What Is Myocardial Ischemia?

Introduction to myocardial ischemia

Ischemic heart disease is the leading cause of death worldwide. Myocardial ischemia is characterised by an imbalance in myocardial oxygen supply and demand. This results in cardiac dysfunction, sudden death, arrhythmias and myocardial infarction (heart attack). There can be various causes of an obstruction of blood flow, including plaques, thrombosis and hyper-constriction. Normally, coronary circulation matches blood flow with the oxygen needs through pairing resistance in microvasculature. In this, endothelial control plays an important role. However, when endothelial action is altered, it can influence a range of cardiovascular diseases. This can be used as a therapeutic target.¹

Anatomy of the heart

The heart is a muscular organ with two key functions. Firstly, it collects blood from the tissues and pumps it to the lungs to be oxygenated. Secondly, it collects blood from the lungs and distributes this to all the tissues of the body. It is made up of four chambers: the left and right atria and the left and right ventricles.^3,4

The right atrium gets deoxygenated blood from the body through the superior vena cava. The blood then flows into the right ventricle. This chamber pumps blood into the pulmonary artery, which sends the blood to the lungs for oxygenation. Oxygenated blood returns to the left atria, where it is pumped to the body.⁴

Principles of myocardial ischemia

Under normal conditions, there is a perfect match between myocardial oxygen consumption and oxygen delivery to the myocardium, and it is this balance that is at the centre of the current understanding of myocardial ischemia.²

Myocardial oxygen consumption can remain fixed on a daily basis, but a change can be seen in patients when discussing their symptoms and exercise. The myocardium is a muscle and like most muscles, it shows a link between velocity of contraction and pre-contraction tension. When there is an increase in velocity, an increase in oxygen is needed. The pre-contraction tension in the myocardium is also linked to the pre-contraction ventricular volume. This is something that can be considered when looking at therapeutic options. Nitrate drugs, often prescribed, were originally thought to act on coronary vasodilation. However, they now seem to work through controlling myocardial wall tension.²

Myocardial oxygen delivery is dependent on oxygen transport by the blood and coronary blood flow. This transport of oxygen can be impacted by a decrease in haemoglobin or a sudden worsening of angina. When a person exercises, coronary blood flow can increase three to fourfold to allow an increase in myocardial oxygen consumption. One factor which is significant to our understanding of coronary blood flow and, therefore, myocardial ischemia is knowledge of the site anatomically. It is also important to understand the resistance in coronary circulation and sites of regulated resistance.²

Myocardial ischemia and coronary artery disease 

Myocardial ischemia is a key target for the treatment of patients with coronary artery disease. There were initial descriptions of ischemic heart disease in the eighteenth century, beginning with patients with angina symptoms. Atherosclerotic lesions have also been associated with the disease. As science has progressed, it is now known that coronary circulation has distinct properties that protect the myocardium. Therefore, whilst there are common findings of atherosclerotic lesions in the coronaries, it does not necessarily mean that they are associated with chronic myocardial ischemia and may only be one part of the problem.⁵

One of the most common causes of limited coronary blood flow in myocardial ischemia is obstruction due to atherosclerosis. Typically, coronary blood flow from epicardial to endocardial layers is quite susceptible to blood flow variations and, therefore, more susceptible to myocardial ischemia. There are also collaterals, which are networks of channels in the heart, connecting epicardial branches from different regions. When they are not stimulated, the channels have a limited ability to allow blood flow as they show a high vascular resistance. It is thought that when there is stimulation, the channels transform to form vascular vessels. Their diameters increase to allow blood flow. When looked at, collaterals are shown supplying myocardial regions with epicardial lesions. Therefore, it is theorised that collaterals could potentially decrease myocardial ischemia. However, there are also suggestions that collaterals could decrease infarct size.⁵

Myocardial ischemia or anatomic disease?

There is a growing amount of evidence suggesting that the relationship between chronic obstructive coronary atherosclerosis and myocardial ischemia may not be as straightforward as initially thought. It should be noted that the current methods used to assess coronary anatomy provide information on methods used to assess myocardial ischemia. Some assess coronary arteries and atherosclerotic lesions, whilst others assess the myocardium. Yet, both methods have their own sensitivities and limitations, and they cannot be analysed as one. Therefore, there are patients frequently observed with coronary artery disease and atherosclerotic lesions who do not show any evidence of myocardial ischemia.⁵

Diagnostics 

When assessing for myocardial ischemia, diagnosis is based on clinical thoughts. This determination is mainly influenced by the presence of angina pectoris, as this is the key clinical manifestation of myocardial ischemia. Coronary artery disease patients present with chest pains, often due to other causes and not ischemic heart disease.⁵

In patients who have ischemic heart disease, myocardial ischemia can be used in determining prognosis. An electrocardiogram (ECG) can be done to observe myocardial ischemia. This will look at the ST segment during exercise. Other things that can be considered in diagnosis are metabolic changes such as pH reduction in the coronary sinus, myocardial lactate production and coronary sinus oxygen desaturation. An alternative method to detect myocardial ischemia is myocardial phosphorus-31 nuclear magnetic resonance spectroscopy. This looks at the levels of phosphocreatine and adenosine triphosphate. Another useful consideration may be any abnormalities in the left ventricular wall. Scans such as PET and MRI can also be useful. PET scans enable coronary blood flow to be calculated, and MRI scans can be used to determine myocardial blood flow.¹

Possible treatments

A trial has looked into the efficacy and tolerability of monotherapy alongside long-acting calcium channel blockers for treating myocardial ischemia in patients with coronary artery disease. A decrease in ischemia was shown in both ambulatory monitoring and exercise testing. This was supported by a decrease in angina. There was also a positive effect shown when an additional drug was used in combination.⁶

When looking at amlodipine and diltiazem, they displayed comparable efficacy when a regular dose was given. However, the impact on myocardial ischemia was considerably different. Amlodipine was shown to be more effective when its anti-ischemic effect was measured over 24 hours after it was administered, whilst diltiazem’s effectiveness was reduced in a few hours. This research has likely application in a clinical setting where patients do not always take their medication at regular intervals.⁶

The CAPE II trial also looked at subjective and objective measurements of treatments. Angina is currently thought to underestimate myocardial ischemia, and heart monitoring allows ischemia activity to be assessed during everyday life. As myocardial ischemia is shown separately during a certain type of heart monitoring, it infers that it is an independent risk of cardiovascular events.⁶

Summary

Myocardial ischemia is an imbalance in myocardial oxygen supply and demand. This results in cardiac dysfunction, sudden death, arrhythmias and myocardial infarction (heart attack). The heart is the key organ in blood flow, and it is separated into four chambers. When there is an increase in velocity, an increase in oxygen is needed in the body tissues. Myocardial oxygen delivery is dependent on oxygen transport by the blood and coronary blood flow. This transport of oxygen can be impacted by a decrease in haemoglobin or a sudden worsening of angina. When a person exercises, coronary blood flow can increase three to fourfold to allow an increase in myocardial oxygen consumption. A common cause of limited coronary blood flow in myocardial ischemia is obstruction due to atherosclerosis. When assessing for myocardial ischemia, diagnosis is based on clinical thoughts. This determination is mainly influenced by the presence of angina pectoris, as this is the key clinical manifestation of myocardial ischemia. Amlodipine is potentially a better treatment option than diltiazem when looking at its effectiveness.