Cardiac Contractility Modulation therapy delivers non-excitatory electrical pulses to the heart and is indicated for adult patients with CHF resulting from left ventricular dysfunction despite appropriate medical treatment. Now, with the Optimizer Smart, the therapy can be given to CHF patients with rhythms that are not sinus. The therapy is mentioned in ESC 2016 guidelines for the diagnosis and treatment of acute and chronic heart failure.
Mechanism of Action
Chronic Heart Failure induces mechanical and neuro-hormonal stresses on myocardial cells. The effects of these stresses have a progressive negative impact on left ventricular function, inducing left ventricular remodeling and recapitulation of the fetal gene program.
Studies performed in humans and in dogs with heart failure have established that Cardiac Contractility Modulation therapy reverses the left ventricular remodeling characteristic of CHF and improves left ventricular contractile strength. These effects are the result of a chain of intracellular molecular processes, which are apparent just seconds after initiating the treatment.
Cardiac Contractility Modulation signals normalize the protein function in a dog model of CHF
The signals have been shown to normalize the phosphorylation of regulatory proteins such as Phospholamban (PLB) in-vitro, within seconds of treatment. Improvement in calcium handling via SERCA2a upregulation and restoration of the sodium/calcium exchanger further increase contractile function in subjects with heart failure.
Cardiac Contractility Modulation reverses the fetal gene program to the normal adult gene program
Among the genes whose expression is down-regulated in heart failure are those of key proteins associated with intracellular cycling of calcium. These abnormalities lead to one of the primary cellular defects that underlies myocardial contractile dysfunction in heart failure. Studies in both human subjects and in dogs with heart failure demonstrated improvements in mRNA expression of several of these important calcium handling proteins in response to Cardiac Contractility Modulation therapy (figure below), consistent with reversal of the fetal gene program. These changes initially occur in the region near the electrodes and, within months, affect all regions of the heart.
Improved regional cardiac function induces global improvements and reverse remodeling
Over time, local changes result in unloading of stress and normalization of gene expression in remote areas across the entire myocardium. These interrupt the “remodeling cascade” and induce global reverse remodeling and improvement in cardiac function (figure below). 3D Echocardiographic studies in humans and ventriculography studies in animals demonstrate reverse remodeling within 3 months of initiating Cardiac Contractility Modulation therapy.
Classic positive ionotropic drug therapies are also known to improve left ventricular systolic function. However, these improvements also result in increased myocardial oxygen consumption (MVO2) which can be detrimental to already over-stressed and failing cardiac tissue. The improvement induced by Cardiac Contractility Modulation therapy, on the other hand, does not result in a detectable increase in MVO2. The improvements in left ventricular function with Cardiac Contractility Modulation are associated with improved left ventricular efficiency, similar to the effects seen with left ventricular pacing.
Imai M et al. Journal of American College of Cardiology 2007; 49:2120-8
Interview with Prof. Dr. Carsten Tschoepe
Implantation
The Optimizer Smart implantation is performed in a minimally-invasive procedure under local anesthesia. The new two lead configuration enables an easier implantation and the device can be positioned flexibly since the charging coil is integrated into the IPG header.
The IPG is generally implanted in the right pectoral region. Two right ventricular leads are placed for delivery of Cardiac Contractility Modulation signals. An optional atrial lead may be placed in the right atrial appendage (RAA) or the atrial lateral wall for additional sensing.
Lead Placement
The preferred ventricular lead arrangement is for one RV lead to be placed in the anterior septal groove and the other in the posterior groove approximately halfway between the base and apex. If the patient has an ICD, a reasonable distance should be ensured between the Cardiac Contractility Modulation leads and an ICD lead (approximately 2cm). In order to verify correct lead placement, appropriate lead impedances are externally measured after lead placement. Cross-talking tests are also performed to eliminate possibility of adverse interaction between Optimizer and ICD.
Insertion of the Optimizer Smart IPG
The Optimizer IPG is placed into a subcutaneous pocket in the right pectoral region. The recommended maximal depth of implant, for proper device interrogation and charging, is 2.5cm. The leads should form a gentle curve and not be under stress/tension. The IPG should be secured to the fascia using a non-absorbable ligature. The pocket is then closed.
Post implantation device interrogation is performed to assure proper device programming and to rule-out lead dislodgement. Thereafter, the patient receives standard post-operative care for a minimum of 24 hours prior to discharge.
