Cardiovascular magnetic resonance imaging and clinical performance of somatostatin receptor positron emission tomography in cardiac sarcoidosis.

ESC HEART FAILURE ORIGINAL RESEARCH ESC Heart Failure 2018; 5: 249–261 Published online 12 December 2017 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ehf2.12243 ARTICLE Cardiovascular magnetic resonance imaging and clinical performance of somatostatin receptor positron emission tomography in cardiac sarcoidosis Carmen Pizarro1*†, Folke Kluenker1†, Darius Dabir2, Daniel Thomas2, Florian C. Gaertner3, Markus Essler3, Christian Grohé4, Georg Nickenig1 and Dirk Skowasch1 1 Department of Internal Medicine II, Cardiology, Pneumology and Angiology, University Hospital Bonn, Bonn, Germany; 2Department of Radiology, University Hospital Bonn, Bonn, Germany; 3Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany; 4Department of Pneumology, Evangelische Lungenklinik Berlin, Berlin, Germany Abstract Aims Cardiac affection constitutes a major limiting condition in systemic sarcoidosis. The primary objective of this study was to investigate the persistence rate of cardiac sarcoid involvement by cardiovascular magnetic resonance (CMR) imaging in patients diagnosed with cardiac sarcoidosis (CS). Moreover, we examined the additional insights into myocardial damage’s characteristics gained by somatostatin receptor scintigraphy. Methods and results In a pilot study, we had previously identified cardiac involvement—diagnosed by CMR imaging—to be present in 29 of 188 patients (15.4%) with histologically proven, extra-CS. Out of these initial 29 CS-positive patients, 27 patients (49.9 ± 11.8 years, 59.3% male) were presently re-examined and underwent a second CMR study and complementary standard clinical testing. Somatostatin receptor scintigraphy using the ligand 68Ga-DOTATOC was additionally performed when clinically indicated (17 patients). Within a median follow-up period of 2.6 years, none of the initial 29 patients deceased or experienced aborted sudden cardiac death. However, two patients developed third-degree atrioventricular block that required device therapy. Among the 27 re-examined CS patients, pathological CMR findings persisted in 14 of 27 patients (51.9%). CS remission was primarily due to a resolution of acute inflammatory processes. 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) identified one patient with regions of raised tracer uptake that concorded with acute inflammatory changes, as assessed by CMR; this patient received no immunosuppressive medication at the time of PET/CT execution. Conclusions Within follow-up, CS persisted in barely half the patients, and the patients were not afflicted with cardiac death. Additional 68Ga-DOTATOC PET/CT allowed for visualization of acute myocardial inflammation. Keywords Cardiac sarcoidosis; Cardiovascular magnetic resonance; 68 Ga-DOTATOC PET/CT Received: 27 March 2017; Revised: 6 October 2017; Accepted: 23 October 2017 *Correspondence to: Carmen Pizarro, Department of Internal Medicine II, Cardiology, Pneumology and Angiology, University Hospital Bonn, Bonn, Germany. Email: †These authors contributed equally to this work. Introduction Sarcoidosis is a multisystem, non-caseating granulomatous disorder of unknown aetiology, whose epidemiology underlies geographic and ethnic variations.1,2 Cardiac sarcoidosis (CS) may occur isolatedly without any concurrent extracardiac presentation or in the context of multiorgan sarcoid affection. The clinical presentation of sarcoidal heart involvement is manifold and comprehends the whole range from clinically silent courses up to non-ischaemic cardiomyopathy and conduction system defects, depending on the location of cardiac granulomatous infiltration.3 Cardiac affection is described to be the second leading cause of death by sarcoidosis worldwide and the most common one in Japan.4,5 In turn, up to 65% of cardiac deceases are due to sudden cardiac death in consequence of conduction © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. 250 blocks or malignant ventricular arrhythmias.6 In keeping with this, the necessity of establishing accurate diagnostic strategies arises that allow for both feasible baseline diagnosis and follow-up monitoring. In a preceding, prospectively conducted trial comprising 188 patients with histologically proven sarcoidosis, we observed a prevalence of cardiovascular magnetic resonance (CMR)-based cardiac affection of 15.4%.7 In order to assess the middle-term persistence rate of CMR findings, we presently took aim at performing longitudinal investigation of CS-positive patients by CMR re-examination and correlated the hereby obtained results with standard clinical testing. Moreover, we assessed the additional insights into myocardial damage’s characteristics gained by somatostatin receptor (SSTR) scintigraphy. As demonstrated previously,8,9 receptors for somatostatin are present in the inflammatory lesions of patients with sarcoidosis and located on, e.g. granuloma epithelioid cells, macrophages, and giant cells. SSTR-directed positron emission tomography (PET) imaging might complement CMR by visualizing the aforementioned inflammatory cell’s distribution within damaged myocardium.10 In a subanalysis, we, therefore, retrospectively identified patients who additionally underwent PET/computed tomography (CT) using the SSTR ligand 68Ga-DOTA-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC) and correlated PET results with CMR findings and clinical parameters. C. Pizarro et al. The study was approved by the ethics committee of the University of Bonn and was according to the principles expressed in the Declaration of Helsinki. Written informed consent was obtained from all patients. Electrocardiography A 12-lead surface ECG was systematically obtained at the time of CMR re-conduction. Pathological electrocardiographic findings comprehended those described to be general risk stratifiers for sudden cardiac death,11 those integrated in the Heart Rhythm Society’s (HRS’s) expert consensus statement on the diagnosis and management of CS-associated arrhythmias,12 and those exposed in the revised Japanese Ministry of Health and Welfare Guidelines (JMHWG).13 All study participants underwent 24 h Holter monitoring, recorded by the SpiderView™ Ambulatory Electrocardiographic Recorder (SORIN GROUP, Munich, Germany). Holter ECG data were analysed for conduction block occurrence, as well as supraventricular and ventricular arrhythmic burden. Moreover, we examined heart rate variability as an established predictor of increased mortality and elevated risk of cardiac events in the general population.14 T-wave alternans that displays heterogeneity in ventricular repolarization and thus predicts ventricular arrhythmias in p (...truncated)