Heart Failure affects (and/or is possibly caused by) several mechanisms that are involved in the heart functioning. Among those mechanisms the expression of some genes may be affected to a depressed or over expressed condition, which affects the normal functioning of the cells and the muscle as a whole. The expression of several genes is also used as a clinical marker for the progression of the disease.
Within the literature dealing with changes in gene expression and proteins associated with heart failure, one could find changes in mRNA gene expression of brain and atrial natriuatic peptides (BNP, ANP), basic fibroblast growth factor (bFGF), mRNA gene expression for alfa myosin heavy chain aMHC, and gap junction protein connexin 43. Plasma levels of brain (B-Type) and atrial (A-Type) natriuretic peptides are increased in heart failure (HF) and are predictive of poor outcome. Increased levels of basic fibroblast growth factor (bFGF) is associated with increased angiogenesis, with increased capillary density, and with improved left ventricular (LV) ejection fraction (as demonstrated also in dogs with heart failure). Myosin heavy chain (MHC) is a key component of the cardiac contractile machinery. Recent studies showed that a switch from the aMHC to the βMHC isoform occurs in patients with heart failure. This switch may partly contribute to the progressive deterioration of left ventricular function characteristic of heart failure.
Loss of gap junctions and impaired intracellular communications are characteristic features of remodeling in heart failure and result from rapid loss of the gap junction protein connexin 43. Loss of connexin 43 has also been reported to result in malignant ventricular arrhythmias in patients with heart failure.
It has previously been shown that in dogs with heart failure, delivery of non-excitatory cardiac contractility modulation (CCM) electrical signals to left ventricular muscle during the absolute refractory period leads to chronic improvement in left ventricular function and remodeling. In patients and dogs with heart failure, chronic CCM therapy was also associated with suppression of ventricular arrhythmias.
Excitable tissue control (ETC) devices are devices which modulate the activity of excitable tissues by application of non-excitatory cardiac contractility modulation (CCM) electrical field signals to the excitable tissue through suitable electrodes in contact with the tissue. For example, ETC devices may be used, inter alia, to increase or decrease the contractility of cardiac muscle in vitro, in vivo and in situ, as disclosed in detail in PCT application No. PCT/IL97/00012 (International Publication No. WO 97/25098) to Ben-Haim et al., titled “ELECTRICAL MUSCLE CONTROLLER” and U.S. Pat. No. 6,317,631, the disclosures of both of which are incorporated herein in their entirety by reference.