Patient training will be limited to the use of the OPTIMIZER Mini Charger and will be
provided by Impulse Dynamics Representatives post implant.
1.9 Scientific Background About Heart Failure and CCM
Heart failure is a condition wherein the heart muscle does not pump blood as well as it
should, generally resulting in reduced cardiac output, possibly due to reduced contraction
force or impaired relaxation or other deficiencies. Chronic heart failure is associated with
cardiac muscle remodeling, which is the result of abnormal genomic, molecular, cellular,
and structural changes that typically manifest clinically as changes in size, shape, and
function of the heart’s ventricles. The reduced cardiac function is associated with
multiple symptoms, such as fatigue, shortness of breath (dyspnea), co-morbidities, and
limited ability to walk, exercise or tolerate effort. The severity of symptoms is often
classified by the physician in accordance with New York Heart Association (NYHA)
classification (for example, NYHA class II represents moderate symptoms and class IV
represents severe symptoms). Over time, chronic heart failure is a leading cause for
hospitalizations and mortality. There are several medications that are used for treating
heart failure according to the guidelines. In patients that are symptomatic despite
appropriate medication, further evaluation of left ventricular ejection fraction (usually
valuated by echocardiography) and QRS duration (evaluated by ECG) are useful in
determining the possible need for an ICD, in cases having low ejection fraction, or a
CRT, in cases with wide QRS, respectively.
CCM™ (Cardiac Contractility Modulation) therapy is based on the delivery of a non-
excitatory electrical signals to the ventricles during the ventricular absolute refractory
period. Published scientific research on CCM therapy in animals and in humans explored
various properties and effects. Some data suggests that CCM has immediate effects on
heart failure tissue, including potentially increasing the contraction force (contractility) of
the muscle, possibly by immediate (i.e. less than a minute) improvement in the activity of
the intracellular proteins that are associated with calcium cycling, for example by
increased phosphorylation of the phospholamban protein, which is believed to modify the
activity level of SERCA-2a, a protein responsible for intracellular calcium handling.
Other data in heart failure animals and in humans suggest that after treating with CCM
for several hours, there may be normalization of mRNA expression levels of plurality of
cardiac genes that are associated with heart failure (e.g. SERCA-2a, ANP, BNP, a-MHC,
and others). Some data suggest that these changes and improvements in contraction are
not associated with increase in myocardial oxygen consumption. Other data in animals
over a period of a few months of CCM delivery suggest the potential for improvements in
the expression levels of several proteins that are associated with heart failure. In addition,
some data suggest that with a few months of CCM delivery, cardiac dimensions,
structure, function (e.g. LVEDD, LVESD, LVEF), cellular function, and/or tissue
behavior may improve, providing the potential for reverse remodeling. Other studies
explored clinical benefits with CCM therapy in chronic heart failure patients, typically
with a narrow QRS and New York Heart Association (NYHA) class of at least II, and
suggest that several months of treatment potentially result in improvements in exercise
tolerance (e.g. by six minute walk tests or by peak oxygen consumption in cardio
pulmonary tests) and in quality of life (e.g. by NYHA classification or by questionnaire).
Various studies explored effects of CCM in patients with NYHA classes II, III and IV,
some with EF up to 35%, some with higher EF (e.g. 40%, 45%). The studies usually
included population with a range of age, gender, etiology (e.g. ischemic, idiopathic) and
other characteristics.
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