Pacemaker implantation due to cardiac conduction disease in patients with subsequent cardiac sarcoidosis may be a marker of early disease and is associated with adverse 5-year clinical outcome
Authors: Slattman A , Chaudhry U , Carlson J , Bollano E , Borgquist R , Platonov P G 
Published: October 2022

Abstract

Background
Sarcoidosis is a rare chronic granulomatous disease of unknown aetiology with potential multi-organ involvement and end-organ dysfunction. Cardiac sarcoidosis (CS) occurs in 5–10% of patients with sarcoidosis though an up to 25% prevalence has been reported by imaging and autopsy studies, suggesting undiagnosed silent disease. Progression of CS, especially if undiagnosed and untreated, may lead to heart failure, atrioventricular block (AVB), ventricular arrhythmias and sudden cardiac death.

Aim
We sought to determine whether signs of cardiac conduction disease (CCD) prior to the clinical diagnosis of sarcoidosis is associated with poor long-term prognosis in patients with imaging-confirmed cardiac involvement.

Method
All patients diagnosed with CS since January 1, 2000, at a tertiary centre (n=112) with either primary cardiac localisation (n=70) or cardiac involvement in otherwise primary non-cardiac sarcoidosis (n=42) as per imaging were included. Swedish pacemaker and ICD registry was used to identify patients who received cardiac implantable electronic device (CIED). CCD-related indications for CIED implant were defined as AVB, bi- or trifascicular block. Kaplan-Meier curve analysis and time-dependent Cox regression analysis were used for estimation of risk of death from any cause (primary endpoint), death or upgrade to cardiac resynchronization therapy (CRT, secondary endpoint) at 5 years after CS diagnosis, stratified for history of CIED implantation due to CCD. Hazard ratios were calculated in a univariate model and adjusted for age, gender and the use of implantable cardioverter-defibrillator (ICD).

Results
Mean age at CS diagnosis was 59±13 years (54% male). Forty-nine patients received CIED implant at a mean age of 54±13 years (14 pacemakers (29%), 14 primary prevention ICDs (29%), 13 secondary prevention ICDs (27%) and 8 CRT-D (16%)). The median time in years from CS diagnosis to CIED implant was for pacemaker −2.5 [IQR 8.5], primary ICD −0.3 [IQR 3.8], secondary ICD −4.0 [IQR 10.4] and CRT-D −0.03 [IQR 1.5]. CIED was implanted prior to CS diagnosis in 29 patients of whom 17 had CCD [MOU1] as the indication for implant. At 5-year follow-up in the CS cohort, 16 patients died and 2 underwent device upgrade to CRT (median 3.2 years [IQR 1.2]). CIED implant prior to CS diagnosis was associated with the primary (HRuni 3.5, 95% CI 1.2–10, p=0.021, Figure 1; HRadj 10.5, 95% CI 1.7–63, p=0.01) and the secondary (HR 3.5, 95% CI 1.2–10, p=0.019; HRadj 8.2, 95% CI 1.6–41.1, p=0.011) endpoints.

Conclusion
CIED implantation due to CCD can be an early manifestation of undiagnosed CS. It was observed in 15% of all patients with CS and was associated with adverse outcome. Identification of signs of CCD necessitating CIED implant in a middle-aged patient may motivate further diagnostic work-up aimed at timely detection of concealed CS.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Hjärt-Lung fondenAvtal om Läkarutbildning och Forskning