Author + information
- David W. Louis, MDa,
- Alexa Papaila, MD, MPHa,
- Wasiq Sheikh, MDa,
- Michael K. Atalay, MD, PhDb and
- Brian G. Abbott, MDa,∗ ()
- aThe Lifespan Cardiovascular Institute, Warren Alpert Medical School of Brown University, Providence, Rhode Island
- bDepartment of Diagnostic Imaging, Warren Alpert Medical School of Brown University, Providence, Rhode Island
- ↵∗Address for correspondence:
Dr. Brian G. Abbott, The Lifespan Cardiovascular Institute, Warren Alpert Medical School of Brown University, 593 Eddy Street, RIH APC 814, Providence, Rhode Island 02903.
We report a case of isolated cardiac sarcoidosis (CS) diagnosed using a multimodality imaging approach. A patient presented after an out-of-hospital, ventricular fibrillation–mediated cardiac arrest. The use of echocardiography, cardiac magnetic resonance, and fluorodeoxyglucose-positron emission tomography enabled the diagnosis of isolated CS. (Level of Difficulty: Beginner.)
- cardiac magnetic resonance
- heart failure
- positron-emission tomography
- ventricular fibrillation
History of Presentation
A 72-year-old Caucasian woman with a history of advanced atrioventricular (AV) block with AV dissociation presented after an out-of-hospital, ventricular fibrillation–mediated cardiac arrest. Physical examination was notable for elevated jugular venous pressure, bibasilar crackles, and cool extremities without edema. Limited bedside echocardiogram revealed severe left ventricular (LV) dysfunction and regional wall motion abnormalities (RWMAs). Emergency coronary angiography revealed nonobstructive coronary artery disease.
• CS should be suspected in patients with nonischemic cardiomyopathy, cardiac conduction disease, and ventricular arrhythmias.
• A multimodality imaging approach should be utilized when diagnosing CS.
• Updated guidelines now allow for a clinical diagnosis of CS without endomyocardial biopsy.
Past Medical History
The patient’s medical history included hypothyroidism and asymptomatic advanced AV block of unknown duration for which she had refused permanent pacemaker placement.
The differential diagnosis for nonischemic cardiomyopathy (NICM) includes infiltrative disease (sarcoidosis and amyloidosis), acute myocarditis (idiopathic giant cell myocarditis, necrotizing eosinophilic myocarditis, and lymphocytic myocarditis), stress-induced cardiomyopathy, left ventricular noncompaction cardiomyopathy, and hypertrophic cardiomyopathy, as well as cardiotoxic drugs (chemotherapeutics), thyroid disease, and illicit substances (cocaine, amphetamines).
Notable laboratory findings on arrival included a peak troponin-I of 0.028 ng/ml, brain-type natriuretic peptide of 585 pg/ml, whole blood lactate of 3.7 mmol/l, and serum creatinine 1.18 mg/dl. Complete blood count, basic metabolic panel, thyroid function tests, and liver function tests were otherwise within normal limits. Admission 12-lead electrocardiogram (Figure 1) revealed varying PR conduction, trigeminy, right bundle branch block, left anterior fascicular block, and ST-segment depressions in V2 to V6. Transthoracic echocardiogram revealed an LV ejection fraction of 15% to 20% and a tricuspid annular plane systolic excursion of 10 mm. Extensive RWMAs were noted with diffuse akinesis of the inferoseptal, inferior, inferolateral, anterolateral, and anterior wall segments, and hypokinesis of the basal and mid-anteroseptal walls. Grade III diastolic dysfunction was noted. Strain imaging was not performed.
Cardiac magnetic resonance (CMR) was performed revealing global hypokinesis of the LV with severely reduced systolic function and extensive areas of both transmural and subepicardial late gadolinium enhancement (LGE) throughout most basal segments, as well as patchy subepicardial LGE in the mid-ventricular and apical segments (Figure 2). No hilar adenopathy was noted. Given our high index of suspicion for isolated cardiac sarcoidosis (CS), fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed, which demonstrated increased FDG uptake in the septal, distal anterior, and mid-to-basal inferior walls of the LV and apical anterior wall of the right ventricle (Figures 3A to 3C, Figure 4). Single-photon emission CT (SPECT) perfusion abnormalities were seen on the accompanying resting myocardial single-photon emission CT perfusion images, most prominently involving the septum (Figures 3D to 3F). Areas of FDG uptake on PET/CT correlated to areas of LGE on CMR.
A diagnosis of isolated CS was established. The patient was initiated on oral prednisone along with lisinopril and spironolactone. Beta blockade was not tolerated. Amiodarone was given to decrease further risk of ventricular arrhythmias. An implantable cardioverter-defibrillator was placed.
Sarcoidosis is a multisystem disease propagated largely by overactivation of tissue macrophages leading to variable combinations of bilateral hilar lymphadenopathy, pulmonary, cardiac, neurologic, bone, ophthalmic, or dermatologic involvement. CS appears to be underdiagnosed by clinicians, as autopsy records have documented cardiac involvement in upwards of 25% of patients with known sarcoidosis. Epidemiological studies have found significantly higher rates of CS in Japanese women over the age of 50 years and African Americans (1).
Signs and symptoms of CS are vague and may include palpitations, pre-syncope, ectopy, ventricular arrhythmias, AV block, bundle branch blocks, and sudden death. Distinguishing CS from acute myocarditis (idiopathic giant cell myocarditis, necrotizing eosinophilic myocarditis, and lymphocytic myocarditis) can be challenging. Symptom onset to time of presentation is more rapid in idiopathic giant cell myocarditis and eosinophilic myocarditis compared with CS (2). Similarly, symptomatic heart failure is more common with myocarditis (2). Elevated eosinophil counts may be suggestive of eosinophilic myocarditis.
Cardiac imaging plays an integral role in the diagnosis of CS (Table 1). Common transthoracic echocardiogram findings include LV systolic dysfunction, RWMA in a noncoronary distribution, interventricular septal thinning, and abnormal strain rates (1,3). CMR is suggestive of CS when LGE is seen in a patchy and multifocal distribution, usually involving the basal septum and basal lateral walls, mid-myocardium, and epicardium of the myocardium (1,3). FDG-PET typically shows focal FDG uptake with or without resting perfusion defects and wall motion abnormalities (1,3). FDG-PET uptake patterns may help differentiate CS from other nonischemic processes including acute myocarditis. In CS, regions of fibrosis along the basal or midventricular septum may be seen, compared with myocarditis, which commonly follows specific vascular territories in the inferior and inferolateral myocardial segments (4). Endomyocardial biopsy can be pursued if histological examination is warranted (5); however, the patchy distribution of fibrosis commonly leads to false negative samples, with sensitivities as low as 20% (6).
Guidelines for the diagnosis of CS have recently been updated to reflect advancements in multimodality cardiac imaging. The 2016 Japanese Circulation Society Guideline on Diagnosis and Treatment of Cardiac Sarcoidosis now separates patients into either a “clinical diagnosis group” or “histological diagnosis group” based on whether or not endomyocardial biopsy has been performed, and provides additional guidelines on diagnosing isolated CS. These guidelines differ from other societal guidelines (7–10), which all require endomyocardial biopsy for diagnostic confirmation. A multimodality imaging approach without endomyocardial biopsy may allow for a more rapid initiation of immunosuppressive therapy and improved outcomes.
Repeat FDG-PET 6 months later revealed improvement in LV ejection fraction from 20% to 58% without significant interval changes in perfusion abnormalities or intense regional FDG uptake. Outpatient PPM interrogation revealed underlying sinus rhythm without further ventricular arrhythmias. Overall, these findings suggest persistent myocardial inflammation despite clinical recovery, possibly indicative of premature follow-up imaging.
Isolated CS should be suspected in patients with an unexplained nonischemic cardiomyopathy, conduction abnormalities, and/or life-threatening arrhythmias. A multimodality imaging approach should be considered in cases of suspected CS. Recent guideline updates now allow for the diagnosis of CS without endomyocardial biopsy.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Case Reports author instructions page.
- Abbreviations and Acronyms
- cardiac magnetic resonance
- cardiac sarcoidosis
- positron emission tomography
- Received February 14, 2020.
- Revision received April 25, 2020.
- Accepted May 6, 2020.
- 2020 The Authors
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