Heart Basics - DrCRaghu

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Background
Management of Heart Failure (HF) continues to be challenging despite the formidable advances in medical and intervention therapy. Establishment of the four pillars – Angiotensin Converting Enzyme (ACE) inhibitors/Angiotensin Receptor Blockers (ARB)/Angiotensin Receptor blocker-Neprilysin inhibitor (ARNi), Beta blockers, Mineralocorticoid Receptor Antagonist (MRA) and Sodium Glucose Co-Transporter2 inhibitors (SGLT2i) in the recent decade has paved way for the effective management of HF. The adaptation of these drugs into clinical practice continues to be low despite the robust evidence in clinical trials. Agents that increase cardiac contractility (inotropes) for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF) – defined as left ventricular ejection fraction (LVEF) of less than 40%, have paradoxically increased the mortality rates instead of improving1. This is due to the increase of myocardial oxygen consumption as well as myocardial injury whilst increasing contractility. The established four pillars of HFrEF management improve the efficiency of heart function through indirect mechanisms rather than directly improving the cardiac contractility.

The Drug
Omecamtiv Mecarbil belongs to a new class of cardiac positive inotrope agents called “myotropes” that improve cardiac contractility without increasing the myocardial oxygen consumption. Phase 2 trials – COSMIC HF and ATOMIC HF with this agent have established the efficacy of this agent. Considering the adverse effects observed previously with other inotrope agents a phase 3 study, is essential for this molecule to be adapted into clinical practice. The recently published Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial, conducted on 8266 patients demonstrated a modest but significant benefit with this agent.

GALACTIC HF analysis
Patients with LVEF less than 35% who are on established medical therapies received Omecamtiv Mecarbil versus placebo in this study. The study agent showed an 8% reduction in the combined event rate of cardiac mortality and HF hospitalization over and above that achieved with the four pillars. At the same time, this agent did not increase myocardial injury or infarction or arrhythmia rates. The benefit of this agent was observed predominantly in those with LVEF <28% in the primary analysis2. Patients admitted into Intensive Care units were also benefitted despite their predicted poor expected outcomes. In a recent sub group analysis, the benefit was most pronounced when the LVEF < 25% and for those in sinus rhythm without increasing sudden cardiac death3. Improvement in LVEF in modest numbers was also found. The use of SGLT2i in only 2% of patients is the limitation for this trial – SGLT2i were not proven to be beneficial in the management of HF when GALCTIC HF trial was conducted.

Take Home Message
Omecamtiv Mecarbil is an important addition rather than an alternative to the established therapies for HFrEF4. Marked benefit seen in patients with LVEF <25% and sinus rhythm highlights the importance of using this agent in select groups leading to a personalized approach to HF therapy5.

References:

  1. Ahmad T, Miller PE, McCullough M, et al. Why has positive inotropy failed in chronic heart failure? Lessons from prior inotrope trials. Eur J Heart Fail 2019; 21: 1064-78.
  2. Swedberg K. Stimulation of Contractility in Systolic Heart Failure. N Engl J Med. 2021; 382: 178-179.
  3. Teerlink JR, Diaz R, Felker GM et al. GALACTIC-HF Investigators. Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF. J Am Coll Cardiol. 2021 Jul 13; 78: 97-108.
  4. Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med 2021; 384:105-16.
  5. Ferreira JP. Omecamtiv Mecarbil: A Personalized Treatment for Patients With Severely Impaired Ejection Fraction. J Am Coll Cardiol. 2021 Jul 13; 78: 109-111.

Key Words:

Heart Failure
Inotropes
Myotropes
GALCTIC HF trial
Personalized Heart Failure treatment


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The heart has 3 layers of tissue:

  • Pericardium – The thin outer layer that protects the heart
  • Myocardium – a thick muscular middle layer that contracts and pumps out blood
  • Endocardium – a thin inner lining

Inside the heart, there are four chambers- the upper two are right and left atria and lower two are right and left ventricles. The atria receive the blood that comes to the heart and the ventricles pump blood out from the heart. The right and left side of the heart is separated by a septum.

The heart also has 4 valves which allow unidirectional flow of blood every time the heart beats.

  • the tricuspid valve is between the right atrium and right ventricle.
  • The pulmonary valve is between the right ventricle and the pulmonary artery.
  • The mitral valve is between the left atrium and left ventricle.
  • The aortic valve is between the left ventricle and the aorta.

The electrical system of heart:

The pumping action of the heart is controlled by the heart’s electric system. As an electrical impulse moves through the heart muscles, the various chamber of heart coordinate and pump out blood.

An electrical stimulus is generated by the sinus node (also called the natural pacemaker) which is located in the right atria of the heart. This stimulus activates the atrial muscles. The electrical stimulus then travels down through the conduction pathways and causes the heart’s ventricles to contract and pump out blood. The atria contract first, just a few milliseconds before the ventricles. This allows the blood from the atria to enter into the ventricles which is pumped out later.



Your heart needs to work 24/7 to keep your body systems working. Like any other body tissue, the heart too needs oxygen and nutrients to function efficiently. For this, we have a network of arteries that supply blood to the heart muscles which are called the coronary arteries. There are two chief coronary arteries:

the left and right coronary arteries, that branch out from the aorta near the point where the aorta and the left ventricle meet.

The right coronary artery supplies blood to the right atrium, the right ventricle, a small bottom area of the left ventricle and the back portion of the septum.

The left coronary artery supplies blood to the left atrium and ventricles and the front portion of the septum.

These coronary arteries give out various branches that supply blood to different parts of the heart.

Coronary artery disease:

When there is high level of unhealthy fats in the blood, they gradually start depositing in the insides of the coronary artery vessel wall and form a fatty plaque(atherosclerosis). This gradually narrows the lumen of the coronary arteries which obstructs blood supply to the heart. This condition is called as coronary artery disease. disruption of blood supply to the heart gives rise to a cluster of symptoms, the most important being chest pain or angina.

  • Warning signs of heart disease
  • Risk factors for heart disease
  • Possible complications of heart disease


Your lifestyle, age, family history and your other health condition can dictate your risk to develop a heart disease. However, the three key risk factors are- smoking, high blood pressure and high cholesterol. Learn about the risk factors and see if you are at risk:

  1. High blood pressure: It is an important factor for many diseases. Blood pressure, if not controlled, can lead to heart disease, stroke, kidney failure and other organ system disorders. Decreasing blood pressure by lifestyle changes and medication can greatly reduce your risk for heart disease.
  2. High cholesterol: Did you know that our hardworking liver can generate all the cholesterol that our bodies need? But we all do take in extra bad cholesterol from diet. These bad cholesterol tend to get deposited in our blood vessels and cause heart disease.
  3. Smoking: Cigarette smoking damages your heart and blood vessels. Nicotine present in cigarette smoke also reduces the amount of oxygen that your blood can carry. Not only that, if you smoke, the people around you are also at a higher risk of getting heart disease.
  4. Obesity: Obesity is linked with high level of bad cholesterol level and low levels of good cholesterol levels. Obesity is not only a risk factor for heart disease, but also increases risk of diabetes and high blood pressure.
  5. Diabetes: People with diabetes or high blood sugars are at greater risk of having heart disease than those who don’t have diabetes.
  6. Unhealthy diet: Oily, junk foods which are high in bad cholesterol, saturated fats and trans fats an can increase your risk of heart disease. Foods that are very salty(have high sodium levels) can also increase your risk of high blood pressure and heart disease.
  7. Physical inactivity: Physical inactivity increase your risk of having high blood pressure and diabetes and eventually heart disease.
  8. Alcohol: Excess and frequent alcohol intake can increase the risk of high blood pressure and hypercholesterolemia. Ideally, women shouldn’t have more than 1 drink a day and men shouldn’t have more than 2 drinks a day.
  9. Family history: Genetic factors seem to play a role in conditions like high blood pressure and heart diseases. However, it is also likely that the members of the family sharing common external environments and culture may be exposed to the same set of risk factors for heart diseases.
  10. Age: The risk of heart disease increases as the a person ages.


There are an array of heart diseases but they do share some common symptoms. If you experience any of these symptoms, it is perhaps a good idea to get yourself tested. Check these out here:

  1. Angina or chest pain described as heaviness, pressure, aching, burning, fullness, squeezing, or painful feeling in your chest.It is often accompanied by pain in the n the neck, jaw, throat, upper abdomen or back
  2. Shortness of breath
  3. Easy fatiguability
  4. Palpitation and rapid heartbeat
  5. Weakness/dizziness
  6. Sweating
  7. Nausea and vomiting
  8. Swelling in the lower extremities
  9. Fainting(syncope)
  10. Coughing and wheezing


For continuous circulation, the left and the right side of the heart must work together. Here are the series of steps that causes the blood to flow in the heart, lungs and body.

  • The right atria receives deoxygenated blood from two large veins- the superior and inferior venacava.
  • When the atria contracts and the blood passes from the right atrium to the right ventricle through the tricuspid valve.
  • When the ventricle fills, the tricuspid valve closes.
  • Next, the ventricle contracts and pushes blood to the pulmonary artery through the pulmonary valve.
  • The pulmonary artery carries the blood to the lungs where the blood gets oxygenated.
  • This oxygenated blood enters the left atria of the heart through the pulmonary vein.
  • Next, the left atria contracts and the blood flows from left atrium into your left ventricle through the open mitral valve.
  • When the ventricle is full, the mitral valve shuts,
  • Next, the ventricle contracts and oxygenated blood is passed to the aorta through which it is sent to various parts of the body.




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Copyright © 2019, Dr C Raghu. All rights reserved.
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Copyright © 2019, Dr C Raghu. All rights reserved.
Designed & Developed by R R Deepak Kambhampati.



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