Immediately after parturition the fetus, once it has been exposed to the environment external to the maternal uterus, becomes a neonate. In Western societies, technological advances have enabled successful management of preterm infants, many at ages that were considered non-viable a decade or two previously. Now, the study of neonatology very much overlaps the later stages of fetal development. Preterm infants, although obviously past organogenetic processes, are still engaged in maturational processes with local interactions and pattern formation driving development at local and body-system levels. The sudden release of such fetuses into a gaseous environment, of variable temperature, with full gravity and a range of microorganisms promotes the rapid maturation of some systems and the compensatory growth, in terms of effect of gravity or enteral feeding or exposure to microorganisms, of others. To understand this multitude of mechanisms operating within a newly delivered fetus, as much information as possible concerning normal embryological and fetal development is required.
Details of the relative positions of the viscera and the skeleton in a full term neonate are shown in Figs 3 and 4. The newborn infant is not a miniature adult, and extremely preterm infants are not the same as full-term infants. Thus, just as there are immense differences in the relations of some structures between the full-term neonate, child and adult, so there are also major differences between the 20 week gestation fetus and the 40 week fetus, just before birth. The study of fetal anatomy at 20, 25, 30 and 35 weeks is vital for the investigative and life-saving procedures carried out on preterm infants today.
Neonatal measurements and period of time in utero The 10th to 90th centile ranges for length of full-term neonates are c.48 cm to c.53 cm Length of the newborn is measured from crown to heel. In utero, length has been estimated either from crown-rump length, i.e. the greatest distance between the vertex of the skull and the ischial tuberosities, with the fetus in the natural curved position, or from the greatest length exclusive of the lower limbs. Greatest length is independent of fixed points and thus much simpler to measure. It is generally taken to be the sitting height in postnatal life. This measurement is recommended by O'Rahilly and Muller (2000) as the standard in ultrasound examination. The 10th to 90th centile ranges for weight of the full-term infant at parturition ranges are c.2700 g to c.3800 g , the average being 3400 g; 75-80% of this weight is body water and a further 15-28% is composed of adipose tissue. After birth, there is a general decrease in the total body water, but a relative increase in intracellular fluid. Normally, the newborn loses c.10% of the birth weight by 3-4 days postnatally, because of loss of excess extracellular fluid and meconium. By 1 year, total body water makes up 60% of the body weight. Two populations of neonates are at particular risk, namely those who are preterm, and those who are small-for-dates, some of whom have suffered 'intrauterine growth restriction'. Low birth weight has been defined as less than 2500 g, very low birth weight as less than 1500 g, and extremely low birth weight as less than 1000 g. Infants may weigh less than 2500 g but not be premature by gestational age. Measurement of the range of weights fetuses may attain before birth has led to the production of weight charts, which allow babies to be described according to how appropriate their birth weight is for their gestational age, e.g. small for gestational age, appropriate for gestational age and large for gestational age. Small for gestational age infants, also termed 'small-for-dates', are often the outcome of intrauterine growth retardation. The causes of growth restriction are many and various and beyond the scope of this text. For both premature and growth-retarded infants, an assessment of gestational age, which correlates closely with the stage of maturity, is desirable. Gestational age at birth is predicted by its proximity to the estimated date of delivery and the results of ultrasonographic examinations during pregnancy. It is currently assessed in the neonate by evaluation of a number of external physical and neuromuscular signs. Scoring of these signs results in a cumulative score of maturity that is usually within ± 2 weeks of the true age of the infant. The scoring scheme has been devised and improved over many years. For an account of methods of assessing gestational age in neonates, consult Gandy (1992).
Syncope Ann Maguire - Kochar's Clinical Medicine for Students, 5th Edition. Lippincott Williams & Wilkins. 2008
Syncope is a sudden and brief loss of consciousness associated with a loss of postural tone. Recovery is usually spontaneous. Syncope is not a disease, but rather a symptom with causes ranging from benign to life-threatening. It is a common reason for emergency department evaluation and hospitalization; however, the etiology is often difficult to identify. The cause of syncope may be “unknown” in more than one third of cases. Because of the potential seriousness of this diagnosis and the high frequency of unknown etiology, it is helpful to approach the evaluation of patients with syncope in an organized fashion. The goal in evaluation of patients with syncope is to distinguish between benign and life-threatening causes of syncope so that hospitalization and invasive testing can be appropriately used in the care of those most at risk for adverse outcomes.
Differential Diagnosis
The causes of syncope can be broadly organized according to six major categories: neurally mediated syncope, cardiac syncope, orthostatic hypotension, neurologic disease, medications, and psychiatric disorders (Table 1).
Neurally Mediated Syncope
Neurally mediated syncope, also known as neurocardiogenic or reflex-mediated syncope, is the most common cause of syncope, particularly in younger patients without a history of organic heart disease. It includes three subtypes: vasovagal attacks or vasodepressor syncope, situational syncope, and carotid-sinus syncope or carotid sinus hypersensitivity. Individuals with neurally mediated syncope appear to be particularly susceptible to activities or exposures that stimulate the Bezold-Jarisch reflex. This reflex is activated via intracardiac vagal mechanoreceptors. Valsalva maneuver or prolonged standing may cause decreased cardiac venous return or venous pooling which leads to a drop in blood pressure and subsequent release of catecholamines. The catecholamine release triggers the Bezold-Jarisch reflex and results in a further increase in vagal tone causing simultaneous bradycardia and peripheral vasodilation. Hypotension and loss of consciousness may follow. This pathway explains vasovagal attacks and situational syncope quite well. In carotid sinus syncope, direct stimulation of the carotid artery can cause a cardioinhibitory (bradycardic) or vasodepressor response regardless of posture or adequacy of cardiac venous return.
Individuals with neurally mediated syncope often report a symptomatic prodrome that includes nausea, feelings of warmth, diaphoresis, and blurring or darkening of vision followed immediately by a brief loss of consciousness. Vasovagal attacks may occur after prolonged standing or intense emotional experiences such as unexpected pain, fear, or unpleasant sights, sounds, and smells. Patients may report syncope associated with throat or facial pain. Common causes of situational syncope include cough, defecation, micturition, or swallowing. Those with carotid-sinus syncope may experience syncope with head rotation or with pressure applied to the carotid sinus caused by shaving, tight collars, or tumors (Table 2).
Table 1 Causes of syncope
Cause
Mean prevalence (range)a
Neurally mediated syncope
Vasovagal attack
18 (8-37)
Situational syncope
5 (1-8)
Carotid-sinus syncope
1 (0-4)
Psychiatric disorders
2 (1-7)
Orthostatic hypotension
8 (4-10)
Medications
3 (1-7)
Neurologic disease
10 (3-32)
Cardiac syncope
Organic heart diseaseb
4 (1-8)
Arrhythmias
14 (4-38)
Unknown
34 (13-41)
aPercent of patients with syncope. bStructural heart disease that causes syncope such as aortic stenosis, pulmonary hypertension, pulmonary embolism, or myocardial infarction. Adapted from Figure 36.1 in Kochar 4th edition, p. 211 and Kapoor WN. Syncope. N Engl J Med 2000;343:1856-1862, with permission.
Cardiac Syncope
Cardiac causes of syncope can be categorized according to the presence or absence of organic heart disease and arrhythmia. Organic heart disease includes structural heart disease due to aortic stenosis, mitral stenosis, hypertrophic cardiomyopathy, and ischemic heart disease as well as vascular causes such as pulmonary embolus and pulmonary hypertension. Syncope in the setting of exertion is characteristic of patients who have severe aortic stenosis, hypertrophic cardiomyopathy, or ischemic heart disease. Syncope due to a sudden drop in cardiac output may also be a presenting symptom of life-threatening diseases such as aortic dissection and pericardial tamponade. Pulmonary embolism and pulmonary hypertension are uncommon vascular causes of syncope. Syncope in the setting of pulmonary embolism is caused by a massive thrombus formation leading to right ventricular failure, diminished right ventricular output, and consequent decreased left ventricular cardiac output.
Arrhythmias, either bradycardic or tachycardic, are more common cardiac causes of syncope. Bradyarrhythmias include sinus node disease, second- and third-degree heart block, and bradycardia associated with pacemaker malfunction. Medications causing bradycardia and syncope will be discussed separately. Tachyarrhythmias include ventricular tachycardia, torsades de pointes, ventricular fibrillation, and supraventricular tachycardia. A known history of ischemic heart disease or a dilated or hypertrophic cardiomyopathy makes arrhythmia more likely to be the cause of syncope. A family history of sudden cardiac death raises the possibility of ventricular fibrillation due to long QT syndrome or Brugada syndrome (pseudo right bundle branch block and persistent ST segment elevation in V1 to V3). Patients with bradycardia often experience sudden loss of consciousness without warning, whereas those with tachyarrhythmias are more likely to describe palpitations.
Orthostatic Hypotension
Syncope associated with changes in position is often due to orthostatic hypotension. When an individual assumes an upright posture, normal homeostatic mechanisms (arteriolar and venous constriction, enhanced heart rate, and increased lower-extremity muscle tone) prevent a significant decrease in systolic blood pressure. Patients with orthostatic hypotension may have inadequate responses or impaired reflexes that cause postural symptoms. Symptomatic orthostatic hypotension may be related to inadequate volume due to dehydration or autonomic impairment caused by a primary autonomic neuropathy secondary to diabetes or other disorders. Medications known to cause orthostatic hypotension will be discussed separately. The hallmark of syncope due to orthostatic hypotension is that it usually occurs immediately upon standing. Vital signs demonstrate an increase in heart rate and a simultaneous drop in blood pressure with position changes from lying to sitting or standing.
Table 2 Clinical features, electrocardiogram, and other key diagnostic testing related to common causes of syncope
Cause
Clinical features
Physical findings
Electrocardiogram
Testing
Vasovagal
Occurs after prolonged standing, associated nausea, diaphoresis, darkened vision
Normal
Normal
History may be diagnostic, tilt table testing
Situational
Occurs with cough, defecation, micturition, or swallowing
Normal
Normal
History may be diagnostic
Carotid sinus
Occurs with head rotation or carotid pressure
Sometimes carotid bruits
Normal
Carotid massage
Organic heart disease
Occurs with exertion, associated dyspnea
Normal exam, murmur
Evidence of ischemia or cardiomyopathy
Stress testing indicated
Arrhythmia
Palpitations prior to syncope
Normal exam or arrhythmia
Prolonged QT or other arrhythmia
Telemetry or Holter monitor
Orthostatic hypotension
Occurs upon standing
Characteristic rise in pulse and fall in blood pressure
Normal
Tilt table testing
Neurologic
Sudden onset, prolonged period of confusion or lethargy
Witnessed seizures, incontinence
Normal
Electroencephalogram
Medication-related
Multiple drugs, older age
Hypotension, bradycardia
Normal or prolonged QT
History may be diagnostic
Psychiatric
Frequent occurrence, young age, no injuries
Normal
Normal
History may be diagnostic
Neurologic Disease
Neurologic disorders are an uncommon cause of syncope. Potential causes include migraine, transient ischemic attack (TIA), seizure, and subclavian steal syndrome. Seizures including unwitnessed grand mal seizures and temporal lobe epilepsy are by far the most common neurologic causes of syncope. TIA involving the vertebrobasilar artery can impair cerebellar circulation and lead to syncope. Basilar artery migraines are another reported cause of syncope. Symptoms that suggest a neurologic cause of syncope include witnessed seizure activity, headache, diplopia, and hemiparesis. Syncope due to cardiac and other causes may also result in brief spells of tonic-clonic activity or irregular muscle twitching making it difficult to distinguish these individuals from those with seizure as the underlying cause of syncope. The presence of incontinence or prolonged postictal lethargy and confusion make seizure activity more likely to be the primary cause.
Medications
Medications can lead to syncope by a variety of different mechanisms. Antihypertensives and antidepressant agents are the drug classes most likely to cause syncope. Diuretics are known to cause orthostatic hypotension. Vasodilating antihypertensives can increase the risk of vasovagal attacks and orthostatic hypotension. Beta blockers, clonidine, and cardioselective calcium channel blockers can lead to bradyarrhythmia and syncope. Tricyclic antidepressants and other drugs that cause QT prolongation can lead to ventricular fibrillation and syncope. Opiates, alcohol, and cocaine have been reported to cause syncope and seizures. Elderly patients in particular are at highest risk for medication-related syncope due to the increased prevalence of polypharmacy in this population, the increased risk for organic heart disease, and the greater prevalence of underlying autonomic impairment.
Psychiatric Disorders
A large proportion of patients with otherwise unexplained syncope have been diagnosed with a psychiatric disorder. Generalized anxiety disorder, panic disorder, major depression, and conversion disorders have all been reported to have an increased prevalence among patients who present with syncope. Psychiatric disorders should be considered as potential causes of syncope in young patients who faint frequently, those in whom syncope does not cause any injury, and in those who report many symptoms associated with their syncopal events.
Evaluation
The most common causes of syncope are vasovagal attacks, organic heart disease, arrhythmias, orthostatic hypotension, and seizures. In many cases, it is possible to identify a potential cause of syncope using history and physical examination alone. Family members and other witnesses can be very helpful historians because they are in some cases better able to describe the events leading up to and following loss of consciousness. History taking should focus on postural symptoms (orthostatic or vasovagal syncope), exertional symptoms or a positive family history of syncope (cardiac syncope, prolonged QT syndromes), palpitations (tachyarrhythmias), postictal symptoms (neurologic syncope), situational symptoms (such as defecation and urination), use of medications, and history of organic heart disease (predisposing to arrhythmias or ischemia). Careful evaluation for the presence of physical findings including murmurs, carotid bruits, asymmetric pulses, and muffled heart sounds is important. Assessment of pulse and blood pressure while lying, sitting, and standing should be performed on all patients presenting with syncope during the initial examination. Every patient should also undergo electrocardiogram (ECG) testing to screen further for evidence of organic heart disease including ischemia, prolonged QT, and arrhythmia (Fig. 1).
Situations in which the history, physical examination, and ECG are often diagnostic in patients with syncope include vasovagal attacks, situational syncope, orthostatic hypotension, and polypharmacy. In other cases, the history, physical examination, and ECG may be highly suggestive. Examples include aortic stenosis, pulmonary embolism, seizure, and individuals in whom there is a strong family history of sudden cardiac death. These individuals should undergo further evaluation with specific testing that is dictated by the clinical scenario. Examples of appropriate testing include echocardiography to confirm valvular heart disease and cardiomyopathy, cardiac catheterization to look for evidence of acute coronary syndromes, ventilation-perfusion scanning or computed tomographic angiography to diagnose pulmonary embolism, electroencephalography to assess for seizures, or computed tomography scan of the brain to identify a focal neurologic lesion. Carotid or transcranial Doppler ultrasonography may be performed in the presence of bruits or when symptoms are suggestive of a neurovascular cause of syncope. Holter monitoring, Loop recorders, and electrophysiologic testing may be indicated when arrhythmia is suspected in individuals with a family history of sudden cardiac death. Routine use of basic laboratory tests is not recommended because of evidence that they rarely yield diagnostically useful information; however, these tests may be performed when they are indicated by the results of the history or physical examination.
Evaluation of Unexplained Syncope
After applying the algorithm (Fig. 1), a potential cause of syncope can be identified in nearly half of all patients. Before proceeding further, remaining patients with unexplained syncope should be stratified according to age and the likelihood that organic heart disease is present. In this way, it is possible to divide unexplained syncope into three branches.
Branch 1: High Likelihood of Underlying Organic Heart Disease
Patients likely to have organic heart disease are characterized by abnormal ECG, exertional symptoms, and sudden syncope without warning symptoms. All patients in this group should undergo echocardiography and cardiac stress testing. When these studies are abnormal, the next step is Holter monitoring or inpatient telemetry to identify arrhythmias. Those with evidence of ischemia will require appropriate revascularization procedures. Symptoms that increase the likelihood that syncope is related to an arrhythmia include: clustering of “spells”, palpitations, sudden loss of consciousness, and use of certain medications. In appropriate cases, patients may require invasive electrophysiologic testing to make a diagnosis of tachyarrhythmia or bradyarrhythmia. If these studies fail to yield a diagnosis, tilt table testing and ultimately psychiatric evaluation is in order.
Branch 2: Age >60 Years, Without Likely Organic Heart Disease
Older individuals are at increased risk for carotid sinus syncope; therefore, this should be evaluated early. After examining the patient to verify the absence of carotid bruits, a carotid massage is diagnostically positive when more than 3 seconds of pressure results in asystole, hypertension, or both. Carotid massage can be performed at the bedside while the patient is monitored or during a tilt test. Following carotid massage, older patients should undergo echocardiography and cardiac stress testing. If there is evidence of organic heart disease, patients should undergo further evaluation as outlined in Branch 1. In the absence of organic heart disease, arrhythmia must be excluded. This can be investigated using Holter or telemetry monitoring and ultimately electrophysiologic testing. In appropriate situations, evaluation for neurally mediated syncope as outlined in Branch 3 is indicated.
Figure 1 Algorithm for diagnosing syncope. CT, computed tomography; ECG, electrocardiogram; EEG, electroencephalogram; EPS, electrophysiology study; OHD, organic heart disease. Adapted from Linzer M, Yang EH, Estes NA, et al. Diagnosing syncope, Part 1: value of history, physical examination, and electrocardiography. Ann Intern Med 1997;126:989-996.)
Branch 3: No Suspected Organic Heart Disease, Age <60>
In this subgroup, the frequency of syncope is most helpful in predicting the need for further testing. Individuals for whom syncope is a frequent occurrence require immediate evaluation with Holter monitoring, Loop recording, and/or tilt table testing. Loop recording is a type of event monitor that is useful in patients with relatively frequent syncopal events that vary from once per week to once every 2 to 3 months. The device can be worn for 30 days or more and patients can make recordings whenever they are symptomatic. Patients who have unexplained recurrent syncope and no evidence of organic heart disease should undergo tilt table testing to confirm the diagnosis of neurally mediated syncope. Most protocols begin with a passive phase where patients are tilted head up for 15 minutes at 60 degrees followed by an isoproterenol infusion that is slowly titrated up to increase the sensitivity of the test as the patient is retilted. If both arrhythmia and neurally mediated syncope are excluded, psychiatric evaluation should be considered. Those with a single episode of syncope can usually be observed without immediate evaluation.
Rheumatic fever is the leading cause of mitral stenosis (MS) (Table 1). Other less common etiologies of obstruction to left atrial outflow include congenital mitral valve stenosis, cor triatriatum, mitral annular calcification with extension onto the leaflets, systemic lupus erythematosus, rheumatoid arthritis, left atrial myxoma, and infective endocarditis with large vegetations. Pure or predominant MS occurs in approximately 40% of all patients with rheumatic heart disease and a history of rheumatic fever. In other patients with rheumatic heart disease, lesser degrees of MS may accompany mitral regurgitation (MR) and aortic valve disease. With reductions in the incidence of acute rheumatic fever, particularly in temperate climates and developed countries, the incidence of MS has declined considerably over the past few decades. However, it remains a major problem in developing nations, especially in tropical and semitropical climates (see "Global Burden of Valvular Heart Disease").
Table 1 Major Causes of Valvular Heart Diseases
Valve Lesion
Etiologies
Mitral stenosis
Rheumatic fever
Congenital
Severe mitral annular calcification
SLE, RA
Mitral regurgitation
Acute
Endocarditis
Papillary muscle rupture (post-MI)
Trauma
Chordal rupture/Leaflet flail (MVP, IE)
Chronic
Myxomatous (MVP)
Rheumatic fever
Endocarditis (healed)
Mitral annular calcification
Congenital (cleft, AV canal)
HOCM with SAM
Ischemic (LV remodeling)
Dilated cardiomyopathy
Aortic atenosis
Congenital (bicuspid, unicuspid)
Degenerative calcific
Rheumatic fever
Aortic regurgitation
Valvular
Congenital (bicuspid)
Endocarditis
Rheumatic fever
Myxomatous (prolapse)
Traumatic
Syphilis
Ankylosing spondylitis
Root disease
Aortic dissection
Cystic medial degeneration
Marfan syndrome
Bicuspid aortic valve
Nonsyndromic familial aneurysm
Aortitis
Hypertension
Tricuspid stenosis
Rheumatic
Congenital
Tricuspid regurgitation
Primary
Rheumatic
Endocarditis
Myxomatous (TVP)
Carcinoid
Congenital (Ebstein's)
Trauma
Papillary muscle injury (post-MI)
Secondary
RV and tricuspid annular dilatation
Multiple causes of RV enlargement (e.g., long-standing pulmonary HTN)
In rheumatic MS, the valve leaflets are diffusely thickened by fibrous tissue and/or calcific deposits. The mitral commissures fuse, the chordae tendineae fuse and shorten, the valvular cusps become rigid, and these changes, in turn, lead to narrowing at the apex of the funnel-shaped ("fish-mouth") valve. Although the initial insult to the mitral valve is rheumatic, the later changes may be a nonspecific process resulting from trauma to the valve caused by altered flow patterns due to the initial deformity. Calcification of the stenotic mitral valve immobilizes the leaflets and narrows the orifice further. Thrombus formation and arterial embolization may arise from the calcific valve itself, but in patients with atrial fibrillation (AF), thrombi arise more frequently from the dilated left atrium (LA), particularly the left atrial appendage.
Pathophysiology
In normal adults, the area of the mitral valve orifice is 4–6 cm2. In the presence of significant obstruction, i.e., when the orifice area is reduced to < ~2 cm2, blood can flow from the LA to the left ventricle (LV) only if propelled by an abnormally elevated left atrioventricular pressure gradient (see Fig. 223-2), the hemodynamic hallmark of MS. When the mitral valve opening is reduced to <1>2, often referred to as "severe" MS, a LA pressure of ~25 mmHg is required to maintain a normal cardiac output (CO). The elevated pulmonary venous and pulmonary arterial (PA) wedge pressures reduce pulmonary compliance, contributing to exertional dyspnea. The first bouts of dyspnea are usually precipitated by clinical events that increase the rate of blood flow across the mitral orifice, resulting in further elevation of the LA pressure (see below).
To assess the severity of obstruction hemodynamically, both the transvalvular pressure gradient and the flow rate must be measured. The latter depends not only on the CO but on the heart rate as well. An increase in heart rate shortens diastole proportionately more than systole and diminishes the time available for flow across the mitral valve. Therefore, at any given level of CO, tachycardia including that associated with AF augments the transvalvular pressure gradient and elevates further the LA pressure. Similar considerations apply to the pathophysiology of tricuspid stenosis.
The LV diastolic pressure and ejection fraction (EF) are normal in isolated MS. In MS and sinus rhythm, the elevated LA and PA wedge pressures exhibit a prominent atrial contraction (ay descent) (see Fig. 223-2). In severe MS and whenever pulmonary vascular resistance is significantly increased, the pulmonary arterial pressure (PAP) is elevated at rest and rises further during exercise, often causing secondary elevations of right ventricular (RV) end-diastolic pressure and volume. wave) and a gradual pressure decline after mitral valve opening
Cardiac Output
In patients with moderate MS (mitral valve orifice 1.0 cm2–1.5 cm2), the CO is normal or almost so at rest but rises subnormally during exertion. In patients with severe MS (valve area <1.0>2), particularly those in whom pulmonary vascular resistance is markedly elevated, the CO is subnormal at rest and may fail to rise or may even decline during activity.
Pulmonary Hypertension
The clinical and hemodynamic features of MS are influenced importantly by the level of the PAP. Pulmonary hypertension results from: (1) passive backward transmission of the elevated LA pressure; (2) pulmonary arteriolar constriction, which presumably is triggered by LA and pulmonary venous hypertension (reactive pulmonary hypertension); (3) interstitial edema in the walls of the small pulmonary vessels; and (4) organic obliterative changes in the pulmonary vascular bed. Severe pulmonary hypertension results in RV enlargement, secondary tricuspid regurgitation (TR) and pulmonic regurgitation (PR), as well as right-sided heart failure.
Symptoms
In temperate climates, the latent period between the initial attack of rheumatic carditis (in the increasingly rare circumstances in which a history of one can be elicited) and the development of symptoms due to MS is generally about two decades; most patients begin to experience disability in the fourth decade of life. Studies carried out before the development of mitral valvotomy revealed that once a patient with MS became seriously symptomatic, the disease progressed continuously to death within 2–5 years.
In patients whose mitral orifices are large enough to accommodate a normal blood flow with only mild elevations of LA pressure, marked elevations of this pressure leading to dyspnea and cough may be precipitated by sudden changes in the heart rate, volume status, or CO, as for example with severe exertion, excitement, fever, severe anemia, paroxysmal AF and other tachycardias, sexual intercourse, pregnancy, and thyrotoxicosis. As MS progresses, lesser stresses precipitate dyspnea, and the patient becomes limited in daily activities, and orthopnea and paroxysmal nocturnal dyspnea develop. The development of permanent AF often marks a turning point in the patient's course and is generally associated with acceleration of the rate at which symptoms progress.
Hemoptysis results from rupture of pulmonary-bronchial venous connections secondary to pulmonary venous hypertension. It occurs most frequently in patients who have elevated LA pressures without markedly elevated pulmonary vascular resistances and is almost never fatal. Recurrent pulmonary emboli, sometimes with infarction, are an important cause of morbidity and mortality late in the course of MS. Pulmonary infections, i.e., bronchitis, bronchopneumonia, and lobar pneumonia, commonly complicate untreated MS, especially during the winter months. Infective endocarditis is rare in isolated MS.
Pulmonary Changes
In addition to the aforementioned changes in the pulmonary vascular bed, fibrous thickening of the walls of the alveoli and pulmonary capillaries occurs commonly in MS. The vital capacity, total lung capacity, maximal breathing capacity, and oxygen uptake per unit of ventilation are reduced. Pulmonary compliance falls further as pulmonary capillary pressure rises during exercise.
Thrombi and Emboli
Thrombi may form in the left atria, particularly in the enlarged atrial appendages of patients with MS. Systemic embolization, the incidence of which is 10–20%, occurs more frequently in patients with AF, in older patients, and in those with a reduced CO. However, systemic embolization may be the presenting feature in otherwise asymptomatic patients with only mild MS.
Physical Findings
Inspection and Palpation
In patients with severe MS, there may be a malar flush with pinched and blue facies. In patients with sinus rhythm and severe pulmonary hypertension or associated tricuspid stenosis (TS), the jugular venous pulse reveals prominent a waves due to vigorous right atrial systole. The systemic arterial pressure is usually normal or slightly low. An RV tap along the left sternal border signifies an enlarged RV. A diastolic thrill may be present at the cardiac apex, with the patient in the left lateral recumbent position.
Auscultation
The first heart sound (S1) is usually accentuated and slightly delayed. The pulmonic component of the second heart sound (P2) also is often accentuated, and the two components of the second heart sound (S2) are closely split. The opening snap (OS) of the mitral valve is most readily audible in expiration at, or just medial to the cardiac apex. This sound generally follows the sound of aortic valve closure (A2) by 0.05–0.12 s. The time interval between A2 and OS varies inversely with the severity of the MS. The OS is followed by a low-pitched, rumbling, diastolic murmur, heard best at the apex with the patient in the left lateral recumbent position (see Fig. 220-4B). It is accentuated by mild exercise (e.g., a few rapid sit-ups) carried out just before auscultation. In general, the duration of this murmur correlates with the severity of the stenosis in patients with preserved CO. In patients with sinus rhythm, the murmur often reappears or becomes louder during atrial systole (presystolic accentuation). Soft grade I or II/VI systolic murmurs are commonly heard at the apex or along the left sternal border in patients with pure MS and do not necessarily signify the presence of MR. Hepatomegaly, ankle edema, ascites, and pleural effusion, particularly in the right pleural cavity, may occur in patients with MS and RV failure.
Associated Lesions
With severe pulmonary hypertension, a pansystolic murmur produced by functional TR may be audible along the left sternal border. This murmur is usually louder during inspiration and diminishes during forced expiration (Carvallo's sign). When the CO is markedly reduced in MS, the typical auscultatory findings, including the diastolic rumbling murmur, may not be detectable (silent MS), but they may reappear as compensation is restored. The Graham Steell murmur of PR, a high-pitched, diastolic, decrescendo blowing murmur along the left sternal border, results from dilatation of the pulmonary valve ring and occurs in patients with mitral valve disease and severe pulmonary hypertension. This murmur may be indistinguishable from the more common murmur produced by aortic regurgitation (AR), though it may increase in intensity with inspiration and is accompanied by a loud P2.
Laboratory Examination
ECG
In MS and sinus rhythm, the P wave usually suggests LA enlargement (see Fig. 221-8). It may become tall and peaked in lead II and upright in lead V1 when severe pulmonary hypertension or TS complicates MS and right atrial (RA) enlargement occurs. The QRS complex is usually normal. However, with severe pulmonary hypertension, right axis deviation and RV hypertrophy are often present.
Echocardiogram
Transthoracic two-dimensional echocardiography (TTE) with color flow Doppler imaging provides critical information, including an estimate of the transvalvular peak and mean gradients and of mitral orifice size, the presence and severity of accompanying MR, the extent of restriction of valve leaflets and their thickness, the degree of distortion of the subvalvular apparatus, and the anatomic suitability for percutaneous mitral balloon valvotomy (PMBV; see below). In addition, TTE provides an assessment of the size of the cardiac chambers, an estimation of LV function, an estimation of the pulmonary artery pressure (PAP), and an indication of the presence and severity of associated valvular lesions. Transesophageal echocardiography (TEE) provides superior images and should be employed when TTE is inadequate for guiding therapy. TEE is especially indicated to exclude the presence of left atrial thrombi prior to PMBV.
Chest X-Ray
The earliest changes are straightening of the upper left border of the cardiac silhouette, prominence of the main pulmonary arteries, dilatation of the upper lobe pulmonary veins, and posterior displacement of the esophagus by an enlarged LA. Kerley B lines are fine, dense, opaque, horizontal lines that are most prominent in the lower and mid-lung fields and that result from distention of interlobular septae and lymphatics with edema when the resting mean LA pressure exceeds approximately 20 mmHg.
Differential Diagnosis
Like MS, significant MR may also be associated with a prominent diastolic murmur at the apex due to increased flow, but in MR this diastolic murmur commences slightly later than in patients with MS, and there is often clear-cut evidence of LV enlargement. An apical pansystolic murmur of at least grade III/VI intensity as well as an S3 suggests significant associated MR. Similarly, the apical mid-diastolic murmur associated with severe AR (Austin Flint murmur) may be mistaken for MS but can be differentiated from it because it is not intensified in presystole. TS, which occurs rarely in the absence of MS, may mask many of the clinical features of MS or be clinically silent.
Atrial septal defect may be mistaken for MS; in both conditions there is often clinical, ECG, and chest x-ray evidence of RV enlargement and accentuation of pulmonary vascularity. However, the absence of LA enlargement and of Kerley B lines and the demonstration of fixed splitting of S2 all favor atrial septal defect over MS.
Left atrial myxoma may obstruct LA emptying, causing dyspnea, a diastolic murmur, and hemodynamic changes resembling those of MS. However, patients with an LA myxoma often have features suggestive of a systemic disease, such as weight loss, fever, anemia, systemic emboli, and elevated serum IgG and interleukin 6 (IL-6) concentrations. The auscultatory findings may change markedly with body position. The diagnosis can be established by the demonstration of a characteristic echo-producing mass in the LA with TTE.
Cardiac Catheterization
Left and right heart catheterization is useful when there is a discrepancy between the clinical and TTE findings that cannot be resolved with either TEE or cardiac magnetic resonance (CMR) imaging. The growing experience with CMR for the assessment of patients with valvular heart disease may decrease the need for invasive catheterization. Catheterization is helpful in assessing associated lesions such as aortic stenosis (AS) and AR. Catheterization and coronary arteriography are not usually necessary to aid in the decision about surgery in younger patients, with typical findings of severe obstruction on clinical examination and TTE. In males over 45 years of age, females over 55 years of age, and younger patients with coronary risk factors, especially those with positive noninvasive stress tests for myocardial ischemia, coronary angiography is advisable preoperatively to detect patients with critical coronary obstructions that should be bypassed at the time of operation. Computed tomographic angiography (CTA) is now used in some centers to screen preoperatively for the presence of coronary artery disease (CAD) in patients with valvular heart disease. Catheterization and left ventriculography are also indicated in most patients who have undergone PMBV or previous mitral valve surgery and who have redeveloped serious symptoms, if questions remain after both TTE and TEE.
Treatment
Management strategy for patients with mitral stenosis (MS) and mild symptoms. There is controversy as to whether patients with severe MS (MVA <1.0>2) and severe pulmonary hypertension(PH) (PASP >60 mmHg) should undergo percutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement (MVR) to prevent right ventricular failure. CXR, chest x-ray; ECG, electrocardiogram; echo, echocardiography; LA, left atrial; MR, mitral regurgitation; MVA, mitral valve area; MVG, mean mitral valve pressure gradient; NYHA, New York Heart Association; PASP, pulmonary artery systolic pressure; PAWP, pulmonary artery wedge pressure; 2D, 2-dimensional. (From Bonow et al.)
Penicillin prophylaxis of Group A β-hemolytic streptococcal infections to prevent rheumatic fever is important for at-risk patients with MS (Table 2). Recommendations for infective endocarditis prophylaxis have recently changed. In symptomatic patients, some improvement usually occurs with restriction of sodium intake and maintenance doses of oral diuretics. Digitalis glycosides usually do not benefit patients with MS and sinus rhythm, but they are helpful in slowing the ventricular rate of patients with AF. Beta blockers and nondihydropyridine calcium channel blockers (e.g., verapamil or diltiazem) are also useful in this regard. Warfarin to an international normalized ration (INR) of 2–3 should be administered indefinitely to patients with MS who have AF or a history of thromboembolism. The routine use of warfarin in patients in sinus rhythm with LA enlargement (maximal dimension >5.5 cm) with or without spontaneous echo contrast is more controversial.
Table 2 Medical Therapy of Valvular Heart Disease
Lesion
Symptom Control
Natural History
Mitral stenosis
Beta blockers, nondihydropyridine calcium channel blockers, or digoxin for rate control of AF; cardioversion for new-onset AF and HF; diuretics for HF
Warfarin for AF or thromboembolism; PCN for RF prophylaxis
Mitral regurgitation
Diuretics for HF
Warfarin for AF or thromboembolism
Vasodilators for acute MR
Vasodilators for HTN
Aortic stenosis
Diuretics for HF
No proven therapy
Aortic regurgitation
Diuretics and vasodilators for HF
Vasodilators for HTN
Note: Antibiotic prophylaxis is recommended according to current American Heart Association guidelines. For patients with these forms of valvular heart disease, prophylaxis is indicated for a prior history of endocarditis. HF is an indication for surgical or percutaneous treatment, and the recommendations here pertain to short-term therapy prior to definitive correction of the valve lesion. For patients whose comorbidities prohibit surgery, the medical therapies listed can be continued according to available guidelines for the management of HF. See text.
Source: Adapted from NA Boon, P Bloomfield: The medical management of valvular heart disease. Heart 87:395, 2002, with permission.
If AF is of relatively recent onset in a patient whose MS is not severe enough to warrant PMBV or surgical commissurotomy, reversion to sinus rhythm pharmacologically or by means of electrical countershock is indicated. Usually, cardioversion should be undertaken after the patient has had at least 3 consecutive weeks of anticoagulant treatment to a therapeutic INR. If cardioversion is indicated more urgently, then intravenous heparin should be provided and a TEE performed to exclude the presence of left atrial thrombus before the procedure. Conversion to sinus rhythm is rarely successful or sustained in patients with severe MS, particularly those in whom the LA is especially enlarged or in whom AF has been present for more than 1 year.
Mitral Valvotomy
Unless there is a contraindication, mitral valvotomy is indicated in symptomatic [New York Heart Association (NYHA) Functional Class II–IV] patients with isolated MS whose effective orifice (valve area) is < ~1.0 cm2/m2 body surface area, or <1.5>2 in normal-sized adults. Mitral valvotomy can be carried out by two techniques: PMBV and surgical valvotomy. In PMBV (Figs. 2 and 3), a catheter is directed into the LA after transseptal puncture, and a single balloon is directed across the valve and inflated in the valvular orifice. Ideal patients have relatively pliable leaflets with little or no commissural calcium. In addition, the subvalvular structures should not be significantly scarred or thickened and there should be no left atrial thombus. The short- and long-term results of this procedure in appropriate patients are similar to those of surgical valvotomy, but with less morbidity and a lower periprocedural mortality rate. Event-free survival in younger (<45>
Inoue balloon technique for mitral balloon valvotomy.A. After transseptal puncture, the deflated balloon catheter is advanced across the inter-atrial septum, then across the mitral valve and into the left ventricle. B. The balloon is then inflated stepwise within the mitral orifice.
Simultaneous left atrial (LA) and left ventricular (LV) pressure before and after percutaneous mitral balloon valvuloplasty (PMBV) in a patient with severe mitral stenosis. (Courtesy of Raymond G. McKay, MD; with permission.)
Transthoracic echocardiography is helpful in identifying patients for the percutaneous procedure, and TEE is performed routinely to exclude left atrial thrombus. An "echo score" has been developed to help guide decision-making. The score accounts for the degree of leaflet thickening, calcification, and mobility, and for the extent of subvalvular thickening. A lower score predicts a higher likelihood of successful PMBV.
In patients in whom PMBV is not possible or unsuccessful, or in many patients with restenosis, an "open" valvotomy using cardiopulmonary bypass is necessary. In addition to opening the valve commissures, it is important to loosen any subvalvular fusion of papillary muscles and chordae tendineae and to remove large deposits of calcium, thereby improving valvular function, as well as to remove atrial thrombi. The perioperative mortality rate is ~2%.
Successful valvotomy is defined by a 50% reduction in the mean mitral valve gradient and a doubling of the mitral valve area. Successful valvotomy, whether balloon or surgical, usually results in striking symptomatic and hemodynamic improvement and prolongs survival. However, there is no evidence that the procedure improves the prognosis of patients with slight or no functional impairment. Therefore, unless recurrent systemic embolization or severe pulmonary hypertension has occurred (PA systolic pressures >50 mmHg at rest or >60 mmHg with exercise), valvotomy is not recommended for patients who are entirely asymptomatic and/or who have mild stenosis (mitral valve area >1/5 cm2). When there is little symptomatic improvement after valvotomy, it is likely that the procedure was ineffective, that it induced MR, or that associated valvular or myocardial disease was present. About half of all patients undergoing surgical mitral valvotomy require reoperation by 10 years. In the pregnant patient with MS, valvotomy should be carried out if pulmonary congestion occurs despite intensive medical treatment. PMBV is the preferred strategy in this setting and is performed with TEE and no or minimal x-ray exposure.
Mitral valve replacement (MVR) is necessary in patients with MS and significant associated MR, those in whom the valve has been severely distorted by previous transcatheter or operative manipulation, or those in whom the surgeon does not find it possible to improve valve function significantly. MVR is now routinely performed with preservation of the chordal attachments to optimize LV functional recovery. Perioperative mortality rates with MVR vary with age, LV function, the presence of CAD, and associated comorbidities. They average 5% overall but are lower in young patients and may be twice as high in older patients with comorbidities (Table 3). Since there are also long-term complications of valve replacement (p. 1480), patients in whom preoperative evaluation suggests the possibility that MVR may be required should be operated on only if they have severe MS—i.e., an orifice area >1 cm2—and are in NYHA Class III, i.e., symptomatic with ordinary activity despite optimal medical therapy. The overall 10-year survival of surgical survivors is ~70%. Long-term prognosis is worse in older patients and those with marked disability and marked depression of the CO preoperatively. Pulmonary hypertension and RV dysfunction are additional risk factors for poor outcome.
MR may result from an abnormality or disease process that affects any one or more of the five functional components of the mitral valve apparatus (leaflets, annulus, chordae tendineae, papillary muscles, and subjacent myocardium) (Table 1). Acute MR can occur in the setting of acute myocardial infarction (MI) with papillary muscle rupture, following blunt chest wall trauma, or during the course of infective endocarditis. With acute MI, the posteromedial papillary muscle is involved much more frequently than the anterolateral papillary muscle because of its singular blood supply. Transient, acute MR can occur during periods of active ischemia and bouts of angina pectoris. Rupture of chordae tendineae can result in "acute on chronic MR" in patients with myxomatous degeneration of the valve apparatus.
Chronic MR can result from rheumatic disease, mitral valve prolapse (MVP) (see "Mitral Valve Prolapse"), extensive mitral annular calcification, congenital valve defects, hypertrophic obstructive cardiomyopathy (HOCM), and dilated cardiomyopathy. Rheumatic heart disease is the cause of chronic MR in only about one-third of cases and occurs more frequently in males. The rheumatic process produces rigidity, deformity, and retraction of the valve cusps and commissural fusion, as well as shortening, contraction, and fusion of the chordae tendineae. The MR associated with both MVP and HOCM is usually dynamic in nature. MR in HOCM occurs as a consequence of anterior papillary muscle displacement and systolic anterior motion of the anterior mitral valve leaflet into the narrowed LV outflow tract. Annular calcification is especially prevalent among patients with advanced renal disease and is commonly observed in elderly women with hypertension and diabetes. MR may occur as a congenital anomaly, most commonly as a defect of the endocardial cushions (atrioventricular cushion defects). A cleft anterior mitral valve leaflet accompanies primum atrial septal defect. Chronic MR is frequently secondary to ischemia and may occur as a consequence of ventricular remodeling, papillary muscle displacement, and leaflet tethering, or with fibrosis of a papillary muscle, in patients with healed myocardial infarction(s) and ischemic cardiomyopathy. Similar mechanisms of annular dilatation and ventricular remodeling contribute to the MR that occurs universally among patients with nonischemic forms of dilated cardiomyopathy once the left ventricular end-diastolic dimension reaches 6.0 cm.
Irrespective of cause, chronic severe MR is often progressive, since enlargement of the LA places tension on the posterior mitral leaflet, pulling it away from the mitral orifice and thereby aggravating the valvular dysfunction. Similarly, LV dilatation increases the regurgitation, which in turn enlarges the LA and LV further, causing chordal rupture and resulting in a vicious circle; hence the aphorism "mitral regurgitation begets mitral regurgitation."
Pathophysiology
The resistance to LV emptying (LV afterload) is reduced in patients with MR. As a consequence, the LV is decompressed into the LA during ejection, and with the reduction in LV size during systole, there is a rapid decline in LV tension. The initial compensation to MR is more complete LV emptying. However, LV volume increases progressively with time as the severity of the regurgitation increases and as LV contractile function deteriorates. This increase in LV volume is often accompanied by a reduced forward CO, though LV compliance is often increased and thus LV diastolic pressure does not elevate until late in the course. The regurgitant volume varies directly with the LV systolic pressure and the size of the regurgitant orifice; as mentioned above, the latter, in turn, is influenced profoundly by the extent of LV and mitral annular dilatation. Since ejection fraction (EF) rises in severe MR in the presence of normal LV function, even a modest reduction in this parameter (<60%)>
During early diastole, as the distended LA empties, there is a particularly rapid y descent in the absence of accompanying MS. A brief, early diastolic LA-LV pressure gradient [often generating a rapid filling sound (S3) and mid-diastolic murmur masquerading as MS] may occur in patients with pure MR as a result of the very rapid flow of blood across a normal-sized mitral orifice.
Quantitative estimates of left ventricular ejection fraction (LVEF), CO, PA pressure, regurgitant volume, regurgitant fraction (RF), and the effective regurgitant orifice area can be obtained during a careful Doppler echocardiographic examination. These measurements can also be obtained with CMR. Left and right heart catheterization with contrast ventriculography is utilized less frequently. Severe MR is defined by a regurgitant volume >60 mL/beat, regurgitant fraction (RF) >50%, and effective regurgitant orifice area >0.40 cm2.
LA Compliance
In acute severe MR, the regurgitant volume is delivered into a normal-sized LA having normal or reduced compliance. As a result, LA pressures rise markedly for any increase in LA volume. The v wave in the LA pressure pulse is usually prominent (see Fig. 223-3), LA and pulmonary venous pressures are markedly elevated, and pulmonary edema is common. Because of the rapid rise in LA pressures during ventricular systole, the murmur of acute MR is early in timing and decrescendo in configuration, as a reflection of the progressive diminution in the LV-LA pressure gradient. LV systolic function in acute MR may be normal, hyperdynamic, or reduced, depending on the clinical context.
Patients with chronic severe MR, on the other hand, develop marked LA enlargement and increased LA compliance with little if any increase in LA and pulmonary venous pressures for any increase in LA volume. The LA v wave is relatively less prominent. The murmur of chronic MR is classically holosystolic in timing and plateau in configuration, as a reflection of the near-constant LV-LA pressure gradient. These patients usually complain of severe fatigue and exhaustion secondary to a low CO, while symptoms resulting from pulmonary congestion are less prominent initially; AF is almost invariably present once the LA dilates significantly.
Most common are patients whose clinical and hemodynamic features are intermediate between those in the two aforementioned groups.
Symptoms
Patients with chronic mild-to-moderate isolated MR are usually asymptomatic. This form of LV volume overload is well tolerated. Fatigue, exertional dyspnea, and orthopnea are the most prominent complaints in patients with chronic severe MR. Palpitations are common and may signify the onset of AF. Right-sided heart failure, with painful hepatic congestion, ankle edema, distended neck veins, ascites, and secondary TR, occurs in patients with MR who have associated pulmonary vascular disease and marked pulmonary hypertension. On the other hand, acute pulmonary edema is common in patients with acute severe MR.
Physical Findings
In patients with chronic severe MR, the arterial pressure is usually normal, though the arterial pulse may show a sharp upstroke. A systolic thrill is often palpable at the cardiac apex, the LV is hyperdynamic with a brisk systolic impulse and a palpable rapid-filling wave (S3), and the apex beat is often displaced laterally.
In patients with acute severe MR, the arterial pressure may be reduced with a narrow pulse pressure, the jugular venous pressure and wave forms may be normal or increased and exaggerated, the apical impulse is not displaced, and signs of pulmonary congestion are prominent.
Auscultation
The S1 is generally absent, soft, or buried in the holosystolic murmur of chronic MR. In patients with severe MR, the aortic valve may close prematurely, resulting in wide but physiologic splitting of S2. A low-pitched S3 occurring 0.12–0.17 s after the aortic valve closure sound, i.e., at the completion of the rapid-filling phase of the LV, is believed to be caused by the sudden tensing of the papillary muscles, chordae tendineae, and valve leaflets. It may be followed by a short, rumbling, mid-diastolic murmur, even in the absence of MS. A fourth heart sound is often audible in patients with acute severe MR who are in sinus rhythm. A presystolic murmur is not ordinarily heard with isolated MR.
A systolic murmur of at least grade III/VI intensity is the most characteristic auscultatory finding in chronic severe MR. It is usually holosystolic (see Fig. 220-4), but as previously noted it is decrescendo and ceases in mid- to late systole in patients with acute severe MR. The systolic murmur of chronic MR is usually most prominent at the apex and radiates to the axilla. However, in patients with ruptured chordae tendineae or primary involvement of the posterior mitral leaflet with prolapse or flail, the regurgitant jet is eccentric, directed anteriorly, and strikes the LA wall adjacent to the aortic root. In this situation, the systolic murmur is transmitted to the base of the heart and therefore may be confused with the murmur of AS. In patients with ruptured chordae tendineae, the systolic murmur may have a cooing or "sea gull" quality, while a flail leaflet may cause a murmur with a musical quality. The systolic murmur of chronic MR not due to MVP is intensified by isometric exercise (handgrip) but is reduced during the strain phase of the Valsalva maneuver.
Laboratory Examination
ECG
In patients with sinus rhythm, there is evidence of LA enlargement, but RA enlargement also may be present when pulmonary hypertension is severe. Chronic severe MR is generally associated with AF. In many patients there is no clear-cut ECG evidence of enlargement of either ventricle. In others, the signs of LV hypertrophy are present.
Echocardiogram
TTE with Doppler imaging is indicated to assess the mechanism of the MR and its hemodynamic severity. LV function can be assessed from LV end-diastolic and end-systolic volumes and EF. Observations can be made regarding leaflet structure and function, chordal integrity, LA and LV size, annular calcification, and regional and global LV systolic function. Doppler imaging should demonstrate the width or area of the color flow MR jet within the LA, the intensity of the continuous wave Doppler signal, the pulmonary venous flow contour, the early peak mitral inflow velocity, and the quantitative measures of regurgitant volume, RF, and effective regurgitant orifice area. In addition, the PA pressures can be estimated from the TR jet velocity. TTE is also indicated to follow the course of patients with chronic MR and to provide rapid assessment for any clinical change. The echocardiogram in patients with MVP is described in the next section. TEE provides greater detail than TTE (see Fig. 222-3).
Chest X-Ray
The LA and LV are the dominant chambers in chronic MR; late in the course of the disease, the former may be massively enlarged and forms the right border of the cardiac silhouette. Pulmonary venous congestion, interstitial edema, and Kerley B lines are sometimes noted. Marked calcification of the mitral leaflets occurs commonly in patients with longstanding combined MR and MS. Calcification of the mitral annulus may be visualized, particularly on the lateral view of the chest. Patients with acute severe MR may have asymmetric pulmonary edema if the regurgitant jet is directed predominantly to the orifice of an upper lobe pulmonary vein.
Treatment
Management strategy for patients with chronic severe mitral regurgitation. *Mitral valve (MV) repair may be performed in asymptomatic patients with normal left ventricular (LV) function if performed by an experienced surgical team and if the likelihood of successful MV repair is >90%. AF, atrial fibrillation; Echo, echocardiography; EF, ejection fraction; ESD, end-systolic dimension; eval, evaluation; HT, hypertension; MVR, mitral valve replacement. (From Bonow et al.)
Medical
(Table 2)
The management of chronic severe MR depends to some degree on its cause. Warfarin should be provided once AF intervenes with a target INR of 2–3. Cardioversion should be considered depending on the clinical context and left atrial size. In contrast to the acute setting, there are no large, long-term prospective studies to substantiate the use of vasodilators for the treatment of chronic, isolated severe MR in the absence of systemic hypertension. The severity of MR in the setting of an ischemic or nonischemic dilated cardiomyopathy may diminish with aggressive, evidence-based treatment of heart failure, including the use of diuretics, beta blockers, ACE inhibitors, and digitalis. Asymptomatic patients with severe MR in sinus rhythm with normal LV size and systolic function should avoid isometric forms of exercise.
Patients with acute severe MR require urgent stabilization and preparation for surgery. Diuretics, intravenous vasodilators (particularly sodium nitroprusside), and even intraaortic balloon counterpulsation may be needed for patients with post-MI papillary muscle rupture or other forms of acute severe MR.
Surgical
In the selection of patients with chronic severe MR for surgical treatment, the often slowly progressive nature of the condition must be balanced against the immediate and long-term risks associated with operation. These risks are significantly lower for primary valve repair than for valve replacement (Table 3). Repair usually consists of valve reconstruction utilizing a variety of valvuloplasty techniques and insertion of an annuloplasty ring. Repair spares the patient the long-term adverse consequences of valve replacement, i.e., thromboembolic and hemorrhagic complications in the case of mechanical prostheses and late valve failure necessitating repeat valve replacement in the case of bioprostheses (see "Valve Replacement"). In addition, by preserving the integrity of the papillary muscles, subvalvular apparatus, and chordae tendineae, mitral repair and valvuloplasty maintain LV function to a relatively greater degree.
Surgery for chronic severe MR is indicated once symptoms occur, especially if valve repair is feasible (Fig. 4). Other indications for early consideration of mitral valve repair include recent-onset AF and pulmonary hypertension, defined as a PA pressure 50 mmHg at rest or 60 mmHg with exercise. Surgical treatment of chronic severe MR is indicated for asymptomatic patients when LV dysfunction is progressive, with LVEF declining below 60% and/or end-systolic cavity dimension on echocardiography rising above 40 mm. These aggressive recommendations for surgery are predicated on the outstanding results achieved with mitral valve repair, particularly when applied to patients with myxomatous disease. Indeed, primary valvuloplasty repair of patients younger than 75 years with normal LV systolic function and no CAD can now be performed by experienced surgeons with <1%>
In patients with significantly impaired LV function (EF <30%), st="on">LV performance is incomplete, and the long-term survival is reduced. However, conservative management has little to offer these patients, so operative treatment may be indicated, and the clinical and hemodynamic improvement that follows surgical treatment of patients with advanced disease is occasionally dramatic, especially when severe CAD is also present and bypass grafting can be performed. Though most patients who survive surgery appear to be greatly improved, some degree of myocardial dysfunction often persists, as indicated by a further fall in LVEF.
Patients with acute severe MR can often be stabilized temporarily with appropriate medical therapy, but surgical correction will be necessary, emergently in the case of papillary muscle rupture and within days to weeks in most other settings.
When surgical treatment is contemplated, left and right heart catheterization and left ventriculography may be helpful in confirming the presence of severe MR in patients in whom there is a discrepancy between the clinical and TTE findings that cannot be resolved with TEE or CMR. Coronary arteriography identifies patients who require concomitant coronary revascularization.
Mitral Valve Prolapse
MVP, also variously termed the systolic click-murmur syndrome, Barlow's syndrome, floppy-valve syndrome, and billowing mitral leaflet syndrome, is a relatively common but highly variable clinical syndrome resulting from diverse pathogenic mechanisms of the mitral valve apparatus. Among these are excessive or redundant mitral leaflet tissue, which is commonly associated with myxomatous degeneration and greatly increased concentrations of acid mucopolysaccharide.
In most patients with MVP, the cause is unknown, but in some it appears to be a genetically determined collagen disorder. A reduction in the production of type III collagen has been incriminated, and electron microscopy has revealed fragmentation of collagen fibrils.
MVP is a frequent finding in patients with heritable disorders of connective tissue, including Marfan syndrome, osteogenesis imperfecta, and Ehler-Danlos syndrome.
MVP may be associated with thoracic skeletal deformities similar to but not as severe as those in Marfan syndrome, encompassing a high-arched palate and alterations of the chest and thoracic spine, including the so-called straight back syndrome.
In most patients with MVP, myxomatous degeneration is confined to the mitral (or, less commonly, the tricuspid or aortic) valves without other clinical or pathologic manifestations of disease. The posterior leaflet is usually more affected than the anterior, and the mitral valve annulus is often greatly dilated. In many patients, elongated, redundant, or ruptured chordae tendineae cause or contribute to the regurgitation.
MVP also may occur rarely as a sequel to acute rheumatic fever, in ischemic heart disease, and in various cardiomyopathies, as well as in 20% of patients with ostium secundum atrial septal defect.
MVP may lead to excessive stress on the papillary muscles, which in turn leads to dysfunction and ischemia of the papillary muscles and the subjacent ventricular myocardium. Rupture of chordae tendineae and progressive annular dilatation and calcification also contribute to valvular regurgitation, which then places more stress on the diseased mitral valve apparatus, thereby creating a vicious circle. The ECG changes (see below) and ventricular arrhythmias appear to result from regional ventricular dysfunction related to increased stress placed on the papillary muscles.
Clinical Features
MVP is more common in females and occurs most commonly between the ages of 15 and 30 years; the clinical course is often benign. MVP may also be observed in older (>50 years) patients, often males, in whom MR is often more severe and requires surgical treatment. There is an increased familial incidence for some patients, suggesting an autosomal dominant form of inheritance. MVP encompasses a broad spectrum of severities, ranging from only a systolic click and murmur and mild prolapse of the posterior leaflet of the mitral valve to severe MR due to chordal rupture and massive prolapse of both leaflets. In many patients this condition progresses over years or decades. In others it worsens rapidly as a result of chordal rupture or endocarditis.
Most patients are asymptomatic and remain so for their entire lives. However, in North America MVP is now the most common cause of isolated severe MR requiring surgical treatment. Arrhythmias, most commonly ventricular premature contractions and paroxysmal supraventricular and ventricular tachycardia, as well as AF, have been reported and may cause palpitations, light-headedness, and syncope. Sudden death is a very rare complication and occurs most often in patients with severe MR and depressed LV systolic function. There may be an excess risk of sudden death among patients with a flail leaflet. Many patients have chest pain that is difficult to evaluate. It is often substernal, prolonged, and poorly related to exertion, and it rarely resembles angina pectoris. Transient cerebral ischemic attacks secondary to emboli from the mitral valve due to endothelial disruption have been reported, though a causal relationship has not been established. Infective endocarditis may occur in patients with MR and/or leaflet thickening.
Auscultation
The most important finding is the mid- or late (nonejection) systolic click, which occurs 0.14 s or more after the S1 and is thought to be generated by the sudden tensing of slack, elongated chordae tendineae or by the prolapsing mitral leaflet when it reaches its maximum excursion. Systolic clicks may be multiple and may be followed by a high-pitched, late systolic crescendo-decrescendo murmur, which occasionally is "whooping" or "honking" and is heard best at the apex. The click and murmur occur earlier with standing, during the strain of the Valsalva maneuver, and with any intervention that decreases LV volume, exaggerating the propensity of mitral leaflet prolapse. Conversely, squatting and isometric exercises, which increase LV volume, diminish MVP, and the click-murmur complex is delayed, moves away from S1, and may even disappear. Some patients have a mid-systolic click without the murmur; others have the murmur without a click. Still others have both sounds at different times.
Laboratory Examination
The ECG most commonly is normal but may show biphasic or inverted T waves in leads II, III, and aVF, and occasionally supraventricular or ventricular premature beats. TTE is particularly effective in identifying the abnormal position and prolapse of the mitral valve leaflets. A useful echocardiographic definition of MVP is systolic displacement (in the parasternal long axis view) of the mitral valve leaflets by at least 2 mm into the LA superior to the plane of the mitral annulus. Color flow and continuous wave Doppler imaging is helpful in revealing and evaluating associated MR. TEE is indicated when more accurate information is required and is performed routinely for intraoperative guidance for valve repair. Invasive left ventriculography is rarely necessary but can also show prolapse of the posterior and sometimes of both mitral valve leaflets.
Mitral Valve Prolapse: Treatment
Infective endocarditis prophylaxis is indicated only for patients with a prior history of endocarditis. Beta blockers sometimes relieve chest pain and control palpitations. If the patient is symptomatic from severe MR, mitral valve repair (or rarely, replacement) is indicated (Fig. 4). Antiplatelet agents such as aspirin should be given to patients with transient ischemic attacks, and if these are not effective, anticoagulants such as warfarin should be considered.
Aortic Stenosis
AS occurs in about one-fourth of all patients with chronic valvular heart disease; approximately 80% of adult patients with symptomatic valvular AS are male.
Etiology
(Table 1)
AS in adults may be due to degenerative calcification of the aortic cusps. It may be congenital in origin or it may be secondary to rheumatic inflammation. Age-related degenerative calcific AS (also known as senile or sclerocalcific AS) is now the most common cause of AS in adults in North America and Western Europe. About 30% of persons >65 years exhibit aortic valve sclerosis; many of these have a systolic murmur of AS but without obstruction, while 2% exhibit frank stenosis. Aortic sclerosis is defined echocardiographically as focal thickening or calcification of the valve cusps with a peak Doppler transaortic velocity of >2.5 m/s. Aortic sclerosis appears to be a marker for an increased risk of coronary heart disease events. On histologic examination these valves frequently exhibit changes similar to those seen with atherosclerosis and vascular inflammation. Interestingly, risk factors for atherosclerosis, such as age, male sex, smoking, diabetes mellitus, hypertension, chronic kidney disease, increased LDL, reduced HDL cholesterol, and elevated C-reactive protein are all risk factors for aortic valve calcification.
The congenitally affected valve may be stenotic at birth and may become progressively more fibrotic, calcified, and stenotic. In other cases the valve may be congenitally deformed, usually bicuspid [bicuspid aortic valve (BAV)], without serious narrowing of the aortic orifice during childhood; its abnormal architecture makes its leaflets susceptible to otherwise ordinary hemodynamic stresses, which ultimately lead to valvular thickening, calcification, increased rigidity, and narrowing of the aortic orifice.
Rheumatic disease of the aortic leaflets produces commissural fusion, sometimes resulting in a bicuspid-appearing valve. This condition in turn makes the leaflets more susceptible to trauma and ultimately leads to fibrosis, calcification, and further narrowing. By the time the obstruction to LV outflow causes serious clinical disability, the valve is usually a rigid calcified mass, and careful examination may make it difficult or even impossible to determine the etiology of the underlying process. Rheumatic AS is almost always associated with involvement of the mitral valve and with AR.
Other Forms of Obstruction to Left Ventricular Outflow
Besides valvular AS, three other lesions may be responsible for obstruction to LV outflow: hypertrophic obstructive cardiomyopathy, discrete congenital subvalvularAS, and supravalvularAS. The causes of left ventricular outflow obstruction can be differentiated on the basis of the cardiac examination and Doppler echocardiographic findings.
Pathophysiology
The obstruction to LV outflow produces a systolic pressure gradient between the LV and aorta. When severe obstruction is suddenly produced experimentally, the LV responds by dilatation and reduction of stroke volume. However, in some patients the obstruction may be present at birth and/or increase gradually over the course of many years, and LV output is maintained by the presence of concentric LV hypertrophy. Initially, this serves as an adaptive mechanism because it reduces toward normal the systolic stress developed by the myocardium, as predicted by the Laplace relation (S = Pr/h, where S = systolic wall stress, P = pressure, r = radius, and h = wall thickness). A large transaortic valvular pressure gradient may exist for many years without a reduction in CO or LV dilatation; ultimately, however, excessive hypertrophy becomes maladaptive, and LV function declines.
A mean systolic pressure gradient >40 mmHg with a normal CO or an effective aortic orifice area < ~1.0 cm2 (or ~<0.6>2/m2 body surface area in a normal-sized adult)—i.e., less than approximately one-third of the normal orifice—is generally considered to represent severe obstruction to LV outflow (see Fig. 223-4). The elevated LV end-diastolic pressure observed in many patients with severe AS signifies the presence of LV dilatation and/or diminished compliance of the hypertrophied LV wall. Although the CO at rest is within normal limits in most patients with severe AS, it usually fails to rise normally during exercise. Loss of an appropriately timed, vigorous atrial contraction, as occurs in AF or atrioventricular dissociation, may cause rapid progression of symptoms. Late in the course, the CO and LV–aortic pressure gradient decline, and the mean LA, PA, and RV pressures rise.
The hypertrophied LV elevates myocardial oxygen requirements. In addition, even in the absence of obstructive CAD, there may be interference with coronary blood flow. This is because the pressure compressing the coronary arteries exceeds the coronary perfusion pressure, often causing ischemia (especially in the subendocardium), both in the presence and in the absence of coronary arterial narrowing.
Symptoms
AS is rarely of clinical importance until the valve orifice has narrowed to approximately 1.0 cm2. Even severe AS may exist for many years without producing any symptoms because of the ability of the hypertrophied LV to generate the elevated intraventricular pressures required for a normal stroke volume.
Most patients with pure or predominant AS have gradually increasing obstruction for years but do not become symptomatic until the sixth to eighth decades. Exertional dyspnea, angina pectoris, and syncope are the three cardinal symptoms. Often there is a history of insidious progression of fatigue and dyspnea associated with gradual curtailment of activities. Dyspnea results primarily from elevation of the pulmonary capillary pressure caused by elevations of LV diastolic pressures secondary to reduced left ventricular compliance. Angina pectoris usually develops somewhat later and reflects an imbalance between the augmented myocardial oxygen requirements and reduced oxygen availability; the former results from the increased myocardial mass and intraventricular pressure, while the latter may result from accompanying CAD, which is not uncommon in patients with AS, as well as from compression of the coronary vessels by the hypertrophied myocardium. Therefore, angina may occur in severe AS even without obstructive epicardial CAD. Exertional syncope may result from a decline in arterial pressure caused by vasodilatation in the exercising muscles and inadequate vasoconstriction in nonexercising muscles in the face of a fixed CO, or from a sudden fall in CO produced by an arrhythmia.
Since the CO at rest is usually well maintained until late in the course, marked fatigability, weakness, peripheral cyanosis, cachexia, and other clinical manifestations of a low CO are usually not prominent until this stage is reached. Orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema, i.e., symptoms of LV failure, also occur only in the advanced stages of the disease. Severe pulmonary hypertension leading to RV failure and systemic venous hypertension, hepatomegaly, AF, and TR are usually late findings in patients with isolated severe AS.
When AS and MS coexist, the reduction in CO induced by MS lowers the pressure gradient across the aortic valve and thereby masks many of the clinical findings produced by AS.
Physical Findings
The rhythm is generally regular until late in the course; at other times, AF should suggest the possibility of associated mitral valve disease. The systemic arterial pressure is usually within normal limits. In the late stages, however, when stroke volume declines, the systolic pressure may fall and the pulse pressure narrow. The peripheral arterial pulse rises slowly to a delayed sustained peak (pulsus parvus et tardus; see Fig. 220-2). In the elderly, the stiffening of the arterial wall may mask this important physical sign. In many patients the a wave in the jugular venous pulse is accentuated. This results from the diminished distensibility of the RV cavity caused by the bulging, hypertrophied interventricular septum.
The LV impulse is usually displaced laterally. A double apical impulse may be recognized, particularly with the patient in the left lateral recumbent position. A systolic thrill is generally present at the base of the heart, in the suprasternal notch, and along the carotid arteries.
Auscultation
An early systolic ejection sound is frequently audible in children and adolescents with congenital noncalcific valvular AS. This sound usually disappears when the valve becomes calcified and rigid. As AS increases in severity, LV systole may become prolonged so that the aortic valve closure sound no longer precedes the pulmonic valve closure sound, and the two components may become synchronous, or aortic valve closure may even follow pulmonic valve closure, causing paradoxic splitting of S2. The sound of aortic valve closure can be heard most frequently in patients with AS who have pliable valves, and calcification diminishes the intensity of this sound. Frequently, an S4 is audible at the apex and reflects the presence of LV hypertrophy and an elevated LV end-diastolic pressure; an S3 generally occurs late in the course, when the LV dilates.
The murmur of AS is characteristically an ejection (mid) systolic murmur that commences shortly after the S1, increases in intensity to reach a peak toward the middle of ejection, and ends just before aortic valve closure (see Fig. 220-4). It is characteristically low-pitched, rough and rasping in character, and loudest at the base of the heart, most commonly in the second right intercostal space. It is transmitted upward along the carotid arteries. Occasionally it is transmitted downward and to the apex, where it may be confused with the systolic murmur of MR (Gallavardin effect). In almost all patients with severe obstruction and preserved CO, the murmur is at least grade III/VI. In patients with mild degrees of obstruction or in those with severe stenosis with heart failure in whom the stroke volume and therefore the transvalvular flow rate are reduced, the murmur may be relatively soft and brief.
Laboratory Examination
ECG
In most patients with severe AS there is LV hypertrophy (see Fig. 221-9). In advanced cases, ST-segment depression and T-wave inversion (LV "strain") in standard leads I and aVL and in the left precordial leads are evident. However, there is no close correlation between the ECG and the hemodynamic severity of obstruction, and the absence of ECG signs of LV hypertrophy does not exclude severe obstruction.
Echocardiogram
The key findings are LV hypertrophy and, in patients with valvular calcification (i.e., most adult patients with symptomatic AS), multiple, bright, thick, echoes from the valve (see Fig. 222-2). Eccentricity of the aortic valve cusps is characteristic of congenitally bicuspid valves. TEE imaging usually displays the obstructed orifice extremely well, but it is not routinely required for adequate characterization. The valve gradient and aortic valve area can be estimated by Doppler measurement of the transaortic velocity. Severe AS is defined by a valve area <1.0>2, whereas moderate AS is defined by a valve area of 1.0–1.5 cm2 and mild AS by a valve area of 1.5–2.0 cm2. LV dilatation and reduced systolic shortening reflect impairment of LV function.
Echocardiography is useful for identifying coexisting valvular abnormalities such as MS and AR, which sometimes accompany AS; for differentiating valvular AS from other forms of outflow obstruction; and for measurement of the aortic root. Aneurysmal enlargement (maximal dimension >4.5 cm) of the root or ascending aorta can occur in up to 20% of patients with bicuspid aortic valve disease, independent of the severity of the valve lesion. Dobutamine stress echocardiography is useful for the evaluation of patients with severe AS and severe LV systolic dysfunction (EF <0.35).>
Chest X-Ray
The chest x-ray may show no or little overall cardiac enlargement for many years. Hypertrophy without dilatation may produce some rounding of the cardiac apex in the frontal projection and slight backward displacement in the lateral view; severe AS is often associated with poststenotic dilatation of the ascending aorta. As noted above, however, aortic enlargement may be an independent process and mediated by the same type of structural changes that occur in patients with Marfan syndrome. Aortic calcification is usually readily apparent on fluoroscopic examination or by echocardiography; the absence of valvular calcification in an adult suggests that severe valvular AS is not present. In later stages of the disease, as the LV dilates there is increasing roentgenographic evidence of LV enlargement, pulmonary congestion, and enlargement of the LA, PA, and right side of the heart.
Catheterization
Right and left heart catheterization for invasive assessment of AS is performed infrequently but can be useful when there is a discrepancy between the clinical and echocardiographic findings. Concerns have been raised that attempts to cross the aortic valve for measurement of left ventricular pressures are associated with a risk of cerebral embolization. Catheterization is also useful in three distinct categories of patients: (1) patients with multivalvular disease, in whom the role played by each valvular deformity should be defined to aid in the planning of definitive operative treatment; (2) young, asymptomatic patients with noncalcific congenital AS, to define with precision the severity of obstruction to LV outflow, since operation [which does not usually require aortic valve replacement (AVR)] or PABV may be indicated if severe AS is present, even in the absence of symptoms; balloon valvotomy may follow left heart catheterization immediately; and (3) patients in whom it is suspected that the obstruction to LV outflow may not be at the aortic valve but rather in the sub- or supravalvular regions.
Coronary angiography is indicated to detect or exclude CAD in patients >45 years old with severe AS who are being considered for operative treatment. The incidence of significant CAD for which bypass grafting is indicated at the time of AVR exceeds 50% among adult patients.
Natural History
Death in patients with severe AS occurs most commonly in the seventh and eighth decades. Based on data obtained at postmortem examination in patients before surgical treatment became widely available, the average time to death after the onset of various symptoms was as follows: angina pectoris, 3 years; syncope, 3 years; dyspnea, 2 years; congestive heart failure, 1.5–2 years. Moreover, in >80% of patients who died with AS, symptoms had existed for <4>2/year and an annual increase in mean gradient averaging 7 mmHg/year.
Aortic Stenosis: Treatment
Management strategy for patients with severe aortic stenosis. Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography. AVA, aortic valve area; BP, blood pressure; CABG, coronary artery bypass graft surgery; echo, echocardiography; LV, left ventricle; Vmax, maximal velocity across aortic valve by Doppler echocardiography. (From Bonow et al. Modified from CM Otto: J Am Coll Cardiol 47:2141, 2006.)
Medical Treatment
In patients with severe AS (<1.0>2), strenuous physical activity should be avoided, even in the asymptomatic stage. Care must be taken to avoid dehydration and hypovolemia to protect against a significant reduction in CO. Medications used for the treatment of hypertension or CAD, including beta blockers and ACE inhibitors, are generally safe for asymptomatic patients with preserved left ventricular systolic function. Nitroglycerin is helpful in relieving angina pectoris. Retrospective studies have shown that patients with degenerative calcific AS who receive HMG-CoA reductase inhibitors ("statins") exhibit slower progression of leaflet calcification and aortic valve area reduction than those who do not. One prospective randomized clinical trial using high-dose atorvastatin failed to show a measurable benefit, although a more recent trial using rosuvastatin did show a beneficial effect. The role of statin medications may be more clearly defined with further study.
Surgical Treatment
Asymptomatic patients with calcific AS and severe obstruction should be followed carefully for the development of symptoms and by serial echocardiograms for evidence of deteriorating LV function. Operation is indicated in patients with severe AS (valve area <1.0>2 or 0.6 cm2/m2 body surface area) who are symptomatic, those who exhibit LV dysfunction (EF <50%),>4.5 cm or annual increase in size >0.5 cm/year), even if they are asymptomatic. In patients without heart failure, the operative risk of AVR is approximately 3% (Table 3). It is prudent to postpone operation in patients with severe calcific AS who are truly asymptomatic and who exhibit normal LV function, i.e., EF >50%, since they may continue to do well for years. However, some advocate AVR in patients with severe valve calcification and rapid progression of obstruction. The risk of surgical mortality exceeds that of sudden death in asymptomatic patients. Exercise testing is employed in many centers to assess objectively the functional capacity of asymptomatic patients for whom the history is ambiguous. As many as one-third of patients will show signs of functional impairment during exercise for which AVR should be considered. AVR is carried out in asymptomatic patients with severe or moderately severe stenosis who undergo coronary artery bypass grafting. AVR is also routinely performed in patients with moderate AS who are undergoing coronary bypass grafting or aortic root reconstruction.
Operation should, if possible, be carried out before frank LV failure develops; at this late stage, the aortic valve pressure gradient declines as the CO, stroke volume, and EF decline (low gradient, low output AS). In such patients the perioperative risk is high (15–20%), and evidence of myocardial disease may persist even when the operation is technically successful. Furthermore, long-term postoperative survival also correlates inversely with preoperative LV dysfunction. Nonetheless, in view of the even worse prognosis of such patients when they are treated medically, there is usually little choice but to advise surgical treatment, especially in patients in whom contractile reserve can be demonstrated by dobutamine echocardiography (defined by a >20% in stroke volume after dobutamine challenge). In patients in whom severe AS and CAD coexist, relief of the AS and revascularization of the myocardium by means of aortocoronary bypass grafting may result in striking clinical and hemodynamic improvement (Table 3).
Because many patients with calcific AS are elderly, particular attention must be directed to the adequacy of hepatic, renal, and pulmonary function before AVR is recommended. Age alone is not a contraindication to AVR for AS. The mortality rate depends to a substantial extent on the patient's preoperative clinical and hemodynamic state. The 10-year survival rate of patients with AVR is approximately 60%. Approximately 30% of bioprosthetic valves evidence primary valve failure in 10 years, requiring re-replacement, and an approximately equal percentage of patients with mechanical prostheses develop significant hemorrhagic complications as a consequence of treatment with anticoagulants (see "Valve Replacement").
Percutaneous Balloon Aortic Valvuloplasty
This procedure is preferable to operation in children and young adults with congenital, noncalcific AS. It is not commonly used in adults with severe calcific AS because of a very high restenosis rate and the risk of procedural complications, but on occasion it has been used successfully as a "bridge to operation" in patients with severe LV dysfunction and shock who are too ill to tolerate surgery.
Aortic Regurgitation
Etiology
(Table 1)
AR may be caused by primary valve disease or by primary aortic root disease.
Primary Valve Disease
In approximately two-thirds of patients with valvular AR, the disease is rheumatic in origin, resulting in thickening, deformity, and shortening of the individual aortic valve cusps, changes that prevent their proper opening during systole and closure during diastole. A rheumatic origin is much less common in patients with isolated AR who do not have associated mitral valve disease. Patients with congenital BAV disease may develop predominant AR. Congenital fenestrations of the aortic valve occasionally produce mild AR. Membranous subaortic stenosis often leads to thickening and scarring of the aortic valve leaflets with secondary AR. Prolapse of an aortic cusp, resulting in progressive chronic AR, occurs in approximately 15% of patients with ventricular septal defect but may also occur as an isolated phenomenon or as a consequence of myxomatous degeneration sometimes associated with mitral (see "Mitral Valve Prolapse") and/or tricuspid valve involvement.
AR may result from infective endocarditis, which can develop on a valve previously affected by rheumatic disease, a congenitally deformed valve, or, rarely, on a normal aortic valve, and may lead to perforation or erosion of one or more leaflets. The aortic valve leaflets may become scarred and retracted during the course of syphilis or ankylosing spondylitis and contribute further to the AR that derives primarily from the associated root disease. Although traumatic rupture or avulsion of the aortic valve is an uncommon cause of acute AR, it does represent the most frequent serious lesion in patients surviving nonpenetrating cardiac injuries. The coexistence of hemodynamically significant AS with AR usually excludes all the rarer forms of AR because it occurs almost exclusively in patients with rheumatic or congenital AR. In patients with AR due to primary valvular disease, dilatation of the aortic annulus may occur secondarily and intensify the regurgitation.
Primary Aortic Root Disease
AR may also be due entirely to marked aortic dilatation, i.e., aortic root disease, without primary involvement of the valve leaflets; widening of the aortic annulus and separation of the aortic leaflets are responsible for the AR. Cystic medial degeneration of the ascending aorta, which may or may not be associated with other manifestations of Marfan syndrome; idiopathic dilatation of the aorta; annulo-aortic ectasia; osteogenesis imperfecta; and severe hypertension may all widen the aortic annulus and lead to progressive AR. Occasionally AR is caused by retrograde dissection of the aorta involving the aortic annulus. Syphilis and ankylosing spondylitis, both of which may affect aortic valves, may also be associated with cellular infiltration and scarring of the media of the thoracic aorta, leading to aortic dilatation, aneurysm formation, and severe regurgitation. In syphilis of the aorta, now a very rare condition, the involvement of the intima may narrow the coronary ostia, which in turn may be responsible for myocardial ischemia.
Pathophysiology
The total stroke volume ejected by the LV (i.e., the sum of the effective forward stroke volume and the volume of blood that regurgitates back into the LV) is increased in patients with AR. In patients with wide-open (free) AR, the volume of regurgitant flow may equal the effective forward stroke volume. In contrast to MR, in which a fraction of the LV stroke volume is delivered into the low-pressure LA, in AR the entire LV stroke volume is ejected into a high-pressure zone, the aorta. An increase in the LV end-diastolic volume (increased preload) constitutes the major hemodynamic compensation for AR. The dilatation and eccentric hypertrophy of the LV allow this chamber to eject a larger stroke volume without requiring any increase in the relative shortening of each myofibril. Therefore, severe AR may occur with a normal effective forward stroke volume and a normal left ventricular EF [total (forward plus regurgitant) stroke volume/end-diastolic volume], together with an elevated LV end-diastolic pressure and volume. However, through the operation of Laplace's law, LV dilatation increases the LV systolic tension required to develop any given level of systolic pressure. Chronic AR is thus a state in which LV preload and afterload are both increased. Ultimately, these adaptive measures fail. As LV function deteriorates, the end-diastolic volume rises further and the forward stroke volume and EF decline. Deterioration of LV function often precedes the development of symptoms. Considerable thickening of the LV wall also occurs with chronic AR, and at autopsy the hearts of these patients may be among the largest encountered, sometimes weighing >1000 g.
The reverse pressure gradient from aorta to LV, which drives the AR flow, falls progressively during diastole (see Fig. 223-5), accounting for the decrescendo nature of the diastolic murmur. Equilibration between aortic and LV pressures may occur toward the end of diastole in patients with chronic severe AR, particularly when the heart rate is slow. In patients with acute severe AR, the LV is unprepared for the regurgitant volume load. LV compliance is normal or reduced, and LV diastolic pressures rise rapidly, occasionally to levels >40 mmHg. The LV pressure may exceed the LA pressure toward the end of diastole, and this reversed pressure gradient closes the mitral valve prematurely.
In patients with chronic severe AR, the effective forward CO usually is normal or only slightly reduced at rest, but often it fails to rise normally during exertion. Early signs of LV dysfunction include reduction in the EF. In advanced stages there may be considerable elevation of the LA, PA wedge, PA, and RV pressures and lowering of the forward CO at rest.
Myocardial ischemia may occur in patients with AR because myocardial oxygen requirements are elevated by LV dilatation, hypertrophy, and elevated LV systolic tension. However, a large fraction of coronary blood flow occurs during diastole, when arterial pressure is subnormal, thereby reducing coronary perfusion pressure. This combination of increased oxygen demand and reduced supply may cause myocardial ischemia, particularly of the subendocardium, even in the absence of concomitant CAD.
History
Approximately three-fourths of patients with pure or predominant valvular AR are males; females predominate among patients with primary valvular AR who have associated mitral valve disease. A history compatible with infective endocarditis may sometimes be elicited from patients with rheumatic or congenital involvement of the aortic valve, and the infection often precipitates or seriously aggravates preexisting symptoms.
In patients with acute severe AR, as may occur in infective endocarditis, aortic dissection, or trauma, the LV cannot dilate sufficiently to maintain stroke volume, and LV diastolic pressure rises rapidly with associated marked elevations of LA and PA wedge pressures. Pulmonary edema and/or cardiogenic shock may develop rapidly.
Chronic severe AR may have a long latent period, and patients may remain relatively asymptomatic for as long as 10–15 years. However, uncomfortable awareness of the heartbeat, especially on lying down, may be an early complaint. Sinus tachycardia, during exertion or with emotion, or premature ventricular contractions may produce particularly uncomfortable palpitations as well as head pounding. These complaints may persist for many years before the development of exertional dyspnea, usually the first symptom of diminished cardiac reserve. The dyspnea is followed by orthopnea, paroxysmal nocturnal dyspnea, and excessive diaphoresis. Anginal chest pain occurs frequently in patients with severe AR, even in younger patients, and it is not necessary to invoke the presence of CAD to explain this symptom in patients with severe AR. Anginal pain may develop at rest as well as during exertion. Nocturnal angina may be a particularly troublesome symptom, and it may be accompanied by marked diaphoresis. The anginal episodes can be prolonged and often do not respond satisfactorily to sublingual nitroglycerin. Systemic fluid accumulation, including congestive hepatomegaly and ankle edema, may develop late in the course of the disease.
Physical Findings
In chronic severe AR, the jarring of the entire body and the bobbing motion of the head with each systole can be appreciated, and the abrupt distention and collapse of the larger arteries are easily visible. The examination should be directed toward the detection of conditions predisposing to AR, such as Marfan syndrome, ankylosing spondylitis, and ventricular septal defect.
Arterial Pulse
A rapidly rising "water-hammer" pulse, which collapses suddenly as arterial pressure falls rapidly during late systole and diastole (Corrigan's pulse), and capillary pulsations, an alternate flushing and paling of the skin at the root of the nail while pressure is applied to the tip of the nail (Quincke's pulse), are characteristic of free AR. A booming "pistol-shot" sound can be heard over the femoral arteries (Traube's sign), and a to-and-fro murmur (Duroziez's sign) is audible if the femoral artery is lightly compressed with a stethoscope.
The arterial pulse pressure is widened, and there is an elevation of the systolic pressure, sometimes to as high as 300 mmHg, and a depression of the diastolic pressure. The measurement of arterial diastolic pressure with a sphygmomanometer may be complicated by the fact that systolic sounds are frequently heard with the cuff completely deflated. However, the level of cuff pressure at the time of muffling of the Korotkoff sounds (Phase IV) generally corresponds fairly closely to the true intraarterial diastolic pressure. As the disease progresses and the LV end-diastolic pressure rises, the arterial diastolic pressure may actually rise as well, since the aortic diastolic pressure cannot fall below the LV end-diastolic pressure. For the same reason, acute severe AR may also be accompanied by only a slight widening of the pulse pressure. Such patients are invariably tachycardic as the heart rate increases in an attempt to preserve the CO.
Palpation
In patients with chronic severe AR, the LV impulse is heaving and displaced laterally and inferiorly. The systolic expansion and diastolic retraction of the apex are prominent. A diastolic thrill is often palpable along the left sternal border, and a prominent systolic thrill may be palpable in the suprasternal notch and transmitted upward along the carotid arteries. This systolic thrill and the accompanying murmur do not necessarily signify the coexistence of AS. In many patients with pure AR or with combined AS and AR, the carotid arterial pulse is bisferiens, i.e., with two systolic waves separated by a trough (see Fig. 220-2D).
Auscultation
In patients with severe AR, the aortic valve closure sound (A2) is usually absent. An S3 and systolic ejection sound are frequently audible, and occasionally an S4 also may be heard. The murmur of chronic AR is typically a high-pitched, blowing, decrescendo diastolic murmur, heard best in the third intercostal space along the left sternal border (see Fig. 220-4B). In patients with mild AR, this murmur is brief but, as the severity increases, generally becomes louder and longer, indeed holodiastolic. When the murmur is soft, it can be heard best with the diaphragm of the stethoscope and with the patient sitting up, leaning forward, and with the breath held in forced expiration. In patients in whom the AR is caused by primary valvular disease, the diastolic murmur is usually louder along the left than the right sternal border. However, when the murmur is heard best along the right sternal border, it suggests that the AR is caused by aneurysmal dilatation of the aortic root. "Cooing" or musical diastolic murmurs suggest eversion of an aortic cusp vibrating in the regurgitant stream.
A mid-systolic ejection murmur is frequently audible in isolated AR. It is generally heard best at the base of the heart and is transmitted along the carotid vessels. This murmur may be quite loud without signifying aortic obstruction. A third murmur frequently heard in patients with severe AR is the Austin Flint murmur, a soft, low-pitched, rumbling mid-diastolic murmur. It is probably produced by the diastolic displacement of the anterior leaflet of the mitral valve by the AR stream but does not appear to be associated with hemodynamically significant mitral obstruction. The auscultatory features of AR are intensified by strenuous handgrip, which augments systemic resistance.
In acute severe AR, the elevation of LV end-diastolic pressure may lead to early closure of the mitral valve, an associated mid-diastolic sound, a soft or absent S1, a pulse pressure that is not particularly wide, and a soft, short diastolic murmur of AR.
Laboratory Examination
ECG
In patients with chronic severe AR, the ECG signs of LV hypertrophy become manifest. In addition, these patients frequently exhibit ST-segment depression and T-wave inversion in leads I, aVL, V5, and V6 ("LV strain"). Left axis deviation and/or QRS prolongation denote diffuse myocardial disease, generally associated with patchy fibrosis, and usually signify a poor prognosis.
Echocardiogram
The extent and velocity of wall motion are normal or even supernormal, until myocardial contractility declines. A rapid, high-frequency fluttering of the anterior mitral leaflet produced by the impact of the regurgitant jet is a characteristic finding. The echocardiogram is also useful in determining the cause of AR, by detecting dilatation of the aortic annulus and root or aortic dissection (see Fig. 222-3). Thickening and failure of coaptation of the leaflets also may be noted. Color flow Doppler echocardiographic imaging is very sensitive in the detection of AR, and Doppler echocardiography is helpful in assessing its severity. With severe AR, the central jet width exceeds 65% of the left ventricular outflow tract, the regurgitant volume is >60 ml/beat, the regurgitant fraction is >50%, and there is diastolic flow reversal in the proximal descending thoracic aorta. The continuous wave Doppler profile shows a rapid deceleration time in patients with acute severe AR, due to the rapid increase in LV diastolic pressure. Serial two-dimensional echocardiography is valuable in assessing LV performance and in detecting progressive myocardial dysfunction.
Chest X-Ray
In chronic severe AR, the apex is displaced downward and to the left in the frontal projection. In the left anterior oblique and lateral projections, the LV is displaced posteriorly and encroaches on the spine. When AR is caused by primary disease of the aortic root, aneurysmal dilatation of the aorta may be noted, and the aorta may fill the retrosternal space in the lateral view. Echocardiography and CT angiography are more sensitive than the chest x-ray for the detection of aortic root enlargement.
Cardiac Catheterization and Angiography
When needed, right and left heart catheterization with contrast aortography can provide accurate confirmation of the magnitude of regurgitation and the status of LV function. Coronary angiography is performed routinely in appropriate patients prior to surgery.
Aortic Regurgitation: Treatment
Management strategy for patients with chronic severe aortic regurgitation. Preoperative coronary angiography should be performed routinely, as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography. "Stable" refers to stable echocardiographic measurements. In some centers, serial follow-up may be performed with radionuclide ventriculography (RVG) or magnetic resonance imaging (MRI) rather than echocardiography (echo) to assess left ventricular (LV) volume and systolic function. AVR, aortic valve replacement; DD, end-diastolic dimension; EF, ejection fraction; eval, evaluation; SD, end-systolic dimension. (Modified from Bonow et al.)
Acute Aortic Regurgitation
Patients with acute severe AR may respond to intravenous diuretics and vasodilators (such as sodium nitroprusside), but stabilization is usually short-lived and operation is indicated urgently. Intraaortic balloon counterpulsation is contraindicated. Beta-blockers are also best avoided so as not to reduce the CO further or slow the heart rate, which might allow proportionately more time in diastole for regurgitation to occur. Surgery is the treatment of choice.
Chronic Aortic Regurgitation
Early symptoms of dyspnea and effort intolerance respond to treatment with diuretics and vasodilators (ACE inhibitors, dihydropyridine calcium channel blockers, or hydralazine) may be useful as well. Surgery can then be performed in more controlled circumstances. The use of vasodilators to extend the compensated phase of chronic severe AR before the onset of symptoms or the development of LV dysfunction is more controversial. Expert consensus is strong regarding the need to control systolic blood pressure (goal <140>
Surgical Treatment
In deciding on the advisability and proper timing of surgical treatment, two points should be kept in mind: (1) patients with chronic severe AR usually do not become symptomatic until after the development of myocardial dysfunction; and (2) when delayed too long (defined as >1 year from onset of symptoms or LV dysfunction), surgical treatment often does not restore normal LV function. Therefore, in patients with chronic severe AR, careful clinical follow-up and noninvasive testing with echocardiography at approximately 6-month intervals are necessary if operation is to be undertaken at the optimal time, i.e., after the onset of LV dysfunction but prior to the development of severe symptoms. Operation can be deferred as long as the patient both remains asymptomatic and retains normal LV function.
AVR is indicated for the treatment of severe AR in symptomatic patients irrespective of LV function. In general, operation should be carried out in asymptomatic patients with severe AR and progressive LV dysfunction defined by an LVEF <50%, st="on">LV end-systolic dimension >55mm or end-systolic volume >55 mL/m2, or an LV diastolic dimension >75 mm. Smaller dimensions may be appropriate thresholds in individuals of smaller stature. Patients with severe AR without indications for operation should be followed by clinical and echocardiographic examination every 3–12 months.
Surgical options for management of aortic valve and root disease have expanded considerably over the past decade. AVR with a suitable mechanical or tissue prosthesis is generally necessary in patients with rheumatic AR and in many patients with other forms of regurgitation. Rarely, when a leaflet has been perforated during infective endocarditis or torn from its attachments to the aortic annulus by thoracic trauma, primary surgical repair may be possible. When AR is due to aneurysmal dilatation of the annulus and ascending aorta rather than to primary valvular involvement, it may be possible to reduce the regurgitation by narrowing the annulus or by excising a portion of the aortic root without replacing the valve. Resuspension of the native aortic valve leaflets is possible in approximately 50% of patients with acute AR in the setting of Type A aortic dissection. In other conditions, however, regurgitation can be eliminated only by replacing the aortic valve, excising the dilated or aneurysmal ascending aorta responsible for the regurgitation, and replacing it with a graft. This formidable procedure entails a higher risk than isolated AVR.
As in patients with other valvular abnormalities, both the operative risk and the late mortality are largely dependent on the stage of the disease and on myocardial function at the time of operation. The overall operative mortality for isolated AVR is about 3% (Table 3). However, patients with marked cardiac enlargement and prolonged LV dysfunction experience an operative mortality rate of approximately 10% and a late mortality rate of approximately 5% per year due to LV failure despite a technically satisfactory operation. Nonetheless, because of the very poor prognosis with medical management, even patients with LV failure should be considered for operation.
Patients with acute severe AR require prompt surgical treatment, which may be lifesaving.
Tricuspid Stenosis
TS, much less prevalent than MS in North America and Western Europe, is generally rheumatic in origin and is more common in females than in males. It does not occur as an isolated lesion and is usually associated with MS. Hemodynamically significant TS occurs in 5–10% of patients with severe MS; rheumatic TS is commonly associated with some degree of TR. Nonrheumatic causes of TS are rare.
Pathophysiology
A diastolic pressure gradient between the RA and RV defines TS. It is augmented when the transvalvular blood flow increases during inspiration and declines during expiration. A mean diastolic pressure gradient of 4 mmHg is usually sufficient to elevate the mean RA pressure to levels that result in systemic venous congestion. Unless sodium intake has been restricted and diuretics administered, this venous congestion is associated with hepatomegaly, ascites, and edema, sometimes severe. In patients with sinus rhythm, the RA a wave may be extremely tall and may even approach the level of the RV systolic pressure. The y descent is prolonged. The CO at rest is usually depressed, and it fails to rise during exercise. The low CO is responsible for the normal or only slightly elevated LA, PA, and RV systolic pressures despite the presence of MS. Thus, the presence of TS can mask the hemodynamic and clinical features of the MS, which usually accompanies it.
Symptoms
Since the development of MS generally precedes that of TS, many patients initially have symptoms of pulmonary congestion. Spontaneous improvement of these symptoms should raise the possibility that TS may be developing. Characteristically, patients complain of relatively little dyspnea for the degree of hepatomegaly, ascites, and edema that they have. However, fatigue secondary to a low CO and discomfort due to refractory edema, ascites, and marked hepatomegaly are common in patients with TS and/or TR. In some patients, TS may be suspected for the first time when symptoms of right-sided failure persist after an adequate mitral valvotomy.
Physical Findings
Since TS usually occurs in the presence of other obvious valvular disease, the diagnosis may be missed unless it is considered and searched for. Severe TS is associated with marked hepatic congestion, often resulting in cirrhosis, jaundice, serious malnutrition, anasarca, and ascites. Congestive hepatomegaly and, in cases of severe tricuspid valve disease, splenomegaly are present. The jugular veins are distended, and in patients with sinus rhythm there may be giant a waves. The v waves are less conspicuous, and since tricuspid obstruction impedes RA emptying during diastole, there is a slow y descent. In patients with sinus rhythm there may be prominent presystolic pulsations of the enlarged liver as well.
On auscultation, an OS of the tricuspid valve may occasionally be heard approximately 0.06 s after pulmonic valve closure. The diastolic murmur of TS has many of the qualities of the diastolic murmur of MS, and since TS almost always occurs in the presence of MS, the less-common valvular lesion may be missed. However, the tricuspid murmur is generally heard best along the left lower sternal margin and over the xiphoid process, and it is most prominent during presystole in patients with sinus rhythm. The murmur of TS is augmented during inspiration, and it is reduced during expiration and particularly during the strain phase of the Valsalva maneuver, when tricuspid blood flow is reduced.
Laboratory Examination
The ECG features of RA enlargement (see Fig. 221-8) include tall, peaked P waves in lead II, as well as prominent, upright P waves in lead V1. The absence of ECG evidence of right ventricular hypertrophy (RVH) in a patient with right-sided heart failure who is believed to have MS should suggest associated tricuspid valve disease. The chest x-ray in patients with combined TS and MS shows particular prominence of the RA and superior vena cava without much enlargement of the PA and with less evidence of pulmonary vascular congestion than occurs in patients with isolated MS. On echocardiographic examination, the tricuspid valve is usually thickened and domes in diastole; the transvalvular gradient can be estimated by Doppler echocardiography. TTE provides additional information regarding mitral valve structure and function, LV and RV size and function, and PA pressure.
Tricuspid Stenosis: Treatment
Patients with TS generally exhibit marked systemic venous congestion; intensive salt restriction, bed rest, and diuretic therapy are required during the preoperative period. Such a preparatory period may diminish hepatic congestion and thereby improve hepatic function sufficiently so that the risks of operation, particularly bleeding, are diminished. Surgical relief of the TS should be carried out, preferably at the time of surgical mitral valvotomy or MVR, in patients with moderate or severe TS who have mean diastolic pressure gradients exceeding ~4 mmHg and tricuspid orifice areas <1.5–2.0>2. TS is almost always accompanied by significant TR. Operative repair may permit substantial improvement of tricuspid valve function. If repair cannot be accomplished, the tricuspid valve may have to be replaced with a prosthesis, preferably a large bioprosthetic valve. Mechanical valves in the tricuspid position are more prone to thromboembolic complications than in other positions.
Tricuspid Regurgitation
Most commonly, TR is functional and secondary to marked dilatation of the tricuspid annulus. Functional TR may complicate RV enlargement of any cause, including inferior wall infarcts that involve the RV. It is commonly seen in the late stages of heart failure due to rheumatic or congenital heart disease with severe pulmonary hypertension (pulmonary artery systolic pressure >55 mmHg), as well as in ischemic heart disease and dilated cardiomyopathy. It is reversible in part if pulmonary hypertension is relieved. Rheumatic fever may produce organic (primary) TR, often associated with TS. Infarction of RV papillary muscles, tricuspid valve prolapse, carcinoid heart disease, endomyocardial fibrosis, infective endocarditis, and trauma all may produce TR. Less commonly, TR results from congenitally deformed tricuspid valves, and it occurs with defects of the atrioventricular canal, as well as with Ebstein's malformation of the tricuspid valve. TR also develops eventually in patients with chronic RV apical pacing.
As is the case for TS, the clinical features of TR result primarily from systemic venous congestion and reduction of CO. With the onset of TR in patients with pulmonary hypertension, symptoms of pulmonary congestion diminish, but the clinical manifestations of right-sided heart failure become intensified. The neck veins are distended with prominent v waves and rapid y descents, marked hepatomegaly, ascites, pleural effusions, edema, systolic pulsations of the liver, and a positive hepatojugular reflux. A prominent RV pulsation along the left parasternal region and a blowing holosystolic murmur along the lower left sternal margin, which may be intensified during inspiration and reduced during expiration or the strain of the Valsalva maneuver (Carvallo's sign), are characteristic findings; AF is usually present.
The ECG usually shows changes characteristic of the lesion responsible for the enlargement of the RV that leads to TR, e.g., inferior wall myocardial infarction or severe RVH. Echocardiography may be helpful by demonstrating RV dilatation and prolapsing, flail, scarred, or displaced tricuspid leaflets; the diagnosis of TR can be made by color flow Doppler echocardiography, and its severity can be estimated by Doppler examination (see Fig. 222-4). Severe TR is accompanied by hepatic vein systolic flow reversal. Continuous wave Doppler is also useful in estimating PA pressure. Roentgenographic examination usually reveals enlargement of both the RA and RV.
In patients with severe TR, the CO is usually markedly reduced, and the RA pressure pulse may exhibit no x descent during early systole but a prominent c-v wave with a rapid y descent. The mean RA and the RV end-diastolic pressures are often elevated.
Tricuspid Regurgitation: Treatment
Isolated TR, in the absence of pulmonary hypertension, such as that occurring as a consequence of infective endocarditis or trauma, is usually well tolerated and does not require operation. Indeed, even total excision of an infected tricuspid valve may be well tolerated for several years if the PA pressure is normal. Treatment of the underlying cause of heart failure usually reduces the severity of functional TR, by reducing the size of the tricuspid annulus. In patients with mitral valve disease and TR secondary to pulmonary hypertension and massive RV enlargement, effective surgical correction of the mitral valvular abnormality results in lowering of the PA pressures and gradual reduction or disappearance of the TR without direct treatment of the tricuspid valve. However, recovery may be much more rapid in patients with severe secondary TR if, at the time of mitral valve surgery, and especially when there is measurable enlargement of the tricuspid valve annulus, tricuspid annuloplasty (generally with the insertion of a plastic ring), open tricuspid valve repair, or, in the rare instance of severe organic tricuspid valve disease, tricuspid valve replacement is performed (Table 3). Tricuspid annuloplasty or replacement may be required for severe TR with primary involvement of the valve.
Pulmonic Valve Disease
The pulmonic valve is affected by rheumatic fever far less frequently than are the other valves, and it is uncommonly the seat of infective endocarditis. The most common acquired abnormality affecting the pulmonic valve is regurgitation secondary to dilatation of the pulmonic valve ring as a consequence of severe pulmonary hypertension. This produces the Graham Steell murmur, a high-pitched, decrescendo, diastolic blowing murmur along the left sternal border, which is difficult to differentiate from the far more common murmur produced by AR. Pulmonic regurgitation is usually of little hemodynamic significance; indeed, surgical removal or destruction of the pulmonic valve by infective endocarditis does not produce heart failure unless serious pulmonary hypertension is also present.
The carcinoid syndrome may cause pulmonic stenosis and/or regurgitation. Pulmonic regurgitation occurs universally among patients who have undergone childhood repair of Tetralogy of Fallot with reconstruction of the RV outflow tract.
Valve Replacement
The results of replacement of any valve are dependent primarily on (1) the patient's myocardial function and general medical condition at the time of operation; (2) the technical abilities of the operative team and the quality of the postoperative care; and (3) the durability, hemodynamic characteristics, and thrombogenicity of the prosthesis. Increased perioperative mortality is associated with advanced age and comorbidity (e.g., pulmonary or renal disease, the need for nonvalvular cardiovascular surgery, diabetes mellitus) as well as with greater levels of preoperative functional disability and pulmonary hypertension. Late complications of valve replacement include paravalvular leakage, thromboemboli, bleeding due to anticoagulants, structural deterioration of the prosthesis, and infective endocarditis.
The considerations involved in the choice between a bioprosthetic (tissue) and artificial mechanical valve are similar in the mitral and aortic positions and in the treatment of stenotic, regurgitant, or mixed lesions. All patients who have undergone replacement of any valve with a mechanical prosthesis are at risk of thromboembolic complications and must be maintained permanently on anticoagulants, a treatment that imposes a hazard of hemorrhage. The primary advantage of bioprostheses over mechanical prostheses is the virtual absence of thromboembolic complications 3 months after implantation, and except for patients with chronic AF, few such instances have been associated with their use. The major disadvantage of bioprosthetic valves is their structural deterioration, the incidence of which is inversely proportional to the patient's age. This deterioration results in the need to replace the prosthesis in up to 30% of patients by 10 years and in 50% by 15 years. Rates of structural valve deterioration are higher for mitral than for aortic bioprostheses. This phenomenon may be due in part to the greater closing pressure to which a mitral prosthesis is exposed.
Traditionally, a mechanical prosthesis was considered preferable for a patient under age 65 who could take anticoagulation reliably. Bioprostheses were recommended for older patients (>65 years) who did not otherwise have an indication for anticoagulation (for example, AF). However, more recent surveys of cardiac surgery in the United States, as reflected in the Society of Thoracic Surgeons database, show a clear and progressive trend favoring the implantation of bioprosthetic valves in younger (<65>
Bioprostheses remain the preferred valve choice for patients >65 years, in both the aortic and mitral position. Bioprosthetic valves are also indicated for women who expect to become pregnant, as well as for others who refuse to take anticoagulation or for whom anticoagulation may be contraindicated. Types of bioprostheses include xenografts (i.e., porcine aortic valves; cryopreserved, mounted bovine pericardium), homograft (allograft) aortic valves obtained from cadavers, as well as pulmonary autografts transplanted into the aortic position. Homograft replacement may be preferred for the management of complicated aortic valve infective endocarditis.
In patients without contraindications to anticoagulants, particularly those under 65 years, a mechanical prosthesis is reasonable. Many surgeons now select the St. Jude prosthesis, a double-disk tilting prosthesis, for replacement of both aortic and mitral valves because of favorable hemodynamic characteristics and possible association with lower thrombogenicity.
Global Burden of Valvular Heart Disease
Primary valvular heart disease ranks well below coronary heart disease, stroke, hypertension, obesity, and diabetes as major threats to the public health. Nevertheless, it is the source of significant morbidity and mortality. Rheumatic fever is the dominant cause of valvular heart disease in developing countries. Its prevalence has been estimated to range from as low as 1.0 per 100,000 school-age children in Costa Rica to as high as 150 per 100,000 in China. Rheumatic heart disease accounts for 12–65% of hospital admissions related to cardiovascular disease and 2–10% of hospital discharges in some developing countries. Prevalence and mortality rates vary among communities even within the same country as a function of crowding and the availability of medical resources and population-wide programs for detection and treatment of Group A streptococcal pharyngitis. In economically deprived areas, tropical and subtropical climates (particularly on the Indian subcontinent), Central America, and the Middle East, rheumatic valvular disease progresses more rapidly than in more-developed nations and frequently causes serious symptoms in patients <20>
TS, a relatively uncommon valvular lesion in North America and Western Europe, is more common in tropical and subtropical climates, especially in southern Asia and in Latin America.
As of the year 2000, worldwide death rates for rheumatic heart disease approximated 5.5 per 100,000 population (n = 332,000), with the highest rates reported from Southeast Asia. Although there have been reports of recent isolated outbreaks of streptococcal infection in North America, valve disease in developed countries is now dominated by degenerative or inflammatory processes that lead to valve thickening, calcification, and dysfunction. The prevalence of valvular heart disease increases with age. Important left-sided valve disease may affect as many as 12–13% of adults over the age of 75.
The incidence of infective endocarditis has increased with the aging of the population, the more widespread prevalence of vascular grafts and intracardiac devices, the emergence of more virulent multidrug-resistant microorganisms, and the growing epidemic of diabetes. Infective endocarditis has become a more frequent cause of acute valvular regurgitation.
Bicuspid aortic valve disease affects as many as 1–2% of the population, and an increasing number of childhood survivors of congenital heart disease present later in life with valvular dysfunction. The past several years have witnessed significant improvements in surgical outcomes with progressive refinement of relatively less-invasive techniques. Percutaneous heart valve replacement or repair is under active clinical investigation.
Figure 1 Timetable of development of the body systems. The development of individual systems can be seen progressing from left to right. Embryonic stages, weeks of development and embryo length are shown. Embryonic stages are associated with external and internal morphological features rather than embryonic length. To identify the systems and organs at risk at any time of development, follow a vertical progression from top to bottom. (Click Image to Enlarge)
Figure 2 The two timescales used to depict human development. Embryonic development, in the upper scale, is counted from fertilization (or from ovulation, i.e. in postovulatory days; see O'Rahilly & Muller 1987). Throughout this book, times given for development are based on this scale. The clinical estimation of pregnancy is counted from the last menstrual period and is shown on the lower scale; throughout this book, fetal ages relating to neonatal anatomy and growth will have been derived from the lower scale. Note that there is a 2 week discrepancy between these scales. The perinatal period is very long, because it includes all preterm deliveries.
Figure 11.4 Topographical representation of the anatomy of a full-term neonate. The surface markings of all organs are shown, with some coloured and others only in outline. The female genital tract is shown on the right of the body in C, with the male tract on the left.
Figure 4. The extent of the ossified skeleton in the full term neonate. Note the derivation of the parts of the skeleton: the skull is derived from paraxial mesenchyme and neural crest mesenchyme; the axial skeleton, vertebrae and ribs are derived from paraxial mesenchyme; the skeletal elements in the limbs are derived from the somatopleuric mesenchyme, which forms the limb buds.
50 mmHg at rest or 
