Tekno Adam

Myocardial infarction, commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia. This usually results from an imbalance in oxygen supply and demand, which is most often caused by plaque rupture with thrombus formation in a coronary vessel, resulting in an acute reduction of blood supply to a portion of the myocardium. The electrocardiographic result of an acute myocardial infarction is seen below. (See Etiology.)

Although the clinical presentation of a patient is a key component in the overall evaluation of the patient with myocardial infarction, many events are either “silent” or are clinically unrecognized, evidencing that patients, families, and health care providers often do not recognize symptoms of a myocardial infarction. (See Clinical Presentation.) The appearance of cardiac markers in the circulation generally indicates myocardial necrosis and is a useful adjunct to diagnosis. (See Workup.)

Myocardial infarction is considered part of a spectrum referred to as acute coronary syndrome (ACS). The ACS continuum representing ongoing myocardial ischemia or injury consists of unstable angina, non–ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). Patients with ischemic discomfort may or may not have ST-segment or T-wave changes denoted on the electrocardiogram (ECG). ST elevations seen on the ECG reflect active and ongoing transmural myocardial injury. Without immediate reperfusion therapy, most persons with STEMI develop Q waves, reflecting a dead zone of myocardium that has undergone irreversible damage and death. Those without ST elevations are diagnosed either with unstable angina or NSTEMI―differentiated by the presence of cardiac enzymes. Both these conditions may or may not have changes on the surface ECG, includingST-segmentdepression or T-wave morphological changes.

Myocardial infarction may lead to impairment of systolic or diastolic function and to increased predisposition to arrhythmias and other long-term complications.

Coronary thrombolysis and mechanical revascularization have revolutionized the primary treatment of acute myocardial infarction, largely because they allow salvage of the myocardium when implemented early after the onset of ischemia. (See Treatment Strategies and Management.) The modest prognostic benefit of an opened infarct-related artery may be realized even when recanalization is induced only 6 hours or more after the onset of symptoms, that is, when the salvaging of substantial amounts of jeopardized ischemic myocardium is no longer likely. The opening of an infarct-related artery may improve ventricular function, collateral blood flow, and ventricular remodeling, and it may decrease infarct expansion, ventricular aneurysm formation, left ventricular dilatation, late arrhythmia associated with ventricular aneurysms, and mortality.

Evidence suggests a benefit from the use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and statins.

The American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology/World Heart Federation released the Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38), which better outlines a universal definition of myocardial infarction, along with a classification system and risk factors for cardiovascular death.

The right and left coronary arteries most often arise independently from individual ostia in association with the right and left aortic valve cusps.

The left anterior descending (LAD) and left circumflex (LCX) coronary arteries arise at the left main coronary artery bifurcation; they supply the anterior LV, the bulk of the interventricular septum (anterior two thirds), the apex, and the lateral and posterior LV walls. The right coronary artery (RCA) generally supplies the right ventricle (RV), the posterior third of the interventricular septum, the inferior wall (diaphragmatic surface) of the left ventricle (LV), and a portion of the posterior wall of the LV (by means of the posterior descending branch).

When the posterior descending coronary artery (PDA), which supplies the posterior interventricular septum, arises from the LCX artery, the circulation is called left dominant. Most often, the PDA arises from the RCA; this anatomy is called right-dominant circulation.

In two thirds of patients, the first branch of the RCA is the conus artery, which supplies the conus arteriosus (RV outflow tract); occasionally the conus arteriosus arises from a separate orifice.

In 60% of patients, the sinus node artery arises from the proximal RCA, and in 40% of patients, it arises from the LCX artery. The anterior branches supply the free wall of the RV, and the acute marginal branches supply the RV. When the RCA extends to the crux (the origin of the PDA), it supplies the atrioventricular (AV) node (90%); otherwise, the AV node is supplied by the LCX.

Therefore, obstruction of the RCA commonly affects the sinus node and the AV node, resulting in bradycardia, with or without heart block. Not surprisingly, RCA occlusion frequently manifests with sinus bradycardia, AV block, RV myocardial infarction, and/or inferoposterior myocardial infarction (of the LV). (See Etiology.)

The spectrum of myocardial injury depends not only on the intensity of impaired myocardial perfusion but also on the duration and the level of metabolic demand at the time of the event. The damage in the myocardium is essentially the result of a tissue response that includes apoptosis (cell death) and inflammatory changes. Therefore, the hearts of patients who suddenly die from an acute coronary event may show little or no evidence of damage response to the myocardium at autopsy.

The typical myocardial infarction initially manifests as coagulation necrosis that is ultimately followed by myocardial fibrosis. Contraction-band necrosis is also seen in many patients with ischemia. This is followed by reperfusion, or it is accompanied by massive adrenergic stimulation, often with concomitant myocytolysis.

The left coronary artery system covers more territory than does the right system; therefore, a myocardial infarction in this system is most likely to produce extensive injury, with impairment of function, pulmonary congestion, and low output. Occlusion of the left coronary artery may also cause a left anterior hemiblock or a left posterosuperior hemiblock conduction abnormality; these effects are evidenced by a change of frontal axis on the electrocardiogram (ECG). (See Electrocardiogram.)

Inferior-wall myocardial infarction and right ventricular myocardial infarction

In severe cases of acute inferior-wall myocardial infarction with RV involvement, the forward delivery of blood from the RV to the LV may be insufficient to fill the LV, resulting in low blood pressure even if the LV is intact. (See Physical Examination.)

Chemoreceptor activation in the myocardium actuates vagal (parasympathetic) efferent discharge, known as the Bezold-Jarisch reflex, which causes bradycardia and vessel dilation that may further lower blood pressure. Adenosine may accumulate in the infarct zone secondary to a local inhibition of adenosine deaminase, for which aminophylline may act pharmacologically as an antagonist. The hemodynamic changes resemble many of those seen with pericardial constriction or tamponade. Patients with this condition respond well to an infusion of normal sodium chloride solution. Improvement with such infusion compensates for failure of the pumping action of the RV; it reduces vagal tone, and it deactivates the pressure sensors that were sending a hormonal signal to the kidneys to retain salt.

Arrhythmogenesis

In addition to the direct effects of ischemia and tissue hypoxia, decreased removal of noxious metabolites, including potassium, calcium, amphophilic lipids, and oxygen-centered free radicals, also impair ventricular performance. These abnormalities promote potentially lethal arrhythmias.

Pericarditis

Epicardial inflammation may initiate pericarditis, which is seen in more than 20% of patients presenting with Q-wave infarctions.

Reduced systolic function

Lack of adequate oxygen and insufficient metabolite delivery to the myocardium diminish the force of muscular contraction and decrease systolic wall motion in the affected territory.

Abnormal regional wall motion

Even brief deprivation of oxygen and the requisite metabolites to the myocardium diminishes diastolic relaxation and causes abnormal regional systolic contractile function, wall thickening, and abnormal wall motion. If the area affected is extensive, diminished stroke volume and cardiac output may result.

Hypokinesis and akinesis

In general, regions of hypokinesis and akinesis of the ventricular myocardium reflect the location and extent of myocardial injury. Evidence of hypokinesis is seen on the echocardiogram below.

Myocardial infarction expansion

In general, expansion of infarcted myocardium and resultant ventricular dilatation (ie, ventricular remodeling) ensues within a few hours after the onset of a myocardial infarction. An expanding myocardial infarction leads to thinning of the infarct zone and realignment of layers of tissue in and adjacent to it, causing ventricular dilatation.

Myocardial rupture

Myocardial rupture was seen in as many as 10% of fatal myocardial infarctions before the era of thrombolytics, but it is now encountered much less often. When rupture occurs, it may be associated with large infarctions; indications include cardiogenic shock or hemodynamically significant arrhythmia. Patients may have a history of hypertension with ventricular hypertrophy.

Ventricular aneurysm

A ventricular aneurysm is an outward bulging of a noncontracting segment. In the early days of cardiac imaging, ventricular aneurysms were seen in as many as 20% of patients with Q-wave myocardial infarction, but now it is seen in less than 8%.

Cardiogenic shock

In patients with extensive myocardial injury, coronary blood flow diminishes as cardiac output declines and heart rate accelerates. Because coronary artery disease is usually generalized or diffuse, ischemia that occurs at a distance from the infracted segment may result in a vicious cycle in which a stuttering and expanding myocardial infarction ultimately leads to profound LV failure, hypotension, and cardiogenic shock.

Effect on diastolic function

Immediately after the onset of myocardial infarction, the ability of ischemic myocardium to relax declines. Relaxation is an active process that uses ATP. Impaired relaxation increases LV end-diastolic volume (LVEDV) and LV end-diastolic pressure (LVEDP).

The increased LVEDP results in ventricular dilation, increased pulmonary venous pressure, decreased pulmonary compliance, and interstitial and (ultimately) alveolar pulmonary edema. These effects lead to increased hypoxemia, which may worsen ischemic injury to the myocardium.

Atherosclerosis is the disease primarily responsible for most acute coronary syndrome (ACS) cases. Approximately 90% of myocardial infarctions result from an acute thrombus that obstructs an atherosclerotic coronary artery. Plaque rupture and erosion are considered to be the major triggers for coronary thrombosis. Following plaque erosion or rupture, platelet activation and aggregation, coagulation pathway activation, and endothelial vasoconstriction occur, leading to coronary thrombosis and occlusion.

Within the coronary vasculature, flow dynamics and endothelial shear stress are implicated in the pathogenesis of vulnerable plaque formation. Evidence indicates that in numerous cases, culprit lesions are stenoses of less than 70% and are located proximally within the coronary tree. Coronary atherosclerosis is especially prominent near branching points of vessels. Culprit lesions that are particularly prone to rupture are atheromas containing abundant macrophages, a large lipid-rich core surrounded by a thinned fibrous cap.

Nonmodifiable risk factors for atherosclerosis include the following:

• Age
• Sex
• Family history of premature coronary heart disease
• Male-pattern baldness
• Modifiable risk factors for atherosclerosis include the following:
• Smoking or other tobacco use
• Diabetes mellitus
• Hypertension
• Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders
• Dyslipidemia
• Obesity
• Sedentary lifestyle and/or lack of exercise
• Psychosocial stress
• Poor oral hygiene
• Type A personality

Elevated homocysteine levels and the presence of peripheral vascular disease are also risk factors for atherosclerosis.

Intramural thrombus development

Inflammation of the endocardial surfaces and stasis of blood flow associated with regional akinesis (no wall motion) or dyskinesis (abnormal, passively reversed wall motion) may lead to the formation of ventricular mural thrombi, which have the potential to embolize.

Patients with acute myocardial infarction are prone to cerebrovascular injury as a result of emboli from ventricular mural thrombi; the rate is approximately 1%.

Causes of myocardial infarction other than atherosclerosis

Nonatherosclerotic causes of myocardial infarction include the following:

• Coronary occlusion secondary to vasculitis
• Ventricular hypertrophy (eg, left ventricular hypertrophy, idiopathic hypertrophic subaortic stenosis [IHSS], underlying valve disease)
• Coronary artery emboli, secondary to cholesterol, air, or the products of sepsis
• Congenital coronary anomalies
• Coronary trauma
• Primary coronary vasospasm (variant angina)
• Drug use (eg, cocaine, amphetamines, ephedrine)
• Arteritis
• Coronary anomalies, including aneurysms of coronary arteries
• Factors that increase oxygen requirement, such as heavy exertion, fever, or hyperthyroidism
• Factors that decrease oxygen delivery, such as hypoxemia of severe anemia
• Aortic dissection, with retrograde involvement of the coronary arteries
• Infected cardiac valve through a patent foramen ovale (PFO)
• Significant gastrointestinal bleed

In addition, myocardial infarction can result from hypoxia due to carbon monoxide poisoning or acute pulmonary disorders. Infarcts due to pulmonary disease usually occur when demand on the myocardium dramatically increases relative to the available blood supply.

Although rare, pediatric coronary artery disease may be seen with Marfan syndrome, Kawasaki disease, Takayasu arteritis, progeria, and cystic medial necrosis.

Imaging studies, such as contrast chest CT scans or transesophageal echocardiograms, should be used to differentiate myocardial infarction from aortic dissection in patients in whom the diagnosis is in doubt. Stanford type A aortic dissections may dissect in a retrograde fashion causing coronary blockage and dissection, which may result in myocardial infarction. In one study, 8% of patients with Stanford type A dissections had ST elevation on ECG. (See Echocardiography.)

Myocardial infarction induced by chest trauma has also been reported, usually following severe chest trauma such as motor vehicle accidents and sports injuries.

Acute myocardial infarction in childhood

Acute myocardial infarction is rare in childhood and adolescence (See Epidemiology). Although adults acquire coronary artery disease from lifelong deposition of atheroma and plaque, which causes coronary artery spasm and thrombosis, children with acute myocardial infarction usually have either an acute inflammatory condition of the coronary arteries or an anomalous origin of the left coronary artery. Intrauterine myocardial infarction also does occur, often in association with coronary artery stenosis.

United States statistics – Incidence and mortality rate

Cardiovascular disease is the leading cause of death in the United States; approximately 500,000-700,000 deaths related to the coronary artery occur each year.

Approximately 1.5 million cases of myocardial infarction occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. The proportion of patients diagnosed with NSTEMI compared with STEMI has progressively increased. Despite an impressive decline in age-adjusted death rates attributable to acute myocardial infarction since the mid-1970s, the total number of myocardial infarction-related deaths in the United States has not declined. This may in part be the result of population growth.

Cardiovascular disease is the leading cause of morbidity and mortality among black, Hispanic, and white populations in the United States.

Cardiovascular disease in industrialized and developing nations

Ischemic heart disease is the leading cause of death worldwide.

Cardiovascular diseases cause 12 million deaths throughout the world each year, according to the third monitoring report of the World Health Organization, 1991-93. They cause half of all deaths in several industrialized countries and are one of the main causes of death in many developing countries; they are the major cause of death in adults everywhere. Of particular concern are projections from the World Heart Federation that the burden of atherosclerotic cardiovascular disease in developing countries will increasingly become commensurate with that seen in industrialized countries. With a decline in infectious disease-related deaths, in conjunction with accelerated economic development and life-style changes that promote atherosclerosis, rates of ischemic heart disease and myocardial infarction are expected to sharply increase in developing countries, especially such countries in Eastern Europe, Asia, and parts of Latin America.

Sex predilection in cardiovascular disease

A male predominance in the incidence of cardiovascular disease exists up to approximately age 70 years, when the sexes converge to equal incidence. Premenopausal women appear to be somewhat protected from atherosclerosis, possibly owing to the effects of estrogen.

Age predilection in cardiovascular disease

The incidence of cardiovascular disease increases with age, with acute myocardial infarction being rare in childhood and adolescence. Most patients who develop an acute myocardial infarction are older than 60 years. Elderly people also tend to have higher rates of morbidity and mortality from their infarcts. Age (≥75 y) is the strongest predictor of 90-day mortality in patients with STEMI undergoing percutaneous coronary intervention. A continued focus on improving outcomes for these high-risk patients is needed.

One third of patients who experience STEMI die within 24 hours of the onset of ischemia, and many of the survivors experience significant morbidity. However, a steady decline has occurred in the mortality rate from STEMI over the last several decades.

Acute myocardial infarction is associated with a 30% mortality rate; half of the deaths occur prior to arrival at the hospital. An additional 5-10% of survivors die within the first year after their myocardial infarction. Approximately half of all patients with a myocardial infarction are rehospitalized within 1 year of their index event.

In a study that assessed the impact of prehospital time on STEMI outcome, Chughatai et al suggest that “total time to treatment” should be used as a core measure instead of “door-to-balloon time.” This is because on-scene time was the biggest fraction of “prehospital time.” The study compared groups with total time to treatment of more than 120 minutes compared with 120 minutes or less and found mortalities were 4 compared with 0 and transfers to a tertiary care facility were 3 compared with 1, respectively.

Overall, prognosis is highly variable and depends largely on the extent of the infarct, the residual left ventricular function, and whether the patient underwent revascularization.

Better prognosis is associated with the following factors:

• Successful early reperfusion (STEMI goals: patient arrival to fibrinolysis infusion within 30 minutes OR patient arrival to percutaneous coronary intervention within 90 minutes)
• Preserved left ventricular function
• Short-term and long-term treatment with beta-blockers, aspirin, and ACE inhibitors

Poorer prognosis is associated with the following factors:

• Increasing age
• Diabetes
• Previous vascular disease (ie, cerebrovascular disease or peripheral vascular disease)
• Elevated Thrombolysis in Myocardial Infarction (TIMI) risk score for unstable angina/NSTEMI (7 factors: Age ≥65 y, ≥3 risk factors for cardiac disease, previous coronary disease, ST segment deviation ≥0.5 mm, ≥2 episodes of angina in last 24 h, aspirin use within prior wk, and elevated cardiac enzyme levels)
• Delayed or unsuccessful reperfusion
• Poorly preserved left ventricular function (the strongest predictor of outcome)
• Evidence of congestive heart failure (Killip classification ≥II) or frank pulmonary edema (Killip classification ≥III)
• Elevated B-type natriuretic peptide (BNP) levels
• Elevated high sensitive C-reactive protein (hs-CRP), a nonspecific inflammatory marker

Blood glucose

Beck et al found that elevated blood glucose level on admission is associated with increased short-term mortality in nondiabetic patients presenting with a first acute myocardial infarction. Analysis of data from a German myocardial infarction registry database showed that among 1,631 nondiabetic acute myocardial infarction patients with admission glucose level more than 152 mg/dL (top quartile), the risk of death within 28 days was higher than among patients in the bottom quartile (odds ratio, 2.82; 95% confidence interval, 1.30-6.12). However, in 659 registry patients with type 2 diabetes, admission glucose levels did not correlate significantly with short-term mortality. Beck et al concluded that nondiabetic acute myocardial infarction patients with elevated glucose levels constitute a high-risk group that requires aggressive intervention.

Psychological depression

The combination of acute myocardial infarction and psychological depression appears to worsen the patient’s prognosis. Acute myocardial infarction may precipitate reactive depression whether or not beta-adrenergic blocking agents or other CNS-active agents are administered.

Myocardial hibernation and stunning

After the occurrence of 1 or more ischemic insults, impaired wall motion is often transient (myocardial stunning) or prolonged (myocardial hibernation). These phenomena occur because of the loss of essential metabolites such as adenosine, which is needed for adenosine triphosphate (ATP)–dependent contraction. Hibernation, a persisting wall-motion abnormality that is curable with revascularization, must be differentiated from permanent, irreversible damage or completed infarct.

Scar tissue and prognosis

Scars involving less than one third of the thickness of the wall, as shown on contrast-enhanced MRI, likely correspond to a recovery of myocardial function, whereas with scars measuring more than one third the thickness of the wall, the potential for recovery with therapy is limited (except in cases involving research cell therapies or surgical scar revision). Other findings associated with recovery are activity on 2-[Fluorine 18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scanning and a monophasic or biphasic contractile response to dobutamine infusion, caused by the induction of ischemia. Cardiac scar tissue is seen in the image below.

As recommended by the most recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of unstable angina/NSTEMI, last updated in 2007, patients with symptoms that suggest an acute coronary syndrome should be referred to a facility where a physician can evaluate these symptoms in person and where a 12-lead ECG and cardiac biomarker testing is available (eg, emergency department, acute care facility).

Patients with active symptoms of ACS should be instructed to call emergency services (eg, 911 in the United State) and should be brought in by emergency medical services personnel, not by themselves, family, or friends. Patients should be instructed to come to the emergency department immediately if the suspected ACS symptoms last longer than 20 minutes at rest or are associated with near syncope/syncope or hemodynamic instability.

If nitroglycerin is prescribed to a patient with suspected ACS, the patient should be instructed to take a dose if symptoms arise. If no relief is experienced 5 minutes after the first dose, the patient should contact emergency services. If relief is experienced within 5 minutes of the first nitroglycerin dose, repeated doses can be given every 5 minutes for a maximum of 3 doses total. If by then the symptoms have not yet fully resolved, the patient, a family member, or caregiver should contact emergency services.

Diet plays an important role in the development of coronary artery disease. Educate post–myocardial infarction patients about the role of a low-cholesterol and low-salt diet. Educate patients about the American Heart Association (AHA) dietary guidelines, including a low-fat, low-cholesterol diet. A dietitian should see and evaluate all patients post myocardial infarction prior to their discharge. Additionally, emphasis on exercise training should be made because current evidence demonstrates that cardiac rehabilitation post myocardial infarction results in lower rates of recurrent cardiovascular events.

A Norwegian randomized trial found that aerobic interval training (treadmill) increased peak oxygen uptake more than the usual care rehabilitation (aerobic exercise training) after myocardial infarction.

Following myocardial infarction, educate all patients regarding the critical role of smoking in the development of coronary artery disease. Smoking cessation classes should be offered to help patients avoid smoking after their myocardial infarction.

For excellent patient education resources, visit eMedicine’s Cholesterol Center. Also, see eMedicine’s patient education articles High Cholesterol, Understanding Your Cholesterol level, Lifestyle Cholesterol Management, Understanding Cholesterol-Lowering Medications, Chest Pain, Coronary Heart Disease, and Heart Attack.

The term coronary artery anomaly refers to a wide range of congenital abnormalities involving the origin, course, and structure of epicardial coronary arteries. By definition, these abnormalities occur in less than 1% of the general population. Coronary artery anomalies are frequently found in association with other major congenital cardiac defects. This article, however, is focused on isolated coronary artery anomalies (ie, in the absence of other major congenital cardiac defects). In adults, the clinical interest in coronary anomalies relates to their occasional association with sudden death, myocardial ischemia, congestive heart failure, or endocarditis. In addition, presence of coronary artery anomalies may, at times, create challenges during coronary angiography, percutaneous coronary interventions, and coronary artery surgery.

Normal coronary artery anatomy

The coronary arteries are the only branches of the ascending aorta, and they supply blood to all structures within the pericardial cavity. Usually, the 2 coronary artery ostia are located in the center of the left and right (anterior) sinuses of the aortic valve. The posterior sinus of the aortic valve contains no coronary ostium and is often designated as the noncoronary sinus.

Left coronary artery

The left coronary artery originates from the left coronary sinus of the aorta, and, after a single initial trunk (left main coronary artery) of variable length and size, it gives rise to the left anterior descending (LAD) and left circumflex (LCx) coronary artery branches. The LAD coronary artery runs along the anterior interventricular sulcus, provides several superficial (diagonal) and multiple deep (septal perforator) branches, and usually reaches the cardiac apex. In some individuals, a diagonal branch may have a very proximal takeoff such that the left main (LM) gives rise to 3 instead of 2 branches. In this case, the additional artery arising from the LM originates in between the LAD and the LCx coronary arteries and is called the ramus intermedius coronary artery. This artery provides blood supply to the anterior left ventricular free wall.

The LCx coronary artery runs in the left atrioventricular groove and usually has 1 or more branches that reach the obtuse margin of the heart (obtuse marginals). The LAD coronary artery supplies blood to the anterior left ventricular wall through its diagonal branches, the anterior two thirds of the interventricular septum through its septal perforator branches, and commonly the cardiac apex by its terminal branches. The LCx coronary artery supplies blood to the left ventricular lateral and posterior walls through its obtuse marginal branches.

Right coronary artery

The right coronary artery (RCA) originates from the right coronary sinus of the aorta and runs in the right atrioventricular groove to reach the crux (junction of the atrioventricular groove and the posterior interventricular sulcus) of the heart. It supplies blood to the inferior (diaphragmatic) left ventricular wall and often the posterior one third of the interventricular septum as well as the free wall of the right ventricular through its right ventricular (acute marginal) branches. The posterior descending branch of the RCA supplies blood to the posterior one third of the interventricular septum. A posterolateral branch of the RCA provides blood supply to the basal most portion of the posterolateral left ventricular wall.

Arterial dominance 

Left or right coronary artery dominance is determined by the origin of the atrioventricular nodal artery at the crux of the heart (see above). The atrioventricular node artery originates from the RCA in approximately 90% of the population and LCx coronary artery in the remaining 10%. The dominant coronary artery also gives off the posterior descending coronary artery that runs in the posterior interventricular sulcus and provides septal perforator branches to the posterior one third of the interventricular septum. In some individuals, both the RCA and the LCx reach the crux and jointly give rise to the posterior descending coronary artery. In such cases, the coronary arterial system is referred to as codominant.

Variations in normal coronary artery anatomy

Absence of the left main coronary artery with separate origin of the LAD and LCx coronary arteries from the left coronary sinus of the aorta has been described in roughly 1% of patients undergoing angiography and is considered a normal variant. In addition, one or more infundibular (conal) arteries may arise from separate ostia in the aorta. As many as 5 separate conal artery ostia have been reported in otherwise normal hearts. Minor variations in the location of ostia within the coronary sinuses of the aorta are observed frequently and are of no clinical significance. A variation in normal coronary artery anatomy is shown below.

Anomalous coronary arteries

The list below presents a classification of major isolated coronary artery anomalies. As seen, coronary artery anomalies may involve abnormalities of number, origin and/or course, termination, or structure of the epicardial coronary arteries.

Normal variations

• Absent left main
• Minor variations in position of ostia within the coronary sinus
• Separate origin of conal branches

Abnormal number

• Duplication of the LAD
• Duplication of the RCA (single or double ostium)

Anomalous origin

• Origin from pulmonary trunk
• Origin from left/right ventricle
• Origin from bronchial/internal mammary/subclavian/right carotid/innominate artery
• High takeoff (>1 cm above sinotubular junction)

Anomalous origin and course

Origin

• Solitary ostium

  • From right coronary sinus
    • RCA continues as LCx and LAD
    • RCA gives off LM
    • RCA gives off LAD and LCx
  • From left coronary sinus
    • LM gives off LAD, LCx, and RCA
    • LCx continues as RCA
    • LCx gives off RCA
    • LAD gives off RCA
• Origin of LAD from RCA
• Origin of LCx from RCA
• Origin of LAD from right coronary sinus
• Origin of LCx from right coronary sinus
• Origin of RCA from left coronary sinus

Course

The anomalous artery takes 1 of 4 aberrant pathways.

• A ( A nterior to right ventricular outflow tract
• B ( B etween aorta and pulmonary trunk)
• C (Through the C rista supraventricularis)
• D ( D orsal to the aorta)

Anomalous course

• Intramyocardial course (myocardial bridging)
• Tangential proximal course into the wall of the aorta

Anomalous termination

• Fistulas to right/left ventricle
• Fistulas to right/left atrium
• Fistulas to coronary sinus
• Fistulas to pulmonary artery

Abnormal coronary structure

• Stenosis
• Atresia
• Hypoplasia

Abnormal number

In some individuals, certain left ventricular territories may be supplied by more than one coronary artery. Duplications of the LAD coronary artery, LCx coronary artery, and RCA have been reported.

• Dual LAD coronary artery consists of one short and another long artery and has been classified into 4 different subtypes.

  • In the most common form (type I), the short and long LAD coronary arteries originate from the normal LAD coronary artery proper. The shorter artery then runs in the anterior interventricular sulcus and terminates abruptly long before reaching the apex. The longer artery, however, runs on the anterior epicardial surface of the left ventricle and returns to the anterior interventricular sulcus in its distal one third and then continues on to the apex. All diagonal branches originate from the longer artery.
  • In the type II variety, the long LAD coronary artery courses over the anterior surface of the right rather than the left ventricle.
  • In the type III dual LAD coronary artery, the long artery has, at least partly, an intramyocardial (bridging) course. Unlike types I and II, the septal perforators arise from the long LAD and the diagonals arise from the short LAD coronary artery.
  • Finally, in the type IV variety, the short LAD coronary artery arises from the LM coronary artery and the long artery anomalously arises from the RCA and courses to the left side anterior to the right ventricular outflow tract.
• Duplications of the RCA have been reported with both single and double ostium in the right coronary sinus. The duplicate vessels may course together in the right atrioventricular groove and/or have separate courses with one coursing on the epicardial surface of the right ventricle. Both vessels give rise to right ventricular branches and generally 1 of the 2 gives off the posterior descending coronary artery.
• We have recently reported duplication of the LCx , or otherwise described as aberrant origin of one OM branch from the LAD, ramus intermedius, or diagonal branch of the LAD, in a case series of 24 patients. In the image below, the anomalous OM courses parallel to the LCx coronary artery and supplies blood to the acute margin of the left ventricle.
  
  Coronary angiography showing the anomalous origin of the left main (LM) coronary artery from proximal right coronary artery (RCA) with subsequent retroaortic (dorsal [type D]) course to the left side.

Anomalous origin

Abnormalities of the origin of coronary arteries with subsequent normal epicardial course relate to the anomalous location of one or both coronary ostia. These include the origin of LM, LAD, LCx, or RCA from the pulmonary trunk. In addition, coronary arteries may originate directly from the left or right ventricles; the bronchial, internal mammary, subclavian, right carotid, or innominate arteries; the aortic arch; or the descending thoracic aorta. High takeoff of the left or right coronary ostia, defined as the location of the ostium of the left or right coronary artery more than 1 cm above the sinotubular junction, has been described.

Anomalous origin and course

Single coronary artery

• The entire coronary artery system may originate from a single ostium (solitary coronary ostium or single coronary artery) in the aorta. This solitary ostium is either located in the left or right coronary sinus of the aorta. When the LM coronary artery originates from the proximal RCA, or vice versa, the anomalous artery takes 1 of 4 aberrant pathways to reach its proper vascular territory. These pathways are designated as type A ( A  nterior to the right ventricular outflow tract), type B ( B etween the aorta and pulmonary trunk), type C ( C  ristal, coursing through the crista supraventricularis portion of the septum), and type D (D  orsal or posterior to the aorta).
• Single coronary arteries may also include the separate origin of the LAD and LCx coronary arteries from the proximal RCA. In this case, the LAD coronary artery takes one of the type A, B, or C pathways, and the LCx coronary artery takes either the B or D pathway. The LCx coronary artery may also originate from the distal RCA. In that case, the LCx coronary artery is merely a continuation of the RCA in the posterior atrioventricular groove. Overall, a total of 20 possible variations of single coronary artery have been described.

Origin from opposite coronary sinus

• Both the left and right coronary arteries may arise from separate ostia located in the same, either left or right, sinus of the aorta. In such cases, the anomalous vessels take 1 of the 4 possible courses to reach their proper territories similar to what was described above for the single coronary artery (types A-D). In the absence of congenital heart disease, anomalous origin of coronary arteries from noncoronary sinus is not reported.

Anomalous course

Otherwise normal coronary arteries may have an intramyocardial course (ie, myocardial bridge). This particular abnormality involves a variable length of the vessel and is observed most commonly in the proximal portion of the LAD coronary artery.

Anomalous termination

Major epicardial coronary arteries may terminate abnormally into one of the cardiac chambers, the coronary sinus, or the pulmonary trunk and, thus, produce fistulas. These fistulas can originate from the left coronary artery system (50-60%), right coronary artery system (30-40%), or both (2-5%). Most fistulas (90%) drain into the right heart.

Abnormal coronary structure

Both congenital stenosis and atresia of the coronary arteries have been described. Congenital epicardial coronary artery stenosis is usually caused by a membrane or a fibrotic ridge. Coronary artery atresia is characterized by the presence of an ostial dimple in the left or right aortic sinus that terminates in a cordlike fibrotic structure without a patent lumen. Atresia may also involve individual major epicardial coronary arteries. Hypoplastic coronary arteries have small luminal diameter (usually < 1 mm) and reduced length.The latter is often associated with the absence of the posterior descending coronary artery.

Frequency

United States

Coronary artery anomalies are observed in 0.3-1.3% of patients undergoing diagnostic coronary angiography, in approximately 1% of routine autopsy examinations, and in 4-15% of young people who experience sudden death. In the general population, the incidence of a single coronary artery is approximately 0.024%, while coronary artery fistulas are found in 0.2% of patients undergoing coronary angiography. Coronary artery fistulas are present in 0.002% of all patients with congenital heart disease. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is reported in 0.0003% of the general population. This anomaly is responsible for 18% of all cases of congestive heart failure in children younger than 2 years.

Mortality/Morbidity

Most coronary artery anomalies are clinically silent and do not affect the quality of life or lifespan of the affected individuals. Specific forms of anomaly, such as the origin of the left main coronary artery from the pulmonary trunk, the aberrant course of the arteries between the great vessels in association with anomalous and slitlike ostium, and large coronary artery fistulas, may be associated with sudden death, myocardial ischemia, congestive heart failure, or endocarditis. Hypoplastic coronary arteries and high take-off of coronary ostia have been occasionally reported to have been associated with sudden death. The exact incidence of these associated clinical events is not known.

Sex

No differences have been reported in incidence of specific coronary artery anomalies among male and female subjects.

Age

• Origin of left main coronary artery from the pulmonary trunk manifests during early infancy.
• Other significant coronary anomalies usually result in symptoms during young adult life.
• The remaining anomalies generally are clinically silent and may be discovered incidentally during noninvasive or invasive diagnostic testing for unrelated symptoms.

Coronary artery vasospasm, or smooth muscle constriction of the coronary artery, is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. It also plays a key role in the development of atherosclerotic lesions.

In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation. Unlike patients with typical angina, exercise tolerance in these patients was characteristically normal and pain patterns tended to be cyclical with most episodes occurring in the early morning hours without regard to cardiac workload. This syndrome became known as Prinzmetal or variant angina, and was believed to be due to vasospasm in coronary arteries without obstructive lesions. Subsequently, Maseri et al described the clinical, electrocardiographic, and angiographic features of 138 patients with variant angina and concluded that the syndrome is considerably more polymorphic than initially inferred by Prinzmetal.

The pathophysiological mechanisms leading to coronary artery vasospasm are incompletely understood at this time. Coronary arterial tone varies normally through physiological mechanisms, but the degree of vasoconstriction can range along a spectrum from undetectable constriction to complete arterial occlusion. In some patients with partial vasoconstriction, symptoms can arise with activities that exceed a threshold of myocardial demand. In other patients, constriction may be so severe that myocardial ischemia develops at rest. Many observers use the presence of constriction-induced ischemia as the threshold for defining clinical coronary artery vasospasm, which has also been called vasospastic angina or variant angina.

Coronary artery vasospasm can be induced through stimulation of alpha receptors or intracoronary injection of the parasympathetic neurotransmitter acetylcholine, implicating different mechanisms of action.

Acetylcholine causes coronary vasodilation in healthy coronary arteries through the release of endothelial nitric oxide; however, in atherosclerotic arteries, vasoconstriction ensues instead. Patients with coronary artery vasospasm appear to have a heightened vasoconstrictor response to acetylcholine as well as an enhanced response to the vasodilator effects of nitrates, an observation that is consistent with a deficiency of endogenous nitric oxide activity. Thus, nitric oxide deficiency is believed to play an important role in the development of coronary artery vasospasm. This may also explain the correlation between coronary artery vasospasm and increased intimal thickening, as nitric oxide deficiency results in enhanced activity of potent vasoconstrictors and stimulators of vascular smooth muscle proliferation, such as angiotensin II and endothelin 1.

Several genetic polymorphisms that compromise endothelial nitric oxide production have been found to be significantly associated with coronary artery vasospasm. Some have even been found to have prognostic value, including the -786T/C polymorphism.

However, additional studies showing that nitric oxide levels are not decreased at the sites of coronary artery vasospasm dispute the primacy of the role of nitric oxide. Alternative (or coexisting) mechanisms of coronary artery vasospasm include enhanced phospholipase C activity. In addition, coronary artery vasospasm is associated with increased markers of oxidative stress and inflammation, including thioredoxin, C-reactive protein, and monocyte levels. Interestingly, certain behavioral traits (such as type A personality, panic disorder, and severe anxiety) have also been described in association with coronary artery vasospasm.

Frequency

United States

The reported prevalence of vasospastic angina varies considerably between clinical studies depending in large part on the geographic location of the population studied as well as the criteria used to test and define the condition. In the United States, the frequency is among the lowest in the world with about 4% of patients undergoing coronary angiography having evidence of focal spasm, when defined as a 75% reduction in artery diameter upon the administration of ergonovine.

International

In France, around 12% of patients had positive ergonovine-based studies, whereas the Japanese literature, from which a preponderance of publications on coronary artery vasospasm originates, reports positive study rates of around 30%. Interestingly, the incidence of coronary artery vasospasm may be increasing in Japan, at least on the basis of provocation of spasm by the administration of acetylcholine.

Mortality/Morbidity

The prognosis of patients with vasospastic angina appears to be dependent upon the degree of coexisting atherosclerotic coronary disease. In patients with no or even single-vessel atherosclerosis, the prognosis is benign with survival rates of up to 99% at 1 year and 94% at 5 years. On the other hand, survival in patients with multivessel atherosclerotic disease fell to 87% at 1 year and 77% at 5 years. Survival rates were also lower in patients with multivessel spasm.

Race

Japanese patients are much more likely to develop coronary artery vasospasm than Caucasian patients. When evaluated by the same team, Japanese patients had a three-fold greater incidence of spasm compared to their Caucasian counterparts even though the two groups of patients had similar average basal coronary tone.

Sex

Variant angina is believed to be more common in female patients, although some prognostic studies of patients with variant angina suggest a male preponderance. Among women, variant angina may be relatively more common in Caucasian patients (22%) than in Japanese patients (11%).

Age

The onset of symptoms occurs at a highly variable age, but, on average, patients are in their 50s when symptoms begin.

Myocardial infarction (MI) due to coronary artery disease is a leading cause of death in the United States, where more than 1 million people have acute myocardial infarctions (AMIs) each year.

The advent of coronary care units and early reperfusion therapy (lytic or percutaneous coronary intervention) has substantially decreased in-hospital mortality rates and has improved the outcome in survivors of the acute phase of MI.

Complications of MI include arrhythmic, mechanical, and inflammatory (early pericarditis and post-MI syndrome) sequelae, as well as left ventricular mural thrombus (LVMT). In addition to these broad categories, right ventricular (RV) infarction and cardiogenic shock are other possible complications of acute MI. (See the image below.)

For other discussions on myocardial infarction, see the overview topicsMyocardial Infarction and Right Ventricular Infarction, as well as the articlesImaging of Acute Myocardial Infarcts and Use of Cardiac Markers in the Emergency Department.

About 90% of patients who have an acute myocardial infarction (AMI) develop some form of cardiac arrhythmia during or immediately after the event. In 25% of patients, such rhythm abnormalities manifest within the first 24 hours. In this group of patients, the risk of serious arrhythmias, such as ventricular fibrillation, is greatest in the first hour and declines thereafter. The incidence of arrhythmia is higher with an ST-elevation myocardial infarction (STEMI) and lower with a non–ST-elevation myocardial infarction (NSTEMI).

The clinician must be aware of these arrhythmias, in addition to reperfusion strategies, and must treat those that require intervention to avoid exacerbation of ischemia and subsequent hemodynamic compromise. Most peri-infarct arrhythmias are benign and self-limited. However, those that result in hypotension, increase myocardial oxygen requirements, and/or predispose the patient to develop additional malignant ventricular arrhythmias should be aggressively monitored and treated.

Pathophysiology of arrhythmic complications

AMI is characterized by generalized autonomic dysfunction that results in enhanced automaticity of the myocardium and conduction system. Electrolyte imbalances (eg, hypokalemia and hypomagnesemia) and hypoxia further contribute to the development of cardiac arrhythmia. The damaged myocardium acts as substrate for re-entrant circuits, due to changes in tissue refractoriness.

Enhanced efferent sympathetic activity, increased concentrations of circulating catecholamines, and local release of catecholamines from nerve endings in the heart muscle itself have been proposed to play roles in the development of peri-infarction arrhythmias. Furthermore, transmural infarction can interrupt afferent and efferent limbs of the sympathetic nervous system that innervates myocardium distal to the area of infarction. The net result of this autonomic imbalance is the promotion of arrhythmias.

Classification of peri-infarction arrhythmias

Peri-infarction arrhythmias can be broadly classified into the following categories:

• Supraventricular tachyarrhythmias, including sinus tachycardia, premature atrial contractions, paroxysmal supraventricular tachycardia,atrial flutter, and atrial fibrillation
• Accelerated junctional rhythms
• Bradyarrhythmias, including sinus bradycardia and junctional bradycardia
• Atrioventricular (AV) blocks, including first-degree AV block, second-degree AV block, and third-degree AV block
• Intraventricular blocks, including left anterior fascicular block, right bundle branch block (RBBB), and left bundle branch block (LBBB)
• Ventricular arrhythmias, including premature ventricular contractions(PVCs), accelerated idioventricular rhythm, ventricular tachycardia, andventricular fibrillation
• Reperfusion arrhythmias

Sinus tachycardia is associated with enhanced sympathetic activity and can result in transient hypertension or hypotension. The elevated heart rate increases myocardial oxygen demand, and a decreased length of diastole compromises coronary flow, worsening myocardial ischemia.

Causes of persistent sinus tachycardia include the following:

• Pain
• Anxiety
• Heart failure
• Hypovolemia
• Hypoxia
• Anemia
• Pericarditis
• Pulmonary embolism

In the setting of an AMI, sinus tachycardia must be identified, and appropriate treatment strategies must be devised. Treatment strategies include adequate pain medication, diuresis to manage heart failure, oxygenation, volume repletion for hypovolemia, administration of anti-inflammatory agents to treat pericarditis, and use of beta-blockers and/or nitroglycerin to relieve ischemia.

Premature atrial contractions

Premature atrial contractions often occur before the development of paroxysmal supraventricular tachycardia, atrial flutter, or atrial fibrillation. The usual cause of these extra impulses is atrial distention due to increased left ventricular (LV) diastolic pressure or inflammation associated with pericarditis.

No specific therapy is indicated. However, attention should be given to identifying the underlying disease process, particularly occult heart failure.

Paroxysmal supraventricular tachycardia

The incidence of a paroxysmal supraventricular tachycardia in the setting of an AMI is less than 10%. In the absence of definitive data in the patient with AMI, the consensus is that adenosine can be used when hypotension is not present. In patients without clinically significant LV failure, intravenous diltiazem or a beta-blocker can be used instead. In patients who develop severe heart failure or hypotension, synchronized electrical cardioversion is required.

Atrial flutter

Atrial flutter occurs in less than 5% of patients with AMI. Atrial flutter is usually transient and results from sympathetic overstimulation of the atria.

Treatment strategies for persistent atrial flutter are similar to those for atrial fibrillation, except that ventricular-rate control with drugs is less easily accomplished with atrial flutter than with atrial fibrillation. Therefore, synchronized electrical cardioversion (beginning with 50 J, or the biphasic equivalent) may be needed relatively promptly because of a decrease coronary blood flow and/or hemodynamic compromise. For patients whose atrial flutter is refractory to medical therapy, overdrive atrial pacing may be considered.

Atrial fibrillation

The rate of atrial fibrillation is 10-15% among patients who have AMIs. The onset of atrial fibrillation in the first hours of AMI is usually caused by LV failure, ischemic injury to the atria, or RV infarction. Pericarditis and all conditions leading to elevated left atrial pressure can also lead to atrial fibrillation in association with an AMI. The presence of atrial fibrillation during an AMI is associated with an increased risk of mortality and stroke, particularly in patients who have anterior-wall MIs.

Immediate electrical cardioversion is indicated for the patient in unstable condition, such as one with new or worsening ischemic pain and/or hypotension. Synchronized electrical cardioversion to treat atrial fibrillation begins with 200 J (or the biphasic equivalent). Conscious sedation (preferred) or general anesthesia is advisable prior to cardioversion.

For patients in stable condition, controlling the ventricular response is the immediate objective. If the atrial fibrillation does not respond to cardioversion, IV amiodarone or IV digoxin (in patients with LV dysfunction or heart failure) can be used to achieve ventricular rate control.

For patients who do not develop hypotension, a beta-blocker can be used. For example, metoprolol may be given in 5-mg intravenous boluses every 5-10 min, with a maximum dose of 15 mg. Intravenous diltiazem is an alternative for slowing the ventricular rate, but it should be used with caution in patients with moderate-to-severe heart failure. In patients with new-onset sustained tachycardia (absent before MI), conversion to sinus rhythm should be considered as an option.

Atrial fibrillation and atrial flutter confer an increased risk of thromboembolism (see Deep Venous Thrombosis and Pulmonary Embolism). Therefore, anticoagulation with either unfractionated heparin or low molecular weight heparin (LMWH) should be started if contraindications are absent. It is unclear whether anticoagulation is needed in cases of transient atrial fibrillation and how long after the onset of atrial fibrillation should the anticoagulation be started.

An accelerated junctional rhythm results from increased automaticity of the junctional tissue that leads to a heart rate of 70-130 bpm. This type of dysrhythmia is most common in patients who develop inferior myocardial infarctions. Treatment is directed at correcting the underlying ischemia.

Sinus bradycardia

Sinus bradycardia is a common arrhythmia in patients with inferior or posterior acute myocardial infarctions (AMIs). The highest incidence, 40%, is observed in the first 1-2 hours after AMI.

The likely mechanism leading to bradycardia and hypotension is stimulation of cardiac vagal afferent receptors that result in efferent cholinergic stimulation of the heart. In the early phases of an AMI, resultant sinus bradycardia may actually be protective, reducing myocardial oxygen demand. Clinically significant bradycardia that decreases cardiac output and hypotension may result in ventricular arrhythmias and should, therefore, be treated aggressively. Isolated sinus bradycardia is not associated with an increase in the acute mortality risk, and therapy is typically unnecessary when the patient has no adverse signs or symptoms.

When emergency therapy is indicated (eg, in a patient with a sinus rate of < 40 bpm with hypotension), atropine sulfate 0.5-1 mg may be given every 3-5 minutes to a maximum of 0.03-0.04 mg/kg. The inability to reverse hypotension with atropine in patients who develop sinus bradycardia and inferior MI suggests volume depletion and/or RV infarction.

When atropine is ineffective and the patient is symptomatic or hypotensive, transcutaneous or transvenous pacing is indicated (see our main article onExternal Pacemakers). Denervate, transplanted hearts do not respond to atropine and, therefore, require cardiac pacing.

If these interventions fail, additional pharmacologic intervention may be useful. Examples are dopamine 5-20 mcg/kg/min given intravenously, epinephrine 2-10 mcg/min, and/or dobutamine.

Junctional bradycardia

Junctional bradycardia is a protective AV junctional escape rhythm at a rate of 35-60 bpm in patients who have an inferior MI. This arrhythmia is not usually associated with hemodynamic compromise, and treatment is typically not required.

First-degree AV block

First-degree AV block is characterized by prolongation of the PR interval to longer than 0.20 seconds. This type of block occurs in approximately 15% of patients who have an acute myocardial infarction (AMI), most commonly an inferior infarction. Almost all patients who develop first-degree AV block have conduction disturbances above the His bundle. In these patients, the progression to complete heart block or ventricular asystole is rare. No specific therapy is indicated unless associated hemodynamic compromise is present.

Calcium channel blockers and beta-blockers may cause or exacerbate a first-degree AV block, but they should be stopped only if hemodynamic impairment or a higher-degree block occurs. For a first-degree AV block associated with sinus bradycardia and hypotension, atropine should be administered. Continued cardiac monitoring is advisable in view of possible progression to higher degrees of block.

Second-degree AV block

Mobitz type I, or Wenckebach, AV block occurs in approximately 10% of patients who have an AMI and accounts for 90% of all patients who have an AMI and a second-degree AV block. A second-degree AV block is associated with a narrow QRS complex and is most commonly associated with an inferior MI. It does not affect the patient’s overall prognosis.

A Mobitz type I block does not necessarily require treatment. If the heart rate is inadequate for perfusion, immediate treatment with atropine 0.5-1 mg administered intravenously is indicated. Transcutaneous or temporary transvenous pacing is rarely required.

A Mobitz type II AV block accounts for 10% of all second-degree AV blocks (overall rate of < 1% in the setting of AMI). A Mobitz type II block is characterized by a wide QRS complex, and it is almost always associated with anterior infarction. This type of block often progresses suddenly to a complete heart block.

Mobitz type II AV blocks are associated with a poor prognosis, as the mortality rate associated with their progression to a complete heart block is approximately 80%. Therefore, this type of second-degree AV block should be immediately treated with transcutaneous pacing or atropine. Atropine helps in about 50% of cases, but it occasionally worsens the block with an increased heart rate. A temporary transvenous pacemaker, and possibly a permanent demand pacemaker, must ultimately be placed.

Third-degree AV block

A third-degree AV block (ie, a complete heart block), occurs in 5-15% of patients who have an AMI and may occur with anterior or inferior infarctions. In patients with inferior infarctions, this type of block usually develops gradually, progressing from first-degree or a type I second-degree block. In most patients, the level of the block is supranodal or intranodal, and the escape rhythm is usually stable with a narrow QRS and rates exceeding 40 bpm. In 30% of patients, the block is below the His bundle, where it results in an escape rhythm with a rate slower than 40 bpm and a wide QRS complex.

Complete heart block in patients with an inferior MI usually responds to atropine. In most patients, it resolves within a few days without the need for a temporary or permanent pacemaker. The mortality rate for patients with inferior MI who develop complete heart block is approximately 15% unless a coexisting RV infarction is present, in which case the mortality rate is higher.

Immediate treatment with atropine is indicated for patients with third-degree AV blocks. As with therapy for a Mobitz type II block, this treatment may not help and may sometimes worsen the block. Temporary transcutaneous or transvenous pacing is indicated for symptomatic patients whose condition is unresponsive to atropine. Permanent pacing should be considered in patients with persistent symptomatic bradycardia that remains unresolved with lysis or percutaneous coronary intervention.

In patients with an anterior MI, an intraventricular block or a Mobitz type II AV block usually precedes a third-degree AV block. The third-degree block occurs suddenly and is associated with a high mortality rate. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (CARISMA) trial monitored patients with acute myocardial infarction and reduced left ventricular ejection fraction and found that high-degree atrioventricular block was the most powerful predictor of cardiac death. Patients with these blocks typically have unstable escape rhythms with wide QRS complexes and at rates of less than 40 bpm.

Immediate treatment with atropine and/or transcutaneous pacing is indicated. This is followed by temporary transvenous pacing. Patients with an anterior MI who develop a third-degree AV block and who survive to hospitalization often receive a permanent pacemaker.

Intraventricular blocks

Conduction from the His bundle is transmitted through 3 fascicles: the anterior division of the left bundle, the posterior division of the left bundle, and the right bundle. An abnormality of electrical conduction in 1 or more of these fascicles is noted in about 15% of patients with AMI. Isolated left anterior fascicular block (LAFB) occurs in 3-5% of patients with AMI; progression to complete AV block is uncommon. Isolated left posterior fascicular block occurs in only 1-2% of patients who have an AMI. The blood supply of the posterior fascicle is larger than that of the anterior fascicle; therefore, a block here is associated with a relatively large infarct and high mortality rate.

The right bundle branch receives its dominant blood supply from the left anterior descending (LAD) artery. Therefore, a new RBBB, which is seen in approximately 2% of patients with AMI, suggests a large infarct territory. However, progression to complete heart block is uncommon. In patients who develop an anterior MI and a new RBBB, the substantial risk for death is mostly from cardiogenic shock, which is presumably due to the large size of the myocardial infarct.

The combination of RBBB with an LAFB is known as bifascicular block and commonly occurs with occlusion of the proximal LAD coronary artery. The risk of developing complete AV block is heightened, but complete block is still uncommon. Mortality is mostly related to the amount of muscle loss. Bifascicular block in the presence of first-degree AV block is called a trifascicular block. In 40% of patients, a trifascicular block progresses to a complete heart block.

Premature ventricular contractions

In the past, frequent premature ventricular contractions (PVCs) were considered to represent warning arrhythmias and indicators of impending malignant ventricular arrhythmias. However, presumed warning arrhythmias are frequently observed in patients who have an acute myocardial infarction (AMI) and who never develop ventricular fibrillation. On the converse, primary ventricular fibrillation often occurs without antecedent premature ventricular ectopy.

For these reasons, prophylactic suppression of PVCs with antiarrhythmic drugs, such as lidocaine, is no longer recommended. Prophylaxis has been associated with an increased risk of fatal bradycardia or asystole because of the suppression of escape pacemakers.

Given this evidence, most clinicians pursue a conservative course when PVCs are observed in a patient with an AMI, and they do not routinely administer prophylactic antiarrhythmics. Instead, attention should be directed toward correcting any electrolytic or metabolic abnormalities, plus identifying and treating recurrent ischemia.

Accelerated idioventricular rhythm

An accelerated idioventricular rhythm is seen in as many as 20% of patients who have an AMI. This pattern is defined as a ventricular rhythm characterized by a wide QRS complex with a regular escape rate faster than the atrial rate, but less than 100 bpm. AV dissociation is frequent. Slow, nonconducted P waves are seen; these are unrelated to the fast, wide QRS rhythm.

Most episodes are short and terminate spontaneously. They occur with equal frequency in anterior and inferior infarctions. The mechanism might involve (1) the sinoatrial node or the AV node, which may sustain structural damage and depress nodal automaticity, and/or (2) an abnormal ectopic focus in the ventricle that takes over as the dominant pacemaker.

The presence of accelerated idioventricular rhythm does not affect the patient’s prognosis; no definitive evidence has shown that an untreated occurrence increases the incidence of ventricular fibrillation or death. This rhythm occurs somewhat more frequently in patients who develop early reperfusion than in others; however, it is neither sensitive nor specific as a marker of reperfusion.

Temporary pacing is not indicated unless the rhythm is sustained and results in hypotension or ischemic symptoms. An accelerated idioventricular rhythm represents an appropriate escape rhythm. Suppression of this escape rhythm with an antiarrhythmic drug can result in clinically significant bradycardia or asystole. Therefore, an accelerated idioventricular rhythm should be left untreated.

Nonsustained ventricular tachycardia

Nonsustained ventricular tachycardia is defined as 3 or more consecutive ventricular ectopic beats at a rate of greater than 100 bpm and lasting less than 30 seconds. In patients who experience multiple runs of nonsustained ventricular tachycardia, the risk for sudden hemodynamic collapse may be substantial.

Nonetheless, nonsustained ventricular tachycardia in the immediate peri-infarction period does not appear to be associated with an increased mortality risk, and no evidence suggests that antiarrhythmic treatment offers a morbidity or mortality benefit. However, nonsustained ventricular tachycardia occurring more than 48 hours after infarction in patients with LV systolic dysfunction (LV ejection fraction < 0.40) poses an increased risk for sudden cardiac death; electrophysiologic testing and appropriate therapy are indicated in these patients.

Multiple episodes of nonsustained ventricular tachycardia require intensified monitoring and attention to electrolyte imbalances. Serum potassium levels should be maintained above 4.5 mEq/L, and serum magnesium levels should be kept above 2.0 mEq/L. Ongoing ischemia should aggressively be sought and corrected if found.

Sustained ventricular tachycardia

Sustained ventricular tachycardia is defined as 3 or more consecutive ventricular ectopic beats at a rate greater than 100 bpm and lasting longer than 30 seconds or causing hemodynamic compromise that requires intervention. Monomorphic ventricular tachycardia is most likely to be caused by a myocardial scar, whereas polymorphic ventricular tachycardia may be most responsive to measures directed against ischemia. Sustained polymorphic ventricular tachycardia after an AMI is associated with a hospital mortality rate of 20%.

Emergency treatment of sustained ventricular tachycardia is mandatory because of its hemodynamic effects and because it frequently deteriorates into ventricular fibrillation. Rapid polymorphic ventricular tachycardia (rate >150 bpm) associated with hemodynamic instability should be treated with immediate direct-current unsynchronized cardioversion of 200 J (or biphasic energy equivalent). Monomorphic ventricular tachycardia should be treated with a synchronized discharge of 100 J (or biphasic energy equivalent).

If sustained ventricular tachycardia is well tolerated, antiarrhythmic therapy with amiodarone (drug of choice) or procainamide may be attempted before electrical cardioversion. Precipitating causes, such as electrolyte abnormalities, acid-base disturbances, hypoxia, or medication, should be sought and corrected. For persistent or recurrent ventricular tachycardia, overdrive pacing may be effective in electrically converting the patient’s rhythm to a sinus rhythm.

Ventricular fibrillation

The incidence of primary ventricular fibrillation is greatest in the first hour after the onset of infarct (4.5%) and declines rapidly thereafter. Approximately 60% of episodes occur within 4 hours, and 80% occur within 12 hours.

Secondary or late ventricular fibrillation occurring more than 48 hours after an MI is usually associated with pump failure and cardiogenic shock. Factors associated with an increased risk of secondary ventricular fibrillation are a large infarct, an intraventricular conduction delay, and an anteroseptal AMI. Secondary ventricular fibrillation in conjunction with cardiogenic shock is associated with an in-hospital mortality rate of 40-60%.

Treatment for ventricular fibrillation is unsynchronized electrical countershock with at least 200-300 J (or biphasic energy equivalent) administered as rapidly as possible. Each minute after the onset of uncorrected ventricular fibrillation is associated a 10% decrease in the likelihood of survival. Restoration of synchronous cardiac electrical activity without the return of effective contraction (ie, electromechanical dissociation, or pulseless electrical activity) is generally due to extensive myocardial ischemia and/or necrosis or cardiac rupture.

Antiarrhythmics, such as intravenous amiodarone and lidocaine, facilitate successful electrical defibrillation and help prevent recurrent or refractory episodes. After ventricular fibrillation is successfully converted, antiarrhythmic therapy is generally continued as a constant intravenous infusion for 12-24 hours.

Prophylactic lidocaine reduces the incidence of ventricular fibrillation, but it is not used because it seems to be associated with an excessive mortality risk owing to bradycardic and asystolic events. On the other hand, early use of beta-blockers in patients with AMI reduces the incidence of ventricular fibrillation as well as death.

In the past, the sudden onset of rhythm disturbances after thrombolytic therapy in patients with AMI was believed to be a marker of successful coronary reperfusion. However, a high incidence of identical rhythm disturbances is observed in patients with AMI in whom coronary reperfusion is unsuccessful. Therefore, these so-called reperfusion arrhythmias are neither sensitive nor specific for reperfusion and should be treated as discussed under Accelerated Idioventricular Rhythm in the Arrhythmic Complications: Ventricular Arrhythmias section above.

The 3 major mechanical complications of AMI are ventricular free wall rupture (VFWR), ventricular septal rupture (VSR), and papillary muscle rupture with severe mitral regurgitation (MR). Each of these complications can result in cardiogenic shock. Clinical issues related to these mechanical problems are discussed below. (See also Myocardial Rupture.)

Overview of ventricular free wall rupture

VFWR is the most serious complication of AMI. VFWR is usually associated with large transmural infarctions and antecedent infarct expansion. It is the most common cause of death, second only to LV failure, and it accounts for 15-30% of the deaths associated with AMI. Incontrovertibly the most catastrophic of mechanical complications, VFWR leads to acute hemopericardium and death from cardiac tamponade.

The overall incidence of VFWR ranges from 0.8-6.2%. The incidence of this complication has declined over the years with better 24 hour systolic blood pressure control; increased use of reperfusion therapy, beta blockers, and ACE inhibitors; and decreased use of heparin.

Data from the National Registry of Myocardial Infarction (NRMI) showed an elevated incidence of in-hospital mortality among patients who received thrombolytic therapy (12.1%) than among patients who did not (6.1%). In the Thrombolysis in Myocardial Infarction Phase II (TIMI II) trial, 16% of patients died from cardiac rupture within 18 hours of therapy. Patients who underwent percutaneous transluminal coronary angioplasty (PTCA) had an incidence of free wall rupture lower than that of patients receiving thrombolytic therapy.

Risk factors for VFWR include advanced age greater than 70 years, female sex, no previous MIs, Q waves on ECG, hypertension during the initial phase of STEMI, corticosteroid or NSAID use, and fibrinolytic therapy more than 14 hours after STEMI onset. Patients with a history of angina pectoris, previous AMI, multivessel coronary disease, and chronic heart failure are less likely than others to develop VFWR of the LV because they develop collaterals and ischemic preconditioning.

Clinical presentation of VFWR

VFWRs are dramatic; they present acutely or occasionally subacutely as pseudoaneurysms; and they most often involve the anterior or lateral wall of the LV. Most VFWRs occur within the first week after AMI.

Becker et al classified the following 3 types of VFWRs :

• Type I – an abrupt slitlike tear that is frequently associated with anterior infarcts and that occurs early (within 24 h)
• Type II – an erosion of infarcted myocardium at the border between the infarcted and viable myocardium
• Type III – an early aneurysm formation correlated with older and severely expanded infarcts

Type III usually occurs later than type I or type II ruptures. Thrombolytic therapy accelerates the occurrence of cardiac rupture in Becker type I and type II VFWRs. In severely expanded infarctions (type III), thrombolytic therapy decreases the incidence of cardiac rupture.

A pseudoaneurysm is formed when adjacent pericardium and hematoma seals off a myocardial rupture or perforation. The wall of a pseudoaneurysm is most often visualized as an aneurysmal outpouching that communicates with the LV cavity by means of a narrow neck. This wall is composed of pericardium and organized thrombus and/or hematoma. It is devoid of myocardial elements, whereas a true aneurysm has all the elements of the original myocardial wall and a relatively wide base. The pseudoaneurysm may vary in size and is at high risk of rupturing.

Clinical presentations of VFWR vary depending on the acuity, location, and size of the rupture. Patients with acute VFWR present with severe chest pain, abrupt electromechanical dissociation or asystole, hemodynamic collapse, and possibly death. In about one third of the patients, the course is subacute, and they present with symptoms such as syncope, hypotension, shock, arrhythmia, and prolonged and recurrent chest pain.

Diagnosis of VFWR

Early diagnosis of VFWRs and intervention are critical to patient survival. A high index of suspicion is required when patients with AMI present with severe chest pain, shock or arrhythmias, and abrupt development of electromechanical dissociation. ECG signs of impending VFWR have limited specificity but include sinus tachycardia, intraventricular conduction defect, and persistent or recurrent ST-segment elevation.

Echocardiography is the diagnostic tool of choice. The key diagnostic finding is a moderate-to-large pericardial effusion with clinical and echocardiographic signs of impending pericardial tamponade. In patients with cardiac tamponade and electromechanical dissociation, moderate-to-severe pericardial effusion increases the mortality risk. Those patients without initial cardiac tamponade, while at a lower rate of mortality, should still be followed, as late rupture may still occur. The absence of pericardial effusion on echocardiography has high negative predictive value. If the ability to obtain transthoracic echocardiograms is limited in patients receiving mechanical ventilation, transesophageal echocardiography can assist in confirming VFWR.

MRI provides superior image quality and permits identification of the site and anatomy of a ventricular pseudoaneurysm (ie, ruptured LV restrained by the pericardium with enclosed clot). However, MRI is of limited use in the acute setting because of the time involved and nonportability of imaging units.

Treatment of VFWR

The most important prevention strategy is early reperfusion therapy, with percutaneous coronary intervention (PCI) being the preferred modality. Fibrinolytic therapy is associated with overall decreased risk of VFWR; however, its use more than 14 hours after STEMI onset can increase the risk of early rupture.

The standard treatment for VFWR is emergency surgical repair after hemodynamic stability is achieved. Patients may first need intravenous fluids, inotropic agents, and emergency pericardiocentesis.

Pifarré and associates recommended the deployment of an intra-aortic balloon pump to decrease systolic afterload and improve diastolic myocardial perfusion.

Several surgical techniques have been applied, including infarctectomy, adhering with biologic glue patches made of polyethylene terephthalate polyester fiber (Dacron; DuPont, Wilmington, DE) or polytetrafluoroethylene fluoropolymer resin (Teflon; DuPont); and use of pledgeted sutures without infarctectomy.

The mortality rate is significantly high and largely depends on the patient’s preoperative hemodynamic status. Early diagnosis, rapid institution of the measures described above to achieve hemodynamic stability, and prompt surgical repair can improve survival rates. A follow-up to the Acorn randomized trial demonstrated long-term improvement in left ventricular structure and function after mitral valve surgery for as long as 5 years. These data provide evidence supporting mitral valve repair in combination with the Acorn CorCap device for patients with nonischemic heart failure with severe left ventricular dysfunction who have been medically optimized yet remain symptomatic with significant mitral regurgitation.

Overview of ventricular septal rupture

VSR is an infrequent but life-threatening complication of AMI. Despite optimal medical and surgical treatment, patients with VSR have a high in-hospital mortality rate. During the prethrombolytic era, VSRs occurred in 1-3% of individuals with MIs. The incidence declined with thrombolytic therapy (to 0.2-0.34%) because of improvements in reperfusion and myocardial salvage. The bimodal distribution of VSR is characterized by a high incidence in the first 24 hours, with another peak on days 3-5 and rarely more than 2 weeks after AMI.

In patients receiving thrombolytics, the median time from the onset of symptoms of AMI to septal rupture was 1 day in the Global Utilization of Streptokinase and TPA [tissue plasminogen activator] for Occluded Coronary Arteries (GUSTO-I) trial and 16 hours in the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock? (SHOCK) trial.

Risk factors for septal rupture include advanced age (>65 y), female sex, single-vessel disease, extensive MI, and poor septal collateral circulation. Before the advent of thrombolytics, hypertension and absence of a history of angina were risk factors for VSR. Extensive infarct size and RV involvement are other known risk factors for septal rupture.

In patients with AMI without reperfusion, coagulation necrosis develops within 3-5 days after infarction. Neutrophils migrate to the necrotic zone and undergo apoptosis, release lytic enzymes, and hasten the disintegration of necrotic myocardium. Some patients have infarcts with large intramural hematomas, which dissect into the tissue and result in early septal rupture. The size of the septal rupture ranges from a few millimeters to several centimeters.

VSR is categorized as simple or complex depending on its length, course, and location. In simple septal rupture, the perforation is at the same level on both sides of the septum, and a direct through-and-through communication is present across the septum. A complex septal rupture is characterized by extensive hemorrhage with irregular, serpiginous tracts in the necrotic tissue.

Septal ruptures are most common in patients with large anterior MIs due to occlusion of the LAD artery causing extensive septal infarcts. These infarcts are associated with ST-segment elevations and Q waves in inferior leads (II, III, aVF) and these ECG changes are therefore more commonly seen in septal ruptures. These ruptures are generally apical and simple.

Septal ruptures in patients with inferior MI occur relatively infrequently. These ruptures involve the basal inferoposterior septum and are often complex.

Clinical presentation of VSR

Symptoms of VSR complicating AMI include chest pain, shortness of breath, hypotension, biventricular failure, and shock within hours to days. Patients often present with a new, loud, and harsh holosystolic murmur. This murmur is loudest along the lower left sternal border and is associated with a palpable parasternal systolic thrill. RV and LV S3 gallops are common.

In patients with cardiogenic shock complicating septal rupture, the murmur and thrill may be difficult to identify. In contrast, patients with acute MR often have a soft systolic murmur at the apex without a thrill.

Diagnosis of VSR

Echocardiography with color flow Doppler imaging is the diagnostic tool of choice for identifying a VSR. (See the image below.) Its sensitivity and specificity have been reported to be as high as 100%. In addition, it can be used for the following:

• Define the site and size of septal rupture
• Assess the LV and RV function
• Estimate the RV systolic pressure
• Quantify the left-to-right shunt

Cardiac catheterization is usually required to confirm the diagnosis, quantitate the degree of left-to-right shunt, differentiate VSR from other conditions (eg, mitral regurgitation), plus visualize the coronary arteries.

In patients with VSR, right-heart catheterization shows a step-up in oxygen saturation from the right atrium to the RV; in contrast, no step-up in oxygen saturation occurs among patients with MR. The presence of large V waves in the pulmonary capillary wedge tracing supports the diagnosis of severe acute MR.

Left ventriculography can also be used to identify the site of ventricular rupture (see Cardiac Catheterization [Left Heart]). However, this study is usually unnecessary after a good-quality echocardiographic and Doppler examination is conducted.

Treatment of VSR

The key to management of VSR is prompt diagnosis and an aggressive approach to hemodynamic stabilization, angiography, and surgery. The optimal approach includes hemodynamic stabilization with the administration of oxygen and mechanical support with use of an intra-aortic balloon pump, as well as the administration of vasodilators (to reduce afterload and thus LV pressure and the left-to-right shunt), diuretics, and inotropic agents.

Cardiac catheterization is needed to define the coronary anatomy; this is followed by urgent surgical repair.

Medical therapy is intended only for temporary stabilization before surgery, as most patients’ conditions deteriorate rapidly and they die in the absence of surgical intervention. In the GUSTO-I trial, the 30-day mortality rate was lower in patients with VSR who underwent surgical repair than in patients treated medically (47% vs 94%), as was the 1-year mortality rate (53% vs 97%). Lemery et al reported a 30-day survival rate of 24% in patients treated medically compared with 47% in those treated surgically.

Current guidelines of the American College of Cardiology/American Heart Association for the treatment of patients with septal rupture complicating AMI highlight urgent surgical intervention, regardless of their clinical status. Surgical management of septal rupture includes the following elements:

• Prompt establishment of hypothermic cardiopulmonary bypass
• An approach to the septal rupture through the infarct area and the excision of all necrotic, friable margins of the septum and ventricular walls to avoid postoperative hemorrhage, residual septal defect, or both
• Reconstruction of the septum and ventricular walls by using prosthetic material and preservation of the geometric configuration of the ventricles and heart function

Percutaneous closure of septal rupture is a relatively new approach, one used in select patients as an alternative to surgical repair or for the acute stabilization of critically ill patients. However, percutaneous closure is currently unavailable in many institutions, and no long-term outcome data are available.

Several studies failed to show a relationship between perioperative mortality and concomitant coronary revascularization (coronary artery bypass grafting). Patients with cardiogenic shock due to septal rupture have the poorest outcome. In the SHOCK trial, the in-hospital mortality rate was higher in patients with cardiogenic shock due to septal rupture (87.3%) than in patients with cardiogenic shock from all other causes (59.2% with pure LV failure and 55.1% with acute MR).

In patients who survive surgical repair, the rate of recurrent or residual septal defect is reported to be about 28%, and the associated mortality rate is high.

Repeat surgical intervention is indicated in patients who have clinical heart failure or a pulmonary-systemic fraction greater than 2.

Overview of acute mitral regurgitation

MR is a common complication of AMI that results from local and global LV remodeling and that is an independent predictor of heart failure and death. MR typically occurs 7-10 days after an AMI, though this onset may vary according to the mechanism of MR. Papillary muscle rupture resulting in MR occurs within 1-14 days (median, 1 d).

Mild-to-moderate MR is often clinically silent and detected on Doppler echocardiography performed during the early phase of AMI. In such cases, MR rarely causes hemodynamic compromise.

Speckle tracking and 3-dimensional echocardiography proved to be important imaging tools in assessing reverse LV remodeling after degenerative mitral valve regurgitation surgery. Subtle regional preoperative changes in diastolic function of the septal and lateral wall could be preoperatively identified, aiding in optimizing the referral timing and recognizing potential culprits as indicators of disease recurrence after mitral repair.

Severe acute MR that results from the rupture of papillary muscles or chordae tendineae results in abrupt hemodynamic deterioration with cardiogenic shock. Rapid diagnosis, hemodynamic stabilization, and prompt surgical intervention are needed because acute severe MR is associated with a high mortality rate.

The reported incidence of MR may vary because of several factors, including the diagnostic methods used, the presence or absence of heart failure, the degree of MR reported, the type of therapy rendered, and the time from infarct onset to testing.

During the GUSTO-I trial, the incidence of MR in patients receiving thrombolytic therapy was 1.73%. The SHOCK trial, which included MI patients presenting with cardiogenic shock, noted a 39.1% incidence of moderate to severe MR. Kinn et al reported that reperfusion with angioplasty resulted in an 82% decrease in the rate of acute MR, as compared with thrombolytic therapy (0.31% vs 1.73%).

Risk factors for MR are advanced age, female sex, large infarct, previous AMI, recurrent ischemia, multivessel coronary artery disease, and heart failure.

Several mechanisms can cause MR after AMI. Rupture of the papillary muscle is the most commonly reported mechanism.

Such rupture occurs in 1% of patients with AMI and frequently involves the posteromedial papillary muscle rather than the anterolateral papillary muscle, as the former has a single blood supply versus the dual supply for the latter. Papillary muscle rupture may lead to flailing or prolapse of the leaflets, resulting in severe MR. Papillary muscle dysfunction due to scarring or recurrent ischemia may also lead to MR in the subacute and chronic phases after MI; this condition can resolve spontaneously.

Large posterior infarctions produce acute MR due to asymmetric annular dilation and altered function and geometry of the papillary muscle.

Clinical presentation of MR

Patients with functional mild or moderate MR are often asymptomatic. The severity of symptoms varies depending on ventricular function. Clinical features of acute severe MR include shortness of breath, fatigue, a new apical holosystolic murmur, flash pulmonary edema, and shock.

The new systolic murmur may be only early-to-mid systolic, not holosystolic. It may be soft or even absent because of the abrupt rise in left atrial pressure, which lessens the pressure gradient between the left atrium and the LV, as compared with chronic MR. The murmur is best heard at the apex rather than the lower left sternal border, and it is uncommonly associated with a thrill. S3 and S4 gallops are expected.

Diagnosis of MR

The clinician cannot rely on a new holosystolic murmur to diagnose MR or assess its severity because of the variable hemodynamic status. In a patient with AMI who presents with a new apical systolic murmur, acute pulmonary edema, and cardiogenic shock, a high index of clinical suspicion for severe MR is the key to diagnosis.

Chest radiography may show evidence of pulmonary edema in the acute setting without clinically significant cardiac enlargement.

Echocardiography with color flow Doppler imaging is the standard diagnostic tool for detecting MR. Transthoracic echocardiography is the preferred initial screening tool, but transesophageal echocardiography is invaluable in defining the severity and exact mechanism of acute MR, especially when suspicion for papillary muscle rupture is high. Cardiac catheterization should be performed in all patients to determine the extent and severity of coronary artery disease.

Treatment of MR

Determination of hemodynamic stability, elucidation of the exact mechanism of acute MR, and expedient therapy are all necessary for a favorable outcome. Medical management includes afterload reduction with the use of diuretics, sodium nitroprusside, and nitrates in patients who are not hypotensive.

In patients who have hemodynamic compromise, intra-aortic balloon counterpulsation should be deployed rapidly. This intervention usually substantially reduces afterload and regurgitant volume, improving cardiac output in preparation for surgical repair. Without surgical repair, medical therapy alone in patients with papillary muscle rupture results in inadequate hemodynamic improvement and a poor short-term prognosis.

Emergency surgical intervention is the treatment of choice for papillary muscle rupture. Surgical approaches may include mitral valve repair or replacement. In the absence of papillary muscle necrosis, mitral valve repair improves the survival rate more than mitral valve replacement does. This difference is because the subvalvular apparatus is usually preserved. Mitral valve repair also eliminates complications related to malfunction of the prosthesis.

In patients with extensive necrosis of papillary muscle and/or ventricular free wall, mitral valve replacement is the preferred modality. Coronary artery bypass grafting (CABG) performed at the time of surgery was shown in one study to improve short- and long-term survival.

The only situation in which emergency surgery can safely be avoided is in the case of intermittent MR due to recurrent ischemia. In these patients, successful myocardial revascularization may be effective. This procedure is accomplished by means of either angioplasty or coronary artery bypass grafting.

Overview of LVA

Left ventricular aneurysm (LVA) is defined as a localized area of myocardium with abnormal outward bulging and deformation during both systole and diastole. The rate of LVAs after AMI is approximately 3-15%. Risk factors for LVA after AMI include female sex, total occlusion of the LAD artery, single-vessel disease, and absence of previous angina.

More than 80% of LVAs affect the anterolateral wall; these are usually associated with total occlusion of the LAD. The posterior and inferior walls are less commonly affected. LVAs generally range from 1-8 cm. Histologically, LVAs are composed of fibrous scar that is notably thinned. This scar is clearly delineated from the adjacent ventricular muscle on microscopic examination.

A history of MI and third or fourth heart sounds are common findings from the patient’s history and physical examination.

Diagnosis of LVA

The chest radiograph may reveal an enlarged cardiac silhouette.

Electrocardiography is characterized by ST elevation that persists several weeks after AMI and that appears in the same leads as those showing the acute infarct. Echocardiography is 93% sensitive and 94% specific for detection of LVA (see the image below), but cardiac catheterization remains the standard for establishing the diagnosis.

Treatment of LVA

Patients with small or clinically insignificant aneurysms can be treated conservatively with close follow-up. Medical therapy generally consists of the use of angiotensin-converting enzyme (ACE) inhibitors, which reduce afterload, infarct extension, and LV remodeling. Anticoagulation is required when patients have severe LV dysfunction and/or thrombus in the LV or aneurysm.

Surgical resection of the LVA is indicated if severe heart failure, ventricular tachyarrhythmias refractory to medical treatment, or recurrent thromboembolism is present.

Left ventricular mural thrombus

LVMT is a well-known complication of AMI and frequently develops after anterior infarcts of the LV wall. The incidence of LVMT as a complication of AMI ranges from 20-40% and may reach 60% in patients with large anterior-wall AMIs who are not treated with anticoagulant therapy. LVMT is associated with a high risk of systemic embolization. Anticoagulant therapy may substantially decrease the rate of embolic events by 33% compared with no anticoagulation.

Factors contributing to LVMT formation include LV regional-wall akinesia or dyskinesia with blood stasis, injury to and inflammation of the endocardial tissue that provides a thrombogenic surface, and a hypercoagulable state. The most common clinical presentation of patients with LVMT complicating an MI is stroke. Most episodes occur within the first 10 days after AMI. Physical findings depend on the site of embolism.

Transthoracic echocardiography remains the imaging modality of choice and is 92% sensitive and 88% specific for detecting LVMT (see the image below). Management of LVMT includes heparin treatment followed by oral warfarin therapy for 3-6 months. In patients with LVAs, lifelong anticoagulation may be appropriate if a mural clot persists.

Pericarditis

The incidence of early pericarditis after MI is approximately 10%, and this complication usually develops within 24-96. Pericarditis is caused by inflammation of pericardial tissue overlying infarcted myocardium. The clinical presentation may include severe chest pain, usually pleuritic, and pericardial friction rub.

The key ECG change is diffuse ST-segment elevation in all or nearly all of leads. Echocardiography may reveal a small pericardial effusion. The mainstay of therapy usually includes aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Colchicine may be beneficial in patients with recurrent pericarditis.

Post-MI syndrome (Dressler syndrome)

Before the era of reperfusion, the incidence of post-MI syndrome ranged from 1-5% after AMI, but this rate has dramatically declined with the advent of thrombolysis and coronary angioplasty.

Although the exact mechanism has yet to be elucidated, post-MI syndrome is considered to be an autoimmune process. Clinical features include fever, chest pain, and other signs and symptoms of pericarditis occurring 2-3 weeks after AMI. Management involves hospitalization and observation for any evidence of cardiac tamponade. Treatment comprises rest, use of NSAIDs, and/or steroids in patients with recurrent post-MI syndrome with disabling symptoms.

Background

Cardiac rehabilitation aims to reverse limitations experienced by patients who have suffered the adverse pathophysiologic and psychological consequences of cardiac events.

Cardiovascular disorders are the leading cause of mortality and morbidity in the industrialized world, accounting for almost 50% of all deaths annually. The survivors constitute an additional reservoir of cardiovascular disease morbidity. In the United States alone, over 14 million persons suffer from some form of coronary artery disease (CAD) or its complications, including congestive heart failure (CHF), angina, and arrhythmias. Of this number, approximately 1 million survivors of acute myocardial infarction (MI), as well as the more than 300,000 patients who undergo coronary bypass surgery annually, are candidates for cardiac rehabilitation.

The image below depicts cardiac rehabilitation after bypass surgery.

Traditionally, cardiac rehabilitation has been provided to somewhat lower-risk patients who could exercise without getting into trouble. However, astonishingly rapid evolution in the management of CAD has now changed the demographics of the patients who can be candidates for rehabilitation training. Currently, about 400,000 patients who undergo coronary angioplasty each year make up a subgroup that could benefit from cardiac rehabilitation. Furthermore, approximately 4.7 million patients with CHF are also eligible for a slightly modified program of rehabilitation, as are the ever-increasing number of patients who have undergone heart transplantation.

This review addresses the objectives, indications, program components, exercise training, monitoring, benefits, risks, safety issues, outcome measures, and cost-effectiveness of cardiac rehabilitation.

Objectives

The identification of the patients at risk for a cardiac event’s recurrence (ie, risk stratification) is central to formulating an appropriate medical, rehabilitative, and surgical strategy to prevent such a recurrence. Patients who are at low or moderate risk typically undergo early rehabilitation. The major goals of a cardiac rehabilitation program are:

• Curtail the pathophysiologic and psychosocial effects of heart disease
• Limit the risk for reinfarction or sudden death
• Relieve cardiac symptoms
• Retard or reverse atherosclerosis by instituting programs for exercise training, education, counseling, and risk factor alteration
• Reintegrate heart disease patients into successful functional status in their families and in society

Cardiac rehabilitation programs have been consistently shown to improve objective measures of exercise tolerance and psychosocial well being without increasing the risk of significant complications.

Utilization

The Agency for Health Care Policy and Research (AHCPR); the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), and the National Heart, Lung and Blood Institute (NHLBI) have recognized the wide variation in awareness and understanding of the role of cardiac rehabilitation among physicians, ancillary health care providers, third-party payers, and patients with heart disease.

In the past, it was found that only 11% of patients participated in such programs following an acute coronary event. However, there is evidence that participation has increased. Approximately 38% of US patients and 32% of Canadian patients with acute MI who were involved in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial were enrolled in cardiac rehabilitation programs.

Outcome Measures

Current cardiac care has already reduced early acute coronary mortality so much so that further exercise training, as an “isolated” intervention, may not be able to cause significant reduction in the morbidity and mortality.^[2]Nonetheless, exercise training has the potential to act as a catalyst for promoting other aspects of rehabilitation, including risk factor modification through therapeutic lifestyle changes (TLC) and optimization of psychosocial support. Therefore, the outcome measures of cardiac rehabilitation now include improvement in quality of life (QOL), such as the patient’s perception of physical improvement, satisfaction with risk factor alteration, psychosocial adjustments in interpersonal roles, and potential for advancement at work commensurate with the patient’s skills (rather than simply return to work).

Similarly, among patients who are elderly, such outcome measures may include the achievement of functional independence, the prevention of premature disability, and a reduction in the need for custodial care.Despite limited data, older male and female patients in observational studies have shown improvement in their exercise tolerance comparable to that of younger patients participating in equivalent exercise programs. In addition, the safety of exercise within cardiac rehabilitation programs, as studied in over 4,500 patients, is well accepted and established.

Cardiac rehabilitation services are, therefore, an effective and safe intervention. These services are undoubtedly an essential component of the contemporary treatment of patients with multiple presentations of coronary heart disease and heart failure.

Related eMedicine topics:

• Angina Pectoris (Cardiology)
• Angina Pectoris (Emergency Medicine)
• Complications of Myocardial Infarction
• Myocardial Infarction (Cardiology)
• Myocardial Infarction (Emergency Medicine)
• Myocardial Infarction in Childhood
• Unstable Angina
• Vascular Diseases and Rehabilitation

Related Medscape topics:

• Resource Center Heart and Lung Transplant
• Resource Center Heart Failure

History

In the 1930s, patients with myocardial infarction (MI) were advised to observe 6 weeks of bedrest. Chair therapy was introduced in the 1940s, and by the early 1950s, 3-5 minutes of daily walking was advocated, beginning at 4 weeks. Clinicians gradually began to recognize that early ambulation avoided many of the complications of bed rest, including pulmonary embolism (PE), and that it did not increase the risk. However, concerns about the safety of unsupervised exercise remained strong; this led to the development of structured, physician-supervised rehabilitation programs, which included clinical supervision, as well as electrocardiographic monitoring.

In the 1950s, Hellerstein presented his methodology for the comprehensive rehabilitation of patients recovering from an acute cardiac event. He advocated a multidisciplinary approach to the rehabilitation program. His approach was adopted by cardiac rehabilitation programs throughout the world. Despite multiple advances, Hellerstein’s original ideas have not been improved upon significantly. However, due to changing patient demographics, many more patients now have the opportunity to receive the benefits offered by cardiac rehabilitation. Multifactorial intervention, including aggressive risk factor modification, has become an integral part of present day cardiac rehabilitation.

Definition

According to the US Public Health Service (USPHS), a cardiac rehabilitation program is defined as a program that involves the following:

• Medical evaluation
• Prescribed exercise
• Education
• Counseling of patients with cardiac disease

Cardiac rehabilitation has to be comprehensive and, at the same time, individualized. The main goals of a cardiac rehabilitation program are noted below.

Short-term goals are as follows:

• “Reconditioning” the patient sufficiently enough to allow him/her to resume customary activities
• Limiting the physiologic and psychological effects of heart disease
• Decreasing the risk of sudden cardiac arrest or reinfarction
• Controlling the symptoms of cardiac disease

Long-term goals are as follows:

• Identification and treatment of risk factors
• Stabilizing or reversing the atherosclerotic process
• Enhancing the psychological status of the patients

Physiology of Exercise and Cardiovascular Benefit

Coronary vasodilatation is mainly driven by the bioavailability of nitric oxide (NO), which is produced by the activities of the endothelially derived enzyme NO synthase and is metabolized by reactive oxygen species. This fine-tuned balance is disturbed in people with CAD. This form of impairment of NO production, along with excessive oxidative stress, results in the loss of endothelial cells via apoptosis. Further aggravation of endothelial dysfunction ensues, which triggers myocardial ischemia in persons with coronary artery disease (CAD). In healthy individuals, an increased release of NO from the vascular endothelium in response to exercise training results from changes in endothelial NO synthase expression, phosphorylation, and conformation.

By the same token, exercise training has assumed a role in the cardiac rehabilitation of patients with CAD, because it reduces mortality and increases myocardial perfusion. This has been largely attributed to the exercise training–mediated correction of coronary endothelial dysfunction in persons with CAD. In persons with CAD, regular physical activity leads to a restoration of the balance between NO production by NO synthase and NO inactivation by reactive oxygen species, thereby enhancing the vasodilatory capacity in various vascular beds.

Because endothelial dysfunction has been identified as a predictor of cardiovascular events, the partial reversal of endothelial dysfunction achieved by regular physical exercise appears to be the most likely mechanism behind the exercise training–induced reduction in cardiovascular morbidity and mortality in patients with CAD.

The amount of exercise in the year before cardiac surgery has been linked to the incidence of postoperative atrial fibrillation during rehabilitation according to a study by Giaccardi et al. The incidence of atrial fibrillation during rehabilitation was significantly higher in patients who performed low-intensity physical exercise the year before surgery compared with those who performed moderate-intensity exercise. The occurrence of atrial fibrillation during the patients’ hospital stay, a larger left atrial volume, and a lower left atrial emptying fraction were independent predictors of atrial fibrillation during rehabilitation.

Cardiac rehabilitation programs include walking as part of the exercise regimen. Gremeaux et al studied the minimal clinically important difference for the 6-minute walk test and the 200-meter fast-walk test for 81 patients with acute coronary syndrome. Results before and after an 8-week cardiac rehabilitation program, and at the 6th and 12th sessions, were reviewed. Patients were asked to rate the change in their walking ability between these two tests. Physiotherapists, who supervised the training, also gave their input. The minimal clinically important difference and mean change in the 6-minute walk test distance was 25 m; no difference was found in the 200-meter fast walk test. These results should help physicians interpret the changes made by their patients in a clinical context and also be used in further studies that use 6 MWD as a measure.

Patient Selection

Cardiac rehabilitation encompasses short-term and long-term goals that are to be achieved through exercise, education, and counseling. Patients generally fall into following categories:

• Lower-risk patients following an acute cardiac event
• Patients who have undergone coronary bypass surgery
• Patients with chronic, stable angina pectoris
• Patients who have undergone heart transplantation
• Patients who have had percutaneous coronary angioplasty
• Patients who have not had prior events but who are at risk because of a remarkably unfavorable risk factor profile
• Patients with stable heart failure
• Patients who have undergone noncoronary cardiac surgery
• Patients with previously stable heart disease who have become seriously deconditioned by intercurrent, comorbid illnesses

The short-term goals of cardiac rehabilitation include the restoration of the physical, psychological, and social condition, while the long-term goals involve the promotion of heart-healthy behaviors that enable the individual to return to productive and/or joyful vocational and avocational activities.

The cardiac rehabilitation programs benefit women and men equally.Elderly patients also can derive significant benefit from rehabilitation programs.

Risk Stratification

The risk stratification process is very valuable for cardiac patients; it serves as the basis for individualizing the prescription of exercise training and for assessing the need and extent of supervision required. The risk stratification process is based on the assessment of the patient’s functional capacity, on the patient’s educational and psychosocial status, on whether alternatives to traditional cardiac rehabilitation can be used, and on whether the patient is suffering from myocardial ischemia, ventricular dysfunction, or arrhythmias.

Functional capacity

The term functional capacity refers to the maximum ability of the heart and lungs to deliver oxygen and the ability of the muscles to extract it. Functional capacity is measured by determining the maximal oxygen uptake (VO₂ max) during incremental exercise.

In most patients, a rough calculation of functional capacity can be performed by using multiples of 1 MET (metabolic equivalent, 3.5 mL O₂uptake/kg/min). In complicated patients, such as those with severe left ventricular (LV) dysfunction and congestive heart failure (CHF), the functional capacity can be ascertained with greater accuracy by using cardiopulmonary exercise (CPX) testing. Most cardiac rehabilitation facilities, however, are not currently equipped for CPX.

The following factors influence functional capacity:

• Age
• Precardiac event physical capacity
• Treatments and bed rest during the event
• Fluid volume, such as relative dehydration or volume overload in patients with CHF
• LV dysfunction
• Residual myocardial ischemia
• Skeletal muscle performance, such as deconditioning or in the presence of concurrent, noncardiac illness
• Autonomic function, such as diabetic neuropathy
• Peripheral vascular status
• Pulmonary status
• Other systemic illnesses, especially orthopedic problems limiting flexibility and locomotion

Every attempt should be made to recognize the potential effects of these factors on functional capacity in order to minimize risk of the individualized reconditioning program that is being formulated.

Myocardial ischemia

Symptomatic or asymptomatic (silent) myocardial ischemia may limit the patient’s exertional capacity by causing limiting angina, dyspnea, or fatigue.

Ventricular dysfunction

Fixed LV dysfunction or damage may be present in the absence of angina. Patients with LV dysfunction develop early dyspnea and easily become fatigued.

Cardiopulmonary exercise testing preferably should be performed to determine the functional capacity in an objective manner.

Exercise intolerance in patients with LV dysfunction is due to skeletal muscle hypoperfusion resulting from inadequate cardiac output that can be better quantified by measuring VO₂ max.

Arrhythmias

Ventricular irritability and complex ventricular arrhythmias require assessment through the use of signal-averaged electrocardiogram (ECG) or electrophysiologic studies.

Appropriate medical or device treatments should be undertaken whenever feasible prior to beginning phase 2 of the cardiac rehabilitation program.

Very close surveillance is necessary in patients with significant cardiac arrhythmias during their exercise training routines. Concomitant rhythm monitoring with telemetry, Holter or event monitoring should be considered. In many cases of serious arrhythmias, therapy remains controversial and the safety of is exercise unclear; such uncertainties complicate the decision-making process.

Patients with severe ventricular arrhythmias and uncontrolled supraventricular arrhythmias should be excluded from exercise training unless proper evaluation and effective therapy has been instituted. Patients with devices, such as pacemakers and defibrillators, should be carefully monitored during exercise. Rate-responsive pacemakers are quite helpful even for those patients who are completely pacemaker-dependent. In case of implantable cardioverter defibrillators (ICDs), exercise training can be provided as long as underlying arrhythmias are controlled with pharmacotherapy. Heart rate should be kept well below the threshold at which the antitachycardia algorithm of the ICD begins.

Educational and psychosocial status

Approximately 20-25% of acute myocardial infarction (MI) patients demonstrate severe psychological stress or major depression; they also show higher morbidity and mortality.Clinically significant depressive symptoms are found in 40-65% of patients after an MI.

Exercise does provide some benefit, but severe cases may require specific therapy that has been shown to enhance the benefits derived from subsequent cardiac rehabilitation.

The promotion of self-efficacy and control over one’s activities is of paramount importance for boosting self-confidence.

Coronary-prone behavior (CPB) is known as a cardiac risk factor, but its effect on prognosis is unclear. Some data suggest that the modification of CPB can improve the coronary disease prognosis.

Initially, continuous ECG monitoring is recommended for most patients during cardiac rehabilitation exercise training; however, clinicians may decide whether to use continuous or intermittent ECG monitoring. After the initial period, the use of electrocardiography depends on the clinical judgment of the supervising physician.

Alternative approaches to cardiac rehabilitation

In carefully selected patients, alternatives to the traditional supervised (group or individual) cardiac rehabilitation program have been examined. These alternatives, which are applicable primarily to very low-risk patients, include the following options:

• Home-based cardiac rehabilitation (effective and safe)
• Exercise with transtelephonic monitoring/surveillance

Cardiac Rehabilitation in Patients with Heart Failure

Heart rate recovery (HRR) following maximal exercise has been found to be a predictor of all-cause mortality. In a 2006 study, Streuber and colleagues hypothesized that aerobic exercise training could improve HRR in patients who have suffered heart failure, because athletes are known to have accelerated HRR, while cardiac rehabilitation has been shown to positively effect such recovery in patients with coronary artery disease (CAD).The authors conducted a retrospective study of 46 patients with heart failure who had completed a phase 2 aerobic cardiac rehabilitation program with entry and exit maximal stress tests. The results indicated that in patients with heart failure who have low exercise capacity, even short-term aerobic training can aid HRR.

Indications

Cardiac rehabilitation initially was designed for low-risk cardiac patients. Now that the efficacy and safety of exercise have been documented in patients previously stratified to the high-risk category, such as those with congestive heart failure (CHF), the indications have been expanded to include such patients. Exercise training benefits persons with the following cardiac conditions:

• Recent myocardial infarction
• Coronary bypass
• Valve surgery
• Coronary angioplasty
• Cardiac transplantation
• Angina
• Compensated CHF

Exercise prescription depends on the results of exercise testing, which often includes cardiopulmonary exercise (CPX) testing.

Modifications of Exercise

Patients with limitations due to chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), stroke, and orthopedic conditions still can be trained in the exercises through special techniques and adaptive equipment (eg, use of arm-crank ergometer).

Contraindications

Cardiac rehabilitation services are contraindicated in patients with the following conditions:

• Severe residual angina
• Uncompensated heart failure
• Uncontrolled arrhythmias
• Severe ischemia, LV dysfunction, or arrhythmia during exercise testing
• Poorly controlled hypertension
• Hypertensive or any hypotensive systolic blood pressure response to exercise
• Unstable concomitant medical problems (eg, poorly controlled or “brittle” diabetes, diabetes prone to hypoglycemia, ongoing febrile illness, active transplant rejection)

In such patients, every effort should be made to correct these abnormalities through optimization of medical therapy, revascularization by angioplasty or bypass surgery, or electrophysiologic testing and subsequent antiarrhythmic drug or device therapy. Patients should then undergo retesting for exercise prescription.

Exercise Testing

Two forms of exercise tests are performed in patients following an acute cardiac event: submaximal exercise testing and symptom-limited exercise testing. Furthermore, CPX also may be performed, particularly in patients with cardiomyopathy or CHF, to determine objectively the patient’s exercise capacity.

Submaximal exercise testing

In this strategy, the patients exercise enough to achieve 70% of maximum predicted heart rate for their age (ie, 70% of 220 minus age in years).

This test is commonly performed prior to discharge and is followed by maximal exercise testing 6-8 weeks later (when patients aim to achieve 90% of maximum predicted heart rate).

Symptom-limited exercise testing

The patients exercise soon after a cardiac event.

A representative schedule might begin exercise at intervals, such as 7-21 days following uncomplicated acute myocardial infarction (MI), 3-10 days following angioplasty, or 14-28 days after bypass surgery.

Submaximal exercise testing is not necessarily safer than symptom-limited testing. In fact, the submaximal strategy may have certain disadvantages; it can lead to inappropriate limitation in the patient’s routine activities and exercise training and to a significant delay in the patient’s return to work. The use of submaximal exercise may also result in a failure to elicit important factors in prognosis, such as ischemia, cardiac dysfunction, and arrhythmia.

CPX testing

Incremental exercise is employed, using modified Naughton protocol for treadmill or modified protocols on a bicycle ergometer.

Concomitant minute-to-minute breath analysis and measurement of oxygen consumption and elimination of carbon dioxide are performed to determine VO₂ max, which is the most objective method of determining functional capacity in patients with cardiac dysfunction, valvular disease, or recent acute cardiac event.

Modified Bruce or Naughton protocols typically are used during the testing phase, because the standard Bruce protocol has been modified to avoid too abrupt an increase in METs (by 2-3 METs per stage).

The modified Naughton protocol starts at a lower MET workload and increases by 1 MET per stage, thus allowing better-tolerated gradual progression in exercise and a more accurate assessment of exertional capacity.

The usual symptomatic endpoints are fatigue and breathlessness.

Severe abnormalities found on stress testing may contraindicate exercise training until they have been corrected. Less severe abnormalities, such as the development of the above symptoms at high workloads, may not necessarily contraindicate exercise training; however, certain modifications and closer surveillance may be required, including ECG monitoring.

Some reports have questioned early exercise training following acute anterior MI, suggesting that it may lead to abnormal scar formation. Nonetheless, evidence is strong that moderate exercise training is not associated with worsening LV function in patients following acute anterior MI.

Exercise Prescription and Surveillance

Phase 2 of a cardiac rehabilitation program is initiated based on the result of the exercise testing, and the exercise prescription is individualized. Three main components of an exercise training program are listed below.

The minimum frequency for exercising to improve cardiovascular fitness is 3 times weekly.

Patients usually need to allow 30-60 minutes for each session, which includes a warm-up of at least 10 minutes

The intensity prescribed is in relation to one’s target heart rate. Aerobic conditioning is emphasized in the first few weeks of exercise. Strength training is introduced later. The Borg scale of Rate of Perceived Exertion (RPE) is used. Patients usually should exercise at an RPE of 13-15.

The Borg scale of perceived exertion is as follows:

• 6
• 7 – Very, very light
• 8
• 9 – Very light
• 10
• 11 – Light
• 12
• 13 – Somewhat hard
• 14
• 15 – Hard
• 16
• 17 – Very hard
• 18
• 19 – Very, very hard
• 20 – Exhaustion

Exercise initiation

Exercise sessions should begin with 10 minutes of warm-up, during which light calisthenics and muscular stretching are performed to avoid muscle injury and to bring about a graded increase in heart rate. This warm-up period is followed by 40 minutes of aerobic exercise (eg, walking, jogging, bicycling) and a final 10 minutes of cool-down period involving muscular stretching. The cool-down period is very important. Gradual cool-down prevents ventricular arrhythmias, which may occur in patients with coronary disease on abrupt cessation of exercise.

Progression

The patient’s peak heart rate is noted. The target is, subsequently, increased by 5-10% of the peak heart rate until the patient is able to exercise at 85% of the peak heart rate. Most patients are able to do so by 2-3 months. A follow-up treadmill test should be performed at 4-8 weeks after the patient starts the program, and the result should be used to fine-tune the exercise training.

Special considerations

In patients with myocardial ischemia, exercise training still can be performed safely. The maximal heart rate should be kept 10 beats per minute (bpm) lower than the heart rate at which ischemia occurred. Closer surveillance and ECG monitoring are recommended in patients following myocardial ischemia. Patients with arrhythmias also need ECG monitoring. Patients with CHF require a much more modified exercise program.

Also, in those with type 2 diabetes who have a hypertensive response to exercise, an increased left ventricular mass, and a higher risk of mortality, exercise training and dietary restrictions are advised. Schultz et al determined in their study that, after 1 year of these lifestyle modifications, patients significantly diminished their exercise blood pressure; however, their cardiac size remained the same.

Cardiac rehabilitation services are divided into 3 phases, as follows:

• Phase 1 – Initiated while the patient is still in the hospital
• Phase 2 – A supervised ambulatory outpatient program spanning 3-6 months
• Phase 3 – A lifetime maintenance phase in which physical fitness and additional risk-factor reduction are emphasized

Phase 1: in-hospital phase

This program begins while patients are still in the hospital.

Phase 1 includes a visit by a member of the cardiac rehabilitation team, education regarding the disease and the recovery process, personal encouragement, and inclusion of family members in classroom group meetings. See the images shown below.

Phase 1: A patient walking in the hallway with a physical therapist following bypass surgery.

Some older patients may serve as volunteers and share their experiences about learning to live with heart disease.

Team members include cardiac nurses, exercise specialists, physical therapists, occupational therapists, dietitians, and social workers.

In the coronary care unit, assisted range-of-motion exercises can be initiated within the first 24-48 hours.

Low-risk patients should be encouraged to sit in a bedside chair and to begin performing self-care activities (eg, shaving, oral hygiene, sponge bathing).

On transfer to the step-down unit, patients should, at the beginning, try to sit up, stand, and walk in their room. Subsequently, they should start to walk in the hallway at least twice daily either for certain specific distances or as tolerated without being unduly pushed or held back. Standing heart rate and blood pressure should be obtained followed by 5 minutes of warm-up or stretching. Walking, often with assistance, is resumed, with a target heart rate of less than 20 beats above the resting heart rate and an RPE of less than 14. Starting with 5-10 minutes of walking each day, exercise time gradually can be increased to up to 30 minutes daily.

Team members including the nurse educator, dietitian, exercise rehabilitation trainer, and physician should incorporate in the discharge planning an appropriate emphasis on secondary prevention through risk factor modification and therapeutic lifestyle changes (TLC), such as aspirin and beta-blocker use in all patients, angiotensin converting enzyme (ACE) inhibitor use in patients with left ventricular ejection fraction of less than 40%,smoking cessation, lipid management, weight management, and stress management. They must also ensure that phase 1 patients get referred to appropriate local, convenient, and comprehensive phase 2 programs.

Phase 1.5: postdischarge phase

This phase begins after the patient returns home from the hospital.

Better understanding of how to keep the heart healthy and strong is emphasized. Team members work with patients and family members.

Team members check the patient’s medical status and continuing recovery; they should offer reassurance as the patient regains health and strength.

This phase of recovery includes low-level exercise and physical activity, as well as instruction regarding changes for the resumption of an active and satisfying lifestyle.

Risk reduction strategies are emphasized again.

After 2-6 weeks of recovery at home, the patient is ready to start phase 2 of his/her cardiac rehabilitation.

Phase 2: supervised exercise

Patients who have completed hospitalization and 2-6 weeks of recovery at home can begin phase 2 of their cardiac rehabilitation program.

The physician and cardiac rehabilitation staff members formulate the level of exercise necessary to meet an individual patient’s needs (see images below).

Exercise treatments usually are scheduled 3 times a week at the rehabilitation facility.

Constant medical supervision is provided; this includes supervision by a nurse and an exercise specialist, as well as the use of exercise ECGs.

In addition to exercise, counseling, and education about stress management, smoking cessation, nutrition, and weight loss also are incorporated into this phase.

Phase 2 may last 3-6 months.

Phase 3: maintenance phase

Phase 3 of cardiac rehabilitation is a maintenance program designed to continue for the patient’s lifetime. The exercise sessions usually are scheduled 3 times a week.

Activities consist of the type of exercises the patient enjoys, such as walking, bicycling, or jogging. A registered nurse supervises these classes.

ECG monitoring usually is not necessary.

The main goal of phase 3 is to promote habits that lead to a healthy and satisfying lifestyle.

Phase 3 programs do not usually require medical or nursing supervision. In fact, most patients participate in “phase 3″ equivalent exercises at the exercise facilities in the community (eg, YMCA, YWCA).

Sexual activity

Common sexual problems encountered by cardiac patients include impotence, premature or delayed ejaculation, and reduced libido (in men and women). These difficulties may be due to medications (eg, beta blockers, diuretics), depression, or fears by the patient and his or her partner of precipitating a cardiac event.

Maximum heart rate during sexual intercourse averages 120 bpm, which is similar to heart rates associated with other routine activities in and around the house.

The hemodynamic response is greater with an unfamiliar sex partner, in unfamiliar surroundings, after eating, or after consuming alcohol.

Adapting less strenuous positions — for example, using a side-to-side arrangement rather than the missionary position — can reduce cardiac stress.

Patients may start sexual activity 2-3 weeks following an uncomplicated myocardial infarction. They must be instructed to report any untoward symptoms to the physician or to a member of the rehabilitation team.

Cardiac rehabilitation provides many benefits for patients. The most important of these are discussed in this section.

Improved exercise tolerance

Cardiac rehabilitation exercise training for patients with coronary heart disease or congestive heart failure (CHF) leads to objectively verifiable improvement in exercise capacity in men and women, regardless of age. Adverse outcomes or complications of exercise are exceedingly rare. The nonfatal infarction rate is 1 patient per 294,000 patient-hours; the cardiac mortality rate is 1 patient per 784,000 patient-hours. The benefits are even greater in patients with diminished exercise tolerance. This beneficial effect does not persist long-term after completion of cardiac rehabilitation without a long-term maintenance program. Therefore, exercise training must be maintained long-term to sustain the improvement in exercise capacity.

Control of symptoms

In patients with coronary heart disease, angina significantly improves during the cardiac rehabilitation exercise program. Objective evidence of improvement in ischemia has been seen by performing interval stress ECG or radionuclide testing. Similarly, patients with LV failure or dysfunction show improvement in the symptoms of heart failure. Use of gas analysis (CPX) has shown that patients’ exertional tolerance improves significantly with exercise training.

Improvement in the blood levels of lipids

Improvements in lipid and lipoprotein levels are observed in patients undergoing cardiac rehabilitation exercise training and education. Exercise must be combined with dietary and medical interventions for required lipid control.

Effect on body weight

Exercise training as a sole intervention has an inconsistent effect on controlling excess weight. Optimal management of obesity requires multifactorial rehabilitation, including nutritional education and counseling, behavioral modification, and exercise training.

Effect on blood pressure

Rehabilitation exercise training as a sole intervention has minimal effect; however, multifactorial intervention has been shown to have beneficial effects. Inconsistencies with this theory remain unresolved.

Reduction in smoking

Cardiac rehabilitation services with well-designed educational, counseling, and behavioral modification programs result in cessation of smoking in a significant number of patients. Cessation of smoking can be expected in 16-26% of patients. This reduction is combined with the spontaneously high smoking cessation rates following acute coronary events.

Improved psychosocial well-being

Cardiac rehabilitation exercise and educational services enhance measures of psychological and social functioning.

Reduction of stress

In multifactorial cardiac rehabilitation programs, improvement in emotional-stress measurements occurs, as does a reduction of type A behavior patterns. This reduction of stress is consistent with improvement in psychosocial outcomes that occurs in nonrehabilitation settings.

Enhanced social adjustment and functioning

Cardiac rehabilitation exercise training improves social adjustment and functioning.

Return to work

Cardiac rehabilitation exercise training exerts less influence on rates of return to work than on other aspects of life. Many nonexercise variables also affect this outcome (eg, prior employment status, employer attitude, economic incentives).

Reduced mortality

Scientific data suggest a survival benefit for patients who participate in cardiac rehabilitation exercise training, but it is not attributable to exercise alone. This survival benefit is due to multifactorial interventions. A meta-analysis of post–myocardial infarction (MI), randomized, controlled trials of exercise showed a 25% reduction in mortality at 3-year follow-up. The magnitude of this benefit is as large as that seen with the post-MI use of beta blockers or with the use of ACE inhibitors in LV dysfunction along with MI. Trials that involve exercise alone still show a 15% mortality reduction.

The scientific evidence pertaining to the relationship between cardiac rehabilitation exercise training and mortality also includes scientific reports that have appeared on the US National Institutes of Health Web site. Among the data in these reports was the finding, through randomized trial, that 3-year coronary mortality and sudden death rates were significantly lower (P < .02) in patients who, after suffering myocardial infarction, underwent multifactorial cardiac rehabilitation, starting 2 weeks after hospital discharge. This beneficial outcome persisted at the 10-year follow-up.

The larger center from a multicenter European trial of exercise-only rehabilitation in males (post-MI) reported significant mortality reduction in the rehabilitation group (P < .01).

Pathophysiologic measures

When combined with intensive dietary intervention, with or without lipid-lowering drugs, exercise training may result in the limitation of progression or in the regression of angiographically documented coronary atherosclerosis.

Exercise training in patients with heart failure and compromised LV ejection fraction produces favorable hemodynamic changes in the skeletal musculature. Therefore, cardiac rehabilitation exercise training is recommended for the improvement of skeletal muscle functioning. However, such training does not seem to improve cardiac hemodynamic function or collateral circulation to any significant degree.

Patients following cardiac transplantation

Following orthotropic cardiac transplantation, rehabilitation exercise training is recommended to improve patients’ exercise tolerance measurements.

Elderly patients and women

Coronary patients who are elderly have exercise trainability comparable to that of younger patients participating in similar rehabilitation programs. Elderly patients (male and female) show comparable improvements. Unfortunately, referrals to cardiac rehabilitation are made less frequently for elderly patients, particularly for elderly women; participation in cardiac rehabilitation also is less frequent among the elderly. No complications or adverse outcomes for elderly patients have been described in any study. Elderly male and female patients should be encouraged to participate in cardiac rehabilitation.

Patients on dialysis and following coronary artery bypass grafting surgery

Patients who are on renal dialysis are at high risk for cardiac death and have a large burden of cardiovascular disease and cardiovascular disease risk factors. Cardiac rehabilitation can promote improved survival of nondialysis patients after coronary artery bypass grafting (CABG) surgery and is covered by Medicare, but no studies have investigated whether dialysis patients’ survival after CABG may be improved as a function of cardiac rehabilitation.

In a 2006 study by Kutner and colleagues, it was found that, in comparison with dialysis patients who did not undergo cardiac rehabilitation, there was a 35% risk reduction for all-cause mortality, as well as a 36% risk reduction for cardiac death, in dialysis patients who had cardiac rehabilitation following CABG; the findings were independent of sociodemographic and clinical risk factors, such as recent hospitalization. In the study, 10% of patients received cardiac rehabilitation after CABG, less than half the estimated share of patients in the general pouplation who such rehabilitation. Women and black patients aged 65 or older, along with lower-income patients of all ages, were significantly less likely to receive cardiac rehabilitation services. This observational study suggests that following CABG, cardiac rehabilitation increases a dialysis patient’s likelihood of survival.

Overview Exercise training involves certain risks, especially in patients with undiagnosed or undertreated myocardial ischemia, ventricular arrhythmias, or LV dysfunction. The intensity of exercise must be kept below the level of exercise at which the abnormalities were elicited during the risk stratification and testing phase.

Selection of Patients

The proper selection of patients is of paramount importance before phase 2 or phase 3 exercise programs are begun.Patients with certain characteristics are at a higher risk and therefore require all attempts at correction of the high-risk condition prior to exercise training. Patients also must be monitored with continuous electrocardiography and be supervised closely. High-risk factors include the following:

• Severe LV dysfunction, LV ejection fraction (EF) less than 30%, congestive heart failure (CHF), and history of cardiogenic shock
• Severe exercise-induced ischemia (such as angina at a workload of less than 5 METs), ST-segment depression of greater than 0.2 mV on an ECG, multiple perfusion defects on exercise nuclear stress testing, or multiple dyskinetic LV segments on stress echocardiography
• Complex ventricular arrhythmias, such as nonsustained ventricular tachycardia (a less than 30-second run of ventricular tachycardia [VT]) at rest or with exercise or a history of previous sudden cardiac arrest (SCA)
• Hypotensive response to exercise (ie, drop in systolic pressure of more than 20 mm Hg at incremental exertion)
• Low functional capacity (ie, peak workload of less than 5 METs, functional capacity determined by CPX testing with reduced peak oxygen [VO₂ max] consumption)
• Patient’s inability to self-monitor his/her heart rate

For some patients, the risks of exercise may outweigh the benefits. In these instances, patients should be counseled against exercise training, and their medical management must first be optimized with thorough supervision.

Surveillance

High-risk patients, constituting approximately 15-25% of all patients referred for cardiac rehabilitation, require the maximum level of supervision and surveillance, including continual ECG monitoring. The group of high-risk patients described above constitutes the bulk of such patients.

Intermediate-risk patients need somewhat less intense surveillance. The level of supervision needed includes unmonitored exercise training in groups in the presence of health professionals who are certified in advanced cardiac life support (ACLS).

Very low-risk patients can exercise safely and independently once they have learned how to monitor their pulse rates and are able to recognize warning signs. Such patients have greater than 8 METs of exercise capacity without symptoms or signs of angina, heart failure, or arrhythmias.

Alternative approaches to the traditional supervised cardiac rehabilitation programs have been evaluated and found to be reasonably safe. These off-site, self-monitored or telemetry-monitored programs are applicable primarily to very low-risk patients and include (1) home-based cardiac rehabilitation (effective and safe) and (2) exercise with trans-telephonic surveillance.

Safety

Supervised exercise training programs have extremely good safety records, despite the inherent potential for cardiovascular complications during exercise. None of the more than 3 dozen randomized controlled trials of cardiac rehabilitation exercise testing and training in patients with coronary heart disease, involving over 4,500 patients, showed any increase in morbidity or mortality in rehabilitation compared with control patient groups.

A 1980-1984 survey of 142 US cardiac rehabilitation programs reported a low rate of nonfatal myocardial infarction (MI; 1 case per 294,000 patient-hours) and cardiac mortality (1 case per 784,000 patient-hours). A total of 21 episodes of cardiac arrest occurred, with resuscitation successfully performed in 17 of these episodes. Therefore, the safety of exercise within cardiac rehabilitation programs is well accepted and established.

Analysis of Cost-Effectiveness

Cardiac rehabilitation, a clinically effective intervention for coronary heart disease, has been subjected to preliminary cost analyses. In a US study, a randomized, 8-week trial of rehabilitation beginning 6 weeks following MI showed a cost-effectiveness of $9,200 per quality adjusted life year. Subsequently, a similar analysis showed a cost-effectiveness of only $4,950 per year of life saved. In contrast, cholesterol lowering for secondary prevention has a cost-effectiveness of $9,630 per year of life saved, thrombolytic therapy for acute MI has a C/E of $32,700 per year of life saved, and bypass surgery has a cost-effectiveness of $18,700 for a year of life saved.

In Sweden, a comprehensive cost analysis of cardiac rehabilitation, performed on patients following MI or bypass surgery (with a 5-year follow-up), showed that rehospitalizations decreased from 16 to 11 days; the study also showed a higher rate of return to work (53% versus 38%). Overall, cardiac rehabilitation programs resulted in cost savings to the Swedish system of $12,000 per patient.

Research therefore indicates that cardiac rehabilitation is not only clinically effective, but is cost-effective as well. Cardiac rehabilitation compares favorably with other medical interventions performed commonly in patients with coronary heart disease.

Cardiac rehabilitation is an important component of the current multidisciplinary approach to the management of the patients with various presentations of coronary heart disease. Cardiac rehabilitation involves exercise training, education, counseling regarding risk reduction and lifestyle modification, and, frequently, behavior interventions.

The goals of cardiac rehabilitation services are to improve the physiologic and psychosocial condition of patients. Physiologic benefits include the improvement of exercise capacity and the reduction of risk factors (eg, cessation of smoking and lowering of lipid levels, body weight, blood pressure, blood glucose), with the exercise component provided through rehabilitation possibly reducing the progression of atherosclerosis. Psychological improvements include the reduction of depression, anxiety, and stress. All of these improvements enable the patient to acquire and maintain functional independence and to return to satisfactory and appropriate activity that benefits the patient and society.

For excellent patient education resources, visit eMedicine’s Public Health Center. Also, see eMedicine’s patient education articles Chest Pain,Coronary Heart Disease, Heart Attack, Walking for Fitness, and Resistance Training.

Angina pectoris is the result of myocardial ischemia caused by an imbalance between myocardial blood supply and oxygen demand. Angina is a common presenting symptom (typically, chest pain) among patients with coronary artery disease. A comprehensive approach to diagnosis and to medical management of angina pectoris is an integral part of the daily responsibilities of health care professionals.

Myocardial ischemia develops when coronary blood flow becomes inadequate to meet myocardial oxygen demand. This causes myocardial cells to switch from aerobic to anaerobic metabolism, with a progressive impairment of metabolic, mechanical, and electrical functions. Angina pectoris is the most common clinical manifestation of myocardial ischemia. It is caused by chemical and mechanical stimulation of sensory afferent nerve endings in the coronary vessels and myocardium. These nerve fibers extend from the first to fourth thoracic spinal nerves, ascending via the spinal cord to the thalamus, and from there to the cerebral cortex.

Studies have shown that adenosine may be the main chemical mediator of anginal pain. During ischemia, ATP is degraded to adenosine, which, after diffusion to the extracellular space, causes arteriolar dilation and anginal pain. Adenosine induces angina mainly by stimulating the A1 receptors in cardiac afferent nerve endings.

Heart rate, myocardial inotropic state, and myocardial wall tension are the major determinants of myocardial metabolic activity and myocardial oxygen demand. Increases in the heart rate and myocardial contractile state result in increased myocardial oxygen demand. Increases in both afterload (ie, aortic pressure) and preload (ie, ventricular end-diastolic volume) result in a proportional elevation of myocardial wall tension and, therefore, increased myocardial oxygen demand. Oxygen supply to any organ system is determined by blood flow and oxygen extraction. Because the resting coronary venous oxygen saturation is already at a relatively low level (approximately 30%), the myocardium has a limited ability to increase its oxygen extraction during episodes of increased demand. Thus, an increase in myocardial oxygen demand (eg, during exercise) must be met by a proportional increase in coronary blood flow.

The ability of the coronary arteries to increase blood flow in response to increased cardiac metabolic demand is referred to as coronary flow reserve (CFR). In healthy people, the maximal coronary blood flow after full dilation of the coronary arteries is roughly 4-6 times the resting coronary blood flow. CFR depends on at least 3 factors: large and small coronary artery resistance, extravascular (ie, myocardial and interstitial) resistance, and blood composition.

Myocardial ischemia can result from (1) a reduction of coronary blood flow caused by fixed and/or dynamic epicardial coronary artery (ie, conductive vessel) stenosis, (2) abnormal constriction or deficient relaxation of coronary microcirculation (ie, resistance vessels), or (3) reduced oxygen-carrying capacity of the blood.

Atherosclerosis is the most common cause of epicardial coronary artery stenosis and, hence, angina pectoris. Patients with a fixed coronary atherosclerotic lesion of at least 50% show myocardial ischemia during increased myocardial metabolic demand as the result of a significant reduction in CFR. These patients are not able to increase their coronary blood flow during stress to match the increased myocardial metabolic demand, thus they experience angina. Fixed atherosclerotic lesions of at least 90% almost completely abolish the flow reserve; patients with these lesions may experience angina at rest.

Coronary spasm can also reduce CFR significantly by causing dynamic stenosis of coronary arteries. Prinzmetal angina is defined as resting angina associated with ST-segment elevation caused by focal coronary artery spasm. Although most patients with Prinzmetal angina have underlying fixed coronary lesions, some have angiographically normal coronary arteries. Several mechanisms have been proposed for Prinzmetal angina: focal deficiency of nitric oxide production, hyperinsulinemia, low intracellular magnesium levels, smoking cigarettes, and using cocaine.

Approximately 30% of patients with chest pain referred for cardiac catheterization have normal or minimal atherosclerosis of coronary arteries. A subset of these patients demonstrates reduced CFR that is believed to be caused by functional and structural alterations of small coronary arteries and arterioles (ie, resistance vessels). Under normal conditions, resistance vessels are responsible for as much as 95% of coronary artery resistance, with the remaining 5% being from epicardial coronary arteries (ie, conductive vessels). The former is not visualized during regular coronary catheterization. Angina due to dysfunction of small coronary arteries and arterioles is called microvascular angina. Several diseases, such as diabetes mellitus, hypertension, and systemic collagen vascular diseases (eg, systemic lupus erythematosus, polyarteritis nodosa), are believed to cause microvascular abnormalities with subsequent reduction in CFR.

The syndrome that includes angina pectoris, ischemialike ST-segment changes and/or myocardial perfusion defects during stress testing, and angiographically normal coronary arteries is referred to as syndrome X. Most patients with this syndrome are postmenopausal women, and they usually have an excellent prognosis. Syndrome X is believed to be caused by microvascular angina. Multiple mechanisms may be responsible for this syndrome, including (1) impaired endothelial dysfunction, (2) increased release of local vasoconstrictors, (3) fibrosis and medial hypertrophy of the microcirculation, (4) abnormal cardiac adrenergic nerve function, and/or (5) estrogen deficiency.

A number of extravascular forces produced by contraction of adjacent myocardium and intraventricular pressures can influence coronary microcirculation resistance and thus reduce CFR. Extravascular compressive forces are highest in the subendocardium and decrease toward the subepicardium. Left ventricular (LV) hypertrophy together with a higher myocardial oxygen demand (eg, during tachycardia) cause greater susceptibility to ischemia in subendocardial layers.

Myocardial ischemia can also be the result of factors affecting blood composition, such as reduced oxygen-carrying capacity of blood, as is observed with severe anemia (hemoglobin, < 8 g/dL), or elevated levels of carboxyhemoglobin. The latter may be the result of inhalation of carbon monoxide in a closed area or of long-term smoking.

Ambulatory ECG monitoring has shown that silent ischemia is a common phenomenon among patients with established coronary artery disease. In one study, as many as 75% of episodes of ischemia (defined as transient ST depression of ≥ 1 mm persisting for at least 1 min) occurring in patients with stable angina were clinically silent. Silent ischemia occurs most frequently in early morning hours and may result in transient myocardial contractile dysfunction (ie, stunning). The exact mechanism(s) for silent ischemia is not known. However, autonomic dysfunction (especially in patients with diabetes), a higher pain threshold in some individuals, and the production of excessive quantities of endorphins are among the more popular hypotheses.

Frequency

United States

Approximately 9.8 million Americans are estimated to experience angina annually, with 500,000 new cases of angina occurring every year. In 2009, an estimated 785 000 Americans will have a new coronary attack, and about 470 000 will have a recurrent attack. Only 18% of coronary attacks are preceded by angina. An additional 195,000 silent first myocardial infarctions are estimated to occur each year.

Mortality/Morbidity

About every 25 seconds, an American will have a coronary event, and about every minute someone will die from one. Coronary heart disease (CHD) caused about 1 of every 5 deaths in the United States in 2005. Final 2005 coronary heart disease mortality in 2005 was 445,687 (232,115 males and 213,572 females). On the basis of 2005 mortality rate data, nearly 2,400 Americans die of cardiovascular disease (CVD) each day—an average of 1 death every 37 seconds. The 2006 overall preliminary death rate from cardiovascular disease was 262.9.

Race

The annual rates per 1000 population of new episodes of angina are as follows:

• Age 45-54 years

  • 8.5 for nonblack men
  • 10.6 for nonblack women
  • 11.8 for black men
  • 20.8 for black women
• Age 55-64 years

  • 11.9 for nonblack men
  • 11.2 for nonblack women
  • 10.6 for black men
  • 19.3 for black women
• Age 65-74 years

  • 13.7 for nonblack men
  • 13.1 for nonblack women
  • 8.8 for black men
  • 10.0 for black women

Sex

Angina pectoris is more often the presenting symptom of coronary artery disease in women than in men, with a female-to-male ratio of 1.7:1. It has an estimated prevalence of 4.6 million in women and 3.3 million in men. In one analysis, this female excess was found across countries and was particularly high in the American studies and higher among nonwhite ethnic groups than among whites. The frequency of atypical presentations is also more common among women compared with men. Women have a slightly higher rate of mortality from coronary artery disease compared with men, in part because of an older age at presentation and a frequent lack of classic anginal symptoms. The estimated age-adjusted prevalence of angina is greater in women than in men.

Age

The prevalence of angina pectoris increases with age. Age is a strong independent risk factor for mortality. More than 150,000 Americans killed by CVD in 2005 were younger than 65 years. However, in 2005, 32% of deaths from cardiovascular disease occurred before the age of 75 years, which is well before the average life expectancy of 77.9 years.

Acute coronary syndrome (ACS) refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non–ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. In terms of pathology, ACS is almost always associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery. (See Etiology.)

In some instances, however, stable coronary artery disease (CAD) may result in ACS in the absence of plaque rupture and thrombosis, when physiologic stress (eg, trauma, blood loss, anemia, infection, tachyarrhythmia) increases demands on the heart. The diagnosis of acute myocardial infarction in this setting requires a finding of the typical rise and fall of biochemical markers of myocardial necrosis in addition to at least 1 of the following (See Workup.):

• Ischemic symptoms
• Development of pathologic Q waves
• Ischemic ST-segment changes on electrocardiogram (ECG) or in the setting of a coronary intervention

The terms transmural and nontransmural (subendocardial) myocardial infarction are no longer used because ECG findings in patients with this condition are not closely correlated with pathologic changes in the myocardium. Therefore, a transmural infarct may occur in the absence of Q waves on ECGs, and many Q-wave myocardial infarctions may be subendocardial, as noted on pathologic examination. Because elevation of the ST segment during ACS is correlated with coronary occlusion and because it affects the choice of therapy (urgent reperfusion therapy), ACS-related myocardial infarction should be designated STEMI or NSTEMI. (See Workup.)

Attention to the underlying mechanisms of ischemia is important when managing ACS. A simple predictor of demand is rate-pressure product, which can be lowered by beta blockers (eg, metoprolol or atenolol) and pain/stress relievers (eg, morphine), while supply may be improved by oxygen, adequate hematocrit, blood thinners (eg, heparin, IIb/IIIa agents such as abciximab, eptifibatide, tirofiban, or thrombolytics), and/or vasodilators (eg, nitrates, amlodipine). (See Medications.)

In 2010, the American Heart Association (AHA) published new guideline recommendations for the diagnosis and treatment of ACS.

Acute coronary syndrome (ACS) is caused primarily by atherosclerosis. Most cases of ACS occur from disruption of a previously nonsevere lesion (an atherosclerotic lesion that was previously hemodynamically insignificant yet vulnerable to rupture). The vulnerable plaque is typified by a large lipid pool, numerous inflammatory cells, and a thin, fibrous cap.

Elevated demand can produce ACS in the presence of a high-grade fixed coronary obstruction, due to increased myocardial oxygen and nutrition requirements, such as those resulting from exertion, emotional stress, or physiologic stress (eg, from dehydration, blood loss, hypotension, infection, thyrotoxicosis, or surgery).

ACS without elevation in demand requires a new impairment in supply, typically due to thrombosis and/or plaque hemorrhage.

The major trigger for coronary thrombosis is considered to be plaque rupture caused by the dissolution of the fibrous cap, the dissolution itself being the result of the release of metalloproteinases (collagenases) from activated inflammatory cells. This event is followed by platelet activation and aggregation, activation of the coagulation pathway, and vasoconstriction. This process culminates in coronary intraluminal thrombosis and variable degrees of vascular occlusion. Distal embolization may occur. The severity and duration of coronary arterial obstruction, the volume of myocardium affected, the level of demand on the heart, and the ability of the rest of the heart to compensate are major determinants of a patient’s clinical presentation and outcome. (Anemia and hypoxemia can precipitate myocardial ischemia in the absence of severe reduction in coronary artery blood flow.)

A syndrome consisting of chest pain, ischemic ST-segment and T-wave changes, elevated levels of biomarkers of myocyte injury, and transient left ventricular apical ballooning (takotsubo syndrome) has been shown to occur in the absence of clinical CAD, after emotional or physical stress. The etiology of this syndrome is not well understood but is thought to relate to a surge of catechol stress hormones and/or high sensitivity to those hormones.

Six-month mortality rates in the Global Registry of Acute Coronary Events (GRACE) were 13% for patients with NSTEMI ACS and 8% for those with unstable angina.

An elevated level of troponin (a type of regulatory protein found in skeletal and cardiac muscle) permits risk stratification of patients with ACS and identifies patients at high risk for adverse cardiac events (ie, myocardial infarction, death) up to 6 months after the index event. (See Workup.)

The PROVE IT-TIMI trial found that after ACS, a J-shaped or U-shaped curve association is observed between BP and the risk of future cardiovascular events.

LeLeiko et al determined that serum choline and free F(2)-isoprostane are also predictors of cardiac events in ACS. The authors evaluated the prognostic value of vascular inflammation and oxidative stress biomarkers in patients with ACS to determine their role in predicting 30-day clinical outcomes. Serum F(2)-isoprostane had an optimal cutoff level of 124.5 pg/mL, and serum choline had a cutoff level of 30.5 µmol/L. Choline and F(2)-isoprostane had a positive predictive value of 44% and 57% and a negative predictive value of 89% and 90%, respectively.

Testosterone deficiency is common in patients with coronary disease and has a significant negative impact on mortality. Further study is needed to assess the effect of treatment on survival.

A study by Sanchis et al suggests renal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEMI ACS. In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEMI ACS. In-hospital management of patients with comorbid conditions merits further investigation.

In a study that assessed the impact of prehospital time on STEMI outcome, Chughatai et al suggest that “total time to treatment” should be used as a core measure instead of “door-to-balloon time.” This is because on-scene time was the biggest fraction of “pre-hospital time.” The study compared groups with total time to treatment of more than 120 minutes compared with 120 minutes or less and found mortalities were 4 compared with 0 and transfers to a tertiary care facility were 3 compared with 1, respectively.

Patient education of risk factors is important, but more attention is needed regarding delays in door-to-balloon time, and one major barrier to improving this delay is patient education regarding his or her symptoms. Lack of recognition of symptoms may cause tremendous delays in seeking medical attention.

Educate patients about the dangers of cigarette smoking, a major risk factor for coronary artery disease (CAD). The risk of recurrent coronary events decreases 50% at 1 year after smoking cessation. Provide all patients who smoke with guidance, education, and support to avoid smoking. Smoking-cessation classes should be offered to help patients avoid smoking after a myocardial infarction. Bupropion increases the likelihood of successful smoking cessation.

Diet plays an important role in the development of CAD. Therefore, prior to hospital discharge, a patient who has had a myocardial infarction should be evaluated by a dietitian. Patients should be informed about the benefits of a low-cholesterol, low-salt diet. In addition, educate patients about AHA dietary guidelines regarding a low-fat, low-cholesterol diet.

A cardiac rehabilitation program after discharge may reinforce education and enhance compliance.

The following mnemonic may useful in educating patients with CAD regarding treatments and lifestyle changes necessitated by their condition:

• A = Aspirin and antianginals
• B = Beta blockers and blood pressure (BP)
• C = Cholesterol and cigarettes
• D = Diet and diabetes
• E = Exercise and education

For patients being discharged home, emphasize the following:

• Timely follow-up with primary care provider
• Compliance with discharge medications, specifically aspirin and other medications used to control symptoms
• Need to return to the ED for any change in frequency or severity of symptoms