How can a pharmaceutical such as Entresto treat heart failure?

Teachable moment in classrooms:

1. heart chapter – functional difference in the thickness of myocardium of atria and ventricle wall
2. heart chapter – conduction system delivers nerve impulses to myocardium
3. heart chapter — importance of stroke volume
4. hemodynamics chapter – effects of angiotensin and ANP on blood pressure and volume

The news item:  Recently the following news report appeared:

Advancement in heart failure medication helping patients at MercyOne

There are some medical issues that are an easy fix and then there are some that are more complex, like heart failure. For those with early signs of heart failure, an advancement in medication is making all the difference for patients at MercyOne…

The article discusses the new drug Entresto that moderates symptoms in heart failure patients. The patient interviewed for this article had Guillain-Barre syndrome that caused severe heart arrhythmia.

So, Why Do I Care??  Heart failure indicates a malfunctioning of one of the most important organ in the body. Over 6 million people in the USA have heart failure, and it is listed as cause of 13% of all deaths.  Heart failure results in worsening quality of life because of the inability to hold a job, inability to participate in social activities and in family life.

Plain English, Please!!! First let’s talk about what heart failure is. Most important to understand here is that heart failure doesn’t mean that the heart stops working. Heart failure means that the heart can not pump enough blood to maintain normal functions of all organs. Heart failure may start with moderately decreased  ability and it may then progress to further loss of pumping to the point where life can not be maintained with very low level of pumping. Loss of pumping ability, the heart failure, may be the consequence of malfunctioning heart valves, arrhythmias (abnormal delivery of nerve impulses to the heart muscle), or the damage or thickening (hypertrophy) of the heart wall.

Second, let’s talk about why hypertrophy of the heart wall can lead to heart failure. While it is intuitive to picture why malfunctioning heart valves, or arrhythmias can cause heart failure, it is not that intuitive to see why thickening (hypertrophy) of the heart wall can be damaging. In most cases hypertrophy thickens the myocardium of the ventricles. Hypertrophy is normal when aerobic exercise causes a proportional growth of the myocardium.  Disease-causing hypertrophy increases the proportion of connective tissue which reduces the power of myocardium, lowers the growth of the capillaries which reduces oxygen flow, and reduces the density of Purkinje fibers which reduces the flow of nerve impulses to the myocardium. In addition, abnormal hypertrophy can obstruct the flow of blood out of the ventricle. For the left ventricle the consequence of these changes is that the stroke volume (blood ejected from the ventricle) will be lower than the 70 ml normal value. Imagine a latex balloon for the normal heart, and imagine a large brown paper bag for the hypertrophic heart. The latex balloon squeezes air out very effectively, but a paper bag, while it might be larger, doesn’t squeeze air out of it very well. That is how the changing composition of the hypertrophic heart lowers the volume of the pumped blood, and that means that not enough blood (not enough oxygen and nutrients), will be delivered for normal organ functions.

Third, let’s talk about how Entresto acts. The surprising goal of Entresto is not to reverse the structural changes of the myocardium. The goal of Entresto is to reduce the workload on the heart to prevent the worsening of hypertrophy. Such lowered workload for the left ventricle means that it pumps lesser volume, and pumps into an aorta that has a lowered blood pressure.  One component of Entresto lowers blood volume by enhancing the effect of naturally-produced atrial natriuretic peptide. The other component of Entresto lowers blood pressure by blocking the effect of the hormone angiotensin that would otherwise increase blood pressure. These two actions reduce the workload on the damaged heart, preserve the pumping ability for a longer duration of time, and, thus, preserve the functionality of the heart longer for the patient to allow them to live longer.