(P138) RELATIONSHIP BETWEEN PVC BURDEN, STEROIDS AND METHOTREXATE IN PATIENTS WITH CARDIAC SARCOIDOSIS; INSIGHTS FROM IMPLANTABLE CARDIOVERTER DEFIBRILLATOR DIAGNOSTICS

Background: Ventricular tachycardia (VT) occurs in cardiac sarcoidosis (CS), due to PVC triggered macro-reentry around fibrosis areas. Immunosuppression (IS) is used, trying to suppress the PVCs triggering the VT; this approach is recommended by guidelines despite minimal data. In contrast, our group recently demonstrated, on average, a three-fold increase in daily PVC count in clinically-manifest CS patients during treatment with corticosteroids compared to pre-treatment. This study extends those findings by examining PVC burden when patients on Methotrexate monotherapy.

METHODS AND RESULTS: A single-centre, prospective cohort study was performed in consecutive patients who met all the following criteria:
1. Presentation with clinically-manifest cardiac sarcoidosis
2. Abnormal myocardial FDG uptake on PET scan
3. Implantation with ICD device reporting accurate PVC count
4. Initiation of systemic corticosteroids after device healing*
5. Initiation of Methotrexate as second-line therapy if patients relapsed (based on PET) after discontinuation of steroids (12-month course)*
(*these are two components of our institutional treatment protocol for clinically manifest CS)
Data was collected for each device interrogation visit for all patients in the study. For each visit, the total number of PVCs since the last device interrogation was obtained. The daily average PVC count was calculated using the total PVC count since the last visit and the total number of days since the last visit. Each inter-visit period was classified into one of the following treatment periods.
1. New diagnosis of treatment-naive active disease and no steroids or other IS initiated during the period.
2. On steroid therapy during the entire period
3. On Methotrexate monotherapy
4. Could not be classified into one of the above (transition periods)
A total of 14 patients with mean age 59.7 ± 7.7 years were recruited (63% were female). Summary data is shown in the table. Patients with active untreated CS had an average of 312.78 ± 402.13 PVCs per day. After treatment with steroids the average daily PVC count increased to 1009.79 ± 1511.66. After treatment with Methotrexate the average PVC count was 490.07±810.93/day.

Conclusion: This study confirmed a three-fold increase in daily PVC count in clinically manifest CS patients during treatment with corticosteroids compared to before any treatment. Following PET documented disease relapse and initiation of Methotrexate therapy, the average PVC count was 57% higher than when patients were treatment-naive. These data suggest that the pro-arrhythmic effect may be largely specific to steroids, perhaps related to a similar mechanism of steroid induced hypertension (cardiac epinephrine receptor blockade).