. Kapur NK, Esposito ML, Bader Y, et al. Mechanical Circulatory Support Devices for Acute Right Ventricular Failure. Circulation. 2017 Jul;136(3):314-326.

11. Toennes, B; Garan, A. Percutaneous Right Ventricular Support Devices for Right Ventricular Failure Mar 01, 2016. ACC journal expert analysis. 

12. Patil NP, Mohite PN, Sabashnikov A, et al. Preoperative predictors and outcomes of right ventricular assist device implantation after continuous-flow left ventricular assist device implantation. J Thorac Cardiovasc Surg. 2015;150(6):1651-1658.

13. Cooper LT Jr, ElAmm C. Giant cell myocarditis: diagnosis and treatment. Herz. 2012;37:632-636

14. Scott RL, Ratliff NB, Starling RC, Young JB. Recurrence of giant cell myocarditis in cardiac allograft. J Heart Lung Transplant. 2001;20:375-380

15. Patel PM, Saxena A, Wood CT, O’Malley TJ, Maynes EJ, Entwistle JWC, Massey HT, Pirlamarla PR, Alvarez RJ, Cooper LT, Rame JE, Tchantchaleishvili V. Outcomes of Mechanical Circulatory Support for Giant Cell Myocarditis: A Systematic Review. J Clin Med. 2020 Dec 1;9(12):3905.


CardioNerds Case Report Production Team

31. Fulminant Myocarditis with Cardiogenic Shock: Case Discussion

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. 

This marks our first episode after 100,000 downloads of the show – and this is a benchmark that we are celebrating together with all of you. Since launch, we have had 82 voices on the show and youtube channel. Our website which collates all the podcast episodes, youtube videos, tweetorials, and more has been accessed in 120 countries. We just cannot thank you enough! 

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.

5 points of maximal impulse in approaching myocarditis

  1. 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.
  2. 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.
  3. Manage the acute cardiac injury, which can range from supportive care to treatment of shock, arrhythmias, and even tamponade.
  4. 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.
  5. Treat the myocarditis: Immunosuppression is often started empirically in fulminant disease, but continuation depends on what you find on pathology.

30. Myocarditis with Drs. JoAnn Lindenfeld, Javid Moslehi and Dr. Enrico Ammirati: Part 2


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).

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.

Take me to the Myocarditis Series Page 
Take me to the COVID-19 Series Page
Take me to the Episode Topics Page

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.

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

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.

Take me to the Myocarditis Series Page 
Take me to the COVID-19 Series Page
Take me to the Episode Topics Page

Interview Questions

  1. What is myocarditis?
  2. How do we classify it?
  3. How do we diagnose myocarditis?
  4. Why don’t we biopsy everyone?
  5. When do we think biopsy may change management?
  6. Do we really understand the mechanism of myocardial injury in what we call myocarditis?
  7. How do we figure mechanisms out and why is this important?

Guests and Experts

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.

21. COVID-19: The Italian Experience with Dr. Gianluca Pontone

Tune in to hear the Italian perspective from a “COVID A” cardiovascular hospital in Milan, the heart of the country’s epidemic shared by Dr. Gianluca Pontone, who serves as Director of Cardiovascular Imaging Department Centro Cardiologico Monzino IRCCS, University of Milan. We discuss management of COVID-19 patients with underlying cardiovascular disease and cardiac manifestations of COVID-19 including acute coronary syndromes, cardiogenic shock, and myocarditis. Dr. Pontone shares his personal experience in terms of how he prepares himself to take care of patients during this time and his message for all CardioNerds to hear. Flutter Moment by Nino Isakadze (Cardiology).

Check out the COVID-19 series page!
Take me to episode topics page
Ventilation primer for the cardiologist (Youtube)

Dr. Gianluca Pontone serves as Director of Cardiovascular Imaging Department Centro Cardiologico Monzino IRCCS, University of Milan, Italy. He graduated with honors in medicine in 1997 followed by post-graduate degree in cardiology and radiology at University of Milan in 2001 and 2006 respectively. He is currently in the board of directors of Society of Cardiovascular Computed Tomography (SCCT), chairman of CT certification committee of European Association of Cardiovascular Imaging (EACVI) and chairman of working group of cardiac magnetic resonance of Italian society of cardiology.