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

With this episode, the CardioNerds family warmly welcomes Indiana University to the CardioNerds Healy Honor Roll. CardioNerds Healy Honor Roll programs are a collection of cardiology fellowship programs across the United States that support and foster the CardioNerds spirit and mission of democratizing cardiovascular education. Honor roll programs nominate fellows who are highly motivated and are passionate about medical education. Indiana University’s fellowship program director, Dr. Deepak Bhakta has nominated Dr. Asad Torabi for this position.

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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

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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

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