Ventricular fibrillation as an initial manifestation of cardiac sarcoidosis

Abstract

Cardiac sarcoidosis is a rare immunologically driven process seen in 2% to 5% of patients with systemic sarcoidosis. We present a 31-year-old woman who presented after a ventricular fibrillation cardiac arrest. A comprehensive diagnostic workup was unrevealing. Despite negative cardiac magnetic resonance imaging, positron emission tomography facilitated the diagnosis. This case illustrates both the limitations of the diagnostic workup of sarcoidosis and the usefulness of positron emission tomography in the early diagnosis of cardiac sarcoidosis.

Sarcoidosis is a multiorgan immunologically driven inflammatory process characterized by the formation of noncaseating granulomas. ¹ With a global prevalence of 4.7 to 64 cases per 100,000 and an annual incidence of 10.9 per 100,000 cases in the United States, sarcoidosis may go unrecognized due to its heterogeneous clinical presentation. ^{1 , 2} While it commonly affects the lungs and lymphatic nodes, up to 30% of patients have extrapulmonary involvement. Clinically manifest cardiac involvement is reported in 5% of patients with systemic sarcoidosis. ^{2 , 3} Previously undiagnosed cardiac sarcoidosis (CS) has been found as an underlying etiology in approximately 16% to 35% of patients presenting with complete atrioventricular block or ventricular arrhythmias of unknown etiology. ^4–6 Herein, we describe a patient in whom ventricular fibrillation/cardiac arrest was an initial presentation of CS. She was diagnosed based on a cardiac fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) scan.

CASE PRESENTATION

A 31-year-old woman with known migraine on sumatriptan was brought to the emergency department following a witnessed out-of-hospital ventricular fibrillation cardiac arrest (Figure 1a). She achieved return of spontaneous circulation with two defibrillation shocks and cardiopulmonary resuscitation before transfer. Laboratory workup was remarkable for an aspartate aminotransferase of 251 U/L and an alanine aminotransferase of 243 U/L. Her cardiac profile revealed serial elevated troponin levels of 0.12, 0.23, and 0.15 ng/mL and an elevated brain natriuretic peptide level of 523 pg/mL. D-Dimer level was 9.23 mg/L. Electrocardiogram depicted sinus rhythm with frequent premature ventricular contractions (Figure 1b). Computed tomography (CT) angiography of the chest revealed diffuse ground-glass opacities. Transthoracic echocardiography revealed an ejection fraction of 50%, with inferolateral, anterolateral, and apical segmental wall hypokinesis. Subsequently, cardiac catheterization revealed normal coronary arteries. To further evaluate for infiltrative cardiomyopathy and myocarditis, the patient underwent cardiac magnetic resonance imaging (CMR), which revealed a mildly enlarged left ventricle with reduced ejection fraction and segmental wall motion abnormalities coinciding with the echocardiographic findings, but without any late gadolinium enhancement.

Figure 1.

(a) Part of the automatic external defibrillator strip showing ventricular fibrillation converted with shock. (b) Initial electrocardiogram strip with normal sinus rhythm and frequent premature ventricular contractions (arrows).

During the hospital stay, the patient was found to have frequent asymptomatic premature ventricular contractions (∼15,000 per day). She was started on flecainide, metoprolol succinate, and losartan and also received a subcutaneous implantable cardioverter defibrillator. A thorough rheumatologic workup was normal (negative antinuclear antibodies and an angiotensin-converting enzyme level of 10 U/L).

Shortly after discharge, given continued high suspicion of sarcoidosis despite the negative CMR, the patient underwent cardiac FDG-PET evaluation, which revealed patchy uptake in the left ventricle consistent with sarcoidosis (Figure 2). She was started on tapering doses of oral prednisone with a starting dose of 60 mg once daily and methotrexate. On her 2-month follow-up, she was asymptomatic and on a maintenance daily dose of 20 mg prednisone. Defibrillator device check at a follow-up visit showed no arrhythmias with normal electrode impedance.

Figure 2.

¹⁸F-fluorodeoxyglucose positron emission tomography–computed tomography scan showing increased uptake predominantly in the inferior basal lateral and to a lesser degree in the anterior apical lateral (arrow), consistent with sarcoidosis.

DISCUSSION

Patients with CS have a worse prognosis than patients with sarcoidosis without cardiac involvement. The extent of left ventricular dysfunction is the most important predictor of survival. ⁷ The most common initial manifestation of CS is atrioventricular block requiring permanent pacemaker. Noncaseating granulomas serve as foci for abnormal automaticity and cause changes in the ventricular activation and recovery process leading to ventricular tachyarrhythmias in CS. ⁸ Reviewing data from the National Inpatient Sample between 2010 and 2014, Desai et al reported the burden of arrhythmias in 369,285 sarcoid patients. The most frequently experienced arrhythmia subtype was atrial fibrillation (n = 10,970), followed by ventricular tachycardia (n = 1967) and atrial flutter (n = 1665). The least common arrhythmia was ventricular fibrillation and ventricular flutter, and the rate of sudden cardiac arrest was 559/100,000. ⁹

CS can involve all areas of the myocardium and manifest morphologically as wall motion abnormalities, dilated ventricles, ventricular systolic or diastolic function abnormalities, aneurysm, or septal wall thinning, all of which may be detected on transthoracic echocardiogram. ^{3 , 10} The utilization of transthoracic echocardiogram is limited by its sensitivity (25%), as it cannot identify and differentiate infiltrative diseases. ¹¹ Furthermore, due to the focal nature of the disease, an endomyocardial biopsy is not recommended as the standard of care due to its high risk profile and low sensitivity (25%) based on the focal nature of the disease. In terms of biological markers, angiotensin-converting enzyme is elevated in 60% of patients with sarcoidosis; brain natriuretic peptide, urinary calcium, and troponin also may be elevated, but they all lack diagnostic sensitivity and specificity. ^{12 , 13} CMR remains a preferred method of diagnostic imaging due to its relatively high sensitivity (76%–100%) and specificity (78%–98%). ^{10 , 14} However, CMR has a limited ability to identify early manifestations of CS. Hence, FDG-PET CT should be considered when there is a high index of suspicion for CS. It has shown promising results in identifying early manifestations of CS. ¹⁵

Cardiac involvement is an indication for immunosuppressive therapy, although there may not be a survival benefit with corticosteroid treatment. However, prior studies have shown that corticosteroids preserve left ventricular function in those with normal systolic function, and the ejection fraction may normalize in those with mild to moderate left ventricular dysfunction. ⁷ The treatment of life-threatening ventricular tachyarrhythmias in patients with CS is challenging, and in many cases, a combination of treatments including systemic corticosteroids, antiarrhythmic medications, implantable cardioverter defibrillator, and catheter ablation are utilized to control the arrhythmias.

This case illustrates both the limitations of the diagnostic workup for sarcoidosis due to its nonspecific presentation and the usefulness of FDG-PET CT in the early diagnostic evaluation for CS. Given the important role of ventricular tachyarrhythmias as the mechanism of sudden death in patients with CS, evaluation for sarcoidosis should be considered in all patients presenting with ventricular tachyarrhythmias of unknown origin. Patients who have normal CMR but with high suspicion for CS should be evaluated with FDG-PET, as it not only diagnoses the condition but may also detect active myocardial inflammation in the early phase of the disease process before formation of scar tissue.