Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial

Adam Ali Ghotbi, Mikael Sander, Lars Køber, Berit Th Philbert, Finn Gustafsson, Christoffer Hagemann, Andreas Kjær, Peter K Jacobsen, Adam Ali Ghotbi, Mikael Sander, Lars Køber, Berit Th Philbert, Finn Gustafsson, Christoffer Hagemann, Andreas Kjær, Peter K Jacobsen

Abstract

Background: The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).

Methods: Twelve CRT patients with non-ischemic heart failure (NYHA class II-III) were enrolled in a randomized, double-blind, crossover trial, in which the basal pacing rate was set at DDD-60 and DDD-80 for 3 months (DDD-R for 2 patients). At baseline, 3 months and 6 months, we assessed sympathetic nerve activity by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL.

Results: DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac cycles vs. 64±14 bursts/100 cardiac cycles, p<0.05). The mean pVO2 increased non-significantly from 15.6±6 mL/min/kg during DDD-60 to 16.7±6 mL/min/kg during DDD-80, and p-NT-proBNP remained unchanged. The QoL score indicated that DDD-60 was better tolerated.

Conclusion: In CRT patients with non-ischemic heart failure, 3 months of DDD-80 pacing decreased sympathetic outflow (burst incidence only) compared to DDD-60 pacing. However, Qol scores were better during the lower pacing rate. Further and larger scale investigations are indicated.

Trial registration: ClinicalTrials.gov NCT02258061.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Study design.
Fig 1. Study design.
Cross-over design, including baseline and 3- and 6-month follow-up. QoL: quality of life questionnaire; MNSA: muscle sympathetic nerve activity; CRT: cardiac resynchronization therapy; bpm: beats per minute.
Fig 2. Mean heart rate, atrial pacing…
Fig 2. Mean heart rate, atrial pacing and biventricular (Biv) pacing (%) in periods 60 bpm vs. 80 bpm.
Fig 3. Top panel: Sympathetic activity in…
Fig 3. Top panel: Sympathetic activity in the 60-bpm vs. 80-bpm period.
Bursts/100 RR: sympathetic bursts per 100 cardiac cycles. Lower panel: Mean NT-proBNP (pmol/L) in the 60-bpm vs. 80-bpm period.
Fig 4. Sympathetic activity at individual levels…
Fig 4. Sympathetic activity at individual levels during the 60-bpm and 80-bpm test periods.
Bursts/100 RR: sympathetic bursts per 100 cardiac cycles during the DDD-60 and DDD-80 periods.
Fig 5. Examples of sympathetic activity and…
Fig 5. Examples of sympathetic activity and ECG recording.
Mean voltage neurograms for MSNA and electrocardiograms (ECG) in two patients. Patient no. 10 (upper panel) had a significant decrease in sympathetic activity during the DDD-80 period, while patient no. 6 (lower panel) experienced an increase in sympathetic activity during the DDD-80 period compared to the DDD-60 period.

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