Question:  Cardiac contractility modulation a treatment for patients with moderate to severe left ventricular systolic heart failure and is delivered by a medical device which uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate what?

Context paragraphs:
Ventricular remodeling: In cardiology, ventricular remodeling (or cardiac remodeling) refers to changes in the size, shape, structure, and function of the heart.  This can happen as a result of exercise (physiological remodeling) or after injury to the heart muscle (pathological remodeling).  The injury is typically due to acute myocardial infarction (usually transmural or ST segment elevation infarction), but may be from a number of causes that result in increased pressure or volume, causing pressure overload or volume overload (forms of strain) on the heart.  Chronic hypertension, congenital heart disease with intracardiac shunting, and valvular heart disease may also lead to remodeling.  After the insult occurs, a series of histopathological and structural changes occur in the left ventricular myocardium that lead to progressive decline in left ventricular performance.  Ultimately, ventricular remodeling may result in diminished contractile (systolic) function and reduced stroke volume.

Istaroxime: Istaroxime is an investigational drug originally patented and developed by the Italian pharmaceutical company Sigma-Tau.  Istaroxime is now under development for treatment of acute decompensated heart failure by CVie Therapeutics, a Taiwanese pharmaceutical company owned by Lee's Pharmaceutical Holdings Limited that in July 2012 has acquired from Sigma-Tau the patents and rights on Istaroxime and related compounds.  It is still in early-stage development, having been evaluated in phase two clinical trials.  Istaroxime is an innovative medication as it is an effective treatment for both systolic and diastolic heart failure.  Systolic heart failure is characterized by impaired ventricular emptying, caused by reduced contractility, and diastolic dysfunction is defined by defective ventricular filling, caused by the heart’s inability to properly relax between beats.  Intracellular calcium fluxes regulate both contraction and relaxation.  Cardiac muscle cells from patients with heart failure show smaller amounts of peak calcium in their cytoplasm during contraction, and slower removal., The mishandling of intracellular calcium is often due to problems in the cells’ ability to mediate calcium influx, and sequestration of calcium back in the sarcoplasmic reticulum. ,

Peripartum cardiomyopathy: Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that is defined as a deterioration in cardiac function presenting typically between the last month of pregnancy and up to six months postpartum.  As with other forms of dilated cardiomyopathy, PPCM involves systolic dysfunction of the heart with a decrease of the left ventricular ejection fraction (EF) with associated congestive heart failure and an increased risk of atrial and ventricular arrhythmias, thromboembolism (blockage of a blood vessel by a blood clot), and even sudden cardiac death.  In essence, the heart muscle cannot contract forcefully enough to pump adequate amounts of blood for the needs of the body's vital organs.

Omecamtiv mecarbil: Omecamtiv mecarbil (INN), previously referred to as CK-1827452, is a cardiac-specific myosin activator.  It is being studied for a potential role in the treatment of left ventricular systolic heart failure.

Diastolic function: In clinical cardiology the term "diastolic function" is most commonly referred as how the heart fills.  Parallel to "diastolic function", the term "systolic function" is usually referenced in terms of the left ventricular ejection fraction (LVEF), which is the ratio of stroke volume and end-diastolic volume.  Due to the epidemic of heart failure, particularly the cases determined as diastolic heart failure, it is increasingly urgent and crucial to understand the meaning of “diastolic function”.  Unlike "systolic function" which can be simply evaluated by LVEF, there are no established dimensionless parameter for "diastolic function" assessment.  Hence to further study "diastolic function" the complicated and speculative physiology must be taken into consideration.

Artificial cardiac pacemaker: A pacemaker (or artificial pacemaker, so as not to be confused with the heart's natural pacemaker) is a medical device which uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart.

Cardiac resynchronization therapy: An implanted cardiac resynchronization device is a medical device used in cardiac resynchronization therapy (CRT).  It resynchronizes the contractions of the heart’s ventricles by sending tiny electrical impulses to the heart muscle, which can help the heart pump blood throughout the body more efficiently.  CRT defibrillators (CRT-D) also incorporate the additional function of an implantable cardioverter-defibrillator, to quickly terminate an abnormally fast, life-threatening heart rhythm.  CRT and CRT-D have become increasingly important therapeutic options for patients with moderate and severe heart failure.

Pacemaker failure: Pacemaker failure is the inability of an implanted artificial pacemaker to perform its intended function of regulating the beating of the heart.  A pacemaker uses electrical impulses delivered by electrodes in order to contract the heart muscles.  Failure of a pacemaker is defined by the requirement of repeat surgical pacemaker-related procedures after the initial implantation.  Most implanted pacemakers are dual chambered and have two leads, causing the implantation time to take longer because of this more complicated pacemaker system.  These factors can contribute to an increased rate of complications which can lead to pacemaker failure.

Cardiac contractility modulation: Cardiac contractility modulation (CCM) is a treatment for patients with moderate to severe left ventricular systolic heart failure (NYHA class II–IV).  The short- and long-term use of this therapy enhances both the strength of ventricular contraction and the heart’s pumping capacity by modulating (adjusting) the myocardial contractility.  The CCM mechanism is based on stimulation of the cardiac muscle by non-excitatory electrical signals (NES).  CCM treatment is delivered by a pacemaker-like device that applies the NES, adjusted to and synchronized with the electrical action in the cardiac cycle.

Electrical muscle stimulation: Electrical muscle stimulation (EMS), also known as neuromuscular electrical stimulation (NMES) or electromyostimulation, is the elicitation of muscle contraction using electric impulses.  EMS has received an increasing amount of attention in the last few years for many reasons: it can be utilized as a strength training tool for healthy subjects and athletes; it could be used as a rehabilitation and preventive tool for partially or totally immobilized patients; it could be utilized as a testing tool for evaluating the neural and/or muscular function in vivo; it could be used as a post-exercise recovery tool for athletes.  The impulses are generated by a device and are delivered through electrodes on the skin near to the muscles being stimulated.  The electrodes are generally pads that adhere to the skin.  The impulses mimic the action potential that comes from the central nervous system, causing the muscles to contract.  The use of EMS has been cited by sports scientists as a complementary technique for sports training, and published research is available on the results obtained.  In the United States, EMS devices are regulated by the U.S. Food and Drug Administration (FDA).

Supporting paragraphs: Cardiac contractility modulation Artificial cardiac pacemaker
Answer: the beating of the heart