Closed loop stimulation in patients with chronic heart failure and severe chronotropic incompetence: Responders versus non-responders.

BACKGROUND: Clinical effects of rate-adaptive pacing (RAP) are unpredictable and highly variable among cardiac resynchronization therapy (CRT) patients with chronotropic incompetence. Physiologic sensors such as Closed Loop Stimulation (CLS), measuring intracardiac impedance changes (surrogate for ventricular contractility), may add clinical benefit and help identify predictors of response to RAP. The objective of the present BIOlCREATE study subanalysis was to identify criteria for selection of CRT patients who are likely to respond positively to CLS-based RAP. METHODS: In the randomized, crossover BIO|CREATE study, CRT patients with severe chronotropic incompetence and NYHA class II/III were randomized to CLS with conventional upper sensor rate programming or to no RAP for 1 month, followed by crossover for another month. At 1-month and 2-month follow-ups, patients underwent treadmill-based cardiopulmonary exercise test. Positive CLS response was defined as a ≥ 5% reduction in ventilatory efficiency slope. Eight of 17 patients (47%) were CLS responders. In this subanalysis, we compared responders and non-responders to explore outcomes, mechanisms, and predictors. RESULTS: All cardiopulmonary variables, health-related quality of life, patient activity status, and NT-proBNP concentration showed favorable trend in CLS responders and unfavorable trend in non-responders, underlining the need to find predictors. Following all analyses, we recommend CLS in heart failure patients with improved left ventricular ejection fraction (LVEF >40%, after a ≥ 10-point increase from a CRT-pre-implant value of ≤40%), corresponding to 'HFimpEF' in the universal classification system. CONCLUSION: HFimpEF patients are likely to benefit from CLS-based RAP, in contrast to 'HFrEF' (heart failure with reduced LVEF [≤40%]).

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

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.