Proff J; Merkely B; Papp R; Lenz C; Nordbeck P; Butter C; Meyerhoefer J;
Doering M; MacCarter DJ; Ingel K; Thouet T; Landmesser U; Roser MJ

Europace. 23(11):1777-1786, 2021 11 08.

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.