Microvascular angina (MVA), previously known as cardiac syndrome X, also known as coronary microvascular dysfunction (CMD) or microvascular coronary disease is a type of

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...

(chest pain) with signs associated with decreased blood flow to heart tissue but with normal

coronary arteries The coronary arteries are the arteries, arterial blood vessels of coronary circulation, which transport oxygenated blood to the Cardiac muscle, heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any ...

. The use of the term cardiac syndrome X (CSX) can lead to the lack of appreciation of how microvascular angina is a debilitating heart related pain condition with the increased risk of heart attack and other heart problems. Some studies have found an increased risk of other vasospastic disorders in cardiac microvascular angina patients, such as

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

and

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically the fingers, and, less commonly, the toes, are involved. Rare ...

. Treatment typically involves beta-blockers, such as metoprolol, however beta blockers can make coronary spasms worse. Microvascular angina is a separate condition from variant angina.

Signs and symptoms

Patients often experience myocardial ischemia symptoms, such as heaviness, tightness, pressure or squeezing in the chest area, which can also include sweating, nausea, shortness of breath (dyspnea), fatigue. While there is no formal definition of microvascular angina, the general consensus is that it entails all of the following: *

Angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...

: This usually does not cause dysfunction on

echocardiogram Echocardiography, also known as cardiac ultrasound, is the use of ultrasound to examine the heart. It is a type of medical imaging, using standard ultrasound or Doppler ultrasound. The visual image formed using this technique is called an echo ...

and can last longer than that of heart disease. * Abnormal

cardiac stress test A cardiac stress test is a cardiological examination that evaluates the cardiovascular system's response to external stress within a controlled clinical setting. This stress response can be induced through physical exercise (usually a treadmill) o ...

: ST segment changes in EKG are typically similar to those of

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...

, and the opposite of those of

Prinzmetal's angina Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable angin ...

Myocardial perfusion imaging Myocardial perfusion imaging or scanning (also referred to as MPI or MPS) is a nuclear medicine procedure that illustrates the function of the heart muscle (myocardium). It evaluates many heart conditions, such as coronary artery disease (CAD), ...

can be abnormal in 30% of patients. *

Coronary angiogram A coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional (treatment) purposes. Coronary cathet ...

: Normal * Other causes of chest pain must be ruled out, including: ** Variant angina / Coronary artery spasm. **

Esophageal spasm Esophageal spasm is a disorder of motility of the esophagus. There are two types of esophageal spasm: * Diffuse or distal esophageal spasm (DES), where there is uncoordinated esophageal contractions * Nutcracker esophagus (NE) also known as hyp ...

Causes

There is no specific known cause for microvascular angina but rather a multitude of risk factors that act together. It is believed that the lack of blood flow caused by a

microvascular disease Microangiopathy (also known as microvascular disease, small vessel disease (SVD) or microvascular dysfunction) is a disease of the microvessels, small blood vessels in the microcirculation. It can be contrasted to macroangiopathies such as atherosc ...

and enhanced pain perception are two of the factors that may cause it. The microvascular dysfunctions refer to the abnormalities in the very small

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s of the heart. The narrowing of these vessels may lead to lack of oxygen in specific areas of the

cardiac muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

causing

chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...

. Several studies have shown that patients living with microvascular angina may have an enhanced pain perception, and usually feel more intense chest pain than individuals without microvascular angina. The risk factors include

abdominal obesity Abdominal obesity, also known as central obesity and truncal obesity, is the human condition of an excessive concentration of visceral fat around the stomach and abdomen to such an extent that it is likely to harm its bearer's health. Abdominal ...

, meaning excessive

visceral fat Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

tissue in and around the abdomen, atherogenic

dyslipidemia Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of ...

which is a blood fat disorder, and elevated

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

. Other risk factors are

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

resistance or intolerance to

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

, prothrombotic state or proinflammatory state. Older people are more at risk to develop this condition, and there is some evidence that suggests that there are genetic mutations that predispose to the syndrome. Women are more prone to this condition than men, as well as those who have a history of

heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...

in the family.

Pathophysiology

This condition is typically characterized by a series of structural and functional changes within the heart's microcirculation, such as endothelial dysfunction (which affects the inner lining of blood vessels), microvascular arteriolar remodeling (changes in the vessel structure) such as intimal thickening,

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...

, perivascular fibrosis, and increased microvascular resistance (which impedes blood flow). There are also differences in coronary blood flow reserve (the capacity to increase blood flow during increased demand) and IMR (index of microcirculatory resistance). In a large percentage of patients, there is a finding of systemic microvascular abnormalities, causing reduced blood flow in the microvasculature of the

s. When the blood vessels constrict and fail to dilate there is decreased oxygen levels to the cardiac muscles resulting in hypoxia which lead to chest pain. While numerous physiological mechanisms have been proposed, none have been proven.

Types of microvascular dysfunction

Structural endotype

Patients with the structural coronary microvascular dysfunction endotype (''inability to dilate)'' tend to have a high vascular tone at rest and high vascular tone at stress. Patients with this endotype typically show normal CBF ( coronary blood flow) at rest, lower stress CBF, lower coronary flow reserve (CFR) and elevated hyperemic index of microcirculatory resistance (hMR). Their microvascular resistance and endothelial dysfunction is elevated. It is characterized by luminal obstruction, vascular-wall infiltration, vascular remodeling, perivascular fibrosis and capillary rarefaction. In this type individuals may have impaired vasodilatory capacity and endothelial function, leading to reduced coronary blood flow and compromised myocardial perfusion, especially during stress or increased demand.

Functional endotype

Functional coronary microvascular dysfunction endotype (''exhausted dilatory capacity'') presents a low vascular tone at rest and low vascular tone at stress. Individuals often display elevated rest CBF, normal stress CBF, lower CFR and normal hMR, normal microvascular resistance and higher nitric oxide synthase (NOS) activity. It is characterized by endothelial dysfunction, smooth-muscle dysfunction and autonomic dysfunction. Endothelial function and vasodilatory capacity is relatively preserved resulting in adequate myocardial perfusion under resting conditions.

Diagnosis

Microvascular angina is a diagnosis of exclusion. Typically this will necessitate both a clinical diagnosis, appropriate stress testing, and a coronary angiogram that meet the above criteria. Cardiac MRI can be used to diagnose microvascular angina. Studies are ongoing to validate this approach. There is growing evidence that microvascular angina is caused by a functional disorder of the

microvessels The microcirculation is the circulatory system, circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ (anatomy), organ Tissue (biology), tissues. The microvessels include terminal ar ...

, coronary microvascular dysfunction (CMD). Blood vessels either fail to dilate or constrict in response to various stressors such as exercise, the cold or emotional stress. An angiogram with acetylcholine can demonstrate microvascular dysfunction which can affect the microvessels and larger coronary arteries leading to either microvascular angina or coronary artery spasms (Prinzmetal's angina). These are considered discrete conditions though some individuals can be affected by both. Microvascular angina can be diagnosed using different tests and exams, but it is mainly a diagnosis of exclusion. However, sedentary and overweight individuals with a family history of type 2 diabetes should be tested regularly to determine whether they have irregular levels of

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

s, or blood pressure abnormalities, factors which are usually associated with microvascular angina. A first test to be taken is an exercise stress test which shows if the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

is not getting blood during

exertion Exertion is the Action (physics), physical or perceived use of energy.Newton's Third Law, Elert, Glenn. “Forces.” ''Viscosity – The Physics Hypertextbook'', physics.info/newton-first/. Exertion traditionally connotes a strenuous or costly ''e ...

. Angiograms may be useful and conclusive when microvascular angina they offer a detailed image of the heart. However, they cannot detect potential abnormalities in the small arteries, and the doctor may ask for more tests in order to rule out other heart conditions, such as Prinzmetal's angina (variant/vasospastic angina, coronary artery spasm) which has similar symptoms.

Differential diagnosis

Chest pain caused by microvascular angina is most of the time unpredictable and it can occur when at rest and/or during exercise. The pain associated with microvascular angina is normally more intense and it lasts for longer periods of time compared to pain caused by other conditions. Many gastric conditions can cause chest pains (sub-sternal pain), while this is usually associated with consumption of food this is not always the case, and is a very common differential diagnosis. For example, a stable angina causes chest pain that goes away when at rest. Another difference is that while chest pain caused by any type of stable angina is relieved with

nitroglycerin Nitroglycerin (NG) (alternative spelling nitroglycerine), also known as trinitroglycerol (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless or pale yellow, oily, explosive liquid most commonly produced by ...

, this drug is not effective in most patients with microvascular angin

Treatment

* Calcium channel blocker, Calcium channel blockers - specifically

nifedipine Nifedipine ( ), sold under the brand name Procardia among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzme ...

and

diltiazem Diltiazem, sold under the brand name Cardizem among others, is a nondihydropyridine calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta b ...

can be effective. * Beta blockers - also work. Can make coronary spasms worse. * Aminophylline - may work by inhibiting adenosine receptors. *

Estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

- may work in women. *

L-Arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the ...

- increases release of NO at vascular level, thus leading to vasodilatory effect. * Ranolazine - shown to improve angina and myocardial ischemia. *

Statins Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

Aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

Clopidogrel Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet drug, antiplatelet medication used to reduce the risk of Cardiovascular disease, heart disease and stroke in those at high risk. It is also used together with aspi ...

ACE inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as ...

and ARBs *Lifestyle changes such as diet and exercise. *Pain management through

cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...

(CBT),

mindfulness meditation Mindfulness is the cognitive skill, usually developed through exercises, of sustaining metacognitive awareness towards the contents of one's own mind and bodily sensations in the present moment. The term ''mindfulness'' derives from the Pali ...

yoga Yoga (UK: , US: ; 'yoga' ; ) is a group of physical, mental, and spiritual practices or disciplines that originated with its own philosophy in ancient India, aimed at controlling body and mind to attain various salvation goals, as pra ...

and

Tai Chi is a Chinese martial art. Initially developed for combat and self-defense, for most practitioners it has evolved into a sport and form of exercise. As an exercise, tai chi is performed as gentle, low-impact movement in which practitioners ...

. Microvascular angina is a chronic long term condition which increases the risk of

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

and other cardiac events such as heart failure and frequent hospital admissions. The treatment consists of drugs, mainly to relieve chest pain, but a very important part of the treatment is regularly visiting the doctor and repeating the tests to make sure the condition was taken care of in full. The first step in managing Microvascular angina is the administration of

nitrate Nitrate is a polyatomic ion with the chemical formula . salt (chemistry), Salts containing this ion are called nitrates. Nitrates are common components of fertilizers and explosives. Almost all inorganic nitrates are solubility, soluble in wa ...

s which may relieve the chest pain. They are used because of their ability to relax the muscles of the heart and blood vessels. However, they prove to be inefficient in as many as half of patients. Alternative treatments may consist of

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s or

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...

s which reduce chest pain by relaxing the muscle cells lining the artery and improving

blood flow Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory system is controlled by homeostasis, homeostatic mechanisms of autoregulation, just as hydrau ...

to the heart while lowering blood pressure. Aminophylline may also work, while estrogen can be effective in women. There is at present no known cure however a change in lifestyle is important. Patients should start following healthier diets which are low in

saturated fat A saturated fat is a type of fat in which the fatty acid chains have all single bonds between the carbon atoms. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone, and fatty acids that each cont ...

s, and should participate in regular physical activities. However, any patient with a heart disease condition should first seek for a medical opinion before starting exercising. Quitting smoking is also highly recommended.

Incidence

The reasons why women are more prone than men to develop a Microvascular angina are still not clear. However, it is believed that

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s along with other risk factors unique to women play a very important role. The constant changing of the estrogen levels may be one of the reasons along with the changes brought by birth.

History

Microvascular angina was first described by H. G. Kemp in 1973 as angina-like chest pain in the absence of angiographic evidence of coronary obstruction.

References

External links

{{DEFAULTSORT:Cardiac Syndrome X Syndromes of unknown causes Syndromes affecting the heart