Assessment of inflammation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia

Maria E Campian, Hein J Verberne, Maxim Hardziyenka, Elisabeth A A de Groot, Astrid F van Moerkerken, Berthe L F van Eck-Smit, Hanno L Tan, Maria E Campian, Hein J Verberne, Maxim Hardziyenka, Elisabeth A A de Groot, Astrid F van Moerkerken, Berthe L F van Eck-Smit, Hanno L Tan

Abstract

Purpose: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a myocardial disease that predominantly affects the right ventricle (RV). Its hallmark feature is fibro-fatty replacement of RV myocardium. However, patchy inflammatory infiltrates in the RV are also consistently reported using autopsy and myocardial biopsy. Although the role of inflammation in ARVC/D is unresolved, the ability to assess inflammation non-invasively may aid in the diagnostic process. We aimed to establish whether cardiac inflammation can be assessed non-invasively in ARVC/D patients.

Methods: In eight ARVC/D patients and nine controls (haematology/oncology patients), the level of inflammatory activation was assessed by measuring plasma levels of inflammatory cytokines. Regional myocardial inflammation was assessed with (67)Ga scintigraphy.

Results: ARVC/D patients had higher plasma levels than controls of the pro-inflammatory cytokines interleukin (IL)-1β (1.22 ± 0.07 vs 0.08 ± 0.01 pg/ml, p < 0.0001), IL-6 (3.16 ± 0.44 vs 0.38 ± 0.04 pg/ml, p < 0.0001) and tumour necrosis factor (TNF)-α (9.16 ± 0.90 vs 0.40 ± 0.06 pg/ml, p < 0.0001), while levels of the anti-inflammatory cytokine IL-10 were not significantly different (1.36 ± 0.15 vs 1.20 ± 0.30 pg/ml, p = 0.74). (67)Ga uptake in the RV was higher in ARVC/D patients than in controls. In ARVC/D patients, (67)Ga uptake in the RV wall was higher than in the interventricular septum or left ventricular wall.

Conclusion: Inflammation in the RV wall of ARVC/D patients can be detected non-invasively with the combined analysis of plasma levels of inflammatory cytokines and cardiac (67)Ga scintigraphy.

Figures

Fig. 1
Fig. 1
Plasma concentrations of cytokines in ARVC/D patients and controls. IL-1β interleukin-1 beta, IL-6 interleukin-6, IL-10 interleukin-10, TNF-α tumour necrosis factor alpha
Fig. 2
Fig. 2
ARVC/D patient with increased 67Ga uptake in the RV wall. Coregistered transaxial images of cardiac magnetic resonance imaging (left) and 67Ga SPECT scintigraphy (right). There is increased 67Ga uptake in the right ventricular (RV) wall. IVS interventricular septum, LV left ventricular free wall
Fig. 3
Fig. 3
Myocardial 67Ga uptake in ARVC/D patients and controls. Semi-quantitative myocardial 67Ga uptake in ARVC/D subjects (a) and controls (b). 67Ga uptake in the RV wall, interventricular septum (IVS) or LV wall was calculated as the ratio of uptake (mean counts per pixel) in this myocardial region over the uptake in the total myocardium (i.e., the sum of all three ROIs)

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