Incidence of abnormal positron emission tomography in patients with unexplained cardiomyopathy and ventricular arrhythmias: The potential role of occult inflammation in arrhythmogenesis

Abstract

Background: The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VAs) is unknown.

Objective: The purpose of this study was to report fasting positron emission tomographic (PET) scan findings in consecutive patients referred with unexplained cardiomyopathy and VA.

Methods: Fluorine-18 fluoro-2-deoxyglucose (18-FDG) PET/computed tomographic (CT) scans with a >16-hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (ejection fraction <55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into 4 groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage).

Results: Over a 3-year period, 103 PET scans were performed, with 49% (AIC+ 17, AIC 33) exhibiting focal FDG uptake. Mean patient age was 52 ± 12 years (ejection fraction 36% ± 16%). Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, P = .002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed nongranulomatous inflammation in 6 patients and sarcoidosis in 18 patients. Ninety percent of patients with AIC/AIC+ were prescribed immunosuppressive therapy, and 58% underwent ablation. Correlation between low voltage regions on electroanatomic mapping and FDG uptake was observed in 74%. Magnetic resonance imaging findings matched abnormal PET regions in only 40%.

Conclusion: Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggest that a significant proportion of patients labeled "idiopathic" may have occult AIC, which may benefit from early detection and immunosuppressive medical therapy.

Keywords: Cardiomyopathy; Inflammation; Positron emission tomography; Ventricular arrhythmia.

FIGURE 1

Classification of patients with abnormal 18-FDG uptake. The presence of perfusion defects differentiates late stage from early stage disease and the increased FDG uptake in the lymph nodes indicates systemic disease (AIC+).

FIGURE 2

Flowchart of patients included in cohort for analysis.

FIGURE 3

Example of patient with late AIC with correlation between perfusion-metabolism mismatch in region of epicardial lateral scar. This patient was diagnosed with presumed post-viral nonischemic cardiomyopathy five years prior to PET scan.

FIGURE 4

Variable correlation between regions of FDG uptake and MRI delayed enhancement. Patients A and B have normal MRI and abnormal PET. Patients C and D have matched findings on MRI and FDG uptake on PET.

FIGURE 5

Gross and histopathologic examination of a patient with late AIC that underwent transplantation with a history of ablation in the RV. Isolated cardiac sarcoidosis was suspected but could not be proven as two biopsies were negative. At autopsy, three non-necrotizing granulomas were seen on the anterolateral epicardium and anterolateral papillary muscle after steroid therapy. (red asterisks indicate fibrosis)

FIGURE 6

Patient with presumed ARVC (RV dysfunction, left bundle branch VT, and precordial T wave inversions) referred for VT ablation that demonstrated focal biventricular FDG uptake and peri-hilar lymphadenopathy consistent with AIC+ by PET. Complete resolution of inflammation was seen on repeat PET after 8 weeks of primary immunosuppressive therapy with elimination of recurrent VT on ICD counter.