Cardiac Contractility Modulation in Patients With Chronic Heart Failure and the Various Forms of Atrial Fibrillation

Study Overview
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Brief Summary
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Chronic heart failure (CHF) is a global pandemic which affects around 26 million people worldwide and develops in 10% of people over 70 years . According to the results of the EPOCHA-CHF study, CHF is detected in 7-10% of cases in the Russian Federation . Atrial fibrillation (AF) is the most common arrhythmia in patients with both preserved (HFpEF) and reduced ejection fraction (HFrEF) heart failure. The prognostic impact of AF on CHF is negative, including the significant increase in mortality and hospitalization. One of the common causes of decompensation of CHF is AF. The debut of AF in CHF is one of the markers of disease progression. Rapid development in interventional cardiology due to the invention of cardiac catheter technologies during the last decades provided a new option for non-pharmacological treatment of CHF. Nowadays the use of electrophysiological methods of treatment can significantly improve the prognosis of CHF. Pacemakers, cardiac resynchronization devices, and cardioverter defibrillators are the most commonly implanted devices in patients with CHF. In 2014, the European Society of Cardiology presented a report of the European Heart Rhythm Association on the use of new devices for CHF, including the Optimizer device for delivery of cardiac contractility modulation therapy (CCM) . It is worth noting that CCM is a new step in the CHF treatment. This device is of proven benefit to patients with symptomatic heart failure on optimal medical therapy who do not qualify for cardiac resynchronization therapy. Multiple studies of CCM show clinical improvement with this therapy, including metrics such as peak VO2, 6MW, and NYHA functional class. However, the vast majority of patients enrolled in these studies were patients in sinus rhythm. As the technology progressed and the need for the trial sensing led wanted, further experiences incorporated patients with AF. A new generation of devices (Optimizer Smart®), which does not require the implantation of an atrial electrode made it possible to implant CCM in patients with AF. The present trial demonstrates the results of a pilot study conducted in National Medical Research Center of Cardiology Ministry of Health of the Russian Federation which compares the efficacy of CCM in patients with AF and ischemic and non-ischemic CHF compared to patients who received only optimal drug therapy CHF

Detailed Description
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Background: Chronic heart failure (CHF) and atrial fibrillation (AF) often coexist and lead to severe decompensation of patients' lifestyle. Nowadays device therapy such as cardiac contractility modulation (CCM), which is used in addition to medical treatment, can significantly impact further prognosis and outcomes of patients with such comorbidities. Methods: In the National Medical Research Center of Cardiology we conducted a study dedicated to investigating the efficacy of CCM in patients with CHF and AF. 200 patients with Hf and AF were included in the study and were divided into two groups according to implantation of a heart contractility modulation device and optimal drug therapy. 100 patients were implanted with a CCM Optimizer device without an atrial lead, per the protocol specifications ( 1 group) and 100 patients ( 2 group) received only optimal drug therapy CHF The following studies were performed in the 200 patients with CHF and AF before implantation of the MCC device and after 2 and 6 и 12 months of follow-up: 12-channel ECG with an estimate of the width of the QRS complex, transthoracic EchoCG, Speckle-tracking EchoCG, Myocardial work, 6-minute walk test, determination of the level of Pro-natriuretic N-terminal peptide (NT-proBNP), Holter ECG, and a questionnaire based on the Minnesota quality of life questionnaire for patients with CHF (MHFLQ),Perfusion Single-Photon Emission Computed Tomography All patients received long-term optimal drug therapy for CHF before surgery.

Official Title
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Cardiac Contractility Modulation in Patients With Chronic Heart Failure and the Various Forms of Atrial Fibrillation

Conditions
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Heart Failure, Atrial Fibrillation, Left Ventricular Ejection Fraction

Intervention / Treatment
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* Device: optimizer smart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HFrEF (20-40%) NYHA FC II-III for at least 3 months before screening AF Optimal CHF therapy and the absence of decompensations in ≥ 1 month. Exclusion Criteria: Refusal to participate in the study Placement on the heart transplant waiting list, or post heart transplantation Terminal CHF Co-morbid diseases that may adversely affect the safety and / or efficacy of treatment Recent surgical intervention or trauma Medical conditions that limit life expectancy to 1 year.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Optimizer device<br>100 patients were enrolled sequentially, 100 patients were implanted with an optimizer smart against the background of optimal drug therapy for heart failure 100 patients were implanted with a CCM Optimizer device without an atrial lead, per the protocol specifications recived optimal drug therapy CHF The following studies were performed in the 100 patients with CHF and AF before implantation of the MCC device and after 2 and 6 и 12 months of follow-up: 12-channel ECG with an estimate of the width of the QRS complex, transthoracic EchoCG,Speckle-tracking EchoCG,Myocardial work, 6-minute walk test, determination of the level of Pro-natriuretic N-terminal peptide (NT-proBNP), Holter ECG, and a questionnaire based on the Minnesota quality of life questionnaire for patients with CHF (MHFLQ). | Device: optimizer smart<br>* The CCM implantation procedure was performed in the right precordial region of the chest (the right subclavian area). Two active fixation Ingevity leads (Boston Scientific) were advanced via the right subclavian vein into the right ventricle (RV) and actively fixed to the right ventricular septum for ventricular sensing and delivery of CCM signals.<br>|
| No Intervention: Without Optimizer device<br>100 patients were enrolled sequentially,100 patients received only optimal drug therapy for chronic heart failure 100 patients ( Without Optimizer device ) with CHF and AF before study and after 2 and 6 и 12 months of follow-up: 12-channel ECG with an estimate of the width of the QRS complex, transthoracic EchoCG,Speckle-tracking EchoCG,Myocardial work, 6-minute walk test, determination of the level of Pro-natriuretic N-terminal peptide (NT-proBNP), Holter ECG, and a questionnaire based on the Minnesota quality of life questionnaire for patients with CHF (MHFLQ). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular death + hospitalization due to decompensation of HF | Number of Participants with cardiovascular death + hospitalization due to decompensation of HF | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death from all causes | Number of Participants with death from all causes | 12 month | 
| hospitalization for any reason | Number of Participants with hospitalization for any reason | 12 month | 
| development of AF paroxysm in patients with paroxysmal AF | Number of Participants with development of AF paroxysm in patients with paroxysmal AF | 12 month | 
| worsening of the course of CHF, which required an outpatient visit and increased doses of diuretics | Number of Participants with worsening of the course of CHF, which required an outpatient visit and increased doses of diuretics | 12 month | 
| complications that required removal of the MCC | Number of Participants with complications that required removal of the MCC | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac contractility modulation, Atrial Fibrillation, Heart Failure, Narrow QRS Complex, left ventricular ejection fraction