Impulse Dynamics out of Stuttgart, Germany launched on the European market its OPTIMIZER IVs Implantable Pulse Generator, a device for treatment of left ventricular dysfunction. Based on non-excitatory electrical pulse technology known as Cardiac Contractility Modulation (CCM), the device is thought to provide intracardiac positive inotropic support to patients with moderate-to-severe congestive heart failure (CHF) that are symptomatic despite optimal medical therapy.
Physiologically, CCM stimulation delivers signals during the ventricular absolute refractory period, and according to a recent review in the European Journal of Heart Failure, CCM is thought to improve cardiac contractility by increasing phosphorylation of some proteins and changing expression of genes.
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CCM Signals have been shown to normalize the phosphorylation of regulatory proteins such as Phospholamban (PLB) in-vitro, within seconds of treatment. This rapid effect allows restoration of cellular function and an acute improvement in contractile force.
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 underlie 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 CCM 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.
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. 3D Echocardiographic studies in humans and ventriculography studies in animals demonstrate reverse remodeling within 3 months of initiating CCM 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 CCM therapy, on the other hand, does not result in a detectable increase in MVO2. The improvements in left ventricular function with CCM are associated with improved left ventricular efficiency, similar to the effects seen with left ventricular pacing.
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