The three classic signs, known as  Beck's triad , are  low blood pressure , jugular-venous distension, and muffled  heart sounds . [ 24 ]  Other signs may include  pulsus paradoxus  (a drop of at least 10 mmHg in arterial blood pressure with inspiration), [ 12 ]  and  ST segment  changes on the  electrocardiogram , [ 24 ]  which may also show low voltage  QRS complexes . [ 15 ]


Tamponade can often be diagnosed radiographically.  Echocardiography , which is the diagnostic test of choice, often demonstrates an enlarged pericardium or collapsed ventricles. A large cardiac tamponade will show as an enlarged globular-shaped heart on chest x-ray. During inspiration, the negative pressure in the  thoracic cavity  will cause increased pressure into the right ventricle.  This increased pressure in the right ventricle will cause the interventricular septum to bulge towards the left ventricle, leading to decreased filling of the left ventricle. At the same time, right ventricle volume is markedly diminished and sometimes it can collapse. [ 15 ]


Initial diagnosis of cardiac tamponade can be challenging, as there is a broad  differential diagnosis . [ 10 ]  The differential includes possible diagnoses based on symptoms, time course, mechanism of injury, patient history. Rapid onset cardiac tamponade may also appear similar to pleural effusions,  obstructive shock , shock, pulmonary embolism, and  tension pneumothorax . [ 13 ] [ 10 ]


If symptoms appeared more gradually, the differential diagnosis includes acute  heart failure . [ 25 ]


In a person with trauma presenting with  pulseless electrical activity  in the absence of hypovolemia and tension pneumothorax, the most likely diagnosis is cardiac tamponade. [ 26 ]


In addition to the diagnostic complications afforded by the wide-ranging differential diagnosis for chest pain, diagnosis can be additionally complicated by the fact that people will often be weak or faint at presentation. For instance, a fast rate of breathing and difficulty breathing on exertion that progresses to air hunger at rest can be a key diagnostic symptom, but it may not be possible to obtain such information from people who are unconscious or who have convulsions at presentation. [ 1 ]


Initial treatment given will usually be supportive in nature, for example administration of  oxygen , and monitoring. There is little care that can be provided pre-hospital other than general treatment for shock. Some teams have performed an emergency  thoracotomy  to release clotting in the  pericardium  caused by a penetrating chest injury. [ citation needed ]


Prompt diagnosis and treatment is the key to survival with tamponade.  Some pre-hospital providers will have facilities to provide  pericardiocentesis , which can be life-saving.  If the person has already suffered a  cardiac arrest , pericardiocentesis alone cannot ensure survival, and so rapid evacuation to a hospital is usually the more appropriate course of action. [ citation needed ]


Initial management in hospital is by pericardiocentesis. [ 13 ]  This involves the insertion of a needle through the skin and into the pericardium and aspirating fluid under ultrasound guidance preferably. This can be done laterally through the intercostal spaces, usually the fifth, or as a subxiphoid approach. [ 27 ] [ 28 ]  A left parasternal approach begins 3 to 5 cm left of the sternum to avoid the left internal mammary artery, in the 5th  intercostal space . [ 29 ]  Often, a  cannula  is left in place during resuscitation following initial drainage so that the procedure can be performed again if the need arises. If facilities are available, an emergency  pericardial window  may be performed instead, [ 13 ]  during which the pericardium is cut open to allow fluid to drain. Following stabilization of the person, surgery is provided to seal the source of the bleed and mend the pericardium. [ citation needed ]


Following heart surgery, the amount of chest tube drainage is monitored.  If the drainage volume drops off, and the blood pressure goes down, this can suggest a tamponade due to chest tube clogging.  In that case, the person is taken back to the operating room for an emergency reoperation. [ citation needed ]


If aggressive treatment is offered immediately and no complications arise (shock, AMI or arrhythmia, heart failure, aneurysm, carditis, embolism, or rupture), or they are dealt with quickly and fully contained, then adequate survival is still a distinct possibility. [ citation needed ]


The frequency of tamponade is unclear. [ 9 ]  One estimate from the United States places it at 2 per 10,000 per year. [ 3 ]  It is estimated to occur in 2% of those with stab or gunshot wounds to the chest. [ 30 ]


Cardiogenic shock  is a medical emergency resulting from inadequate blood flow to the body's organs due to the dysfunction of the  heart . Signs of inadequate blood flow include low urine production (<30 mL/hour), cool arms and legs, and decreased level of consciousness. People may also have a severely low blood pressure and heart rate.


Causes of cardiogenic shock include  cardiomyopathic , arrhythmic, and mechanical. Cardiogenic shock is most commonly precipitated by  a heart attack . [ 4 ]


Treatment of cardiogenic shock depends on the cause with the initial goals to improve blood flow to the body. If cardiogenic shock is due to a heart attack, attempts to  open the heart's arteries  may help. Certain medications, such as dobutamine and milrinone, improve the heart's ability to contract and can also be used. When these measures fail, more advanced options such as mechanical support devices or heart transplantation can be pursued.


Cardiogenic shock is a condition that is difficult to fully reverse even with an early diagnosis. [ 4 ]  However, early initiation of treatment may improve outcomes. Care should also be directed to any other organs that are affected by this lack of blood flow (e.g.,  dialysis  for the kidneys, mechanical ventilation for lung dysfunction).


Mortality rates for cardiogenic shock are high but have been decreasing in the United States. This is likely due to its rapid identification and treatment in recent decades. Some studies have suggested that this is possibly related to new treatment advances. Nonetheless, the mortality rates remain high and multi-organ failure in addition to cardiogenic shock is associated with higher rates of mortality. [ 5 ]


The presentation is the following: [ citation needed ]


Cardiogenic shock is caused by the failure of the heart to pump effectively.  It is due to damage to the  heart muscle , most often from a heart attack or  myocardial contusion . [ 6 ]  Other causes include  abnormal heart rhythms ,  cardiomyopathy ,  heart valve  problems, ventricular outflow obstruction (i.e. systolic anterior motion in  hypertrophic cardiomyopathy ), or ventriculoseptal defects. It can also be caused by a sudden decompressurization (e.g. in an aircraft), where air bubbles are released into the bloodstream ( Henry's law ), causing  heart failure . [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ]


An  electrocardiogram  helps to establish the exact diagnosis and guides treatment, it may reveal:


Echocardiography  may show poor ventricular function, signs of PED, [ clarification needed ]  rupture of the  interventricular septum , an obstructed outflow tract or cardiomyopathy. [ citation needed ]


The  Swan–Ganz catheter  or pulmonary artery catheter may assist in the diagnosis by providing information on the  hemodynamics . [ citation needed ]


When cardiomyopathy is suspected as the cause of cardiogenic shock, a  biopsy  of heart muscle may be needed to make a definite  diagnosis . [ citation needed ]


If the  cardiac index  falls acutely below 2.2 L/min/m 2 , the person may be in cardiogenic shock. [ citation needed ]


Initial management of cardiogenic shock involves medications to augment the heart's function. Certain medications, such as  dobutamine  or  milrinone , enhance the heart's pumping function and are often used first-line to improve the low blood pressure and delivery of blood to the rest of the body. [ 4 ]


Patients who have cardiogenic shock unresponsive to medication therapy may be candidates for more advanced options such as a mechanical circulatory support device. There are several types of mechanical circulatory support devices, the most common being intra-aortic balloon pumps, left ventricular assist devices, and venous-arterial extra-corporeal membrane oxygenation. It is important to note, however, that none of these devices are permanent solutions but rather are a bridge to a more definitive therapy such as a  heart transplantion .


An intra-aortic balloon pump is a device placed by a cardiac surgeon into the  descending aorta . It consists of a small balloon filled with helium that helps the heart to pump blood by inflating during  diastole  (the resting phase of the cardiac cycle) and deflating during  systole  (the contracting phase of the cardiac cycle). [ 16 ]  Intra-aortic balloon pumps do not directly increase cardiac output, but importantly, they decrease the amount of pressure that the heart has to pump against, thereby allowing for more blood flow and oxygen to be delivered to the heart muscles. [ 17 ]


Intra-aortic balloon pumps have been around for several decades and are most commonly used first-line of the mechanical circulatory support devices. [ 4 ]  However, it is not without its potential complications. Potential complications include injury upon insertion of the device to arteries supplying the spinal cord as well as risks with any procedure such as bleeding and infection. [ 17 ]  Contraindications to intra-aortic balloon pumps include aortic dissection, an abdominal aortic aneurysm, and irregularly fast heart beats. [ 16 ]


There are several types of left ventricular assist devices, with the Impella devices being some of the most common. This device is placed by a cardiac surgeon into the  left ventricle  of the heart and essentially acts as a pump, drawing blood from the left ventricle and pushing it out into the aorta so that it could be delivered to the rest of the body. [ 4 ]  Unlike intra-aortic balloon pumps, the Impella acts independently from the cardiac cycle. [ 17 ]  It can be adjusted to pump at faster rates to take blood out of the left ventricle and into the aorta more quickly, thereby decreasing the amount of work that the left ventricle has to do. [ 4 ]  While the Impella is commonly used in settings of cardiogenic shock, some evidence suggests that it placing an Impella device in an acute cardiogenic shock setting, where the heart fails to pump suddenly, may not necessarily guarantee increased survival. [ 18 ]


Potential complications specific to an Impella device include  hemolysis  (shearing of the blood cells) as well as the formation of lesions on the heart valve, namely the  mitral  or  aortic valves . [ 17 ]  Contraindications to an Impella device insertion include aortic dissection, the presence of a mechanical aortic valve, and the presence of a blood clot in the left ventricle. [ 16 ]


Venous-arterial extra-corporeal membrane oxygenation is a circuit support system that is meant to replace the function of the heart as it heals or awaits a more definitive treatment. [ 17 ]  It consists of a circuit that essentially drains blood from a patient's venous system, runs that blood through a circulator which adds oxygen and removes carbon dioxide, and ultimately returns blood back into the patient's arterial system where the newly oxygenated blood can be delivered to the person's organs. Some evidence suggests that the combination of both an Impella device and Venous-arterial extra-corporeal membrane oxygenation may decrease the heart's  pulmonary capillary wedge pressure , thereby decreasing the amount of stress on the cardiac muscles. [ 19 ]


Because Venous-arterial extra-corporeal membrane oxygenation is a very invasive procedure, it is not usually the first-line chosen device for patients in cardiogenic shock and is often reserved only for patients who have not only cardiogenic shock but also respiratory failure and/or concomitant  cardiac arrest . [ 17 ]


Complications of venous-arterial extra-corporeal membrane oxygenation include an  air embolism ,  pulmonary edema , and blood clotting in the circuit machine. [ 17 ]


Cardiorenal syndrome (CRS)  is an  umbrella term  used in the medical field that defines disorders of the heart and kidneys whereby "acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other". [ 1 ]  When one of these organs fails, the other may subsequently fail. [ 2 ]  The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. Patients who have renal failure first may be hard to determine if  heart failure  is concurrent. [ 3 ]  These two organs communicate with one another through a variety of pathways in an interdependent relationship. In a 2004 report from the  National Heart, Lung and Blood Institute , CRS was defined as a condition where treatment of congestive heart failure is limited by decline in kidney function. [ 4 ]  This definition has since been challenged repeatedly but there still remains little consensus over a universally accepted definition for CRS. At a consensus conference of the Acute Dialysis Quality Initiative (ADQI), the CRS was classified into five subtypes primarily based upon the organ that initiated the insult as well as the acuity of disease. [ 5 ]


Cardiorenal Syndrome is characterized by the dysfunction of both the cardiac and renal systems, resulting in a range of clinical manifestations. Many patients will have volume overload and therefore may show clinical signs such as jugular venous distension, generalized swelling of the abdomen and/or the lower legs, and difficulty breathing. [ 6 ]


Patients with Type 1 CRS, have a rapid worsening of cardiac function leading to  Acute Kidney Injury , which may manifest as oliguria or anuria. [ 6 ]


The following risk factors have been associated with increased incidence of CRS. [ 7 ]


The pathophysiology of CRS can be attributed to two broad categories of "hemodynamic factors" such as low cardiac output, elevation of both intra-abdominal and central venous pressures, and non-hemodynamic factors or "cardiorenal connectors" such as neurohormonal and inflammatory activation. [ 8 ]  It was previously believed that low cardiac output in heart failure patients results in decreased blood flow to the kidneys which can lead to progressive deterioration of kidney function. As a result, diuresis of these patients will result in  hypovolemia  and pre-renal azotemia. However, several studies did not find an association between kidney dysfunction and cardiac output or other hemodynamic parameters. [ 9 ]  In addition, CRS has been observed in patients with diastolic dysfunction who have normal left ventricular systolic function. [ 5 ]  Therefore, there must be additional mechanisms involved in the progression of CRS. Elevated intra-abdominal pressures resulting from ascites and abdominal wall edema may be associated with worsening kidney functions in heart failure patients. Several studies have shown that as a result of this increased intra-abdominal pressure there is increased central venous pressure and congestion of the kidneys' veins, which can lead to worsening kidney function. [ 5 ]  In addition, many neurohormonal and inflammatory agents are implicated in the progression of CRS. These include increased formation of  reactive oxygen species , endothelin, arginine vasopressin, and excessive sympathetic activity which can result in myocardial hypertrophy and necrosis. [ 10 ]  Other cardiorenal connectors include renin-angiotensin-system activation,  nitric oxide / reactive oxygen species  imbalance, inflammatory factors and abnormal activation of the  sympathetic nervous system , which can cause structural and functional abnormalities in both heart and/or the kidney. There is a close interaction within these cardiorenal connectors as well as between these factors and the hemodynamic factors which makes the study of CRS pathophysiology complicated. [ 8 ]


It is critical to diagnose CRS at an early stage in order to achieve optimal therapeutic efficacy. However, unlike markers of heart damage or stress such as  troponin , creatine kinase, natriuretic peptides, reliable markers for acute kidney injury are lacking. Recently, research has found several biomarkers that can be used for early detection of  acute kidney injury  before serious loss of organ function may occur. Several of these biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-B-D-glucosaminidase (NAG), Cystatin C, and kidney injury molecule-1 (KIM-1) which have been shown to be involved in tubular damage. [ 5 ]  Other biomarkers that have been shown to be useful include BNP, IL-18, and fatty acid binding protein (FABP). [ 5 ]  However, there is great variability in the measurement of these biomarkers and their use in diagnosing CRS must be assessed. [ 11 ]


Ronco et al. first proposed a five-part classification system for CRS in 2008 which was also accepted at ADQI consensus conference in 2010. [ 1 ]  These include:


The distinction between CRS type 2 and CRS type 4 is based on the assumption that, also in advanced and chronic disease, two different pathophysiological mechanisms can be distinguished, whereas both CKD and HF often develop due to a common pathophysiological background, most notably  hypertension  and  diabetes mellitus . Furthermore, the feasibility of the distinction between CRS type 2 and 4 in terms of diagnosis can be questioned. [ 12 ]


Braam et al. argue that classifying the CRS based on the order in which the organs are affected and the timeframe (acute vs chronic) is too simplistic and without a mechanistic classification it is difficult to study CRS. [ 8 ]  They view the cardiorenal syndrome in a more holistic, integrative manner. [ 8 ] [ 13 ]  They defined the cardiorenal syndrome as a pathophysiological condition in which combined heart and kidney dysfunction amplifies progression of failure of the individual organ, by inducing similar pathophysiological mechanisms. Therefore, regardless of which organ fails first, the same neurohormonal systems are activated causing accelerated cardiovascular disease, and progression of damage and failure of both organs. These systems are broken down into two broad categories of "hemodynamic factors" and non-hemodynamic factors or "cardiorenal connectors". [ 8 ]


Medical management of patients with CRS is often challenging as focus on treatment of one organ may have worsening outcome on the other. It is known that many of the medications used to treat HF may worsen kidney function. "As the population ages and the burden of renal disease and cardiovascular disease continue to rise, efforts to better understand the complicated relationship between these two organ systems are greatly needed." [ 14 ]  In addition, many trials on HF excluded patients with advanced kidney dysfunction. Therefore, our understanding of CRS management is still limited to this date. [ 15 ]  One study shows how ACE inhibitors and angiotensin II receptor antagonists have been found to prevent nephropathy in patients who have diabetes. [ 16 ]  Patients with kidney failure are less likely to get all guideline-based therapies. Patients who have moderate to severe CKD was seen to have similar care when compared to those patients who had normal kidney function. This helps show how healthcare workers can do more to increase the outcome of those suffering. [ 17 ]


Kidney failure is very common in patients with  congestive heart failure . It was shown that kidney failure complicates one-third of all admissions for heart failure, which is the leading cause of hospitalization in the United States among adults over 65 years old. [ 5 ]   Not only is this the leading cause of hospitalization, it also increases the stays in the ICU. [ 21 ]  These complications led to longer hospital stay, higher mortality, and greater chance for readmission. The inpatient mortality was seen to be much higher for patients with much more sever renal dysfunction. [ 17 ]  The increase of hospital and ICU stays also increases the cost of care in the hospital. Not only are there patients suffering from their disease, they are also suffering financially due to the cost of the hospital stays. [ 21 ]  Another study found that 39% of patients in NYHA class 4 and 31% of patients in NYHA class 3 had severely impaired kidney function. [ 22 ]  Similarly, kidney failure can have deleterious effects on cardiovascular function. It was estimated that about 44% of deaths in patients with  end-stage kidney failure  (ESKF) are due to cardiovascular disease. [ 23 ]


Cardiotoxicity  is the occurrence of heart dysfunction as electric or  muscle damage , resulting in heart toxicity. [ 1 ]  This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy in patients. [ 2 ]  Some effects are reversible, while in others, permanent damage requiring further treatment may arise. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by  chemotherapy  (a usual example is the class of  anthracyclines ) [ 3 ] [ 4 ]  treatment and/or radiotherapy; [ 5 ]  complications from  anorexia nervosa ; adverse effects of  heavy metals  intake; [ 6 ]  the long-term abuse of or ingestion at high doses of certain strong  stimulants  such as  cocaine ; [ 7 ]  or an incorrectly administered drug such as  bupivacaine . [ 8 ]


Many mechanisms have been used to explain cardiotoxicity. While many times, differing etiologies share the same mechanism, it generally depends on the agent inducing cardiac damage. For example, the primary mechanism is thought to be oxidative stress on cardiac myocytes. [ 8 ]  It is thought that reactive oxygen species (ROS) overwhelm the antioxidant defenses of cardiac cells, causing direct cellular damage. This oxidative damage can disrupt mitochondrial function, therefore disrupting energy production in the heart muscle itself, leading to energy depletion via depleted ATP and promoting cell death through apoptosis or necrosis. [ 9 ]


Other mechanisms of cardiotoxicity include inflammatory, [ 10 ]  DNA damaging, and disrupted cell signaling. DNA damage and disrupted cellular signaling are the proposed mechanism for many cardiotoxic chemotherapeutics. [ 11 ]


Regardless of the mechanism, clinical manifestations include heart failure, arrhythmia, myocarditis, and cardiomyopathy that can be permanent. [ 2 ]  These conditions can greatly alter mortality and morbidity in patients meaning careful monitoring is necessary in patients exposed to cardiotoxic agents.


The list of inciting agents is vast and involves various classes of medication as well as environmental agents. The effects of the cardiotoxic substances vary and are not all identical.


Source: [ 12 ]


Source: [ 17 ]


These agents can lead to varying degrees of cardiotoxicity, and their effects may be dose-dependent and influenced by individual factors such as pre-existing cardiovascular disease and genetic predispositions that can foster greater sensitivity to any cardiac damage.


The most likely effective treatment is to stop exposure to the inciting agent as soon as possible whether a pharmacologic or environmental agent. While some may fully recover from cardiotoxicity caused from exposure, many are left with permanent damage that may need further management. The management varies on the damage sustained, but generally follows guidelines for each condition such as heart failure, arrhythmias, and myocarditis. [ 20 ]


Patients taking anthracyclines can take Dexrazoxane as a cardioprotective agent to prevent extensive cardiac damage. [ 21 ]


Carditis  (pl.  carditides ) is the  inflammation  of the  heart . [ 1 ]


It is usually studied and treated by specifying it as: [ citation needed ]


Coronary artery  aneurysm  is an abnormal dilatation of part of the  coronary artery . This rare disorder occurs in about 0.3–4.9% of patients who undergo  coronary angiography . [ 2 ]


The majority of individuals suffering from coronary artery aneurysms do not exhibit any symptoms; the development of complications or concurrent atherosclerotic  coronary artery disease  is what causes clinical manifestations to occur. The most common complications include  coronary spasm , distal  embolization ,  aneurysm  rupture, local  thrombosis , and compression of surrounding structures due to massive enlargement of coronary artery aneurysm. [ 3 ]


Acquired causes include  atherosclerosis  in adults, [ 4 ]   Kawasaki disease  in children [ 5 ]  and  coronary catheterization . With the invention of drug eluting stents, there has been more cases implying stents lead to coronary aneurysms. The pathophysiology, although not completely understood, might be comparable to that of aneurysms of larger vessels. This includes disruption of the arterial media, weakening of the  arterial wall , increased wall strain and slow dilatation of the coronary artery portion. [ 2 ]


It can also be congenital. [ 6 ] [ 7 ]  The following risk factors are thought to be associated with coronary artery aneurysms:


It is often found coincidentally on  coronary angiography . [ 3 ]  Other modalities that can be used to diagnose a coronary artery aneurysm include  echocardiography ,  magnetic resonance imaging  and  computerized tomography . Although coronary  angiography  remains to be the gold standard, the invasive procedure comes with its associated risks, is more expensive than other modalities and the size of the aneurysm might be miscalculated if there is a thrombus in place. [ 2 ]


Treatment for coronary artery aneurysm include medical management, surgery and percutaneous intervention. Underlying coronary artery risk factors should be addressed in patients with  atherosclerosis  and proper guideline-mediated medications should be started. In those with risk for embolism or  thrombosis , anti-platelet or anticoagulation therapy should be contemplated. [ 2 ]


In patients with  Kawasaki disease  prompt administration of intravenous  immunoglobulin (IVIG) therapy  should be given to prevent complication of coronary artery aneurysm. [ 9 ]


Generally, it has a good prognosis. [ 3 ]
The prognosis of coronary artery aneurysm is dependent on its diameter. The smaller the aneurysm the better the prognosis. There is less risk for ischemic myocardial damage and mortality with smaller aneurysms. Aneurysms with an internal diameter > 8 mm have poorer outcomes, since these aneurysms can be occluded and be associated with complications such as  arrhythmias ,  myocardial infarction , or sudden death. [ 2 ]


Coronary artery anomalies  are variations of the  coronary circulation , affecting <1% of the general population. Symptoms include chest pain, shortness of breath and  syncope , although cardiac arrest may be the first clinical presentation. Several varieties are identified, with a different potential to cause  sudden cardiac death .


Coronary arteries  are vessels supplying blood and nutrients to the heart muscle ( myocardium ). [ 1 ]


Coronary arteries arise from ostia, openings of the  aorta  (the largest artery in the human body) at the upper third or middle third of the  sinuses of Valsalva  (the first part of the big pipe coming off the main pumping chamber). The walls of coronary arteries consist of three layers: the  tunica intima  or inner layer (possible site of lipid deposits and fibrosis, during life), the  tunica media  (a smooth muscle layer whose tone is modulated by the nervous system, influencing vessel diameter and resistance) and  adventitia  (where nervous endings are located). Normally, the initial portion of coronary arteries lies onto the external surface of the heart (epicardium) where fat deposits tend to form during life. [ citation needed ]


In normal anatomy, three essential coronary arteries are identified:  right coronary artery  (RCA),  left anterior descending artery  (LAD) and  left circumflex artery  (LCx). LAD and LCx usually originate from the bifurcation of a common vessel known as  left main  trunk or left coronary artery (LM or LCA).  [ citation needed ]


Coronary arteries are identified according to the myocardial territory they feed: [ citation needed ]


1)   the LAD supplies the anterior interventricular septum and anterior left ventricular free wall;


2)   the LCx supplies the posterolateral left ventricular free wall;


3)   the RCA supplies the right ventricular free wall;


In fact, despite a certain degree of variability in coronary artery anatomy among individuals, there is greater consistency in the  regions  of the heart that are supplied by the different coronary arteries. [ citation needed ]


The  posterior descending artery , providing blood flow to the infero-posterior wall of the heart, originates from the RCA in 70-90% of individuals (“right coronary dominance”), whereas in 10-15% cases it originates from the LCx (“left coronary dominance”). [ citation needed ]


Coronary vessels diameter progressively decreases proceeding from their origin to the periphery. Besides the LM, LAD, LCx and RCA, arterial vessels that are large enough to be identified by clinical angiography are called “branches”, while  capillaries  represent the smallest peripheral vessels of the coronary tree that lack muscular tissue (and capacity to cause  spasm ) and are responsible for oxygen and nutrients exchange within the myocardium. [ citation needed ]


Regarding coronary artery anatomy, a distinction must be provided when assessing abnormalities: [ citation needed ]


-       normal : any morphological feature observed in >1% of an unselected population


-       normal variant : an alternative, unusual but benign morphological feature identified in >1% of the same population (e.g. left main is absent in 1-2% of the general population with LAD and LCx originating from separate ostia - “absent left trunk” variant)


-       coronary artery anomaly (CAA) : a morphological feature seen in <1% of that population, capable of causing dysfunction


The prevalence of coronary artery anomalies is inconsistent across the scientific literature, but they are considered to affect <1% of the general population. Specifically, recent data came from  MRI  screening of a large population (more than 5000 young children) and provided a precise estimate, suggesting that coronary artery anomalies are present in 0.45% of the US population (approximately 1.300.000 people). [ 2 ]


Anomalous origin of a coronary artery from the opposite sinus are relevant on a clinical level due to a significant association with sudden cardiac death, if they are accompanied by intramural course. Indeed, the main feature responsible for adverse outcomes is the “intramural” course (sometimes improperly referred to as inter-arterial) characterized by an acute ostial angulation (tangential course), “slit-like” ostium (compressed inside the aortic wall), and a proximal or initial section penetrating into the aortic tunica media (coronary arteries normally take off at a 90 degree angle) with subsequent course reaching the “correct” side of the heart. As a consequence, lateral compression of the coronary artery leads to coronary luminal (inside opening) narrowing, with reduced supply of blood and oxygen to the depending myocardial tissue, that is phasic (worse in  systole , the phase of cardiac contraction, and tachycardia). Furthermore, the intramural segment of the ectopic artery, located inside the aorta, is typically but variably “ hypoplastic ”, smaller in circumference than the distal, extramural segments (it is unable to grow properly either before or after birth). [ citation needed ]


Autonomic  and/or  endothelial dysfunction  may occur and induce spasm and/or  thrombosis  at anomalous sites (and critical  ischemia ), although intracoronary clotting has been rarely observed. Therefore,  stenosis  of an intramural proximal segment, lateral compression and spastic hyperreactivity are the mechanisms that have been linked to clinical manifestation. Coronary narrowing is most likely the main process implied in ACAOS, and it may result in symptoms such as chest pain (“ angina pectoris ”),  dyspnea  (shortness of breath), palpitations, cardiac  arrhythmias  (heart rhythm disorders),  syncope  (fainting). In most cases, however, coronary artery anomalies are silent for many years and the first clinical manifestation of these pathological entities is sudden cardiac death (e.g. due to malignant arrhythmias such as  ventricular fibrillation ) typically after strenuous physical exertion (when arterial compression is more severe, and cardiac work is maximal) such as in young athletes or military recruits. Of note, 19-33% (in different studies) of sudden deaths in young athletes are due to coronary artery anomalies. Clinical manifestations can be found in non-athletic, older individuals and are commonly associated with  hypertension  and aortic dilatation with worsening degree of compression.


L-ACAOS-IM  (intramural) is seen in 0.1% of young children and, among coronary anomalies, it has the highest probability of clinical repercussions, being consistently associated with sudden cardiac death following physical exercise.


Several more varieties of L-ACAOS are described:


-       prepulmonic  (L-ACAOS-PP): origin of the LCA (or only the LAD) from the right sinus of Valsalva (RSV) with an epicardial course (on the surface of the heart) anterior to the pulmonary outflow tract - this does not usually cause stenosis nor requires intervention (benign anomaly, unless spasm occurs);


-       subpulmonary, infundibular or intraseptal ( L-ACAOS-SP): the LCA (or only the LAD) originates from the RSV, initially runs inter-arterially (outside the aortic wall) then intramyocardially inside in the ventricular septum and finally epicardially in the anterior interventricular groove - this anomaly is considered benign since it is not associated with significant fixed degree of stenosis (but it could cause spasm);


-       retroaortic  (L-ACAOS-RA): origin of the LCA or the only LCx from the RSV or from the RCA, running behind the aortic root and at the central fibrous mitro-aortic septum – this is considered as a benign anomaly (but it could cause spasm);


-       retrocardiac  (L-ACAOS-RC) – LCA originates from the RCA at the atrioventricular groove - or wrap-around the apex (L-ACAOS-WA) – generally benign, unless spasm occurs.


R-ACAOS-IM [ 3 ]  is observed in a higher percentage of cases (0.35% of adolescents) than L-ACAOS-IM [ 4 ]  but is less likely to be associated with sudden cardiac death in athletes. Varieties of R-ACAOS such as prepulmonic, retroaortic and intraseptal can occur and are considered generally benign.


The most frequent symptomatic coronary anomaly in infants and young children is anomalous origin of the left coronary artery from the  pulmonary artery , which may cause acute  myocardial infarction  at neonatal age and requires emergent surgery at the time of diagnosis. [ 5 ]


Anomalies at the mid segments  include  myocardial bridges , affecting >1% of the clinical population, and characterized by an intramyocardial course of coronary arteries within the muscle fibers. This may lead to systolic compression which is usually mild (coronary blood flow is mostly  diastolic ). Significant ischemia is rare in isolated myocardial bridges, and if present this is generally due to localized endothelial dysfunction with a tendency to spasm. Most myocardial bridges are benign and do not require any intervention.


Coronary artery  aneurysms  are defined as a > 50% increase of the vessel diameter. Some cases are congenital/idiopathic, but most are secondary to atherosclerosis or  Kawasaki disease  (an immuno-inflammatory disease especially targeting coronary vessels wall). Potential complications include localized thrombosis, distal embolization, rupture, or late lipid deposits.


Coronary arteriovenous fistulas  are anomalies at the termination consisting of an anomalous connection of coronary arteries to coronary veins, veins of the pulmonary or systemic circulations, or to any cardiac cavity. Smaller fistulas are usually benign, and only severe cases can be complicated by aneurysmatic dilatation with potential thrombosis and distal embolization, volume overload or “blood steal” from arterial circulation and subsequent ischemia. Treatment is generally not required.


There is an open debate about the cost/efficiency of generalized diagnostic  screening  in large populations. Carriers of coronary artery anomalies may receive positive results following stress/imaging tests. However, only in a minority of cases ischemia in the context of coronary artery anomalies is reproducible by stress or imaging testing and is mainly associated with particular conditions such as intense (maximal) exercise, which may lead to confusing results and misdiagnosis by techniques such as treadmill test or nuclear testing.


Nonetheless, routine screening of high-risk populations (e.g. individuals participating in competitive sports) should be generally encouraged in clinical practice of sports cardiologists.


Various imaging tests have a potential to identify coronary artery anomalies.  Echocardiography  (ultrasound scanning of the heart) is simple, non-invasive and economical. Its use for CAAs screening is limited because its diagnostic sensitivity is highly dependent on the operator's skills and is significantly lower in larger individuals (>40 kg). The diagnostic power of echocardiography is generally poor in most cases after infancy.  Especially if clinical suspicion for CAAs is high (e.g. syncope following exertion and/or history of aborted sudden cardiac death).
 Cardiac magnetic resonance  (CMR) is an excellent tool to identify coronary artery anomalies with a significantly higher diagnostic accuracy than standard echocardiography. Compared to CMR,  coronary computed tomographic angiography  (CCTA) provides more precise assessment of coronary anatomy, course and degree of  stenosis , but its clinical use for screening is strongly limited by its cost, the need for ionizing radiation, intravenous contrast and, in many cases, drugs administration. Assessment of severity of stenosis is best achieved by intravascular ultrasound (IVUS) imaging and it should be considered in known carriers of ACAOS-IM or that have symptoms or positive stress test results or are involved in competitive exercises. IVUS consists of cross-sectional imaging of coronary arteries in a  catheterization laboratory  by advancing a thin probe inside the vascular lumen, obtaining precise in-vivo information about degree of area stenosis in different arterial segments, providing a solid basis for treatment strategies.


CAAs include a wide spectrum of entities with different severity. We can schematically distinguish anomalies at the ostium, such as congenital ostial atresia or stenosis or anomalous origin of a coronary artery from the opposite sinus [ACAOS] (examples: right coronary artery anomalous origin from the opposite sinus [R-ACAOS] and left coronary artery origin from the opposite sinus [L-ACAOS]); anomalies at the mid segments (such as  myocardial bridge  [MB]); anomalies at the termination (such as coronary arteriovenous fistulas). [ citation needed ]


Criteria for intervention in ACAOS-IM are:


-      symptoms of effort-related chest pain, shortness of breath, syncope or aborted sudden cardiac death (Class I, Level of Evidence A/B) and/or high-risk professional lifestyle.


-      positive treadmill stress test, ideally by nuclear technology, in the correct dependent myocardial territory, in the presence of intramural course (Class I, Level of Evidence B)


For special populations, e.g. athletes, treatment may be indicated with specific advice of medical experts, in the absence of the previously mentioned criteria. Cut-off for stenosis severity requiring intervention is not clear, although narrowing >50% in comparison to the distal normal segment is generally accepted as a marker of severity in L-ACAOS-IM. Decisions on treatment should be guided by the patient's individual characteristics such as age, symptoms, profession and level of engagement in physical activity. Pharmacological treatment and observation may be appropriate in selected, low-risk patients. Importantly, untreated carriers of significant ACAOS should not generally engage in competitive sports or strenuous activities.


Treatment options for ACAOS-IM include both catheter-based procedures ( percutaneous coronary intervention  [PCI]) and surgical interventions. PCI consists of stent angioplasty of the proximal, intramural segment by placing a thin metal tube (a stent) in order to keep open the narrowed artery. PCI of R-ACAOS-IM is feasible and quite successful, but further experience is needed in L-ACAOS-IM since few cases have been treated percutaneously, while surgery is the recommended treatment in this subpopulation, at this time. Surgery consists of “unroofing” or denudation of the intramural coronary segment from the aortic wall: this approach is currently the gold standard.  Coronary artery bypass grafting  (CABG) and reimplantation of the ectopic artery are obsolete and not indicated, because of competitive flow in mild resting narrowings. [ 6 ]


Coronary artery disease  ( CAD ), also called  coronary heart disease  ( CHD ), or  ischemic heart disease  ( IHD ), [ 13 ]  is a type of  heart disease  involving  the reduction of blood flow  to the  cardiac muscle  due to a build-up of  atheromatous plaque  in the  arteries of the heart . [ 5 ] [ 6 ] [ 14 ]  It is the most common of the  cardiovascular diseases . [ 15 ]  CAD can cause  stable angina ,  unstable angina , myocardial ischemia, [ 16 ]  and  myocardial infarction . [ 17 ]


A common symptom is angina, which is  chest pain  or discomfort which may travel into the shoulder, arm, back, neck, or jaw. [ 4 ]  Occasionally it may feel like  heartburn . In  stable angina , symptoms occur with exercise or emotional  stress , last less than a few minutes, and improve with rest. [ 4 ]   Shortness of breath  may also occur and sometimes no symptoms are present. [ 4 ]  In many cases, the first sign is a  heart attack . [ 5 ]  Other complications include  heart failure  or an  abnormal heartbeat . [ 5 ]


Risk factors include  high blood pressure ,  smoking ,  diabetes , lack of exercise,  obesity ,  high blood cholesterol , poor diet,  depression , and excessive  alcohol  consumption. [ 6 ] [ 7 ] [ 18 ]  A number of tests may help with diagnosis including:  electrocardiogram ,  cardiac stress testing ,  coronary computed tomographic angiography , biomarkers ( high-sensitivity cardiac troponins ) and  coronary angiogram , among others. [ 8 ] [ 19 ]
Ways to reduce CAD risk include eating a  healthy diet , regularly  exercising , maintaining a healthy weight, and not smoking. [ 20 ] [ 9 ]  Medications for diabetes, high cholesterol, or high blood pressure are sometimes used. [ 9 ]  There is limited evidence for screening people who are at low risk and do not have symptoms. [ 21 ]  Treatment involves the same measures as prevention. [ 10 ] [ 22 ]  Additional medications such as  antiplatelets  (including  aspirin ),  beta blockers , or  nitroglycerin  may be recommended. [ 10 ]  Procedures such as  percutaneous coronary intervention  (PCI) or  coronary artery bypass surgery  (CABG) may be used in severe disease. [ 10 ] [ 23 ]  In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improves  life expectancy  or decreases heart attack risk. [ 24 ]


In 2015, CAD affected 110 million people and resulted in 8.9 million deaths. [ 11 ] [ 12 ]  It makes up 15.6% of all deaths, making it the  most common cause of death  globally. [ 12 ]  The risk of death from CAD for a given age decreased between 1980 and 2010, especially in  developed countries . [ 25 ]  The number of cases of CAD for a given age also decreased between 1990 and 2010. [ 26 ]  In the United States in 2010, about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45; [ 27 ]  rates were higher among males than females of a given age. [ 27 ]


The most common symptom is  chest pain  or discomfort that occurs regularly with activity, after eating, or at other predictable times; this phenomenon is termed stable  angina  and is associated with  narrowing  of the  arteries  of the  heart . Angina also includes chest tightness, heaviness, pressure, numbness, fullness, or squeezing. [ 28 ]  Angina that changes in intensity, character or frequency is termed unstable.  Unstable angina  may precede  myocardial infarction . In adults who go to the emergency department with an unclear cause of pain, about 30% have pain due to coronary artery disease. [ 29 ]  Angina, shortness of breath, sweating, nausea or vomiting, and lightheadedness are signs of a heart attack or myocardial infarction, and immediate emergency medical services are crucial. [ 28 ]


With advanced disease, the narrowing of coronary arteries reduces the supply of oxygen-rich blood flowing to the heart, which becomes more pronounced during strenuous activities during which the heart beats faster and has an increased oxygen demand. [ 30 ]  For some, this causes severe symptoms, while others experience no symptoms at all. [ 4 ]


Symptoms in females can differ from those in males, and the most common symptom reported by females of all races is shortness of breath. [ 31 ]  Other symptoms more commonly reported by females than males are extreme fatigue, sleep disturbances, indigestion, and anxiety. [ 32 ]  However, some females experience irregular heartbeat, dizziness, sweating, and nausea. [ 28 ]  Burning, pain, or pressure in the chest or upper abdomen that can travel to the arm or jaw can also be experienced in females, but females less commonly report it than males. [ 32 ]  Generally, females experience symptoms 10 years later than males. [ 33 ]  Females are less likely to recognize symptoms and seek treatment. [ 28 ]


Coronary artery disease is characterized by heart problems that result from atherosclerosis. [ 34 ]  Atherosclerosis is a type of arteriosclerosis which is the "chronic inflammation of the arteries which causes them to harden and accumulate cholesterol plaques (atheromatous plaques) on the artery walls". [ 35 ]  CAD has several well-determined risk factors that contribute to atherosclerosis. These risk factors for CAD include "smoking, diabetes, high blood pressure (hypertension), abnormal (high) amounts of cholesterol and other fat in the blood (dyslipidemia), type 2 diabetes and being overweight or obese (having excess body fat)" due to lack of exercise and a poor diet. [ 36 ]  Some other risk factors include  high blood pressure ,  smoking ,  diabetes , lack of exercise,  obesity ,  high blood cholesterol , poor diet,  depression ,  family history ,  psychological stress  and excessive  alcohol . [ 6 ] [ 7 ] [ 18 ]  About half of cases are linked to genetics. [ 37 ]  Smoking and obesity are associated with about 36% and 20% of cases, respectively. [ 38 ]  Smoking just one cigarette per day about doubles the risk of CAD. [ 39 ]  Lack of exercise has been linked to 7–12% of cases. [ 38 ] [ 40 ]  Exposure to the  herbicide   Agent Orange  may increase risk. [ 41 ]  Rheumatologic diseases such as  rheumatoid arthritis ,  systemic lupus erythematosus ,  psoriasis , and  psoriatic arthritis  are independent risk factors as well. [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ excessive citations ]


Job stress appears to play a minor role accounting for about 3% of cases. [ 38 ]  In one study, females who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. [ 46 ]  In contrast, females who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. [ 46 ]  Having a  type A behavior pattern , a group of personality characteristics including time urgency, competitiveness, hostility, and impatience, [ 47 ]  is linked to an increased risk of coronary disease. [ 48 ]


The consumption of different types of  fats  including  trans fat  (trans unsaturated), and  saturated fat , in a diet "influences the level of cholesterol that is present in the bloodstream". [ 49 ]  Unsaturated fats originate from plant sources (such as oils). There are two types of unsaturated fats, cis and trans isomers. Cis unsaturated fats are bent in molecular structure and trans are linear in structure. Saturated fats originate from animal sources (such as animal fats) and are also molecularly linear in structure. [ 50 ]  The linear configurations of unsaturated trans and saturated fats allow them to easily accumulate and stack at the arterial walls when consumed in high amounts (and other positive measures towards physical health are not met).


High levels of cholesterol in the bloodstream lead to atherosclerosis. With increased levels of LDL in the bloodstream, "LDL particles will form deposits and accumulate within the arterial walls, which will lead to the development of plaques, restricting blood flow". [ 49 ]  The resultant reduction in the heart's blood supply due to atherosclerosis in coronary arteries "causes shortness of breath, angina pectoris (chest pains that are usually relieved by rest), and potentially fatal heart attacks (myocardial infarctions)". [ 36 ]


The  heritability  of coronary artery disease has been estimated between 40% and 60%. [ 51 ]   Genome-wide association studies  have identified over 160 genetic susceptibility loci for coronary artery disease. [ 52 ]


Several  RNA Transcripts  associated with CAD -  FoxP1 ,  ICOSLG ,  IKZF4/Eos ,  SMYD3 ,  TRIM28 , and  TCF3/E2A  are likely markers of  regulatory T cells  (Tregs), consistent with known reductions in Tregs in CAD. [ 53 ]


The RNA changes are mostly related to ciliary and endocytic transcripts, which in the circulating immune system would be related to the  immune synapse . [ 54 ]  One of the most differentially expressed genes,  fibromodulin  (FMOD), which is increased 2.8-fold in CAD, is found mainly in connective tissue [ 55 ]  and is a modulator of the TGF-beta signaling pathway. However, not all of the RNA changes may be related to the immune synapse. For example,  Nebulette , the most down-regulated transcript (2.4-fold), is found in cardiac muscle; it is a 'cytolinker' that connects actin and desmin to facilitate cytoskeletal function and vesicular movement. The endocytic pathway is further modulated by changes in  tubulin , a key microtubule protein, and  fidgetin , a tubulin-severing enzyme that is a marker for cardiovascular risk identified by  genome-wide association study . Protein recycling would be modulated by changes in the proteasomal regulator  SIAH3 , and the ubiquitin ligase  MARCHF10 . On the ciliary aspect of the immune synapse, several of the modulated transcripts are related to ciliary length and function.  Stereocilin  is a partner to  mesothelin , a related  super-helical  protein, whose transcript is also modulated in CAD.  DCDC2 , a double-cortin protein, is a modulator of ciliary length. In the signaling pathways of the immune synapse, there were numerous transcripts that related directly to T cell function and the control of differentiation.  Butyrophilin  is a co-regulator for T cell activation.  Fibromodulin  is a modulator of the TGF-beta signaling pathway, a primary determinant of Tre differentiation. Further impact on the  TGF-beta  pathway is reflected in concurrent changes in the BMP receptor 1B RNA (BMPR1B), because the bone morphogenic proteins are members of the TGF-beta superfamily, and likewise impact Treg differentiation. Several of the transcripts ( TMEM98 ,  NRCAM ,  SFRP5 ,  SHISA2 ) are elements of the Wnt signaling pathway, which is a major determinant of Treg differentiation.


Limitation of blood flow to the heart causes  ischemia  (cell starvation secondary to a lack of oxygen) of the heart's  muscle cells . The heart's muscle cells may die from lack of  oxygen  and this is called a  myocardial infarction  (commonly referred to as a heart attack). It leads to damage, death, and eventual scarring of the heart muscle without regrowth of heart muscle cells. Chronic high-grade  narrowing  of the coronary arteries can induce transient  ischemia  which leads to the induction of a  ventricular arrhythmia , which may terminate into a dangerous heart rhythm known as  ventricular fibrillation , which often leads to death. [ 64 ]


Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a  coronary artery  (the arteries that supply blood to the heart muscle) develops  atherosclerosis . With atherosclerosis, the artery's lining becomes hardened, stiffened, and accumulates deposits of calcium, fatty lipids, and abnormal inflammatory  cells  – to form a  plaque . Calcium phosphate (hydroxyapatite) deposits in the muscular layer of the blood vessels appear to play a significant role in stiffening the arteries and inducing the early phase of coronary  arteriosclerosis . This can be seen in a so-called metastatic mechanism of  calciphylaxis  as it occurs in  chronic kidney disease  and  hemodialysis . [ citation needed ]  Although these people have kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing partial obstruction to blood flow. People with coronary artery disease might have just one or two  plaques  or might have dozens distributed throughout their  coronary arteries .  A more severe form is  chronic total occlusion  (CTO) when a coronary artery is completely obstructed for more than 3 months. [ 65 ]


Microvascular angina  is a type of  angina pectoris  in which chest pain and chest discomfort occur without signs of blockages in the larger  coronary arteries  of their hearts when an  angiogram  (coronary angiogram) is being performed. [ 66 ] [ 67 ]
The exact cause of microvascular angina is unknown. Explanations include  microvascular dysfunction  or  epicardial  atherosclerosis. [ 68 ] [ 69 ]  For reasons that are not well understood, females are more likely than males to have it; however,  hormones  and other risk factors unique to females may play a role. [ 70 ]


The diagnosis of CAD depends largely on the nature of the symptoms and imaging. The first investigation when CAD is suspected is an  electrocardiogram  (ECG/EKG), both for  stable angina  and acute coronary syndrome. An  X-ray of the chest ,  blood tests  and resting  echocardiography  may be performed. [ 71 ] [ 72 ]


For stable symptomatic patients, several non-invasive tests can diagnose CAD depending on pre-assessment of the risk profile. Noninvasive imaging options include;  Computed tomography angiography  (CTA) (anatomical imaging, best test in patients with low-risk profile to "rule out" the disease),  positron emission tomography  (PET),  single-photon emission computed tomography (SPECT)/nuclear stress test/myocardial scintigraphy  and  stress echocardiography  (the three latter can be summarized as functional noninvasive methods and are typically better to "rule in").  Exercise ECG  or stress test is inferior to non-invasive imaging methods due to the risk of false negative and false positive test results. The use of non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease. [ 73 ] [ 74 ]  Invasive testing with  coronary angiography  (ICA) can be used when non-invasive testing is inconclusive or show a high event risk. [ 72 ]


The diagnosis of  microvascular angina  (previously known as  cardiac syndrome X  – the rare coronary artery disease that is more common in females, as mentioned, is a diagnosis of exclusion. Therefore, usually, the same tests are used as in any person suspected of having coronary artery disease: [ 75 ]


Stable angina  is the most common manifestation of ischemic heart disease, and is associated with reduced quality of life and increased mortality. It is caused by epicardial coronary stenosis which results in reduced blood flow and oxygen supply to the myocardium. [ 76 ]
Stable angina is short-term chest pain during physical exertion caused by an imbalance between myocardial oxygen supply and metabolic oxygen demand. Various forms of  cardiac stress tests  may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG),  echocardiography  (using  ultrasound  of the heart) or  scintigraphy  (using uptake of  radionuclide  by the heart muscle). If part of the heart seems to receive an insufficient blood supply,  coronary angiography  may be used to identify  stenosis  of the coronary arteries and suitability for  angioplasty  or  bypass surgery . [ 77 ]


In minor to moderate cases, nitroglycerine may be used to alleviate acute symptoms of stable angina or may be used immediately before exertion to prevent the onset of angina. Sublingual nitroglycerine is most commonly used to provide rapid relief for acute angina attacks and as a complement to anti-anginal treatments in patients with refractory and recurrent angina. [ 78 ]  When nitroglycerine enters the bloodstream, it forms free radical nitric oxide, or NO, which activates guanylate cyclase and in turn stimulates the release of cyclic GMP. This molecular signaling stimulates smooth muscle relaxation, ultimately resulting in vasodilation and consequently improved blood flow to regions of the heart affected by atherosclerotic plaque. [ 79 ]


Stable coronary artery disease (SCAD) is also often called stable ischemic heart disease (SIHD). [ 80 ]  A 2015 monograph explains that "Regardless of the nomenclature, stable angina is the chief manifestation of SIHD or SCAD." [ 80 ]  There are U.S. and European  clinical practice guidelines  for SIHD/SCAD. [ 81 ] [ 82 ] [ 72 ]  In patients with non-severe asymptomatic  aortic valve stenosis  and no overt coronary artery disease, the increased  troponin T  (above 14 pg/mL) was found associated with an increased 5-year event rate of  ischemic cardiac events  ( myocardial infarction ,  percutaneous coronary intervention , or  coronary artery bypass surgery ). [ 83 ]


Diagnosis of  acute coronary syndrome  generally takes place in the  emergency department , where ECGs may be performed sequentially to identify "evolving changes" (indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show elevation of the " ST segment ", which in the context of severe typical chest pain is strongly indicative of an acute  myocardial infarction  (MI); this is termed a STEMI (ST-elevation MI) and is treated as an emergency with either urgent  coronary angiography  and  percutaneous coronary intervention  (angioplasty with or without  stent  insertion) or with  thrombolysis  ("clot buster" medication), whichever is available. In the absence of ST-segment elevation, heart damage is detected by  cardiac markers  (blood tests that identify heart muscle damage). If there is evidence of damage ( infarction ), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI). If there is no evidence of damage, the term "unstable angina" is used. This process usually necessitates hospital admission and close observation on a  coronary care unit  for possible complications (such as  cardiac arrhythmias  – irregularities in the heart rate). Depending on the risk assessment, stress testing or angiography may be used to identify and treat coronary artery disease in patients who have had an NSTEMI or unstable angina. [ citation needed ]


There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on the different variables above. A notable example is  Framingham Score , used in the  Framingham Heart Study . It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking, and systolic blood pressure. When predicting risk in younger adults (18–39 years old), the Framingham Risk Score remains below 10–12% for all deciles of baseline-predicted risk. [ 84 ]


Polygenic score  is another way of risk assessment. In one study the relative risk of incident coronary events was 91% higher among participants at high genetic risk than among those at low genetic risk. [ 85 ]


Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. [ 86 ] [ 87 ]  Prevention involves adequate physical  exercise , decreasing  obesity , treating  high blood pressure , eating a  healthy diet , decreasing  cholesterol  levels, and  stopping smoking . Medications and exercise are roughly equally effective. [ 88 ]  High levels of physical activity reduce the risk of coronary artery disease by about 25%. [ 89 ]  Life's Essential 8 are the key measures for improving and maintaining cardiovascular health, as defined by the American Heart Association. AHA added sleep as a factor influencing heart health in 2022. [ 90 ]


Most guidelines recommend combining these preventive strategies. A 2015 Cochrane Review found some evidence that counseling and education to bring about behavioral change might help in high-risk groups. However, there was insufficient evidence to show an effect on mortality or actual cardiovascular events. [ 91 ]


In  diabetes mellitus , there is little evidence that very tight  blood sugar  control improves cardiac risk although improved sugar control appears to decrease other problems such as  kidney failure  and  blindness . [ 92 ]


A 2024 study published in  The Lancet Diabetes & Endocrinology  found that the oral glucose tolerance test (OGTT) is more effective than hemoglobin A1c (HbA1c) for detecting dysglycemia in patients with coronary artery disease. [ 93 ]  The study highlighted that 2-hour post-load glucose levels of at least 9 mmol/L were strong predictors of cardiovascular outcomes, while HbA1c levels of at least 5.9% were also significant but not independently associated when combined with OGTT results. [ 94 ]


A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. [ 95 ]   Vegetarians  have a lower risk of heart disease, [ 96 ] [ 97 ]  possibly due to their greater consumption of fruits and vegetables. [ 98 ]  Evidence also suggests that the  Mediterranean diet [ 99 ]  and a  high fiber diet  lower the risk. [ 100 ] [ 101 ]


The consumption of  trans fat  (commonly found in  hydrogenated  products such as  margarine ) has been shown to cause a precursor to  atherosclerosis [ 102 ]  and increase the risk of coronary artery disease. [ 103 ]


Evidence does not support a beneficial role for  omega-3 fatty acid  supplementation in preventing  cardiovascular disease  (including  myocardial infarction  and  sudden cardiac death ). [ 104 ] [ 105 ]  There is tentative evidence that intake of menaquinone ( Vitamin K 2 ), but not phylloquinone ( Vitamin K 1 ), may reduce the risk of CAD  mortality . [ 106 ]


Secondary prevention is preventing further sequelae of already established disease. Effective lifestyle changes include:


Aerobic exercise , like walking, jogging, or swimming, can reduce the risk of mortality from coronary artery disease. [ 109 ]  Aerobic exercise can help decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also increases HDL cholesterol. [ 110 ]


Although exercise is beneficial, it is unclear whether doctors should spend time counseling patients to exercise. The  U.S. Preventive Services Task Force  found "insufficient evidence" to recommend that doctors counsel patients on exercise but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity, and mortality", only the effectiveness of counseling itself. [ 111 ]  The  American Heart Association , based on a non-systematic review, recommends that doctors counsel patients on exercise. [ 112 ]


Psychological symptoms are common in people with CHD, and while many psychological treatments may be offered following cardiac events, there is no evidence that they change mortality, the risk of revascularization procedures, or the rate of non-fatal myocardial infarction. [ 108 ]


Antibiotics for secondary prevention of coronary heart disease


Early studies suggested that antibiotics might help patients with coronary disease to reduce the risk of heart attacks and strokes. [ 113 ]  However, a 2021 Cochrane meta-analysis found that antibiotics given for secondary prevention of coronary heart disease are harmful for people with increased mortality and occurrence of stroke. [ 113 ]  So, the use of antibiotics is not currently supported for preventing secondary coronary heart disease.


A thorough systematic review found that indeed there is a link between a CHD condition and brain dysfunction in females. [ 114 ]  Consequently, since research is showing that cardiovascular diseases, like CHD, can play a role as a precursor for dementia, like Alzheimer's disease, individuals with CHD should have a neuropsychological assessment. [ 115 ]


There are a number of treatment options for coronary artery disease: [ 116 ]


It is recommended that blood pressure typically be reduced to less than 140/90 mmHg. [ 121 ]  The diastolic blood pressure however should not be lower than 60 mmHg. Beta-blockers are recommended first line for this use. [ 121 ]


In those with no previous history of heart disease, aspirin decreases the risk of a myocardial infarction but does not change the overall risk of death. [ 122 ]  Aspirin therapy to prevent heart disease is thus recommended only in adults who are at increased risk for cardiovascular events, which may include  postmenopausal   females, males above 40, and younger people with risk factors for coronary heart disease, including  high blood pressure , a family history of heart disease, or  diabetes . The benefits outweigh the harms most favorably in people at high risk for a cardiovascular event, where high risk is defined as at least a 3% chance over a five-year period, but others with lower risk may still find the potential benefits worth the associated risks. [ 123 ]


Clopidogrel  plus aspirin (dual anti-platelet therapy) reduces cardiovascular events more than aspirin alone in those with a  STEMI . In others at high risk but not having an acute event, the evidence is weak. [ 124 ]  Specifically, its use does not change the risk of death in this group. [ 125 ]  In those who have had a stent, more than 12 months of clopidogrel plus aspirin does not affect the risk of death. [ 126 ]


Revascularization for  acute coronary syndrome  has a mortality benefit. [ 127 ]  Percutaneous revascularization for  stable  ischaemic heart disease does not appear to have benefits over medical therapy alone. [ 128 ]  In those with disease in more than one artery,  coronary artery bypass grafts  appear better than  percutaneous coronary interventions . [ 129 ]  Newer "anaortic" or no-touch off-pump coronary artery revascularization techniques have shown reduced postoperative stroke rates comparable to percutaneous coronary intervention. [ 130 ]  Hybrid coronary revascularization has also been shown to be a safe and feasible procedure that may offer some advantages over conventional CABG though it is more expensive. [ 131 ]


As of 2010, CAD was the leading cause of death globally resulting in over 7 million deaths. [ 133 ]  This increased from 5.2 million deaths from CAD worldwide in 1990. [ 133 ]  It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life. [ 134 ]  Males are affected more often than females. [ 134 ]


The  World Health Organization  reported that: "The world's biggest killer is ischemic heart disease, responsible for 13% of the world's total deaths. Since 2000, the largest increase in deaths has been for this disease, rising by 2.7 million to 9.1 million deaths in 2021." [ 135 ]


It is estimated that 60% of the world's cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the world's population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the  Indian Heart Association  are working with the  World Heart Federation  to raise awareness about this issue. [ 136 ]


Coronary artery disease is the leading cause of death for both males and females and accounts for approximately 600,000 deaths in the United States every year. [ 137 ]  According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old  females. [ 138 ]  It is the most common reason for death of males and females over 20 years of age in the United States. [ 139 ]


After analysing data from 2 111 882 patients, the recent meta-analysis revealed that the incidence of coronary artery diseases in breast cancer survivors was 4.29 (95% CI 3.09–5.94) per 1000 person-years. [ 140 ]


Other terms sometimes used for this condition are "hardening of the arteries" and "narrowing of the arteries". [ 141 ]  In Latin it is known as  morbus ischaemicus cordis  ( MIC ).


The Infarct Combat Project (ICP) is an international  nonprofit organization  founded in 1998 which tries to decrease  ischemic heart diseases  through education and research. [ 142 ]


In 2016 research into the archives of the  [ failed verification ] Sugar Association , the  trade association  for the  sugar industry  in the US, had sponsored an influential  literature review  published in 1965 in the  New England Journal of Medicine  that downplayed early findings about the role of a diet heavy in sugar in the development of CAD and emphasized the role of fat; that review influenced decades of research funding and guidance on  healthy eating . [ 143 ] [ 144 ] [ 145 ] [ 146 ]


Research efforts are focused on new  angiogenic  treatment modalities and various (adult)  stem-cell therapies . A region on  chromosome 17  was confined to families with multiple cases of myocardial infarction. [ 147 ]  Other genome-wide studies have identified a firm risk variant on  chromosome 9  (9p21.3). [ 148 ]  However, these and other  loci  are found in intergenic segments and need further research in understanding how the  phenotype  is affected. [ 149 ]


A more controversial link is that between  Chlamydophila pneumoniae  infection and atherosclerosis. [ 150 ]  While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. [ 151 ]  Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases. [ 152 ]


Myeloperoxidase  has been proposed as a  biomarker . [ 153 ]


Plant-based nutrition has been suggested as a way to reverse coronary artery disease, [ 154 ]  but strong evidence is still lacking for claims of potential benefits. [ 155 ]


Several immunosuppressive drugs targeting the chronic inflammation in coronary artery disease have been tested. [ 156 ]


Spontaneous coronary artery dissection  ( SCAD ) is an uncommon but potentially lethal condition in which one of the  coronary arteries  that supply the heart, spontaneously develops a blood collection, or  hematoma , within the artery wall due to a tear in the wall. SCAD is one of the  arterial dissections  that can occur. [ 1 ]


SCAD is a major cause of  heart attacks  in young, otherwise healthy women who usually lack typical cardiovascular risk factors. While the exact cause is not yet known, SCAD is likely related to changes that occur during and after pregnancy, or possibly genetics, hormonal influences, inflammatory issues or changes due to disease. These changes lead to the dissection of the wall which restricts blood flow to the heart and causes symptoms. SCAD is often diagnosed in the  cath lab  with  angiography , though more advanced confirmatory tests exist. While the risk of death due to SCAD is low, it has a relatively high rate of recurrence leading to further heart attack-like symptoms in the future.


SCAD often presents like a  heart attack  in young to middle-aged, healthy women. [ 2 ]  This pattern usually includes chest pain, rapid heartbeat, shortness of breath, sweating, extreme tiredness, nausea, and dizziness. [ 3 ]  A minority of people with SCAD may also present in  cardiogenic shock  (2-5%),  ventricular arrhythmias  (3-11%), or after  sudden cardiac death . [ 4 ]  Pregnancy- and postpartum-associated SCAD generally have worse outcomes compared to other cases. [ 4 ]


Risk factors include pregnancy and the  postpartum  period. Evidence suggests that  estrogen - and  progesterone -related vascular changes affect the coronary arteries during this period, contributing to SCAD. [ 4 ]  Some case reports and case series suggest associations with autoimmune inflammatory diseases, but there have not been larger studies to explore this relationship. [ 4 ]  Underlying heritable conditions such as  fibromuscular dysplasia [ 5 ]  and connective-tissue disorders (e.g.,  Marfan syndrome ,  Ehlers–Danlos syndrome , and  Loeys–Dietz syndrome ) are associated with SCAD, [ 6 ] [ 4 ]  SCAD triggers may include severe physical or emotional stress, but many cases have no obvious cause. [ 7 ] [ 8 ]


SCAD symptoms are the result of a restriction in the size of the lumen of the affected coronary artery. A bleed within the wall of the artery ( tunica intima ) originating from the microvessels that perfuse this muscular layer ( vasa vasorum ) leads to a collection of blood, or  hematoma , between the layers of the artery wall. [ 1 ]
The hematoma pushes close the lumen, preventing blood from flowing to the heart muscle ( myocardium ). In some cases (~30%) this hematoma (also referred to as an intramural hematoma) is also accompanied by a tear in the inner most layer of the artery - a monolayer of  endothelial cells  called the  tunica intima . It is not clear if this precedes or follows a bleed within the wall of the artery. [ 9 ]  The tracking of blood within the artery wall (both in the presence or absence of an intimal tear) is referred to as a "false  lumen ". [ 10 ] [ 11 ] [ 12 ]  The restriction of blood flow in the 'true' lumen limits the availability of oxygen and nutrients to the heart muscle, or  myocardium . As a result, the myocardium continues to demand oxygen but is not adequately supplied by the coronary artery. This imbalance leads to  ischemia , damage, and in some cases can lead to death of the myocardium tissue, causing a heart attack ( myocardial infarction ).


While the molecular mechanisms that underpin SCAD are still poorly understood, studies have implicated dysfunction of the  vasa vasorum , the microvessels that perfuse the muscular layer of the coronary artery, lead to the bleed. There is an inverse correlation between the amount of  vasa vasorum  present in regions of the  coronary artery  and the likelihood of an area being affected by a SCAD. [ 1 ]  It has been hypothesized that alterations in vessel wall strength, owing to dysfunction in the  TGF-β  pathway, the  extracellular matrix , and  vascular smooth muscle cell  contractility alter the capacity of the  vasa vasorum  to perfuse the vessel wall, leading  to either (1)  a potential microthrombi and bleed, or (2) an area of hypoxia, which would likely induce new microvessel formation  angiogenesis  of new immature (and thus leaky) vessels. [ 1 ]


It is likely that both genetics and environment play a role in SCAD onset. A number of genetic variants have been linked to an increased the risk of SCAD. As with  dissection (medical)  generally, the genes identified implicate dysfunction in four main cellular molecular pathways: the  TGF-β  pathway, [ 13 ]   extracellular matrix  pathway,  vascular smooth muscle cell  contractility, and cellular metabolism. [ 1 ]
Variants in genes including  ALDH18A1, COL3A1, COL4A1, FBN1  and  ACVR1  were implicated in a study of 91 unrelated SCAD cases. [ 13 ]


Given the demographics of SCAD, it is important to maintain a high index of suspicion for the condition in otherwise low-risk women presenting with symptoms of  acute coronary syndrome . Initial evaluation may show  ECG  changes of ST elevation, like heart attacks due to other causes. SCAD comprises 2-4% of all cases of acute coronary syndrome. [ 14 ]


With typically elevated cardiac biomarkers and ECG changes, people will often undergo  coronary angiography  evaluation. [ 4 ] [ 15 ] [ 16 ]  It is important to recognize SCAD through angiography as other confirmatory measures carry increased risks. [ 17 ]


There are 3 types of SCAD based on angiographic and anatomical criteria; with the designations based on the location and extent of the hematoma within the walls of the coronary arteries. [ 18 ]  Type 1 SCAD results from an  intimal  tear of the coronary artery (a tear of the innermost layer of the arterial wall) creating a false  lumen  as blood flows into the new space. [ 18 ]  A type 1 SCAD lesion is seen on angiography or  intravascular imaging  as a  radiolucent  flap separating the two flow channels; separating the false lumen from the true lumen of the coronary artery. [ 18 ]  Type 2 SCAD, the most common type of SCAD lesions, seen in 60-75% of patients, occurs due to an intramural hematoma or a collection of blood in the  muscular layer  of the coronary artery wall with the absence of intimal tearing. [ 18 ]  This is seen on coronary angiography as an abrupt change in coronary caliber with a long segment of a diffusely narrowed artery (typically longer than 20 mm). [ 18 ]  Type 2 SCAD is subdivided into type 2A where the narrowed segment of the coronary artery is flanked by normal caliber segments and type 2B where the stenosis continues to the terminus of a coronary artery. [ 18 ]  Type 3 SCAD, the least common type, is also due to an intramural hematoma causing coronary stenosis, but the lesions are shorter than as seen in type 2 SCAD, being less than 20 mm in length. [ 18 ]  Due to the short segment of coronary stenosis in type 3 SCAD, it is often difficult to differentiate type 3 SCAD lesions from coronary stenosis due to atherosclerotic plaques and intra-coronary imaging is often needed to distinguish between the two. [ 18 ]  Some authors have proposed a fourth designation of SCAD, type 4 SCAD, in which there is a complete intraluminal occlusion of the coronary artery due to any of the  previously mentioned types (Type 1–3). [ 18 ]


Intracoronary imaging (ICI), consisting of  intracoronary optical coherence tomography  (OCT) and  intravascular ultrasound  (IVUS) can help distinguish SCAD from an  atherosclerotic lesion  when it is difficult to do so with angiography. [ 19 ]  ICI techniques provide a direct view of the walls of the coronary artery to confirm SCAD, but may actually worsen the dissection as the probes are inserted into the damaged area. [ 4 ]  ICI confers a 3.4% risk of  iatrogenic  dissection in people with SCAD compared to 0.2% risk in the general population. [ 4 ]  Between the two ICI methods, OCT - a newer technique - has superior spatial resolution than IVUS and is the preferred technique if ICI is required, [ 4 ]  but the need to inject extra contrast with OCT poses risk for worsening the dissection. [ 14 ]


Some studies propose  coronary CT angiography  to evaluate SCAD in lower-risk people, with research into the approach ongoing. [ 4 ] [ 17 ]


Management depends upon the presenting symptoms. In most people who are hemodynamically stable without high-risk coronary involvement, conservative medical management with blood pressure control is recommended. [ 4 ] [ 20 ] [ 21 ]  In these people, especially if angiography demonstrates adequate coronary flow, the most likely course usually leads to spontaneous healing, often within 30 days. [ 22 ]  Anti-coagulation should be discontinued upon diagnosis of SCAD on coronary angiography as continuation of anti-coagulation may lead to hematoma and dissection propagation. [ 18 ]


In cases involving high-risk coronaries, hemodynamic instability, or a lack of improvement or worsening after initial attempts at treatment, urgent treatment with  coronary stents  or  coronary artery bypass surgery  may be necessary. [ 17 ]  Stents carry the risk of worsening the dissection or have an increased risk of other complications as the vessel walls in SCAD are already weak due to the disease before introducing the stent. [ 4 ]  Large studies into coronary artery bypass surgery are lacking, but this approach is used to redirect blood to the heart around the affected area for cases involving the  left main coronary artery  or when other approaches fail. [ 4 ] [ 23 ] [ 24 ]


Angina , or chest pain due to coronary insufficiency may persist for months after SCAD, sometimes even when repeat angiography shows vessel healing. Anti-anginal agents such as  nitrates ,  calcium channel blockers  and  ranolazine  are indicated as anti-anginal pharmacologic agents after SCAD. [ 18 ]  Control of hypertension is also indicated after SCAD, with  beta blockers  especially showing a reduction in the recurrence of SCAD. [ 18 ]   Statins  are not recommended in the treatment post-SCAD (in the absence of other indications for statins) as the myocardial infarctions in SCAD are not the result of atherosclerotic plaques. [ 18 ]   Cardiac rehabilitation  is recommended for all patients after myocardial infarction due to SCAD and is associated with a reduction in anginal symptoms increased psychological well-being. [ 18 ]   Dual antiplatelet therapy  should be started after percutaneous coronary intervention (stents) is used to treat SCAD and continued for at least 1 year afterwards. [ 18 ]  Dual antiplatelet therapy during the acute phase and for at least 1 year after medically treated SCAD may be also used, based on expert consensus. [ 18 ]


Physical stress is associated with SCAD recurrence but there are no heart rate, blood pressure or weight exercise parameters that are established in those with SCAD. In general, it is recommended that those with SCAD avoid  isometric exercise , high intensity endurance training, exercising to the point of exhaustion and activities involving a prolonged  Valsalva  to reduce the risk of SCAD recurrence. [ 18 ]


After addressing the SCAD, people are often treated with typical post-heart attack care, though people who are pregnant may need altered therapy due to the possibility of some  teratogenic  cardiac medications affecting  fetal development . [ 17 ]  Depending on the clinical situation, providers may screen for associated connective tissue diseases. [ 17 ]


People with SCAD have a low in-hospital mortality after treatment. However, the lesion may worsen after leaving the hospital within the first month. [ 17 ] [ 25 ]  One study suggested a 1.2% mortality rate following SCAD but a 19.9% risk for either death, heart attacks, or strokes. [ 26 ]  Even afterwards, SCAD has a high recurrence risk at 30% within 10 years, often at a different site than the initial lesion - meaning that stents placed in the location of the first lesion may not protect against a second. [ 17 ]  Given the lack of consensus on the cause of SCAD, prevention of future SCAD may include medical therapy, counseling about becoming pregnant again (for those who had pregnancy-associated SCAD), or avoidance of estrogen therapy. [ citation needed ]


Research is currently being carried out to identify what causes SCAD, in an effort to prevent recurrence, or potentially onset in at risk family members of SCAD patients. Australian researchers at the  Victor Chang Cardiac Research Institute , for example, have generated  induced pluripotent stem cell  (iPSC) lines from patients to model SCAD 'in a dish'.  [ 27 ]


SCAD is the most common cause of  heart attacks  in pregnant and  postpartum  women. Over 90% of people who develop SCAD are women. [ 25 ]  It is especially common among women aged 43–52. [ 17 ]  With angiography and improved recognition of the condition, diagnosis of SCAD has improved since the early 2010s. While prior studies had reported a SCAD prevalence of less than 1% in patients presenting with acute coronary syndrome, more recent data suggests the prevalence of SCAD in acute coronary syndrome patients may be between 2-4%. [ 28 ]


SCAD was first described in the year 1931, at postmortem examination, in a 42-year-old woman. [ 29 ] [ 28 ]  Due to a lack of recognition and diagnostic technology though, SCAD literature until the 21st century included only case reports and series. [ 28 ]  With the recent advent of coronary angiography and intracoronary imaging, recognition and diagnosis of SCAD has greatly increased, especially in the 2010s. [ 28 ]


Coronary artery ectasia  is a rare disease that occurs in only 0.3-4.9% of people in North America. Coronary artery ectasia is characterized by the enlargement of a  coronary artery  to 1.5 times or more than its normal diameter. [ 1 ]  The disease is commonly  asymptomatic  and is normally discovered when performing tests for other conditions such as  coronary artery disease ,  stable angina  and other acute coronary syndromes. [ 2 ] [ 3 ]  Coronary artery ectasia occurs 4 times more frequently in males than in females and in people who have risk factors for heart disease such as smokers. [ 1 ] [ 4 ] [ 5 ]   While the disease is commonly found in patients with  atherosclerosis  and coronary artery disease, it can occur by itself and in both cases, it can cause health problems. The disease can cause the heart tissue to be deprived of blood and die due to decreased blood flow, and blockages due to blood clots or spasms of the blood vessel. [ 2 ]  This blood flow disruption can cause permanent damage to the muscle if the deprivation is prolonged. Coronary artery ectasia also increases the chance of developing large weak spots in the affected coronary arteries, or  aneurysms  that can rupture and result in death. [ 1 ]  The damage can result in angina which is pain in the chest and is a common complaint in these patients.


Coronary artery ectasia is commonly found in patients with diseases of the connective tissue and an increased inflammatory response such as  Marfan syndrome  and  Kawasaki Disease . [ 6 ]   It can also be found transiently in patients that have undergone stent placement resulting in the stretching of the vessels 1. Coronary artery ectasia is characterized by an increased wall stress of the vessel, thinning of the arterial wall which causes progressive dilation and remodelling of the vessel. [ 2 ]  The permanent dilation of the artery is thought to be mainly caused by inflammation, triggered by disease, chemicals, or physical stress of the vessel. [ 3 ]  A meta-analysis study has shown that The pooled unadjusted OR of CAE in subjects with HTN in comparison by subjects without HTN was estimated 1.44 (95 % CI, 1.24 to 1.68)  Bahremand, M., Zereshki, E., Matin, B.K. et al. Hypertension and coronary artery ectasia: a systematic review and meta-analysis study. Clin Hypertens 27, 14 (2021). https://doi.org/10.1186/s40885-021-00170-6 .The inflammatory response results in an over expression of  matrix metalloproteinases , cysteine proteinases, and serine proteinases that causes the partial breakdown of the vessel and weakens it. [ 3 ] [ 7 ]   The  inflammation response will also trigger  platelet  activation which increases the risk of blood clots. The risk of blood clots will increase due to the turbulent blood flow of the enlarged vessel which can activate platelets and form clots. [ 8 ]  Inflammation elevated oxidative stress is increased, and antioxidant activity is depressed in coronary artery ectasia. This imbalance can cause damage to the cells and cause them to die, weakening the vessels further. [ 9 ]  The activation of the inflammatory response causes a detectable increase in  C reactive protein ,  interleukin-6 ,  tumor necrosis factor alpha  and  cell adhesion molecules , which can be used as a diagnostic marker,. [ 5 ] [ 10 ]


To discover the extent and severity of coronary artery ectasia there are a variety of diagnostic tools used. The most common method for discovering the disease is through  angiography . Angiography is the procedure where a contrast dye is entered into the vessels and an x-ray is taken, which will allow the vessels to be seen on the x-ray. [ 10 ]  Using angiography clinicians are able to display the size, location and number of vessels affected by the disease. [ 10 ]  Is can also be analyzed through other methods such as  intravascular ultrasound , and  magnetic resonance imaging . [ 10 ]  Using these diagnostic methods, it has been discovered that the disease normally occurs most often in the  right coronary artery , followed by the  left anterior descending artery , and finally the  left anterior circumflex artery . [ 11 ]  Using these methods Coronary artery ectasia can be divided into four different types: Type 1¬→diffuse ectasia in 2-3 different vessels, Type 2¬→ diffuse disease in 1 vessel and local disease in another, Type 3¬→ diffuse disease in one vessel and Type 4¬→ localized or segmental ectasia. [ 11 ]


There are currently no cardiovascular society guidelines or recommendations for the treatment of coronary artery ectasia. Experts in the field urge clinicians to consider anti-platelet therapy, such as Aspirin, to reduce thrombus formation in pocket vortices associated with turbulent blood flow. Dual anti-platelet therapy and full anticoagulation are currently under investigation. The primary etiology of coronary ectasia in adults is atherosclerosis, thus treatment with statin therapy should be considered. Statin therapy may also reduce inflammation and matrix metalloproteinase activation which may reduce the progression of vessel ectasia. Some studies have also suggested the use of  angiotensin converting enzyme inhibitors , as ACE gene polymorphisms have been implicated in disease progression. Risk factor modification is recommended; including tobacco cessation, blood pressure control and avoidance of illicit substance use, specifically cocaine. [ citation needed ]


A  coronary occlusion , or  coronary artery disease , is the partial or complete  obstruction  of blood flow in a  coronary artery . This condition was first discussed in 1910 by  Sir William Osler . [ 1 ]  This condition slows or blocks the supply of oxygen-rich blood to the  heart . [ 2 ]  This condition can lead to  myocardial ischemia [ 2 ]  and if untreated, may cause a  heart attack  and heart failure. [ 3 ]  It is the most common form of  cardiovascular disease , and is the leading cause of death in the United States, affecting 18 million adults. [ 4 ]


A coronary occlusion can be caused by smoking, having other heart or blood conditions, or being physically inactive. It is also  hereditary . [ 4 ]  Symptoms include chest pain, shortness of breath, pain in upper body, fatigue, nausea, an irregular heartbeat, and drowsiness. [ 5 ]


To diagnose a coronary occlusion, a doctor may view a patient's medical history, or perform a coronary angiography; a doctor will stick a  catheter  into the wrist or groin, lead it to the heart, and inject a liquid for X-ray imaging. [ 4 ]


To treat a coronary occlusion, medication may be used to relieve symptoms.  Percutaneous coronary intervention  or  coronary artery bypass surgery  may also be used. [ 4 ]


Symptoms include chest pain or  angina ,  shortness of breath , and  fatigue . [ 6 ]


A completely blocked coronary artery will cause a heart attack. [ 6 ]  Common heart attack symptoms include chest pain or  angina , pain or discomfort that spreads to the shoulder, arm, back, neck jaw, teeth or the upper belly, cold sweats, fatigue,  heartburn ,  nausea ,  shortness of breath , or  lightheadedness . [ 6 ]


Coronary occlusion is caused by the buildup of  fats ,  cholesterol  and other substances in and on the walls of the hearts  arteries . [ 6 ]  As plaque builds up, the arteries narrow. [ 7 ]  Plaque often starts building up during childhood and is heavily influence by genetics, but also lifestyle and high blood cholesterol. [ 7 ]  This condition is referred to as  atherosclerosis . [ 6 ]  The buildup on the walls of the hearts arteries is referred to as plaque. Plaque causes arteries to narrow and block blood flow. [ 6 ]


Conditions that aid in the development of coronary artery disease are  diabetes  or  insulin resistance ,  high blood pressure ,  sedentary lifestyle , and  smoking  or  tobacco  use. [ 6 ]


Risk Factors that are not controllable are age,  birth sex , and  family history . [ 6 ]  Getting older increases the risk of damaged and narrowed arteries. [ 6 ]  Men are at a greater risk of coronary artery disease, with women's risk increasing after menopause. [ 6 ]


Coronary occlusion is caused by plaque inside of the blood vessels that direct oxygen rich blood to the heart. [ 8 ]  Plaque is caused by fatty deposits and scar tissue that cling to the walls of coronary arteries. [ 9 ]  The development of plaque takes years and leads to  stenosis  of the  coronary arteries  and progressively reduces blood flow. [ 8 ]  Due to the slower development of this condition, the body will adapt and create small blood vessels that circumvent the blockage. [ 8 ]  The small  blood vessels  form a natural bypass of the blockage, but often do not supply enough blood to meet an increased demand when stressors are applied like  exercise . [ 8 ]


When a plaque has a greater than 50% diameter stenosis, the reduced blood flow through the coronary artery during exertion may lead to  angina . [ 10 ]  Acute coronary events occur when a  thrombus  forms due to disruption of a plaque. [ 10 ]  In acute heart attack, occlusion is greater than in  unstable angina , where arterial occlusion is not full blockage. Downstream embolism of thrombus may also produce  microinfarcts . [ 10 ]


Heart disease is often undiagnosed until a serious problem occurs, such as  heart attack  or  cardiac arrest . [ 11 ]  Regular checkups can lead to an early diagnosis and  preventative treatment . [ 11 ]  Screening tests and risk assessments should begin around age 20 if one does not have any risk factors. [ 11 ]  Screenings should begin in childhood if one has risk factors such as  obesity , sedentary lifestyle, or a family history of  heart conditions . [ 11 ]


Healthcare providers will run blood tests to check for  cholesterol ,  triglycerides ,  lipoproteins ,  sugar , or  proteins  that are a sign of  inflammation . [ 11 ]


To assist in a diagnosis, healthcare providers may also order a  electrocardiogram  (ECG or EKG),  coronary calcium scan,   stress test ,  cardiac magnetic resonance imaging  (MRI),  cardiac positron emission tomography ( PET), invasive  coronary angiography,  and/or  coronary CT angiography . [ 11 ]


Healthcare providers may recommend lifelong  heart-healthy  lifestyle choices. [ 12 ]  These choices included a  heart-healthy eating plan , physical activity, quitting smoking, improved  sleep hygiene ,  weight loss ,  blood pressure control ,  cholesterol  control, blood  pressure  control, and  stress management . [ 12 ]


Some medications may be prescribed to allow the blood vessels to widen and help the heart pump include  ACE inhibitors ,  beta blockers ,  calcium channel blockers ,  nitrates , and  Ranolazine . [ 12 ]


Some medications may be prescribed to manage cholesterol include  statins , nonstatins, and  fribrates . [ 12 ]


Some medications may be prescribed for other risk factors for heart disease like blood sugar and obesity such as  empagliflozin ,  canagliflozin ,  metformin ,  liraglutide ,  orlistat , and  semaglutide . [ 12 ]


Heart surgery  may be needed to treat this condition. Some procedures include  percutaneous coronary intervention  (PCI),  coronary artery bypass grafting  (CABG), and  transmyocardial laser revascularization  ( coronary endarterectomy ). [ 12 ]


Preventative procedures like  bariatric surgery  can help lower coronary heart disease risk. [ 12 ]


Coronary artery disease cannot be reversed.  [ 3 ]  To reduce future problems, a patient may be referred to get exercise-based  cardiac rehabilitation . [ 13 ]


Patients with coronary artery disease over 15-year period based off expectations in a 1-year follow up saw a  mortality  rate of those in the highest  quartiles  of expectations are 28-30 deaths per 100 patients. [ 14 ]  The lowest  quartile  of expectations are 50-57 deaths per 100 patients. [ 14 ]


Prognosis for heart attacks when people reach emergency care promptly improve dramatically, though many people still die before reaching the hospital. [ 15 ]  One out of every 10 patients who have a heart attack die within the first three to four months. [ 9 ]


Coronary artery disease is the leading cause of death in men and women. [ 16 ]  This condition is the cause of one third of all deaths, which is especially worse in areas with lower  socioeconomic  status. [ 16 ]  Mortality is nearly five times higher in men than women, but mortality difference narrows with age. [ 16 ]


Black women are more likely than white women to have a heart attack. Black adults have a higher mortality rate than white adults from heart attack.  [ 17 ]


Asian adults have the least incidence of  coronary artery disease . Asian Indian men, Filipino men and Filipino women have a higher risk than white people. [ 17 ]


Young Hispanic women who have a heart attack have a higher mortality rate than young Hispanic men. They have a higher mortality rate than young Black adults and young white adults. [ 17 ]


Recent studies focus on advanced imagining techniques, pharmacological advancements, and  regenerative therapies . A new heart disease diagnosis approach has led to a 99.1% accuracy in diagnosing heart disease. [ 18 ]  This new diagnosis approach uses  CT-scan  imagery to focus on coronary artery diseases and blockages in contrast to  angiography . [ 18 ]


Further research directions in preventing and treating coronary artery disease include: [ 19 ]


Coronary occlusion was first discussed in 1910 by  Sir William Osler  who discussed coronary occlusion during the  Lumleian Lectures . [ 1 ]


In 1912,  James Herrick  published an article in  JAMA  documenting his findings on coronary occlusion in animals. [ 20 ]


According to  Robert K. Massie 's  Nicholas and Alexandra: The Fall of the Romanov Dynasty ,  Tsar Nicholas II  may have suffered a coronary occlusion right before he was toppled from his throne during the Russian Revolution in 1917. [ 21 ]


Coroners cited a coronary occlusion as the cause of death for  Mongomery Clift .