Pilot Study to Investigate the Creation of Physiological Rhythm by Closed Loop Stimulation in hEart Failure pAtients With chronoTropic incompEtence

Study Overview
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Brief Summary
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The study assesses the effect of Closed Loop Stimulation (CLS) on the ventilatory efficiency slope and estimates the patient responder rate to CLS in patients with severe chronotropic incompetence treated with a cardiac resynchronization therapy (CRT) device.

Detailed Description
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In patients with pharmacological refractory heart failure (HF), systolic dysfunction, and cardiac dyssynchrony, the cardiac resynchronization therapy (CRT) reduces the risk of death, and improves symptoms and quality of life. A considerable portion (80%) of patients with a CRT indication has a chronotropic incompetence (CI). CI usually induces a stress intolerance which negatively affects the quality of life. In addition of being a marker of diminished exercise capacity, severe CI (sCI) may be an independent predictor of mortality. The sensor-based rate adaption provided by the implanted CRT device delivers a possible therapeutic approach for the CI. Usually, rate adaption is achieved by an accelerometer. The previous studies in terms of effectiveness of rate adaption in CRT patients with CI showed inconsistent results. In addition to an accelerometer to deliver the rate adaption BIOTRONIK provides closed loop stimulation (CLS) as unique feature in a CRT device. CLS determines the appropriate heart rate based on intra-cardiac impedance measurements. These measurements reflect changes of the cardiac contraction dynamics in reaction to information coming from the autonomic nervous system. CLS takes the information on the contraction dynamics and translates it into an adequate heart rate adaptation, thus delivering physiologically appropriate therapy.

Official Title
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BIO|CREATE Pilot Study

Conditions
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Heart Failure, CPX

Intervention / Treatment
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* Device: Cardiac Resynchronization therapy device with Closed Loop Stimulation (CLS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CRT class I indication at time of implantation, according to current guidelines Implantation of CRT-device including CLS > 6 months prior to enrollment Stable heart failure status for at least 1 month Optimal cardiovascular drug treatment according to current guidelines NYHA class II or III Patient is able to comply with the protocol Patient provided written informed consent Stable location of residence Exclusion Criteria: Planned cardiovascular intervention within the next 3 months Admission for decompensated heart failure or acute coronary syndrome in the preceding 3 months Ongoing symptoms of myocardial ischemia Known persistent, long-standing persistent or permanent atrial fibrillation COPD with GOLD ≥ 3 Planned absence of residence for more than one week during study period Pregnant or breast-feeding women Participation in another interventional clinical investigation Age < 18 years Placed in an institution due to official decree or judicial order Dependent from the sponsor, the clinical site or the investigators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients are randomized in two different pacing modes (CLS versus intrinsic rhythm) after one month after enrollment. The cross-over takes place after one month after the randomization.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pacing mode with CLS<br> | Device: Cardiac Resynchronization therapy device with Closed Loop Stimulation (CLS)<br>* The feature CLS will be programmed ON or Off according to a randomization list after one month after baseline visit. One month later the alternate will be programmed.<br>* Other names: Cardiac Resynchronization therapy device without Closed Loop Stimulation (CLS);|
| Active Comparator: Intrinsic mode<br> | Device: Cardiac Resynchronization therapy device with Closed Loop Stimulation (CLS)<br>* The feature CLS will be programmed ON or Off according to a randomization list after one month after baseline visit. One month later the alternate will be programmed.<br>* Other names: Cardiac Resynchronization therapy device without Closed Loop Stimulation (CLS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory efficiency slope | The slope of VE/VCO2 describes the ventilatory efficiency during effort, showing the amount of air that must be ventilated to eliminate 1 litre of CO2. | 2 months |