The Harm of Delayed Diagnosis of Arrhythmogenic Cardiac Sarcoidosis

A Case Series

Jarieke C. Hoogendoorn; Maarten K. Ninaber; Sebastiaan R.D. Piers; Marta de Riva; Robert W. Grauss; Frank M. Bogun; Katja Zeppenfeld


Europace. 2020;22(9):1376-138. 

In This Article


Study Population

From the Leiden VT ablation registry, consecutive adult patients from the Netherlands with structural heart disease who underwent VT ablation between 2008 and 2018 were screened for eligibility. After exclusion of patients with other known underlying aetiologies (including coronary artery disease, inherited cardiomyopathy with likely pathogenic or pathogenic variants, congenital heart disease, hypertrophic obstructive cardiomyopathy, myocarditis, primary valve abnormalities, and exercise-induced arrhythmogenic remodelling), 129 of 531 patients were classified as 'idiopathic' non-ischaemic (left- or right-dominant) cardiomyopathy (Figure 1). Of these 129 patients, 15 patients (12%) were finally diagnosed with CS, according to Japanese or Heart Rhythm Society (HRS) Guidelines,[5,6] and were included. The study was approved by the local ethics committee (G19.005 and C16.010). All patients provided written informed consent. The data underlying this article are available in the article and in its online supplementary material.

Figure 1.

Flow chart of patients screened for eligibility. All consecutive adult patients with structural heart disease referred for catheter ablation of VT between 2008 and 2018 were screened. *Class IV- or V mutation. ARVC, arrhythmogenic right ventricular cardiomyopathy; VT, ventricular tachycardia.

Data Collection

Data on symptoms potentially related to cardiac- and extracardiac sarcoidosis (Supplementary material online, Figure S1), presence of cardiac devices, results of electrocardiography (ECG), cardiac imaging studies (including all available echocardiograms, late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), cardiac computed tomography (CT), and 18F-FDG-PET), and biopsies (both cardiac and extracardiac) were collected from medical records. In addition, documentation of VTs on ECG, Holter or device interrogation were reviewed. Details of VT ablations, pharmacological treatment and clinical outcomes were obtained.

Supplementary Figure S1.

symptoms of cardiac-(1) and extracardiac sarcoidosis(2)

Data Analysis and Definitions

First cardiac presentation was defined as first presentation at the cardiology department with symptoms and/or signs compatible with CS. The date of diagnosis was defined as the moment when diagnostic criteria were fulfilled. Time from first presentation until diagnosis was calculated per patient. Patients were divided into an 'early' and 'late' diagnosis group; 'late' diagnosis was arbitrarily defined as diagnosis later than 6 months after first cardiac presentation or post-mortem diagnosis. Signs, symptoms, and diagnostic tests at first cardiac presentation were compared between patients with early and late diagnosis.

Isolated CS was defined as no signs of extracardiac involvement, after comprehensive evaluation, including whole body 18F-FDG-PET. Arrhythmogenic CS was defined as CS with ventricular arrhythmias.

Per Patient Timeline

Per patient, a timeline was created, including onset of findings potentially related to cardiac sarcoidosis (AV-conduction disturbances, sustained VT, and cardiac dysfunction), time of diagnosis (both cardiac and extracardiac), and clinical outcomes (including VT episodes, admission for VT ablations, admission for heart failure, heart transplantation, and death). Atrioventricular conduction disturbances included 1st degree (PR > 220ms), 2nd and 3rd degree AV-block. Ventricular tachycardias occurring in clusters (within 1 month) were considered as one VT episode. If, however, VT recurred after treatment changes (e.g. change of anti-arrhythmic drugs), this was counted as a new VT episode. Ventricular tachycardia ablations included endocardial, epicardial, and surgical ablations. If during the admission a second procedure (e.g. epicardial or surgical) was planned due to mid-myocardial or epicardial substrate, this was considered as one procedure.

Cardiac Function Over Time

All available echocardiograms were reviewed from the medical records with regard to biventricular function. Both left- (LV) and right ventricular (RV) functions were divided into four categories, namely good function, mildly decreased function, moderately decreased function, and severely decreased function (Supplementary material online, Table S1).

For comparison of cardiac function over time between patients with early and late diagnosis, at least one echocardiogram per year was selected, unless there were treatment changes. As CS may affect the RV, LV, or both, the ventricle with the greatest increase or decrease in function over time was selected for the analysis of change of cardiac function. If cardiac function remained stable, the function of the most severely affected ventricle was reported.

Statistical Analysis

Categorical variables are expressed as numbers and percentages (%) and compared using the Fisher's Exact test. Continuous variables are expressed as mean ± SD or median (IQR) and compared between groups using the Student's t-test or Mann–Whitney U test. Analysis was performed using IBM SPSS Version 25 (IBM Corporation, New York, USA) and Microsoft Excel (2016). A P-value ≤0.05 was considered significant.