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Hypertrophic Obstructive Cardiomyopathy
Definition
Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disorder characterized by left and/or right ventricular hypertrophy that is usually, but not always, asymmetric and is associated with microscopic evidence of myocardial fiber disarray and fibrosis. Degree of hypertrophy at any given site can vary substantially and influences clinical manifestations of the disease.
Ventricular septal hypertrophy is the most common type of asymmetric hypertrophy, with midventricular, apical, and other types occurring much less frequently. Forms interfering with left ventricular (LV) emptying, termed hypertrophic obstructive cardiomyopathy (HOCM) or (obsolete) idiopathic hypertrophic subaortic stenosis (IHSS), are of surgical importance and are characterized by a variable dynamic obstruction that is usually subaortic and is associated with abnormal systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. The more commonly occurring nonobstructive forms are not amenable to surgical treatment except for cardiac transplantation (see Chapter 21 ). Prevalence of HCM in the general population is about 1 in 500 (0.2%).
Historical Note
Pathologic findings compatible with HOCM were described by two 19th-century French pathologists, Hallopeau and Liouiville, and an early 20th-century German pathologist, Schmincke. In 1952, Davies described a family from Cardiff, Wales, with five of nine siblings affected and three dying suddenly who probably had this disease. Although these reports and the surgical report of Brock in 1957 described diffuse muscular subaortic stenosis, the disease was first accurately categorized by Teare, a London pathologist, in 1958. Teare described both disproportionate thickening of the ventricular septum compared with the free wall and presence of myocardial fiber disarray in young people who died suddenly. These pathologic findings were rapidly confirmed, and clinical features were further elucidated by Braunwald and colleagues and others. To distinguish it from other cardiomyopathies, Goodwin and colleagues named it hypertrophic obstructive cardiomyopathy , whereas Braunwald and colleagues called it idiopathic hypertrophic subaortic stenosis and Wigle and colleagues, muscular subaortic stenosis .
At that time, LV outflow tract obstruction was thought to be distinctive for the disease. That the anterior mitral leaflet contributed to the obstruction was first documented in 1964 by Fix and colleagues, and SAM of the mitral valve was subsequently demonstrated angiographically. By the mid-1960s, HCM was a well-defined clinical entity, with the realization that some patients had a form of the disease characterized by no or minimal obstruction. Particular attention was paid to this group of patients by Goodwin and Oakley, who emphasized the importance of reduced LV compliance as the major determinant of cardiac dysfunction (“inflow” or diastolic obstruction) rather than outflow obstruction. Knowledge that nonobstructive HCM was much more common awaited introduction of echocardiography, which detected asymmetric septal hypertrophy (ASH), one of the hallmarks of the disease, as well as the presence or absence of SAM. During the early 1970s, ASH and SAM were thought to be specific for HCM, but this is now known to be incorrect. Echocardiography not only established that HCM is relatively common, but also that it is usually genetically transmitted rather than sporadic.
Surgical awareness of the obstructive form of the disease began with Brock's reports in 1957 and 1959. However, in his patients and in the first patient operated on at Mayo Clinic in February 1958, nothing was done surgically, because the nature of the disease was not understood. Credit for the first myotomy, consisting of a simple incision of the prominent anterior muscular ridge in the septum, probably belongs to Cleland. Myotomy was used by a number of other surgeons about this same time.
At Mayo Clinic, a left ventriculotomy was performed to allow adequate excision (myectomy) of muscle under direct vision. Over the next few years the surgical approach to septal myectomy was modified in several ways. Dobell and Scott used a left atrial approach, exposing the hypertrophied septum by dividing the anterior mitral leaflet across its center, whereas Lillehei and Levy used a similar approach but detached the base of the anterior mitral leaflet near the anulus. Swan used a corkscrew to excise septal muscle from a limited LV approach. Julian and colleagues used a “fish mouth” LV incision that detached the lower part of the free wall from the septum and gave excellent exposure of the subaortic septal bulge, which was then excised. Cooley and colleagues developed an approach through the right ventricle used first by Harken, in which septal muscle was shaved off the right ventricular side, judging septal thickness by means of a finger inserted into the LV through the aortic valve. None of these techniques is currently in use.
Simple myotomy using an aortic approach was used for a time by the Toronto group. Later, they modified the procedure to include excision of muscle (myectomy) as advocated by Morrow. Other procedures have also been used, including mitral valve replacement by Cooley and colleagues, use of an LV-aortic valved conduit to bypass the obstruction, and a modified Konno procedure preserving the aortic valve (see “ Modified Konno Operation ” under Technique of Operation in Section II of Chapter 47 ).
Morphogenesis and Morphology
Morphogenesis
HCM is caused by a missense mutation in one of at least 11 genes that encode the proteins of the cardiac sarcomere. These include mutations in the β-myosin heavy-chain gene (chromosome 14q11-q12), in cardiac troponin-T (chromosome 1), and in α-tropomyosin (chromosome 15q2). It is transmitted as an autosomal dominant trait, although nonfamilial cases probably occur as well.
Morphology
Muscular hypertrophy present in HCM involves the interventricular septum and LV, and is variable in its location and severity.
Ventricular Septum
In classic HOCM, hypertrophy is maximal in the cephalad portion of the ventricular septum ( Fig. 19-1 ). Point of maximal thickening lies just apical (caudad) to the free edge of the anterior mitral leaflet in its open position. This muscular prominence (mound) tapers off gradually toward the LV-aortic junction and toward the apex. At the point opposite the free edge of the anterior mitral leaflet, LV endocardium is often thickened by a localized plaque of fibrous tissue that lies at right angles to the long axis of the outflow tract. Because it is present in both nonobstructive and obstructive forms of HCM, this plaque is presumably related to contact between the anterior mitral leaflet and septal bulge in diastole rather than systole, with the leaflet snapping open rapidly at the onset of diastole (in part because of high left atrial pressure) and contacting the ventricular septal prominence.
![Figure 19-1, Ventricular septal hypertrophy in hypertrophic obstructive cardiomyopathy. Longitudinal section of heart from a 32-year-old woman who died suddenly while receiving propranolol therapy. Hemodynamic investigation had confirmed presence of subaortic obstruction and mitral regurgitation, partially resulting from an abnormal mitral valve (insertion of anomalous papillary muscle [arrow] onto the ventricular surface of the anterior mitral leaflet). Note asymmetric hypertrophy with grossly thickened ventricular septum and narrowed outflow tract between upper septum and anterior mitral leaflet, which is very thickened and fibrosed from repeated mitral leaflet–septal contact. There was microscopic evidence of extensive myocardial fiber disarray involving both septum and free wall of the left ventricle.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/HypertrophicObstructiveCardiomyopathy/0_3s20B978141606391900019X.jpg "Figure 19-1, Ventricular septal hypertrophy in hypertrophic obstructive cardiomyopathy. Longitudinal section of heart from a 32-year-old woman who died suddenly while receiving propranolol therapy. Hemodynamic investigation had confirmed presence of subaortic obstruction and mitral regurgitation, partially resulting from an abnormal mitral valve (insertion of anomalous papillary muscle [arrow] onto the ventricular surface of the anterior mitral leaflet). Note asymmetric hypertrophy with grossly thickened ventricular septum and narrowed outflow tract between upper septum and anterior mitral leaflet, which is very thickened and fibrosed from repeated mitral leaflet–septal contact. There was microscopic evidence of extensive myocardial fiber disarray involving both septum and free wall of the left ventricle.")
Ventricular septal hypertrophy is not always maximal in its anterior basal parts. Occasionally, it may be maximal at a site below the anterior mitral leaflet adjacent to the papillary muscles, producing midventricular hypertrophy leading to obstruction, to which the papillary muscles and free-wall hypertrophy contribute ( Fig. 19-2 ). There is no SAM or mitral regurgitation. Apical LV aneurysm in the presence of normal coronary arteries occasionally occurs with midventricular hypertrophy. Hypertrophy may be confined to the posterior or apical septum. Localized apical hypertrophy is apparently most common among the Japanese. Occasionally the entire septum may be of uniform thickness.
Dynamic Morphology of Septum and Mitral Valve
When septal hypertrophy is classic, obstruction is sited in the LV outflow tract between the hypertrophied ventricular septum and anterior mitral leaflet. In systole the posterior mitral leaflet closes against the body of the elongated anterior leaflet at about the junction of the middle and free-edge thirds (rather than near the free edge as in the normal heart). The free-edge portion of the anterior mitral leaflet beyond the point of coaptation hinges (angulates) on the remainder of the leaflet in a cephalad direction toward the aortic anulus ( Fig. 19-3 ). This brings the free edge of the anterior mitral leaflet in contact with the ventricular septum. This SAM of the anterior leaflet is a constant feature of classic HOCM; degree of movement correlates with severity of obstruction, as does diameter of the LV outflow tract at this point. Ventricular ejection is rapid and early, mostly within the first half of systole. SAM is temporally related to peak LV outflow gradient and to cessation of flow in the ascending aorta.
The mechanism of SAM is probably multifactorial. Most likely, SAM is secondary to forward (anterior) displacement of the elongated mitral valve relative to the septum during systole, and to subsequent movement of the distal portion of the mitral valve apparatus. In association with marked septal hypertrophy opposite the mitral leaflet and rapid and early ventricular ejection, the Venturi effect of the high-velocity stream of blood carries the protruding edge of the anterior mitral leaflet toward the aortic anulus in early systole. As a secondary event, the higher pressure below the anterior leaflet then forces it further into the outflow tract. SAM is absent in nonobstructive HCM and when the obstruction is at a lower level. SAM can occur in transposition of the great arteries with intact ventricular septum (see “Left Ventricular Outflow Tract Obstruction” under Morphology in Chapter 52 ) and rarely in other disease states. SAM may also appear after mitral valve repair.
Left Ventricular Free Wall
In obstructive HCM with ASH, free-wall hypertrophy is more marked than in nonobstructive forms and is fairly uniform, particularly in the anterolateral and apical portions. There is, however, less thickening of the posterior free wall in almost all varieties of HCM. Thus, the ratio between the thick upper anterior part of the ventricular septum and the thinner posterior wall beneath the posterior mitral leaflet (the portion through which the beam passes in M-mode echocardiography ) is 1.3 or more in almost all cases of HCM, with or without obstruction. ASH may be absent when septal hypertrophy is unusually located, and because it is occasionally present in diseases other than HCM, ASH is not pathognomonic of HCM. In fact, ASH has been demonstrated in numerous types of congenital heart disease, particularly in neonates and infants ; in association with anomalies producing long-standing right ventricular hypertension ; in discrete subvalvar and valvar aortic stenosis; and even in normal hearts. When present in early life in association with congenital heart disease, ASH tends to lessen or disappear with somatic growth. ASH and SAM have been described in infants of diabetic mothers; this transient nonfamilial condition is not true HCM.
Unusual combinations and sites of septal and free-wall thickening in HCM result in a variable pattern of hypertrophy and obstruction. There can be midcavity obstruction, but more often in this variety, obstruction is absent and hypertrophy is symmetric rather than asymmetric or involves a portion of septum or free wall in the sinus portion of the ventricle rather than in the outflow region. Rarely, the posterobasal free wall may show localized hypertrophy, whereas the ventricular septum is of normal thickness. Extreme hypertrophy of the apical portion of the septum and free wall can result in obliteration of the apical portion of the LV cavity in the absence of either SAM or ASH.
Left Ventricular Cavity
In association with unusual shape of the ventricular septum, the LV cavity is small, even when heart failure occurs in later stages of HOCM, and has an S or sigmoid shape in systole when viewed in its longitudinal axis ( Fig. 19-4 ). A sigmoid shape is characteristic of patients younger than age 40 and is rare in patients older than 65. When ventricular hypertrophy is located in the midportion of the ventricle, a dumbbell-shaped cavity results ; when it is confined to the apex, there may be complete obliteration of the lower half of the cavity and a spade-shaped basal portion. LV apical aneurysms are present in approximately 2% of patients with HCM and occur over a wide age range.
Rarely the LV may become dilated in the late stages of HOCM. This dilatation may result from transmural myocardial infarction (MI) or severe progression of the disease process, with or without heart failure. Prognosis of patients with progressive LV wall thinning is poor, and concomitant cardiac failure is usually refractory to treatment. Most patients show an “hourglass” contour of the cardiac border, with midventricular hypertrophy and intracavitary gradients.
Histopathology of Left Ventricle
Microscopic findings in the hypertrophied ventricular septum are distinctive. Increased wall thickness is mainly caused by increased fibrous tissue, particularly in the ventricular septum but also in the free wall. Increase in muscle cell diameter and number of cell layers also contributes, with cell diameters being largest in layers closest to the cavity, perhaps because this is the site of greatest wall stress.
In addition, numerous foci of disarrayed muscle cells are interspersed between areas of hypertrophied but normally arranged (parallel) cells. In areas of disarray, muscle cells are wider and shorter than those present in hypertrophied muscle in other diseases, with increased cellular branching, extensive side-to-side intercellular junctions, widened Z bands, and formation of new sarcomeres. There are also abnormalities in orientation of myofibrils. In obstructive forms of HCM, muscle cell disarray is confined to the ventricular septum, whereas in nonobstructive forms it may also occur in the LV free wall.
Using a quantitative histologic method to determine extent of myocardial fiber disarray, Maron and Roberts found that the average degree of cell disarray in the ventricular septum of patients with HCM was 30%, compared with 1.5% in hearts with congenital or acquired cardiac disease or in normal hearts, and that when more than 5% of the relevant areas of the tissue section were involved, cell disarray was both highly sensitive (90%) and specific (93%) for HCM. By contrast, Bulkley and colleagues concluded that myocardial fiber disarray found in HCM was qualitatively and quantitatively similar in the LV of hearts with aortic atresia and a patent mitral valve and in the right ventricle of hearts with pulmonary atresia and intact ventricular septum. Thus, it is unlikely that cell disarray is a morphologic manifestation of a genetically transmitted myocardial defect in HCM ; rather, it is likely the result of uncoordinated muscular contraction occurring in these conditions.
Histologic ventricular abnormalities in HCM lead to more forceful LV contraction and rapid early ventricular emptying. In addition, reduced distensibility (compliance) and impaired relaxation result in a prolonged early filling phase and a decrease in rate and volume of the rapid phase of LV filling. Consequently, there is a compensatory increase in the contribution of atrial systole to overall LV filling.
Left Atrium
The left atrium is often dilated and thick walled as a result of decreased compliance of the LV and presence of mitral regurgitation.
Mitral Valve
In obstructive forms of HCM, the mitral valve is positioned closer to the ventricular septum than in the normal heart. Mitral valve leaflets are disproportionately elongated and thickened, particularly the leading edge of the anterior leaflet. This is presumably the result of SAM. The mitral anulus forcefully constricts during systole, and this purse-string action gathers the mitral leaflets into folds.
A further consequence of SAM is production of mitral regurgitation in mid- or late systole as the anterior leaflet moves forward (see Fig. 19-3 ). Studies by Bonow and by Wigle and colleagues indicate a direct relation between magnitude of the pressure gradient and degree of mitral regurgitation. It is likely that severity of mitral regurgitation, magnitude of the pressure gradient, and degree of prolongation of LV ejection time are determined by time of onset and duration of mitral leaflet–septal contact.
Mitral regurgitation occurs independently of SAM in about 20% of patients with HOCM. It can result from mitral valve prolapse, chordal rupture, anomalous attachment of a papillary muscle to the anterior leaflet, extensive anterior leaflet fibrosis resulting from repeated mitral leaflet–septal contact, congenital abnormalities, rheumatic disease, or mitral anular calcification. Presence of mitral regurgitation likely contributes to the exercise intolerance often present in patients with HOCM. Mitral anular calcification is frequently present in older patients with HOCM.
Right Ventricle
The right ventricular chamber is distorted by the hypertrophied ventricular septum, which projects into the right ventricular outflow tract. This hypertrophy may cause an important pressure gradient in the right ventricular outflow tract and, in long-standing cases, hypertrophy of the free wall. Right ventricular hypertrophy may also occur secondary to pulmonary hypertension from long-standing left-sided heart failure and elevated left atrial pressure. Unverferth and colleagues demonstrated an important increase in amount of fibrous tissue in the right ventricular free wall in HCM, as well as an increase in myocyte cell diameter in the subendocardial layer.
Coronary Arteries
In HCM, coronary arteries are larger in diameter than normal. Important coronary arteriosclerosis is present in about 5% of patients. Spray and colleagues and Maron and colleagues noted wall thickening and luminal narrowing of the intramural coronary arterial branches, located primarily in the ventricular septum and also occasionally in the left and right ventricular free wall in about half of patients with HCM. These abnormalities are not unique to HCM but are much less common in other forms of hypertrophy. Muscular bridging of the left anterior descending coronary artery (LAD) during part of its course is more common in HCM than in normal hearts. The LAD may become totally occluded during systole at these sites or may have an irregular sawtooth appearance. Septal perforating arteries may be obliterated or severely narrowed during systole. Hemodynamic effect of these changes is not known, although Maron and colleagues and Waller and colleagues have reported that transmural myocardial infarction occurs in HCM in the absence of arteriosclerotic coronary artery disease. Using thallium perfusion imaging and computed tomography, O’Gara and colleagues demonstrated that myocardial ischemia can occur in HCM both at rest and after exercise. This could be caused by systolic arterial compression or spasm, narrowing of intramural branches, inadequate capillary density, or reduction in diastolic coronary flow from impaired ventricular relaxation.
Associated Lesions
There is a specific association between HCM and diffuse lentiginosis. No evidence indicates that the latter is inherited. Association with essential hypertension noted in Brock's original report is probably coincidental, although Wei and colleagues suggest that a “hypertrophic cardiomyopathy” with features indistinguishable from some forms of HCM can occur in a number of other disease states including severe long-standing hypertension and severe aortic valvar stenosis. Similarly, there may be a coincidental association of HCM with other congenital or acquired cardiac diseases such as atrial septal defect and rheumatic heart disease. With HOCM, functional impairment of von Willebrand factor (a plasma glycoprotein required for normal hemostasis) is frequent and is closely and independently related to the magnitude of outflow obstruction. A resting peak gradient of 15 mmHg is sufficient to impair function of this glycoprotein and may result in abnormal spontaneous bleeding.
Clinical Features and Diagnostic Criteria
HOCM symptoms and signs are usually such that diagnosis can be made with confidence on clinical grounds. Subaortic or midventricular obstruction may be latent (provocable), labile, or persistent (obstruction at rest). In contrast, in nonobstructive HCM there may be no symptoms or signs, particularly in mild forms. In the text that follows, only obstructive HCM (HOCM) is discussed.
Symptoms
Symptoms associated with HOCM can occur at any age from infancy to beyond 70 years. They include angina, effort dyspnea, syncope, and dizziness on exertion, singly or in combination. However, these symptoms may not be related directly to the magnitude of LV outflow gradient. Rather, they are caused by a complex interaction of diastolic dysfunction, arrhythmias, myocardial ischemia, and outflow gradient.
Palpitation may occur, usually from atrial fibrillation, which may initially be paroxysmal but is permanent in about 10% of patients in the later stages of the disease. Onset of atrial fibrillation is usually heralded by a sudden increase in dyspnea and sometimes by heart failure and hypotension because of the rapid rate and loss of the atrial component of ventricular filling. Almost half of patients presenting with atrial fibrillation have a history of systemic embolism. Arrhythmia may also be caused by ventricular premature beats or bouts of ventricular tachycardia or supraventricular tachycardia, and can result in sudden death.
Later stages of HOCM are associated with severe and progressive heart failure with paroxysmal nocturnal dyspnea, orthopnea, and pulmonary edema. Rarely, ascites and peripheral edema develop in association with tricuspid regurgitation.
Signs
The three cardinal signs of HOCM are (1) late-onset systolic ejection murmur between the left sternal edge and apex, (2) bifid arterial pulse, and (3) palpable left atrial contraction.
The physical signs in typical cases of HOCM differ in important respects from other forms of aortic outflow obstruction. The pulse is jerky (bifid) with a rapid upstroke, in contrast to the anacrotic pulse of valvar aortic stenosis. An abnormal jugular a wave is frequently present, and occasionally, a short, low-pitched diastolic flow murmur that is enhanced by inspiration; both are the result of vigorous atrial contraction. The thrusting, overactive LV impulse is frequently double because of transmission of the forceful atrial contraction, which may also be audible as a fourth heart sound. Frequently, there is a third sound at the apex. Splitting of the second heart sound may be paradoxical, but this feature, as well as a gallop rhythm, is characteristically variable because of dynamic and variable obstruction. A midsystolic murmur that is roughly proportional in intensity to the degree of obstruction is maximal between the left sternal edge and apex of the heart rather than in the aortic area, although it radiates to the base; a thrill may be present. The murmur increases in intensity after a Valsalva maneuver (or inhalation of amyl nitrite), because both increase the degree of obstruction. When important mitral regurgitation is present, the murmur is maximal at the apex and pansystolic. There is no aortic ejection click. Valvar calcification and an aortic diastolic murmur are also absent (except in occasional cases in which the valve is abnormal). Infants and young children presenting with severe HOCM may be cyanotic from reversal of shunt flow at the atrial level.
Ventricular Function
Although in early stages of HCM, LV systolic function is usually normal or occasionally supranormal, with high ejection fraction in both the obstructive and nonobstructive forms of the disease, in HOCM (i.e., in later stages), impaired systolic function of both left and right ventricles occurs, primarily as a result of myocardial fibrosis. Fibrosis can result from fibrous transformation of loose intracellular connective tissue located between the myocardial fibers, or from myocardial ischemia and infarction caused by small-vessel or arteriosclerotic coronary artery disease. Myocardial fibrosis may result in thinning of the wall, reduction or loss of outflow obstruction, reduced ejection fraction, and increased end-systolic volume.
Diastolic dysfunction was initially attributed to decreased ventricular compliance. However, it now appears that impaired relaxation is the more important cause. Increased chamber stiffness increases diastolic pressure with respect to volume (dP/dV), and the diastolic pressure-volume curve is shifted upward and to the left.
Electrocardiography
The electrocardiogram (ECG) in HOCM characteristically shows an LV strain pattern, although Q waves may be present, and rarely, minimal changes indicative of LV hypertrophy despite an important gradient. Occasionally the ECG shows complete right or left bundle branch block and more often left anterior hemiblock. Giant negative T waves in V 4 -V 6 are typical of isolated apical hypertrophy. ECG features of left atrial enlargement are often noted, but those of right atrial enlargement less often.
Chest Radiography
Chest radiography shows mild to moderate cardiomegaly more often in HOCM than in other forms of aortic outflow obstruction. The aorta is typically small. The raised left atrial pressure may be reflected in the lung fields by evidence of pulmonary venous hypertension or frank interstitial edema.
Echocardiography
Transthoracic echocardiography (TTE) is the most important diagnostic study. Diagnosis can usually be established by M-mode echocardiography because, with rare exceptions, patients with familial HOCM have ASH, and all those with obstruction should demonstrate SAM, although this may appear only on provocation (e.g., after Valsalva maneuver). Standard echocardiography combined with Doppler color flow interrogation can be used to identify systolic and diastolic ventricular dysfunction, degree and direction of mitral regurgitation, presence of additional mitral valve abnormalities, and size of the left atrium. Transesophageal echocardiography (TEE) with Doppler color flow interrogation is invaluable for defining extent and level of outflow obstruction and abnormalities of the mitral valve ( Fig. 19-5 ). It should be used preoperatively for planning the operative procedure and intraoperatively to assess its effectiveness ( Fig. 19-6 ).
Exercise Echocardiography
Exercise echocardiography may identify LV outflow obstruction in symptomatic patients who would not otherwise be regarded as candidates for interventional treatment. Maron and colleagues reported on 320 patients with HCM judged to be eligible for exercise testing, of whom 201 underwent standard exercise testing with echocardiography; 119 had LV outflow tract gradients at rest of 50 mmHg or more and were not tested. In the 201 patients, LV outflow tract gradient increased from 4 ± 9 (median ≈ 0) mmHg at rest to 45 ± 49 (median ≈ 30) mmHg after exercise. In 106 patients (52%), gradients of 30 mmHg or more developed, including 76 (38%) that were 50 mmHg or more. Only a minority of the exercised patients with gradients developed severe mitral regurgitation, suggesting that the long-term consequences of obstruction are likely caused by the subaortic gradient and elevated LV pressure rather than by mitral regurgitation.
Cardiac Catheterization and Cineangiography
The diagnostic accuracy of echocardiography has substantially reduced the need for invasive studies in patients with HOCM. Cardiac catheterization and cineangiography are generally reserved for patients in whom echocardiographic studies are inconclusive, those in whom arteriosclerotic coronary artery disease is likely to be present, and those for whom surgical treatment (septal myectomy, dual-chamber pacemaker insertion, or cardiac transplantation) is being considered.
Right-sided heart catheterization will show any infundibular stenosis (occasionally severe) and elevation of pulmonary artery pressure, which may also be substantial because of high left atrial pressure. Retrograde left-sided heart catheterization will quantify and localize the obstruction. The catheter tip should be positioned near the base of the LV close to the mitral valve to avoid apical entrapment, which can produce a falsely high LV pressure. LV end-diastolic pressure is usually increased, often greatly, because of transmission of a large left atrial a wave ( Fig. 19-7 ). Central and peripheral arterial pulse contours show a rapidly ascending limb with a short upstroke (0.06 to 0.085) but a total ejection time greater than 0.335. A secondary systolic atrial wave results in the characteristic “spike and dome” (bifid) pulse contour initially described by Benchimol and colleagues. The beat following a ventricular ectopic beat shows an abnormal response—a reduced arterial pulse pressure (and an exaggerated spike-and-dome contour) secondary to increased obstruction generated by the ectopic beat. Obstruction is increased by any maneuver that increases LV contractility or decreases LV preload or afterload. Whenever the obstruction increases, pulse pressure decreases and total LV ejection time increases.
This dynamic characteristic of the obstruction can be confirmed by various provocative maneuvers such as isoproterenol administration, exercise, and Valsalva maneuver, which increase the gradient, and by methoxamine administration, which decreases it.
Systolic LV outflow gradient often is not increased during exercise but becomes dramatically increased almost immediately after exercise. The increase usually becomes maximal 3 to 5 minutes into the recovery period. Presumably, increased systemic venous return prevents substantial reduction of LV volume (and increase in the gradient) during exercise despite increased myocardial contractility, heart rate, and cardiac output and a reduced systemic vascular resistance. After exercise, decreased venous return allows a reduction in LV volume and an increase in systolic gradient.
LV cineangiography is best performed in the left lateral view because in this position the cardiac apex moves caudally and does not overshadow the mitral area.
The prominent characteristic septal bulge can be seen to form the anterior boundary of the outflow tract and the anterior mitral leaflet to form its posterior boundary. SAM can usually be demonstrated when obstruction is present ( Fig. 19-8 ).
Degree of mitral regurgitation can be assessed from the LV cineangiogram. However, multiple ectopic beats can make quantitation difficult. Coronary angiography should be added to the procedure in patients older than age 30 years in whom coronary artery occlusive disease is suspected or known to be present.
Natural History
In familial HCM, isolated ASH, identified by M-mode echocardiography, is an important part of the clinical spectrum and has the same genetic implications as HOCM. It is uncertain whether isolated ASH, an asymptomatic disease, develops into clinical obstructive cardiomyopathy (HOCM); if so, this sequence is uncommon after age 20 years.
HCM can present at any age from early infancy to the sixth or seventh decade. Echocardiographic studies of patients with HCM, including those with isolated ASH, suggest that obstruction is present in only about 20%. Infants and young children presenting with symptomatic HOCM represent the more severe end of the spectrum, with gross LV hypertrophy, frequent episodes of heart failure, and a high prevalence of sudden death. Progression of disease may be more rapid in children and young adults.
The natural history of HCM is typically variable. Although the clinical course is often stable over long periods, adverse events such heart failure, syncope, sudden cardiac death, and peripheral embolization can occur. Sudden onset of heart failure is frequently precipitated by atrial fibrillation, which may be associated with subsequent embolism. In patients with HOCM, correlation between symptomatic class and degree of obstruction has generally not been close, although in the multicenter trial reported by Shah and colleagues, there were no asymptomatic patients once the gradient exceeded 100 mmHg. Frank and Braunwald documented a substantially higher gradient in patients in New York Heart Association (NYHA) classes III and IV compared with those without symptoms. In the experience of Wigle and colleagues, presyncope and syncope on exertion are encountered most frequently in patients with HOCM.
Annual HCM-related mortality reported from referral centers has ranged from 4% to 6% in children and 2% to 4% in adults ( Figure 19-9 ). In contrast, studies involving largely unselected patients with HCM report annual mortality of 0.5% to 1.5%, similar to that for the adult general population.
Sudden cardiac death is common in patients with HCM. Risk factors for sudden death include a basal (resting) peak instantaneous gradient of at least 30 mmHg, young age, syncope, family history of malignancy, myocardial ischemia (particularly in the young), sustained ventricular tachycardia on electrophysiologic testing, and ventricular tachycardia on ambulatory monitoring. HCM is the most common association with unexplained sudden death in otherwise apparently healthy competitive athletes. Midventricular obstruction is an independent predictor of adverse outcomes especially for the combined endpoint of sudden death and potentially lethal arrhythmic events.
Neurologic death from cerebral embolism occurs in patients with permanent or paroxysmal atrial fibrillation or, infrequently, as a result of infective endocarditis on aortic and mitral valves. In the multicenter study by Shah and colleagues in patients with obstruction, but not operated on and followed for an average of 5.2 years, only one died from heart failure and two from infective endocarditis, but 23 from sudden cardiac death.
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