Reduced cardiac contractility is central to heart failure with reduced ejection fraction (HFrEF) manifestation and progression

References

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HFrEF is a progressive disorder that occurs when the heart is unable to maintain sufficient cardiac output to accommodate the body’s metabolic requirements and venous return.1

Failing hearts undergo pathologic remodeling, producing inefficiencies that increase demand for ATP while decreasing capacity for ATP

Surrogate Measures of Contractility

Because it is difficult to measure contractility directly, there are three main surrogate measures: dP/dt, systolic ejection time (SET), and left ventricular ejection fraction (LVEF).7,10-13,15

Lower values of dP/dtmax, SET, and LVEF are associated with increases in morbidity and mortality in patients with HFrEF.11,13-15

Please choose from the dropdown options to learn more about these surrogate measures.

The maximum rate of rising LV pressure during the isovolumic contraction phase of LV systole (dP/dtmax) is a surrogate measure of LV contractility.10

In HFrEF, there is an opportunity to explore treatment options that directly impact contractility

SET is defined by the opening and closing of the aortic valve.11,12

In HFrEF hearts, contractility drives performance

In HFrEF, SET is shortened as the rate of LV pressure generation is diminished, resulting in prolongation of the pre-ejection, isovolumic contraction period.11,17,19

The actin-myosin interaction drives contractility, and contractility drives performance

The degree of LV shortening correlates with LV dysfunction and is associated with increased morbidity and mortality.11,19

Direct electrical stimulation of contractility in patients with HFrEF resulted in greater exercise capacity and improved HRQoL, as well as reductions in mortality and HF hospitalizations

LVEF is a classic surrogate measure of contractility, measurable by echocardiography or radionuclide ventriculography. These techniques also measure how much ventricular dilation has occurred.1,13,20

Compensatory mechanisms can become maladaptive, leading to reduced systolic function and stroke volume—the hallmarks of HFrEF
Optimizing load-independent cardiac contractility is a valuable approach for improving heart muscle function

To maintain cardiac output, the failing heart dilates to increase stroke volume.20

Myotropes are a class of molecules that directly target the myosin and actin within the cardiac sarcomere through calcium-independent mechanisms Cardiac calcitropy, also known as traditional inotropy augments myocardial force by increasing intracellular Ca2+ concentration Moving beyond inotropes: a new way of classifying therapeutic agents

Along with LV dilation in the failing heart, LV filling pressure also rises.1

Calcitropes (traditional inotropes) are a class of molecules that augment myocardial force by altering intracellular calcium concentrations

Decreased contractility, poor cardiac output, and elevated LV filling pressures result in the signs and symptoms of HF.21,22

Cardiac contractility modulation (CCM) devices enhance the strength of cardiac muscle contraction using electrical signals
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