Dual Medical Therapy for Treatment of Arrhythmias in Cardiac Sarcoidosis

Abstract

Anti-arrhythmics can be useful for ventricular arrhythmias in cardiac sarcoidosis (CS) that are refractory to immunosuppression. However, there is conflicting evidence on the efficacy of immunosuppression for treating arrhythmias in CS patients and a lack of data to support using immunosuppression alone as an initial strategy. The objective of this study was to assess for differences in arrhythmia burden over time with currently used immunosuppression and anti-arrhythmic regimens. Patients with CS and implanted cardiac devices were identified from a single-center registry. Study participants were retrospectively classified based on the medication regimen as follows: control (no therapy), immunosuppression, anti-arrhythmics, or dual therapy. Device interrogations were reviewed for premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT), and device firings over time. Interrogations for 42 patients were reviewed over a mean period of 31 months. Regression analysis showed a significant decrease in the frequencies of PVCs (slope, -1.47; P = .04) and NSVT (slope, -0.05; P = .01) for patients on dual therapy compared to an increase or no change in the other groups. Across all patients, there was no difference between groups in the percentage of patients experiencing device firings. In a subset analysis of patients with implantable cardioverter-defibrillators for primary prevention, 6% on dual therapy required device firings compared to 43% and 40% on single or no therapy, respectively (P = .049, χ² = 6.02). In conclusion, patients on both immunosuppression and anti-arrhythmics had a reduction in PVCs and NSVT over time. Overall, there were no differences between groups in terms of device firings, except in a subset analysis of patients with no history of ventricular tachycardia.

Keywords: Anti-arrhythmics; cardiac devices; immunosuppression; sarcoidosis; ventricular arrhythmias.

Figure 1:

Fluorodeoxyglucose positron emission tomography myocardial metabolic evaluation for patient 42 showing focal uptake in the basal septum, left ventricular anterior wall, and (to a lesser extent) the free wall of the right ventricle, suggestive of active inflammation.

Figure 2:

Patients with cardiac sarcoidosis reviewed for inclusion and exclusion. Device firing was defined as any indicated anti-tachycardia pacing or shock. Abbreviations: ICD, implantable cardioverter-defibrillator; NSVT, non-sustained ventricular tachycardia; PPM, permanent pacemaker; PVC, premature ventricular contraction.

Figure 3:

Premature ventricular complexes (PVCs) per hour over time for patients on immunosuppression alone compared to dual therapy. Patients on immunosuppression alone had a statistically significant increase in PVCs over time, whereas those on dual therapy had a decrease in PVCs over time. P values were calculated for the significance of the x variable (slope). The graphs for PVCs/h for the remaining treatment groups are provided in the Supplement. Abbreviation: PVC, premature ventricular contraction.

Figure 4:

Non-sustained ventricular tachycardia (NSVT) episodes per month over time for patients on immunosuppression alone compared to dual therapy. The immunosuppression-alone patients had no significant change in the number of NSVT events over time, while those on dual therapy had a statistically significant decrease. The P value denotes significance of the x variable (slope). The graphs for NSVTs over time for the remaining treatment groups are provided in the Supplement. Abbreviation: NSVT, non-sustained ventricular tachycardia.

Figure 5:

Non-sustained ventricular tachycardia (NSVT) episodes per month over time for a subgroup of patients on dual therapy whose regimen included a class III anti-arrhythmic (amiodarone or sotalol). Medical therapy in this group had a significant impact, with almost no NSVT events recorded after 5 months. The P value denotes significance of the x variable (slope). Abbreviations: ICD, implantable cardioverter-defibrillator; NSVT, non-sustained ventricular tachycardia.

Figure S1:

Premature ventricular contractions (PVCs) per hour for group 4b (immunosuppression + amiodarone or sotalol) over time. Patients on dual therapy that included amiodarone or sotalol experienced a marked decrease in PVCs over the course of the study.

Figure S2:

Premature ventricular contractions (PVCs) per hour for each interrogation over the follow-up period by treatment group. The blue markers and bars denote median and interquartile range (IQR) values, respectively. The PVC values for each group were as follows. Group 1 (no therapy) (n = 43): median, 17.3; IQR, 7.0–38.5. Group 2 (immunosuppression alone) (n = 30): median, 16.5; IQR, 1.4–87.3. Group 3 (anti-arrhythmic alone) (n = 49): median, 5.7; IQR, 0.9–54.8. Group 4 (dual therapy) (n = 199): median, 22.5; IQR, 3.5–101.8. Group 3 had a statistically lower median PVC count than group 4 (P = .035); otherwise, there were no differences between groups. Abbreviations: PVC/h, premature ventricular contractions per hour; n, number of PVC readings (1 per interrogation).

Figure S3:

Average non-sustained ventricular tachycardia (NSVT) events per month from all interrogations over the follow-up period by treatment group. The blue markers and lines denote median and interquartile range (IQR) values, respectively. The NSVT values for each group were as follows. Group 1 (no therapy) n = 35: median, 0.0; IQR 0.0–0.43. Group 2 (immunosuppression alone) (n = 57): median, 0.0; IQR 0.0–2.08, Group 3 (anti-arrhythmic alone) (n = 57): median, 0.0; IQR, 0.0–0.68. Group 4 (dual therapy) (n = 246): median, 0; IQR, 0.0–1.0. Abbreviation: n, total number of NSVT values (1 value per interrogation).

Figure S4:

Non-sustained ventricular tachycardia (NSVT) episodes per month for patients on dual therapy, including amiodarone or sotalol, over time. There was a significant decrease in NSVT episodes over time in this subset of patients, with almost no episodes of NSVT occurring after 5 months of therapy.