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

Fifteen patients were included (60% male, 51 ± 8 years at first presentation). The final diagnosis of CS was based on histology in 10 patients: positive cardiac histology in 6 patients and positive extracardiac histology in conjunction with cardiac signs in 4 patients (HRS guidelines[5]). The remaining five patients did not have histological confirmation, but they fulfilled clinical and imaging criteria according to the Japanese guidelines.[6]

Isolated CS was present at moment of diagnosis in five patients (33%); three of them had histological confirmation and two patients had a clinical diagnosis. Of note, of the 10 patients with systemic sarcoidosis, only 2 had complaints of extracardiac involvement; the remaining were diagnosed after comprehensive evaluation without symptoms of extracardiac disease. Presence of major diagnostic criteria per patient are listed in Supplementary material online, Table S2.

Patients With Early Diagnosis

Five patients were diagnosed early (Table 1 and Figure 2). All of them had an early arrhythmogenic presentation with VTs, prompting appropriate additional evaluation with biopsy and/or 18F-FDG-PET.

Figure 2.

Per patient timeline from first presentation related to (extra)cardiac sarcoidosis until last follow-up or death, ordered by time between first presentation and diagnosis. On the Y-axis gender (M/F) and age at first cardiac presentation (years). Diagnosed at autopsy. AV, atrioventricular; CS, cardiac sarcoidosis; F, female; M, male; VT, ventricular tachycardia.

Patients With Late Diagnosis

Ten patients were diagnosed late, with a median delay of 24 (IQR 15–44) months (Table 1 and Figure 2). One patient with a delayed diagnosis was diagnosed at autopsy. First clinical presentation was VT in five, AV-block in three, and heart failure (in combination with 1st degree AV-block) in one. One patient was known with histologically proven extracardiac sarcoidosis and referred for cardiac evaluation because of an abnormal 12-lead surface ECG.

The most common misdiagnoses in patients with delayed diagnosis was arrhythmogenic right ventricular cardiomyopathy and ischaemic cardiomyopathy despite normal angiogram (Figure 3A). Of importance, in six patients, the diagnosis of CS was suspected during electroanatomical voltage mapping (EAVM). In these patients, the EAVM scar pattern was not consistent with the diagnosis at referral, leading to additional evaluation with biopsy and/or 18F-FDG-PET (Figure 3B).

Figure 3.

Misdiagnosis and reason for suspicion of cardiac sarcoidosis in patients with delayed diagnosis. Misdiagnosis in patients with delayed diagnosis (A) and reason for suspicion of diagnosis in these patients (B). ARVC, arrhythmogenic right ventricular cardiomyopathy; CT, computed tomography; EAVM, electroanatomical voltage mapping; EMB, endomyocardial biopsy; ICM, ischaemic cardiomyopathy; NICM, non-ischaemic cardiomyopathy; VT, ventricular tachycardia.

Comparison of Patients With Early vs. Late Diagnosis

Symptoms of cardiac and extracardiac disease at first cardiac presentation were similar between patients with early and late diagnosis (Table 1).

However, of importance, 18F-FDG-PET was performed at first cardiac presentation in four of five patients with early diagnosis, showing focal myocardial FDG-uptake in all of them. On the contrary, 18F-FDG-PET was not performed in any of the patients with late diagnosis at first presentation. Similarly, in four of five patients with early diagnosis cardiac biopsy was performed, whilst in only one patient with late diagnosis (with a negative result).

There was no difference between early and late diagnosed patients, with regard to the first arrhythmic presentation (electrical storm and/or out of hospital cardiac arrest). Besides, the characteristics of the VT were also not different between groups at first arrhythmic presentation. The cycle length of the VT was available in all early diagnosed patients and 7 (70%) late diagnosed patients and did not differ significantly (median 400 ms vs. 375 ms, respectively; P = 0.530).

Cardiac Function Over Time

Cardiac function over time in patients with early and late diagnosis is shown in Figure 4. All patients with early diagnosis had active disease (on biopsy and/or 18F-FDG-PET) and were treated with immunosuppressive therapy. Of interest, in all but one patient, cardiac function was mildly decreased at baseline and remained stable during follow-up.

Figure 4.

Cardiac function over time. Cardiac function from first cardiac presentation until last follow-up or death in patients with early diagnosis (A) and late diagnosis (B). Red lines indicate undiagnosed cardiac sarcoidosis (CS), green lines indicate diagnosed CS, and dashed lines show treatment with immunosuppressive therapy.

On the contrary, 9 of 10 patients with late diagnosis had a preserved function at baseline (good to mildly decreased). However, 7 of 10 patients with late diagnosis had a decrease in function before diagnosis. Six of seven patients with decrease in function were treated with immunosuppressive therapy after diagnosis because of active sarcoidosis (biopsy and/or 18F-FDG-PET), and only in one of them function recovered with immunosuppressive therapy. One patient with a mildly decreased function at baseline and stable function over time died before immunosuppressive therapy, with active sarcoidosis at autopsy.

Treatment and Outcomes

Median follow-up time from first cardiac presentation until last follow-up was 55 (IQR 25–88) months. All patients were implanted with an implantable cardiac defibrillator (ICD); six patients (40%) received cardiac resynchronization therapy (CRT).

With regard to treatment, more than one admission for VT ablation was needed in 10 patients (67%). Notably, median number of VT ablations was 1 (IQR 1–2) in the early diagnosed group, compared to 3 (IQR 2–4) in patients with late diagnosis (P = 0.056). Beside, anti-arrhythmic (AAD) therapy was escalated in 11 patients including amiodarone (n = 6) and mexiletine (n = 3).

Heart failure admission was needed in only one patient with early diagnosis, compared to five patients with late diagnosis.

Six patients died (40%), of which five had a late diagnosis. The cause of death was terminal heart failure (n = 3; two awaiting transplant), ventricular arrhythmias unresponsive to ICD therapy (n = 1) and infection (n = 2) (Figure 2).