Giant Cell Myocarditis Presenting With Cardiogenic Shock

Abstract

Giant cell myocarditis (GCM) is a rare but often fatal inflammatory cardiomyopathy characterized by aggressive myocardial inflammation and necrosis. Prompt recognition and immunosuppressive therapy are critical for improving outcomes. A 48-year-old woman with no prior cardiac history presented with dyspnea, orthopnea, and hypotension. Electrocardiography showed wide complex tachycardia with retrograde V-to-A conduction. Laboratory findings revealed rising high-sensitivity troponin, hepatic injury, and leukocytosis. Echocardiography showed biventricular failure, and cardiac magnetic resonance imaging showed myocardial edema and subepicardial enhancement. Endomyocardial biopsy confirmed GCM. Immunosuppressive therapy with corticosteroids, tacrolimus, and mycophenolate mofetil led to clinical improvement, avoiding transplantation. GCM remains a diagnostic and therapeutic challenge due to its rapid progression and arrhythmic burden. This case highlights the importance of early biopsy, tailored immunosuppression, and vigilant monitoring in managing fulminant myocarditis.

Graphical Abstract

Giant cell myocarditis (GCM) is a rare yet frequently fatal inflammatory cardiomyopathy that predominantly affects young and middle-aged adults. It is believed to be driven primarily by T-cell–mediated myocardial injury, resulting in aggressive myocardial inflammation and necrosis. Clinically, GCM can present with fulminant heart failure symptoms and arrhythmias that overlap with other inflammatory or ischemic cardiomyopathies, creating a diagnostic challenge. Because of this overlap, endomyocardial biopsy is crucial for confirming the diagnosis and initiating aggressive immunosuppressive therapy. Early intervention is associated with improved outcomes, including longer transplantation-free survival, underscoring the high stakes of rapid recognition and treatment in this patient population.1, 2, 3, 4

Take-Home Messages

• •Timely endomyocardial biopsy and early immunosuppression are essential for improving outcomes.
• •Multidisciplinary management enhances survival and recovery.

History of presentation

A 48-year-old woman with no prior cardiac history presented with dyspnea on exertion, orthopnea, and bilateral lower extremity swelling. One week earlier, she had experienced nasal congestion and a cough that were treated with azithromycin; after initial improvement, she developed palpitations and worsening dyspnea. On arrival, her blood pressure was 80/40 mm Hg and her heart rate was 144 beats/min. She required 3 L of supplemental oxygen via nasal cannula due to hypoxemia and was afebrile at 97 °F. Cardiovascular examination revealed tachycardia with elevated jugular venous pressure, although no murmurs, rubs, or gallops were noted. Bilateral lower lobe crackles were present, and both lower extremities had 2+ pitting edema. Laboratory data showed leukocytosis (white blood cell count 16,400/μL), lactic acid 6.8 mmol/L, and troponin rising from 91.5 ng/L to 105 ng/L, indicative of myocardial injury. Markedly elevated liver enzymes (alanine aminotransferase 1,355 U/L, aspartate aminotransferase 974 U/L, and total bilirubin 3.5 mg/dL) suggested significant hepatic involvement. The chest x-ray showed bilateral patchy infiltrates consistent with pulmonary edema, whereas serial electrocardiograms (ECGs) show right bundle branch block, left anterior fascicular block, and prolonged corrected QT interval, progressing to accelerated idioventricular rhythm, slow ventricular tachycardia with atrioventricular dissociation, and ventricular tachycardia (126 beats/min) (Figure 1). A respiratory viral panel was negative.

Figure 1.

Electrocardiographic Data

(A) Electrocardiogram (ECG) on presentation shows sinus rhythm, right bundle branch block (RBBB), left anterior fascicular block, and prolonged QTc (523 ms). (B) Accelerated idioventricular rhythm (heart rate, 97 beats/min). Notice the change in RBBB morphology compared to ECG shown in A, positive aVR, and fusion beats (complexes 11 and 15). (C) Slow ventricular tachycardia (heart rate, 111 beats/min). Capture beats (complexes 12 and 13), fusion beat (complex 8), and atrioventricular dissociation. (D) Ventricular tachycardia (heart rate, 126 beats/min).

Past medical history

The patient’s past medical history was significant only for obesity. She denied any history of autoimmune, cardiac, or respiratory disorders and reported no tobacco, alcohol, or recreational drug use. Her only surgery had been a cesarean section. Occupationally, she worked in a factory with potential exposure to fumes from propane, plastics, and chemicals — although no direct link to her presentation was evident.

Differential diagnosis

Initial considerations included viral myocarditis—especially in the context of a recent upper respiratory infection—as well as arrhythmogenic cardiomyopathy and ischemic heart disease. Obesity and mildly elevated cardiac enzymes contributed to the ischemic differential. However, the onset of nonsustained ventricular tachycardia and the rapid decline in hemodynamics placed GCM at the forefront of diagnostic possibilities.

Investigations

A high-sensitivity troponin T assay (institutional abnormal cutoff 14 ng/L) rose to 105 ng/L, confirming myocardial injury. An ECG (Figure 1) showed wide-complex tachycardia; retrograde ventriculoatrial (V-to-A) conduction ultimately established an accelerated idioventricular rhythm. Coronary angiography revealed no obstructive coronary artery disease. An initial right heart catheterization revealed a right atrial pressure of 15 mm Hg, mean pulmonary arterial pressure of 39 mm Hg, pulmonary capillary wedge pressure of 19 mm Hg, cardiac index (1.95 L/min/m² by thermodilution) (2.29 L/min/m² by the Fick method) whereas on dobutamine 5 μg/kg/min, and reduced mixed venous oxygen saturation. These values fluctuated throughout hospitalization, aligning with changes in cardiac index, biomarkers, and immunosuppressive therapy initiation, as shown in Figures 2A and 2B.

Figure 2.

Clinical Data Used in Diagnosis and Management of Giant Cell Myocarditis

(A) Trends in right heart catheterization (RHC) pressures and cardiac output (CO) and cardiac index (CI) over time. The left y-axis represents right atrial pressure (RAP) (green), mean pulmonary arterial pressure (mPAP) (blue), pulmonary capillary wedge pressure (PCWP) (orange), and cardiac output (CO) (red). The right y-axis represents CI (purple). The trends show an overall decline in filling pressures and improvement in CO and CI following treatment initiation. (B) Trends in alanine aminotransferase (ALT), high-sensitivity (Hs)–troponin T, and left ventricular function (LVEF) over time. The left y-axis represents ALT (orange), showing a progressive decline, consistent with hepatic recovery. The right y-axis represents Hs-troponin T (green) and LVEF (blue), showing a reduction in myocardial injury and gradual improvement in LVEF with immunosuppressive therapy. (A, B) The gold star represents dobutamine 5 μg/kg/min. The red triangle represents triple immunosuppressive therapy started with high-dose intravenous methylprednisolone (1 g/d), tacrolimus (3 mg twice daily), and mycophenolate mofetil (1,000 mg twice daily). The green star represents dobutamine 2.5 μg/kg/min. The blue star represents dobutamine discontinued. (C) Hematoxylin and eosin stain (original magnification ×400). Endomyocardium with myocyte loss and scattered, multinucleated giant cells (arrows). (D) Short-axis right ventricle (RV) and left ventricle (LV) views on a cardiac magnetic resonance image revealed abnormal delayed subepicardial enhancement involving base to distal anterior, anteroseptal, and anterolateral walls (red arrows). Normal left ventricular size and thickness.

Short-axis cardiac magnetic resonance imaging (MRI) with anatomical labeling revealed biventricular enlargement, a septal bounce, diffuse myocardial edema, and abnormal delayed subepicardial enhancement in the base to distal anterior, anteroseptal, and anterolateral walls—findings supportive of acute myocarditis.^5,6 Endomyocardial biopsy confirmed GCM, demonstrating patchy lymphohistiocytic inflammatory infiltrates with multinucleated giant cells and occasional eosinophils.⁷ Negative special stains ruled out fungal and mycobacterial infections. Taken together, histopathologic findings, imaging results, and elevated biomarkers satisfied definitive myocarditis criteria.⁸

Management

On confirming GCM, a carefully staged immunosuppressive strategy was undertaken. High-dose intravenous methylprednisolone (1 g/d for 3 days) was initiated first, targeting rapid immunosuppression due to the patient’s critical hemodynamic instability and biventricular failure. Following steroid loading, tacrolimus (3 mg twice daily) and mycophenolate mofetil (1,000 mg twice daily) were added sequentially to maintain longer-term T-cell suppression, aligning with the pathophysiology of GCM. Rigorous hemodynamic monitoring via right heart catheterization informed therapy adjustments, particularly as the patient required dobutamine for inotropic support early in her hospitalization, afterload reduction, and diuresis. Clinical decision-making was further guided by serial biomarker measurements, echocardiographic assessments of left ventricular function, and vigilant monitoring of drug side effects, especially renal function while on tacrolimus.

This treatment approach highlights the adaptive nature of GCM management, wherein therapy sequencing depends on dynamic hemodynamics.

A comprehensive timeline (Figures 2A and 2B) outlines biomarker fluctuations, hemodynamic parameters, and therapy initiation. Continuous telemetry revealed intermittent wide-complex tachycardia; the key feature of retrograde V-to-A conduction again supported ventricular tachycardia (Figure 1). During these episodes, the patient experienced chest pain and presyncope. Intravenous lidocaine initially reduced ventricular tachycardia frequency, but persistent arrhythmias required additional intravenous amiodarone to achieve longer periods of rhythm stability. Complications such as heparin-induced thrombocytopenia and acute kidney injury prompted a change from heparin to argatroban, with later bridging to warfarin. Given the high likelihood of rapid decompensation, heart transplantation evaluation began early in her admission.

Discussion

Pathogenesis and diagnosis

GCM is marked by T-cell–mediated myocardial injury and histologically manifests as necrosis with lymphohistiocytic infiltration and multinucleated giant cells.^1,2 Although cardiac MRI can identify diffuse edema and subepicardial enhancement (Figure 2D), definitive diagnosis relies on endomyocardial biopsy (EMB), especially in acute, rapidly deteriorating presentations.^3,5, 6, 7 Biopsy provided conclusive evidence in our patient and aligned with European Society of Cardiology recommendations for prompt EMB in myocarditis.⁴

Therapeutic strategy

Aggressive, multidrug immunosuppression is essential to mitigate ongoing myocardial damage and reduce progression to transplantation. The combination of high-dose corticosteroids, tacrolimus, and mycophenolate mofetil is supported by institutional protocols and mounting evidence for improved transplantation-free survival in GCM.^2,3 Rapid anti-inflammatory action from corticosteroids is complemented by sustained immunomodulation from tacrolimus and mycophenolate mofetil. The 2024 American College of Cardiology Expert Consensus Decision Pathway further advocates incorporating genetic testing and serial imaging to optimize long-term outcomes.⁹ Treatment sequencing can vary, but in this case, critical hemodynamic compromise mandated early, high-intensity immunosuppression.

Arrhythmia and hemodynamics

Arrhythmias are common in GCM and can be life-threatening. Here, wide-complex tachycardia with retrograde V-to-A conduction was confirmed as a ventricular rhythm, underscoring the diagnostic value of careful ECG interpretation. Intravenous lidocaine and amiodarone helped manage ventricular arrhythmias, whereas a temporary pacemaker addressed bradycardia concerns and need for tachycardia overdrive pacing. Reports show that up to 65% of GCM survivors experience sustained ventricular arrhythmias, often warranting implantable cardioverter-defibrillator placement.¹⁰ This emphasizes the importance of integrated arrhythmia management involving pharmacologic agents, potential device therapy, and ongoing surveillance.

Long-term monitoring and follow-up

Recurrence risk and arrhythmogenic complications necessitate diligent long-term follow-up. Our strategy included serial multigated acquisition scans and echocardiographic evaluations to track left ventricular ejection fraction (LVEF) and guide immunosuppressive titration. Outpatient care also featured guideline-directed medical therapy, consisting of sacubitril–valsartan and empagliflozin, with intermittent furosemide, to support myocardial function and reduce heart failure risk. Current guidelines advise periodic reassessment of cardiac status and immunosuppressive dosing to prevent disease resurgence.⁹ This individualized, flexible approach underlines the complexities of GCM management over time and detect any delayed relapse in cardiac function.⁹

After initial stabilization, the patient’s cardiac function improved significantly. Although her presentation was complicated by acute kidney injury, shock liver, and ventricular tachycardia, her LVEF rose from 20% to 40% to 50% within a month. Antiarrhythmic therapy transitioned to oral amiodarone and mexiletine, reflecting the high prevalence of ongoing arrhythmogenic risk.^1,8 Additional challenges included a right internal jugular vein thrombosis and heparin-induced thrombocytopenia, necessitating a shift from heparin to argatroban and eventual bridging to warfarin. Four months post-presentation, her LVEF reached 61%, prompting re-evaluation of transplantation candidacy. Seven months later, she was de-listed due to stable clinical status. Tacrolimus levels were maintained at 6 to 8 ng/mL, and prednisone was tapered to 2.5 mg daily per established GCM protocols. This multifaceted approach underscores the value of individualized therapy, continuous imaging, and close clinical follow-up in ensuring durable remission.

Conclusions

Our experience with biopsy-confirmed GCM aligns with the 2024 ACC Expert Consensus Decision Pathway on Myocarditis, which highlights EMB, cardiac MRI, serial imaging, and biomarker evaluation as cornerstones of diagnosis and management. The rising importance of genetic testing in suspected inherited predispositions further expands the diagnostic toolkit.⁹ Clinicians should integrate these evolving strategies into their protocols when faced with severe myocarditis.

This case shows the vital importance of early EMB, prompt immunosuppression, and rigorous long-term monitoring in the management of GCM. Despite substantial recovery and de-listing from transplantation consideration, the possibility of recurrence and significant arrhythmias persists. Timely, multidrug immunosuppression can favorably alter the natural course of GCM, extending survival and improving quality of life. Further research is needed to refine immunosuppressive regimens and follow-up strategies for this rare yet devastating cardiomyopathy. Clinicians must maintain a high index of suspicion in acute heart failure presentations and be prepared to escalate care rapidly with biopsy and aggressive immunosuppressive therapy.1, 2, 3^,9

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.