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

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

Study Overview

• Status: Completed
• Conditions: Heart Failure; Atrial Fibrillation; Left Ventricular Ejection Fraction
• Intervention / Treatment: Device: optimizer smart

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 121552
    • Alfiya Safiullina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Optimizer device; 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; 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.
NO_INTERVENTION: Without Optimizer device; 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?

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

Collaborators and Investigators

• Sponsor: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• Collaborators: Ministry of Health, Russian Federation
• Investigators: Principal Investigator: Alfiya Safiullina, phd, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Publications and helpful links

General Publications

• Uskach TM, Safiullina AA, Sapel'nikov OV, Amanatova VA, Nikolaeva OA, Grishin IR, Nazarov BM, Tereshchenko SN. [Modulation of cardiac contractility in patients with chronic heart failure and atrial fibrillation]. Ter Arkh. 2020 Oct 14;92(9):8-14. doi: 10.26442/00403660.2020.09.000598. Russian.
• Dobrovolskaya SV, Saidova MA, Safiullina AA, Uskach TM, Tereshchenko SN. [Evaluation of the effectiveness of the chronic heart failure therapy using the device cardiac contractility modulation according to the new non-invasive method of the myocardium work analysis]. Kardiologiia. 2021 Dec 31;61(12):31-40. doi: 10.18087/cardio.2021.12.n1849. Russian.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 31, 2018
• Primary Completion (ACTUAL): December 10, 2019
• Study Completion (ACTUAL): March 30, 2022

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (ACTUAL): September 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Heart Failure; Atrial Fibrillation; left ventricular ejection fraction; Cardiac contractility modulation; Narrow QRS Complex
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Failure; Atrial Fibrillation
• Other Study ID Numbers: КА-027-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No