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Randomized Controlled Trial
. 2024 Jul 2;26(7):euae175.
doi: 10.1093/europace/euae175.

Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions

Ennio C L Pisanò  1 , Valeria Calvi  2 , Miguel Viscusi  3 , Antonio Rapacciuolo  4 , Ludovico Lazzari  5 , Luca Bontempi  6 , Gemma Pelargonio  7 , Giuseppe Arena  8 , Vincenzo Caccavo  9 , Chun-Chieh Wang  10 , Béla Merkely  11 , Lian-Yu Lin  12 , Il-Young Oh  13 , Emanuele Bertaglia  14 , Davide Saporito  15 , Maurizio Menichelli  16 , Antonino Nicosia  17 , Domenico M Carretta  18 , Aldo Coppolino  19 , Chi Keong Ching  20 , Álvaro Marco Del Castillo  21 , Xi Su  22 , Martina Del Maestro  23 , Daniele Giacopelli  23 , Alessio Gargaro  23 , Giovanni L Botto  24
Affiliations
Randomized Controlled Trial

Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions

Ennio C L Pisanò et al. Europace. .

Erratum in

Abstract

Aims: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing.

Methods and results: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms.

Conclusion: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.

Keywords: Accelerometer pacemaker sensor; Atrial fibrillation; Atrial high-rate episodes; Closed loop stimulation; Rate-adaptive pacing; Stroke.

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Conflict of interest statement

Conflict of interest: G.L.B. received speaker’s fee from Abbott, Biotronik, Boston Scientific, Medtronic, and MicroPort. M.D.M., D.G., and A.G. are employees of Biotronik Italia S.p.A., an affiliate of Biotronik SE & Co. KG (study sponsor and manufacturer of investigational devices). All remaining authors have declared no conflicts of interest.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Trial flow chart (CONSORT diagram). All patients had an implanted device at enrolment. The randomization visit took place 90 ± 30 days after implantation. CLS, closed loop stimulation; DDDR, dual-chamber rate-adaptive.
Figure 2
Figure 2
Kaplan–Meier estimate for the incidence of AHRE ≥ 6 min by study arm on the intention-to-treat basis. P-value was calculated using Cox proportional hazard models stratified by site. AHRE, atrial high-rate episode; CI, confidence interval; CLS, closed loop stimulation; DDDR, dual-chamber rate-adaptive; HR, hazard ratio.
Figure 3
Figure 3
Percentage of atrial pacing in the two study arms. Data are shown as box plot with boxes representing median values (inner lines) and the IQR and whiskers representing adjacent value ranges (1.5 times the range of the nearest quartile). CLS, closed loop stimulation; DDDR, dual-chamber rate-adaptive.
Figure 4
Figure 4
Subgroup analyses of AHRE ≥ 6 min stratified by site (intention-to-treat). For CHA2DS2-VASc, see Table 1. CI, confidence interval; HR, hazard ratio.
Figure 5
Figure 5
Kaplan–Meier estimate for the incidence of AHRE ≥ 6 min in patients without vs. with AV block (A), and in patients without vs. with history of AF (B). P-values were calculated using Cox proportional hazard models stratified by site. AF, atrial fibrillation; AHRE, atrial high-rate episode; AV, atrioventricular; CI, confidence interval; CLS, closed loop stimulation; DDDR, dual-chamber rate-adaptive; HR, hazard ratio.
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