Impact of closed loop stimulation on prognostic cardiopulmonary variables in patients with chronic heart failure and severe chronotropic incompetence: a pilot, randomized, crossover study

Abstract

Aims Clinical effects of rate-adaptive pacing in heart failure patients with chronotropic incompetence (CI) undergoing cardiac resynchronization therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS in CRT patients with severe CI, focusing primarily on key prognostic variables assessed by cardiopulmonary exercise (CPX) testing. Methods and results In the randomized, crossover, multicentre BIO|CREATE study, 20 CRT patients with severe CI and NYHA Class II/III (60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode, or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode). Patients underwent symptom-limited treadmill-based CPX test in each mode. An improvement (decrease) of the ventilatory efficiency (VE) slope of ≥5% during CLS was regarded as positive response to CLS. Seventeen patients with full data sets had a mean intra-individual VE slope change of −1.8 ± 3.0 (−4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS responders, with a −6.1 ± 2.7 (−16.4%) slope change (P = 0.029). Compared to non-responders, CLS responders had a higher left ventricular (LV) ejection fraction (46 ± 3 vs. 36 ± 9%; P = 0.0070), smaller end-diastolic LV volume (121 ± 34 vs. 181 ± 41 mL; P = 0.0085), smaller end-systolic LV volume (65 ± 23 vs. 114 ± 39 mL; P = 0.0076), and were predominantly in NYHA Class II (P = 0.0498). Conclusion The data of the present pilot study are compatible with the notion that CLS activation may improve VE slope in CRT patients with severe CI and less advanced heart failure. Further research is needed to determine the long-term clinical outcomes of CLS.

Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial

“…Previous studies in heart failure patients undergoing CRT and CI have shown that the CLS mode can improve VE/VCO 2 and the QoL. 7 , 15 , 16 Notably, patients with CRT with improved ejection fraction were more likely to respond positively to CLS-based rate-adaptive pacing, whereas those with reduced ejection fraction were less likely to respond. 7 , 16 …”

“…In accordance with criteria chosen based on previous studies, CI was defined as a maximum HR < 75% of the age-predicted maximum HR (APMHR = 220—age, applicable to healthy populations) during the exercise test. 7 , 9 , 12 Patients who did not meet the criteria for CI were subsequently excluded from further participation in the study.…”

Application and optimization of the rate response function in dual-chamber pacemakers: Prospective, randomized, cross-over clinical trial study protocol

“…The current state of knowledge on the use and optimization of the function of frequency adaptation in pacemakers is insufficient due to the small number of studies available and the contradictory results that have been recorded [4][5][6][7][8][9]. Furthermore, specific recommendations in the guidelines of the European Society of Cardiology on cardiac pacing and cardiac resynchronization therapy are limited [2,3].…”

“…Furthermore, specific recommendations in the guidelines of the European Society of Cardiology on cardiac pacing and cardiac resynchronization therapy are limited [2,3]. Many studies rely on the electrocardiographic treadmill exercise test as an objective method of assessment of physical performance and progress in cardiac rehabilitation or for optimization of settings of implantable devices and cardiac [7,12,13]. Therefore, this study will deepen the research on the impact of the rate response function on physical performance in a homogeneous group of patients and will reveal which patients would benefit the most from rate-adapted pacing.…”

“…However, the impact of this function in dual-chamber pacemakers on the physical performance remains to be fully elucidated [2][3]. Results from previously conducted studies are inconsistent as to the method of optimal programming of the rate response function [4][5][6][7][8][9]. The European Society of Cardiology guidelines do not contain exhaustive recommendations on how to program, and for which parameters to optimize, the rate response function in patients with cardiological disorders coexisting with chronotropic insufficiency [2][3].…”