Obstructive hypertrophic cardiomyopathy

Definition

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disorder characterized by left and right ventricular hypertrophy ( Fig. 19.1 ) associated with microscopic evidence of myocardial fiber disarray and fibrosis. Distribution and degree of hypertrophy can vary substantially and influence clinical manifestations of the disease and surgical management.

A cross-section of a heart showing the left ventricle and septum. A small-scale bar is placed against the thick muscular septal wall to indicate dimensions. — • Figure 19.1

Subaortic ventricular septal hypertrophy is the most common type of asymmetric hypertrophy, with midventricular, apical, and other types occurring less frequently ( Fig. 19.2 ) . Phenotypes interfering with left ventricular (LV) emptying, termed obstructive HCM or (obsolete) idiopathic hypertrophic subaortic stenosis (IHSS), are of surgical importance and are characterized by a variable dynamic obstruction that is usually subaortic and associated with abnormal systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. Some forms of nonobstructive HCM in which LV diastolic volume is reduced are also amenable to surgical treatment. ^, The prevalence of HCM in the general population is about 1 in 200 to 500 adults. ^,

An illustration comparing a normal septum with three patterns of septal hypertrophy in H C M. The illustration presents four heart sections labeled A through D to compare septal morphology. Section A shows a normal left ventricle with a uniform septal contour. Section B presents subaortic hypertrophy where the basal septum appears thickened. Section C presents midventricular hypertrophy with prominent thickening in the mid portion of the septum. Section D presents apical hypertrophy where the thickening is greatest near the apex. — • Figure 19.2

Historical note

Pathologic findings compatible with obstructive HCM 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 1959 described diffuse muscular subaortic stenosis, HCM was first accurately identified in 1958 by Teare, a London pathologist. Teare described both disproportionate thickening of the ventricular septum compared with the free wall and the 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 obstructive cardiomyopathy. At that time, LV outflow tract obstruction was thought to be distinctive for the disease.

Goodwin and Oakley later emphasized the importance of reduced LV compliance as a major determinant of cardiac dysfunction (“inflow” or diastolic obstruction) rather than outflow obstruction, but the knowledge that nonobstructive HCM was also common awaited the 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 of the mitral valve. ^, During the early 1970s, ASH and SAM of the mitral valve 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.

The contribution of the anterior mitral leaflet to subaortic 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. ^,

More than 75 names have been used to describe HCM, and many focused on LV outflow obstruction. Braunwald and colleagues called it IHSS, and Wigle and colleagues used the designation “muscular subaortic stenosis.” In current practice, however, and throughout the chapter, this cardiac disorder is termed HCM with or without outflow obstruction.

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 (LA) 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 left ventricle through the aortic valve.

Simple myotomy using an aortic approach was used for a time by the Toronto group. Later, they modified the procedure to include the 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.

Morphogenesis and morphology

Morphogenesis

HCM is caused by a missense mutation in one of at least 12 genes that encode the proteins of the cardiac sarcomere. ^, HCM was initially regarded as a monogenic cardiac disease, but it is now recognized that many variants in genes encoding proteins of the cardiac sarcomere (or sarcomere-related structures) have been implicated in causing LV hypertrophy (LVH), the sine qua non of HCM. Among patients with HCM, approximately 30% to 60% have an identifiable pathogenic or likely pathogenic genetic variant. Confounding the genotype-phenotype association is the fact that specific mutations have variable penetrance and expressivity. Further, a substantial proportion of patients with HCM may have a sarcomeric mutation and family history of HCM but no clinical evidence of disease (genotype-positive, phenotype-negative). At present, few echocardiographic or clinical characteristics reliably predict disease progression in such patients, and risk of sudden cardiac death (SCD) appears to be low.

Beta myosin heavy chain 7 (MYH7) and myosin-binding protein C3 (MYBPC3) have been identified in 70% of variant-positive patients ( Fig. 19.3 ), while other genes (TNNI3, TNNT2, TPM1, MYL2, MYL3, ACTC1) account for a small proportion of patients (1% to 5%). Within these genes, more than 1500 variants have been recognized, the majority of which are unique to the individual family. HCM is transmitted as an autosomal dominant trait, ^, ^, although nonfamilial cases occur as well. The complexity of the genotype-phenotype relationship is illustrated further by the finding of variable septal morphology within the same family. ^,

A molecular schematic of a cardiac sarcomere showing interactions between actin, myosin heads, troponin complex, and binding protein C during calcium-induced contraction. This colorful schematic shows the molecular components of a cardiac sarcomere during the process of contraction. At the top of the image is the thin filament consisting of a chain of pink spheres representing Actin, which is intertwined with a thin blue strand labeled alpha-tropomyosin. Attached to this filament is the troponin complex, with specific labels for Troponin I, Troponin T, and Troponin C, with a small orange sphere representing Calcium bound to the complex. Vertical blue chains of beads represent Myosin binding protein C, which connects the top actin filament to the thick myosin filament below. The thick filament is depicted as a large horizontal brown cylinder composed of Myosin rods. Prominent yellow oval structures known as Myosin heads extend from the thick filament toward the actin filament, with specific parts of the structure labeled as the beta-Myosin heavy chain and Myosin light chain. The diagram demonstrates how the binding of calcium to the troponin complex allows the myosin heads to interact with the actin filaments, a process that stimulates A T P ase activity and generates the mechanical force necessary for the heart to pump. — • Figure 19.3

Genetic testing is generally recommended for patients with a clinical diagnosis of HCM in which mutation-specific confirmation would benefit immediate family members and, potentially, other relatives. The absence of a sarcomere mutation cannot rule out familial HCM, and variants of uncertain significance are more frequent in individuals with a lower clinical pretest probability of a pathogenic mutation. Identification of a genetic mutation has little impact on risk assessment and management of the affected patient. Although evidence suggests that the presence of >1 likely pathogenic or pathogenic variant may be associated with more severe disease outcomes, including SCD, the role of the genetic test result in determining risk of SCD is uncertain and not used for prognosis or decisions related to use of an implantable cardioverter defibrillator (ICD).

Genetic testing may be helpful in identifying HCM phenocopies if there is clinical suspicion of a systemic disorder, including PRKAG2 (glycogen storage disease), LAMP2 (Danon disease), GLA (Fabry disease), transthyretin amyloid cardiomyopathy, and disease genes related to RASopathies. Results of such genetic tests may alter the management of the index case; for example, enzyme replacement therapy in patients with Fabry disease or more aggressive clinical management of patients with Danon disease.

Morphology

Muscular hypertrophy in HCM involves the interventricular septum and left ventricle and varies in location and severity. The basal anterior septum, in continuity with the anterior free wall, is the most common location for LVH. Echocardiography reports often describe ventricular morphology as sigmoidal, reverse curve, or neutral ( Fig. 19.4 ). Elderly patients with HCM display a predominantly sigmoid septal morphologic subtype and uncommonly have known genetic mutations associated with the disease. Indeed, independent of age, septal morphologic subtype strongly predicts the presence or absence of HCM-associated myofilament mutations and may guide genetic testing for HCM.

A comparison of four heart septal shapes, Sigmoidal, Reverse curve, Neutral, and Apical, is shown through color diagrams and corresponding black and white echocardiogram images. The medical illustration is organized into a four-column grid that compares different ventricular septal morphologies through anatomical sketches and corresponding echocardiographic images. The top row contains four color-coded anatomical diagrams of the heart in cross-section, showing the left ventricle and the varying thickness of the muscular septum. Each diagram is labeled below with its specific subtype. The first diagram, labeled Sigmoidal, shows a prominent bulge at the top of the septum near the aorta. The second, labeled Reverse curve, depicts a thick septum that bows into the left ventricular cavity, creating a crescent shape. The third, labeled Neutral, shows a relatively straight and uniformly thickened septum. The fourth, labeled Apical, shows the thickest part of the muscle concentrated at the very bottom or apex of the heart. The bottom row features four matching black and white echocardiogram views that provide a real-world clinical view of these same four patterns: Sigmoidal, Reverse curve, Neutral, and Apical. These ultrasound images show the bright white outlines of the heart chambers against a dark background, mirroring the structural differences illustrated in the diagrams above to help clinicians categorize the specific shape of a patient's heart wall. — • Figure 19.4

In a subset of patients, hypertrophy can be limited and focal, confined to only 1 or 2 LV segments with relatively normal LV mass. Although common in HCM, neither SAM of the mitral valve nor hyperdynamic LV function is required for a clinical diagnosis. Several other morphologic abnormalities are also not diagnostic of HCM but can be part of the phenotypic expression of the disease, including hypertrophied and apically displaced papillary muscles, anomalous insertion of a papillary muscle directly in the anterior leaflet of the mitral valve (in the absence of chordae tendineae), elongated mitral valve leaflets, myocardial bridging, and right ventricular hypertrophy.

Ventricular septum.

In classic obstructive HCM, hypertrophy is maximal in the cephalad portion of the ventricular septum. This muscular prominence (mound) tapers gradually toward the apex. At the point opposite the anterior mitral leaflet, the LV endocardium is often thickened by a localized plaque of fibrous tissue, presumably related to contact with the anterior mitral leaflet. The septal contact associated with SAM of the mitral valve differs from the membrane in congenital subaortic stenosis in that it does not contribute to outflow obstruction and cannot be easily separated from underlying muscle.

Ventricular septal hypertrophy may be maximal at a site below the anterior mitral leaflet adjacent to the papillary muscles ( Fig. 19.5 ) , producing midventricular hypertrophy leading to obstruction , to which the papillary muscles and free-wall hypertrophy contribute. With isolated midventricular obstruction, there is no SAM of the mitral valve nor mitral regurgitation (MR). Hypertrophy may be confined to the posterior or apical septum. Localized apical hypertrophy ( Fig. 19.6 ) was first described in Japan and is more prevalent in Asia than North America. ^, Apical LV aneurysm in the presence of normal coronary arteries occasionally occurs with midventricular and apical hypertrophy ( Fig. 19.7 ). ^, Occasionally, the entire septum may be of uniform thickness ( Fig. 19.8 ) .

A four-part view showing midventricular obstruction via echocardiography and M R I during systole and diastole, with arrows highlighting thickened ventricular walls. The four-part labeled A, B, C, and D, providing a comparison of cardiac imaging techniques. Panels A and B are black and white two-dimensional transthoracic echocardiogram images displaying a grainy, high-contrast view of the heart's chambers. In panel A, the heart is shown in diastole, while panel B shows the heart in systole, with a white arrow in both images pointing to the significantly thickened muscular wall at the midventricular level. Panels C and D provide cardiac M R I which offers a smoother, more detailed gray-scale view of the heart's internal structure and valves. Panel C depicts the diastolic phase and panel D depicts the systolic phase, where arrows again indicate the increased ventricular wall thickness at the level of the papillary muscles. Across all four panels, the white arrows consistently highlight the narrowed central cavity caused by the encroaching muscle tissue, visually demonstrating the midventricular cavitary obstruction during different points of the heart's pumping cycle. — • Figure 19.5

A postmortem heart specimen showing apical H C M with left atrial enlargement and apical displacement of the papillary muscles. The postmortem heart specimen is sectioned to display the chambers and the ventricular apex. The left atrium appears enlarged, and the ventricular apex shows papillary muscles displaced downward. An arrow marks the displaced papillary muscles to guide recognition of the apical involvement characteristic of apical H C M. — • Figure 19.6

Atwo-part view shows left ventriculogram and intraoperative photo of a heart with midventricular H C M, where arrows highlight a distinct apical aneurysm at the tip of the ventricle. The two-part view labeled A and B which provide different views of a heart condition. Panel A is a black and white frame from a left ventriculogram showing a dark, contrast-filled ventricular cavity against a gray background. The cavity is severely narrowed in the middle due to midventricular hypertrophic cardiomyopathy, but it expands at the very bottom into a rounded bulb-like shape. A white arrow in panel A points directly to this expanded area, identifying it as an apical aneurysm. Panel B is a high-detail, full-color intraoperative photograph of the same heart during surgery. A surgeon's gloved hand is visible on the left, gently holding the heart to expose the exterior surface. The heart muscle appears reddish-pink with yellowish fatty deposits on the surface. An arrow in panel B points to a darkened, bulging area at the apex of the ventricle that corresponds to the aneurysm seen in the radiographic image. The juxtaposition of the two panels demonstrates how the internal cavity expansion seen on the ventriculogram manifests as a visible physical bulge on the exterior of the heart muscle. — • Figure 19.7

A two-part cardiac M R I frames comparing Diastole and Systole in an H C M patient, showing uniform wall thickening and complete cavity obliteration during the systolic phase. The two-part cardiac magnetic resonance imaging frames labeled Diastole on the left and Systole on the right. In the Diastole frame, the left ventricular cavity as a dark, open space surrounded by thickened muscular walls. A single white asterisk marks the left ventricular posterior wall, while double white asterisks are placed on the interventricular septum, showing the uniform nature of the muscle thickening. In the Systole frame, the ventricular walls have contracted toward each other so significantly that they meet, resulting in systolic cavity obliteration. A long yellow double-headed arrow runs along the length of the septum to indicate the extent of this obliteration, and a smaller double-headed arrow at the top represents the height of the small residual cavity left at the end of the contraction. A leader line points to this narrowed area and is labeled Slitlike cavity. These images provide a clear comparison of how the oversized heart muscle physically fills the ventricular space during a heartbeat, effectively eliminating the volume available for blood. — • Figure 19.8

Dynamic morphology of septum and mitral valve.

When septal hypertrophy is classic, obstruction in the LV outflow tract can occur between the hypertrophied ventricular septum and anterior mitral leaflet. As illustrated in Fig. 19.9 , 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 mechanism of SAM of the mitral valve is probably multifactorial. Most likely, it is secondary to the forward (anterior) displacement of the elongated mitral valve relative to the septum during systole and to the 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. Jain and colleagues found that SAM-related LV outflow tract obstruction was associated with abnormal mitral valve coaptation length and narrowing of the outflow area due to septal hypertrophy.

A diagram of the heart labeled diastole and systole shows mitral valve movement with systolic anterior motion and mitral regurgitation indicated by arrows. The diagram of two heart sections shows the diastole and systole phases. The diastole section shows the ventricle in a relaxed state with blood flowing from the atrium into the ventricle. The systole section shows labeled systolic anterior motion and mitral regurgitation. The systolic anterior motion label marks the forward movement of the mitral valve leaflet, while the mitral regurgitation label marks the backward flow of blood toward the atrium. Both sections clearly show valve positions, directional flow, and chamber outlines. — • Figure 19.9

In patients with obstruction, LV outflow tract peak velocity and calculated pressure gradient occur at approximately the same time as maximal mitral-septal apposition, followed by midsystolic reduction or cessation of flow in the ascending aorta 20 to 30 ms later.

The SAM-induced LV outflow obstruction produces a late peaking velocity signal on Doppler echocardiography, and the reduction or cessation of blood flow in late systole correlating with obstruction has been demonstrated in direct flow measurements intraoperatively ( Fig. 19.10 ).

A six-graph comparing pressure, aortic flow, and L V-Ao gradient between obstructive H C M and aortic stenosis during regular and post-P V C beats over time. The six-part line graph organized into two columns labeled A for obstructive H C M and B for valvular aortic stenosis. Each column contains three vertically stacked graphs showing Pressure in millimeters of mercury, Flow in milliliters per second, and L V-A o gradient in mmHg, all plotted against Time in seconds. In all graphs, a solid blue line represents a regular heart beat and a dashed line represents the beat following a premature ventricular contraction. In the obstructive H C M column, the pressure graph shows a distinct notch on the aortic pressure tracing during the post-P V C beat, while the aortic flow graph shows a mid-to-late plateau with a decreased area under the dashed line, indicating reduced stroke volume. The gradient graph for H C M shows an early plateau in the L V-A o gradient. In contrast, the aortic stenosis column shows that flow and pressure gradually increase and decrease during ejection for both types of beats. The post-P V C beat in aortic stenosis shows an increased peak flow and an increased area under the flow tracing, signifying a higher stroke volume compared to the regular beat. The axes are labeled with Pressure from 0 to 250, Flow from 0 to 600, and Gradient from 0 to 160 for the H C M column, while the aortic stenosis column uses scales of 0 to 200 for pressure, 0 to 600 for flow, and 0 to 120 for gradient. These comparative tracings highlight that a post-P V C beat worsens obstruction in H C M but improves flow through a fixed valvular stenosis. — • Figure 19.10

SAM of the mitral valve is absent in nonobstructive HCM and when the obstruction is at a lower midventricular level. It can occur in transposition of the great arteries with an intact ventricular septum (see “ Left Ventricular Outflow Tract Obstruction ” under Morphology in Chapter 44 ) and rarely in other disease states. ^, SAM may also appear after mitral valve repair, particularly if there is basal septal hypertrophy. ^,

Left ventricular free wall.

In obstructive HCM with ASH, there is 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 is 1.3 or more in most 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 subvalvular and valvular 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 of the mitral valve have been described in infants of diabetic mothers; this transient nonfamilial condition is not true HCM.

Left ventricular cavity.

In association with the unusual shape of the ventricular septum, the LV cavity is small, even when heart failure occurs in later stages of obstructive HCM, and may have an S or sigmoid shape in systole when viewed in its longitudinal axis. 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. ^,

Rarely, the left ventricle may become dilated in the late stages of obstructive HCM. This dilation may result from transmural myocardial infarction or severe progression of the disease process, with or without heart failure. The prognosis of patients with progressive LV wall thinning is poor, and concomitant cardiac failure is usually refractory to treatment.

Histopathology of left ventricle.

As illustrated in Fig. 19.11 , patients with obstructive HCM have varying degrees of cardiomyocyte hypertrophy, myocyte disarray, interstitial fibrosis, and endocardial thickening. There is an increase in muscle cell diameter and number of cell layers, with cell diameters being largest in layers closest to the cavity, perhaps because this is the site of greatest wall stress.

A four-part microscopic view of heart tissue in H C M showing enlarged cells, chaotic cell arrangement, fiber-like scarring between cells, and thickened heart lining. The four-part histological panels labeled A through D, each showing stained heart tissue under a microscope. Panel A displays myocyte hypertrophy, where individual heart muscle cells appear significantly enlarged and elongated with dark, prominent nuclei. Panel B illustrates myocyte disarray, showing a chaotic and disorganized arrangement where the muscle cells are oriented in various crisscrossing directions rather than in parallel rows. Panel C highlights interstitial pericellular-type fibrosis, marked with a asterisk, where pink fibrous connective tissue has accumulated in the spaces between individual myocytes. Panel D shows endocardial fibrosis, indicated by a long vertical black double-headed arrow, which identifies a thick, dense layer of light pink fibrous tissue that has formed over the inner lining of the heart. Together, these panels visually document the structural abnormalities at a microscopic level that contribute to the thickening and stiffening of the heart muscle in obstructive H C M. — • Figure 19.11

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 the orientation of myofibrils.

Maron and Roberts reported 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. In contrast, Bulkley and colleagues concluded that myocardial fiber disarray found in HCM was qualitatively and quantitatively similar in the left ventricle 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. ^,

Left atrium.

The left atrium is often dilated and thick-walled as a result of decreased compliance of the left ventricle and the presence of MR. Enlargement of the left atrium in HCM is associated with adverse cardiovascular outcomes, including higher rates of all-cause mortality, atrial fibrillation, thromboembolic stroke, and heart failure. ^,

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. Although there is wide variation among patients, mitral valve leaflet elongation appears to be a distinct feature of HCM as it is not present in patients with valvular aortic stenosis who also have LVH and pressure overload or surgical patients without ventricular hypertrophy.

It is still debatable whether elongated anterior mitral valve leaflets are determinant in the pathophysiology of LV outflow tract obstruction. Some studies suggest an association between greater anterior mitral leaflet length and higher LV outflow tract gradients, but other investigations have not confirmed this relationship. In a recent report of patients undergoing septal myectomy, the severity of LV outflow tract obstruction was weakly related to length of the mitral valve leaflets, but there was no association of preoperative leaflet length with postoperative LV outflow tract gradients ( Fig. 19.12 ). In another observational study, however, the coaptation length of the leaflets was significantly associated with provocation-induced LV outflow tract obstruction. It is important to note that the difference in anterior leaflet length comparing patients with obstructive HCM to normal control patients or those with aortic stenosis or coronary artery disease is only 5 to 7 mm, ^, and the corresponding surface of septal contact can be reached in almost all patients through the aortic valve.

A three-part scatter plots showing near-flat relationships between A M V L, P M V L, and coaptation length versus postoperative L V O T gradient, all with non-significant P-values. The three-part scatter plots showing the relationship between mitral valve dimensions and postoperative left ventricular outflow tract or L V O T gradient in mmHg. All three graphs share a vertical y-axis labeled Postop L V O T millimeters of mercury graduated from 0 to 50 in increments of 10. The first graph on the left plots A M V L length in mm on the x-axis from 15 to 45 and shows a nearly flat trend line with a P value of.54. The middle graph plots P M V L length in mm on the x-axis from 5 to 25 and also shows a flat trend line with a P value of.06. The third graph on the right plots Coaptation length in mm on the x-axis from 2 to 12 and displays a similar horizontal trend line with a P value of.28. Each graph demonstrates that there is no significant correlation between the length of the anterior or posterior mitral valve leaflets or their coaptation length and the residual pressure gradient after surgery. The relatively low and stable position of the blue lines near the 10 millimeters of mercury mark indicates that greater leaflet length was not associated with higher postoperative gradients or less gradient reduction across the patient population. — • Figure 19.12

A further consequence of SAM of the mitral valve is production of MR in mid- or late systole as the anterior leaflet moves forward (see Fig. 19.9 ). Studies by Bonow and by Wigle and colleagues indicate a direct relationship between the magnitude of the pressure gradient and the degree of MR. ^, ^, It is likely that the severity of MR, the magnitude of the pressure gradient, and the degree of prolongation of LV ejection time are determined by the time of onset and duration of mitral leaflet–septal contact. On Doppler echocardiography, the color jet of MR due to SAM is typically directed posteriorly. When present, the posteriorly directed jet has a high predictive probability of SAM-related MR but low negative probability ( Fig. 19.13 ). Thus, in the absence of an identifiable mitral leaflet abnormality, a nonposteriorly directed MR jet may be due to systolic anterior mitral leaflet motion.

A four-part color Doppler echocardiogram shows pre-bypass and post-bypass views of posterior and central S A M-mediated mitral regurgitation, demonstrating complete resolution after myectomy. The four-part color Doppler echocardiogram panels labeled A, B, C, and D, which compare heart blood flow before and after surgical intervention. Panels A and B demonstrate posterior mitral regurgitation, or M R, mediated by systolic anterior motion, or SAM. Panel A is labeled PRE BYPASS and shows a large, turbulent jet of blood colored in bright yellow and orange flowing toward the back of the heart chamber, indicating significant regurgitation. Panel B is labeled POST BYPASS and shows the same heart view after a myectomy alone, where the turbulent jet has disappeared, indicating the resolution of the S A M-mediated M R. Panels C and D illustrate central SAM-mediated MR. Panel C, labeled PRE BYPASS, shows a large central jet of multicolored blood flow indicating regurgitation in the middle of the valve area. Panel D, labeled POST BYPASS, shows the successful resolution of this central jet following the myectomy procedure. Each panel contains technical echocardiographic data in the top left corner, including depth and frequency settings, and a color flow scale on the right side graduated from 64 to-64. These images collectively demonstrate that addressing the septal hypertrophy through myectomy can be curative for certain types of mitral regurgitation without needing direct valve surgery. — • Figure 19.13

Mitral valve regurgitation independent of SAM (intrinsic mitral valve disease) occurs in about 15% to 20% of patients with obstructive HCM. ^, ^, It can result from mitral valve prolapse, chordal rupture, extensive anterior leaflet fibrosis due to repeated mitral leaflet–septal contact, congenital abnormalities, rheumatic disease, or mitral anular calcification, ^, ^, which is frequently present in older patients with obstructive HCM. ^,

Right ventricle.

The right ventricular chamber is distorted by the hypertrophied ventricular septum, which projects into the right ventricular outflow tract. Associated right ventricular hypertrophy is present in 30% to 40% of patients with HCM and may cause a pressure gradient in the right ventricular outflow tract. The anatomical aspects of right ventricular involvement in HCM were initially described by Maron and colleagues, who suggested that in contrast to the dynamic lesions occurring in the left ventricle associated with SAM of the mitral valve, obstruction in the right ventricle was due to static and fixed impediments to right ventricular outflow. Combined right ventricular and LV obstruction can lead to severe diastolic dysfunction with restrictive physiology. Biventricular involvement is more common in children than adults and is associated with syndromic conditions, such as Noonan syndrome or Pompe disease.

Right ventricular hypertrophy may also occur secondary to pulmonary hypertension from long-standing left-sided heart failure and elevated LA pressure. ^, Unverferth and colleagues demonstrated an important increase in the 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. Depending on the population studied, atherosclerotic coronary artery disease is present in approximately 5% to 15% of patients with HCM. Sorajja and colleagues reported that significant coronary artery disease was detected in half of patients selected for coronary angiography, and the disease was severe in 26%. In another study of patients undergoing septal myectomy, significant coronary atherosclerosis was identified in 11% of patients. Survival of HCM patients with obstructive coronary artery disease is reduced compared with HCM patients without coronary artery disease. The deleterious effect of coronary artery disease on survival is also seen in patients undergoing septal myectomy and coronary artery bypass.

Although coronary arteries are larger than normal in patients with HCM, and basal coronary flow is increased in the resting state, coronary flow reserve is decreased in symptomatic HCM patients compared with normal patients. Phasic coronary flow is abnormal with greater flow during diastole, flow reversal in systole, and more rapid deceleration of diastolic blood flow compared with normal patients. Decreased flow reserve is associated with a reduction in coronary resistance, suggesting that the mechanism is not due to narrowing of intramyocardial small arteries or compression of the microcirculation; indeed, the reduction in coronary flow reserve in patients with HCM may be the result of nearly maximal vasodilation of the microcirculation in the basal state.

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.

Myocardial bridging of the left anterior descending (LAD) coronary artery is not uncommon ( Fig. 19.14 ), occurring in 15% of patients with HCM undergoing coronary angiography in one study. It is unclear whether bridging of the LAD plays a pathophysiologic role in the disease and associated symptom of angina. However, for adult patients with HCM, the risk of death and, in particular, the risk of SCD is not increased with myocardial bridging. In contrast, among children with HCM, systolic compression of the LAD was associated with a greater occurrence of chest pain (60% vs. 19%), cardiac arrest with subsequent resuscitation (50% vs. 4%), and ventricular tachycardia (80% vs. 8%).

A pair of coronary angiography scans labeled A and B shows a normal left anterior descending artery and a narrowed segment indicated by an arrow. The pair of coronary angiography scans labeled A and B shows contrast-filled coronary arteries. Panel A shows a smooth left anterior descending coronary artery with no constriction. Panel B shows a subsequent spasm in its midportion marked by an arrow. Both panels display branching coronary vessels extending across the cardiac surface, and the contrast outlines the arterial flow path along the vascular branches. — • Figure 19.14

Autopsy studies have demonstrated that transmural myocardial infarction occurs in HCM in the absence of arteriosclerotic coronary artery disease. ^, Also, a study using thallium perfusion imaging and computed tomography demonstrated that myocardial ischemia could occur in HCM both at rest and after exercise. This may be caused by vessel spasm or inadequate capillary density.

Associated conditions.

With obstructive HCM, functional impairment of von Willebrand factor (a plasma glycoprotein required for normal hemostasis) is frequent and closely and independently related to the magnitude of LV outflow obstruction. A resting peak gradient of 15 mmHg is sufficient to impair the function of this glycoprotein and may result in abnormal spontaneous bleeding. In one study, complete remission of gastrointestinal bleeding was observed in 85% of patients following relief of LV outflow tract obstruction by septal myectomy. Only 8% of the patients had recurrent gastrointestinal bleeding due to angiodysplasia or unknown causes.

There is a specific association between HCM and diffuse lentiginosis. HCM is particularly common in Noonen syndrome with multiple lentigines (NSML, formerly known as LEOPARD syndrome), and NSML-associated HCM presents at the most extreme end of the phenotypic spectrum. ^, Similar to primary HCM, myocardial hypertrophy in NSML is associated with a risk of fatal cardiac events.

Clinical features and diagnostic criteria

The symptoms and signs of obstructive HCM are usually such that the diagnosis can often be made 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.

Symptoms

Symptoms associated with obstructive HCM 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 the resting LV outflow gradient. Indeed, patients with latent, provokable LV outflow gradients often have symptoms indistinguishable from patients with resting obstruction. ^, As many as one-third of patients with obstructive HCM experience an exacerbation of symptoms after meals. ^, Postprandial worsening of symptoms is related to dynamic LV outflow tract obstruction, and in patients with minimal or no gradient at rest should prompt further evaluation with provocative maneuvers, including standing postexercise Doppler echocardiography after a meal.

Palpitations may occur, often from atrial fibrillation. Transient episodes are unpredictable in frequency and timing and can lead to debilitating symptoms. However, with current treatment protocols, paroxysmal atrial fibrillation infrequently progresses to long-term persistent atrial fibrillation. Atrial fibrillation is an important cause of embolic stroke in HCM patients but is not a major contributor to heart failure morbidity or sudden death.

Signs

The three cardinal signs of obstructive HCM are (1) late-onset systolic ejection murmur between the left sternal edge and apex, (2) bifid arterial pulse, and (3) palpable LA contraction. These findings in typical cases of obstructive HCM 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 valvular 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 result from 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 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 provocation by Valsalva or repetitive squat-to-stand maneuvers or inhalation of amyl nitrite because these maneuvers increase the degree of obstruction. When important MR is present, the murmur is maximal at the apex and pansystolic. There is no aortic ejection click. Valvular calcification and a diastolic aortic murmur are also absent (except in occasional cases in which the valve is abnormal). Rarely infants and young children presenting with severe obstructive HCM may be cyanotic from reversal of shunt flow at the atrial level.

Ventricular function

In the early stages of HCM, LV systolic function is usually normal or supranormal, with high ejection fraction in both the obstructive and nonobstructive forms of the disease. In later stages of the disease, impaired systolic function of both left and right ventricles may occur, primarily as a result of myocardial fibrosis. Fibrosis can result from fibrous transformation of loose intracellular connective tissue located between 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. This end-stage of HCM may develop in as many as a quarter of patients during late follow-up.

Diastolic dysfunction was initially attributed to decreased ventricular compliance. ^, Increased chamber stiffness can result from hypertrophy and fibrosis of cardiac muscle and, in some patients, by severe hypertrophy, usually apical, that encroaches on LV end-diastolic volume. Each of these factors contributes to increased diastolic pressure with respect to volume (dP/dV) , and the diastolic pressure-volume curve is shifted upward and to the left. ^,

Electrocardiography

There is nothing pathognomonic for HCM on the electrocardiogram (ECG), but a normal tracing is observed only in 5% to 10% of patients. Characteristic findings include an LV strain pattern, although Q waves may be present, and rarely, minimal changes indicative of LVH 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 LA enlargement are often noted, but those of right atrial enlargement are less often seen.

Chest radiography

Chest radiography shows mild to moderate cardiomegaly more often in obstructive HCM than in other forms of aortic outflow obstruction. The aorta is typically small. The raised LA 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. Doppler echocardiography provides information on ventricular morphology, hemodynamics, and valve function. The most common pattern of hypertrophy involves the ventricular septum, and the average LV wall thickness is 20 to 22 mm in patients with HCM. LV wall thickness is markedly increased in 5% to 10% of patients, measuring 30 to 50 mm ( Fig. 19.15 ). Morphology of the septum appears to vary according to age, and a sigmoid configuration is common in older patients. During TTE examination, maneuvers such as the Valsalva, inhalation of amyl nitrate, and exercise may demonstrate latent obstruction ( Fig. 19.16 ).

A four-part echocardiogram showing a 48 millimeter thick septum in diastole and systole, with a white arrow highlighting a severely narrowed, small left ventricular cavity. The four-part echocardiographic panels labeled A, B, C, and D, showcasing different views of a heart with severe hypertrophy. Panels A and B provide long-axis views, while panels C and D show short-axis views. Panel A, labeled Diastole at the bottom right, features a double-headed arrow measuring the thickness of the interventricular septum during the heart's relaxation phase. Panel B, labeled Systole at the bottom right, shows the same view during contraction, with text indicating a Septal thickness of 48 milliemter. Panel C shows the heart in a short-axis diastolic view with a yellow arrow again indicating the massive muscular wall. Panel D shows the short-axis systolic view where a white arrow points to a tiny dark space labeled L V cavity, illustrating how the 48 mm thick septum nearly obliterates the internal chamber space. Each panel includes a small E K G tracing at the bottom left to indicate the timing within the cardiac cycle and a scale bar on the right. Collectively, these images demonstrate the extreme physical encroachment of thickened muscle on the blood-carrying capacity of the left ventricle. — • Figure 19.15

A three-Doppler echocardiography panel with three waveform graphs labeled Rest, Valsalva, and Amyl shows increasing downward velocity patterns marked with a one meter per second reference arrow. The three-part Doppler echocardiography panel displays three vertically aligned spectral waveforms labeled Rest, Valsalva, and Amyl. Each section shows a dark triangular Doppler jet extending downward from the baseline. The Rest graph shows a moderate flow velocity, the Valsalva graph shows a larger triangular waveform extending further downward, and the Amyl graph shows a similar extended waveform pattern. A vertical double-headed arrow labeled one meter per second appears on the left as a velocity scale reference. — • Figure 19.16

Transesophageal echocardiography (TEE) is used intraoperatively, and preoperative TEE is unnecessary in most patients. ^, However, TEE can be useful when there is uncertainty regarding mitral valve structural abnormalities, mechanism of MR, or suspicion of alternative causes of outflow obstruction (discrete subaortic stenosis, valvular stenosis) on TTE or suspected by other clinical findings.

Cardiac magnetic resonance imaging

Although not necessary for surgical planning in most patients with subaortic LV outflow tract obstruction, cardiac magnetic resonance imaging (CMR) is an important complementary imaging method for defining HCM phenotype, risk assessment for SCD, and, in some centers, for family screening. CMR provides clear, detailed images of LV wall thickness, distribution of hypertrophy, LV cavity volume, and presence or absence of apical aneurysms. Further, the detection of late gadolinium enhancement, considered to represent myocardial fibrosis, can aid in the assessment of risk for ventricular arrhythmias and the need for an ICD. CMR is useful when echocardiographic windows are inadequate. In some patients, CMR imaging may not be possible due to the presence of transvenous pacemakers or ICDs or patient factors such as claustrophobia, body habitus, or the need for anesthesia for young patients.

Exercise echocardiography and cardiopulmonary exercise tests

Exercise echocardiography by treadmill or bicycle ergometry is a physiologic form of provocation for latent LV outflow tract obstruction. Such studies are useful in patients who have typical symptoms but do not demonstrate LV outflow tract obstruction on TTE with maneuvers such as Valsalva, repetitive squat-to-stand, or amyl nitrite inhalation. ^, Maron and colleagues reported that among 201 patients with resting gradients <50 mmHg who underwent standard exercise testing with echocardiography, 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.

Cardiopulmonary exercise testing (CPET) with simultaneous measurement of respiratory gases provides objective data on the severity and mechanism of functional limitation. This test is useful preoperatively in evaluation of patients to determine if a functional limitation is related to cardiopulmonary impairment and in patients who may minimize symptoms and not realize the extent of their cardiac disability. Further, up to one-third of adults with HCM have hypotension or a failure to augment the systolic blood pressure during exercise, and an abnormal exercise blood pressure response may be associated with a greater risk of SCD. Among patients undergoing septal myectomy, reduced peak V o ₂ and normal pulse oxygen increase on preoperative CPET is associated with increased late mortality.

Exercise abnormalities are common in childhood HCM. In a multicenter study of pediatric patients, an abnormal exercise test was independently associated with lower transplant-free survival, especially in patients with an ischemic or abnormal blood pressure response with exercise.

Cardiac catheterization and cineangiography

The diagnostic accuracy of echocardiography has substantially reduced the need for invasive studies in patients with obstructive HCM. ^, 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 cardiac transplantation is being considered. Right-sided heart catheterization is rarely necessary. However, there may be patients with suspected LV outflow tract obstruction not documented on Doppler echocardiography with standard provocative maneuvers. Elesber and colleagues reported results of isoproterenol challenge during cardiac catheterization in 25 patients with HCM. During isoproterenol infusion, the gradient increased to >50 mmHg in 14 patients. Eight of these patients underwent septal myectomy and had sustained relief of symptoms during follow-up.

Retrograde left-sided heart catheterization can quantify and localize the obstruction. The catheter tip should be positioned near the base of the left ventricle 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 the transmission of a large LA a wave. 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 ( Fig. 19.17 ). 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.

A pair of pressure tracing graphs labeled A and B shows electrocardiogram lines above and pressure curves of left ventricle and aorta plotted over time. The pair of pressure tracing graphs labeled A and B shows the electrocardiogram and pressure recordings. Each panel has the horizontal axis labeled time in seconds from 2 to 8 and the vertical axis labeled pressure in millimeters of mercury from 0 to 200. Panel A shows curves representing left ventricular and aortic pressures with two boxed regions marking pulse pressure intervals. Panel B shows similar ranges and tracings with curves running parallel, and no boxes. Both panels include electrocardiogram waveforms above the pressure tracings showing aligned rhythmic peaks. — • Figure 19.17

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 reduced systemic vascular resistance. After exercise, decreased venous return results in reduced LV volume and an increase in systolic gradient.

The degree of mitral valve regurgitation can be assessed from the LV cineangiogram, but this is rarely necessary in current practice. Coronary angiography should be added to the catheterization procedure in patients in whom coronary artery occlusive disease is known to be present or suspected due to symptoms of angina and/or risk factors such as older age, diabetes mellitus, or peripheral artery disease. In one study, however, important occlusive coronary artery disease was present in only 11% of patients undergoing angiography in preparation for septal myectomy, and concomitant coronary artery bypass grafting (CABG) was performed in 7%. Indeed, there was only a 10% or less probability of coronary artery disease detected during angiography among males with HCM aged 52 years or younger and females aged 66 years or younger; in the absence of diabetes and peripheral artery disease, the age threshold increased to 54 and 69 years for males and females, respectively.

Natural history

Although more commonly encountered in adults, HCM can present at any age, from early infancy to the sixth or seventh decade. Infants and young children presenting with symptomatic obstructive HCM represent the more severe end of the spectrum, with gross LVH, frequent episodes of heart failure, and a high prevalence of sudden death. ^, The etiology of HCM is heterogeneous in pediatric patients and includes inborn errors of metabolism, neuromuscular disorders, and malformation syndromes. In contrast to individuals with neuromuscular disorders who are more often diagnosed in adolescence, patients with metabolic or syndromic HCM tend to present in infancy or early childhood, and progression of the 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 as heart failure, syncope, SCD, and peripheral embolization can occur. The sudden onset of heart failure is frequently precipitated by atrial fibrillation, which may be associated with subsequent embolism. In patients with obstructive HCM, the correlation between symptomatic class and degree of obstruction has generally not been close. However, in the multicenter trial reported by Shah and colleagues, there were no asymptomatic patients once the gradient exceeded 100 mmHg. In the experience of Wigle and colleagues, presyncope and syncope on exertion are encountered most frequently in patients with obstructive HCM.

Annual HCM-related mortality reported from referral centers has ranged from 4% to 6% in children and 2% to 4% in adults. ^, ^, ^, In contrast, studies involving largely unselected patients with HCM report annual mortality of 0.5% to 1.5%, similar to that for the general adult population. ^,

SCD is a potentially unpredictable and devastating complication of HCM, and younger patients are at higher risk than older patients. But in contemporary practice, risk of SCD is 0.8% to 1.0% per year. The availability of the ICD and standardized algorithms for estimating and managing SCD risk has dramatically reduced death from arrhythmic events. Midventricular obstruction is an independent predictor of adverse outcomes, especially for the combined endpoint of sudden death and potentially lethal arrhythmic events. It is often associated with apical aneurysms. ^, In a review of 196 patients undergoing myectomy for midventricular obstruction, Sun and colleagues found apical aneurysms in 30 patients (15%) who had isolated midventricular obstruction or both subaortic and midventricular obstruction. Prevalence of apical aneurysm among patients with isolated midventricular obstruction (30%) was 5-fold greater than that in patients who had both midventricular and subaortic obstruction (5.2%, P <.001).

Neurologic death from cerebral embolism occurs in patients with long-standing persistent or paroxysmal atrial fibrillation. In one study with an average of 8 years of follow-up, ischemic stroke occurred in 20% of the patients with, and 0.7% without, atrial fibrillation. Importantly, 89% of the patients with HCM who experienced at least 1 episode of ischemic stroke had atrial fibrillation at baseline. In the general population, the estimated in-hospital mortality of ischemic stroke is 4.9%, and patients with atrial fibrillation have a 30% to 70% increased risk of in-hospital death after adjusting for other risk factors. Compared to patients without HCM, prognosis of acute ischemic stroke is worse in patients with HCM. Cerebral embolism can also occur as a result of infective endocarditis on aortic and mitral valves in patients with HCM. ^, ^,

Technique of operation

Myectomy by aortic approach

A median sternotomy is preferred for almost all patients as more limited incisions can hinder exposure of the septum through the aortic valve. Cardiopulmonary bypass at normothermia or mild hypothermia is established in the standard fashion using a single, two-stage venous cannula (see Chapter 2 ). The aorta is clamped, and cold blood cardioplegia (1000 to 1200 mL) is infused through the aortic needle vent to arrest the heart. Repeat infusions of cardioplegia are administered directly into the coronary ostia as necessary.

Several maneuvers help optimize exposure of the subaortic septum. Pericardial stay sutures are used only on the right side to elevate the pericardium and right-sided heart structures toward the surgeon. Next, an oblique aortotomy is made slightly closer to the sinutubular ridge than usual for aortic valve replacement. The incision is carried through the midpoint of the noncoronary aortic sinus of Valsalva to a level approximately 1 cm above the valve anulus. This oblique incision is preferred over a transverse incision as it facilitates instrumentation in the subaortic area. Stay sutures are used to hold the edge of the proximal aorta, and a cardiotomy sucker is placed through the aortic valve to depress the anterior leaflet of the mitral valve to protect it from injury. Using the cardiotomy sucker for exposure eliminates the need for a separate vent. Alternatively, a vent can be passed into the ventricle through a purse string suture in the right superior pulmonary vein. It is important to minimize instrumentation across the valve as these may injure aortic valve cusps.

The right aortic valve cusp is collapsed against the sinus wall, where it will usually stay. If the noncoronary aortic valve cusp interferes with exposure, it can be held away with a traction suture of 5-0 polypropylene passed through the free edge at the nodule of Arantius ( Fig. 19.18 ). A sponge stick is used to depress the right ventricle and to rotate the septum posteriorly, bringing it into better view through the aortotomy, as suggested by Morrow.

A pair of labeled surgical diagrams A and B shows suturing steps within the opened aortic root to secure and retract the noncoronary cusp for septal exposure. The pair of labeled surgical diagrams A and B shows the transaortic septal myectomy technique. Panel A shows a surgical instrument placing a mattress stay suture through the nodule of Arantius of the noncoronary cusp, with two guiding sutures held at the upper edge. Panel B shows the same operative field after the suture is secured, with the aortic wall and medial aspect of the right atrium exposed. Both panels display the opened aortic root, adjacent muscle tissue, and suture positioning to improve visualization of the subaortic septum. — • Figure 19.18

Myectomy is performed using a standard No. 10 scalpel blade, initially incising the septum just to the right of the nadir of the right aortic sinus ( Fig. 19.19 ). The incision in the septum is made upward and then leftward over to the anterior leaflet of the mitral valve. This initial excision of septal myocardium is completed with scissors, and the area of septal excision is deepened and lengthened toward the apex of the heart, being certain to excise hypertrophied septum beyond the endocardial contact lesion ( Fig. 19.20 ). Trabeculations are excised, and the myectomy site can be further extended using pituitary rongeurs. Adequate septal myectomy usually yields 3 to 12 g of muscle. The aortotomy is then closed, and the operation proceeds as usual.

A pair of surgical diagrams labeled A and B shows steps of septal incision during transaortic myectomy with an inset showing a removed muscle specimen. The pair of surgical diagrams labeled A and B shows procedural steps in transaortic septal myectomy. Panel A shows an open aortic view with an instrument making an upward incision in the septum marked by a dotted line within a clock face reference, starting near the one o’clock position and extending counterclockwise. Panel B shows the incision carried across toward the mitral valve attachment with the instrument inserted into the septal region. The inset in panel B shows an excised elongated septal muscle specimen. Both panels depict the surgical field including the aortic valve cusps and surrounding tissue boundaries. — • Figure 19.19

A pair of surgical diagrams labeled A and B shows steps in septal muscle resection during transaortic myectomy with insets showing excised muscle portions. The pair of surgical diagrams labeled A and B shows progressive stages of transaortic septal myectomy. Panel A shows instruments inserted through the aortic opening while the resection of the septal muscle proceeds, with an inset displaying a partially removed septal segment. Panel B shows deepening of the septal incision using surgical tools guided from above, indicated by an arrow marking downward traction. The inset in panel B shows the extended resection plane along the septum. Both panels include valve cusps, retractor placement, and the surgical access path through the aorta. — • Figure 19.20

Relief of the LV outflow tract obstruction is confirmed by transesophageal Doppler echocardiography and simultaneous measurement of aortic and LV pressures by direct needle puncture. ^, Before cardiopulmonary bypass, LV outflow gradients are measured at rest and after provocation by a premature ventricular beat to elicit the dynamic gradient produced by the Brockenbrough phenomenon; the same maneuver is repeated after myectomy. If a residual gradient of more than 10 to 15 mmHg is present, cardiopulmonary bypass should be re-established and additional muscle resected.

The previously described technique for more extended myectomy differs from the standard Morrow operation, in which parallel incisions create a trough in the septum that extends up to 3 cm from the aortic valve. In the extended myectomy, wider excision of muscle in the immediate subaortic area improves exposure of the distal extent of the hypertrophied septum, and excision extends up to 5 to 7 cm from the aortic valve. A guiding principle during operation is recognizing that inadequate septal myectomy results more often from failure to excise sufficient length of the septum (toward the apex) than from inadequate depth or rightward extent of excision. This is important because addressing residual gradients by deepening the myectomy site will not only be ineffective but also risks creating a septal defect.

In pediatric patients, obstructive HCM has a more variable morphologic spectrum. ^, The major site of obstruction may be subaortic, although it can occur at the midventricular or apical levels. The transaortic approach for septal myectomy may be difficult in small children due to poor exposure through a small aortic anulus. In selected pediatric patients, a transatrial approach to the septum may be advantageous. Biventricular obstruction is more common in children than adults, and repair includes transaortic septal myectomy and right ventricular myectomy performed through a subpulmonary longitudinal ventriculotomy closed with a bovine pericardial or polyester patch. Another strategy for patients with severe biventricular hypertrophy is excision of the thickened septal muscle through a right ventriculotomy removing one-third to one-half of the interventricular septal thickness. The more extensive myectomy through the right ventricle relieves LV outflow tract obstruction by allowing the septum to move rightward during systole and has been effective in patients with midventricular obstruction.

Adjuncts to conventional myectomy

Adjuncts to septal myectomy for obstructive HCM have been advocated to improve LV outflow tract gradient relief. Plication of the anterior leaflet of the mitral valve with myectomy , first proposed by Cooley and later by McIntosh and colleagues, has been performed in patients judged at operation to be at increased risk for a suboptimal hemodynamic result because of the morphology of the mitral valve (increased mobility, size, or length of the anterior leaflet with respect to LV outflow tract dimension). Plication can be performed through the aortic valve either in the horizontal direction or vertically (tip of the leaflet to base) using several interrupted polypropylene sutures. ^,

Anterior leaflet extension by inserting a pericardial patch into the body of the anterior leaflet has been employed by some groups. This maneuver is thought to increase leaflet stiffness, which causes lateral displacement of the secondary chordae tendineae and functions hemodynamically as a spinnaker sail to eliminate SAM of the mitral valve.

Other proposed adjuncts to septal myectomy include division of anterior leaflet secondary chordae, ^, papillary muscle repositioning, and tethering the anterior leaflet with an Alfieri suture. ^, These maneuvers are performed frequently in some centers; others reserve adjunctive mitral valve procedures for patients undergoing myectomy who have moderate ventricular hypertrophy. It is unclear, however, whether any additional procedures directed at the mitral valve are necessary if the septal myectomy is properly performed. In one large series of more than 2000 patients undergoing septal myectomy, additional mitral valve interventions were performed in only 2% of patients without intrinsic mitral valve disease.

Mitral valve replacement

The role of mitral valve replacement with or without septal myectomy is controversial. Excision of the anterior mitral leaflet relieves LV outflow tract obstruction in most patients. ^, ^, The small size and, at times, abnormal shape of the LV cavity require use of a low-profile prosthesis, most often a mechanical valve, and a concomitant septal myectomy should be performed in most patients. If mitral valve replacement is performed, the entire anterior leaflet of the mitral valve must be excised. If hypertrophied and contributing to obstruction, the papillary muscles are excised.

However, mitral valve replacement with a mechanical prosthesis leaves the patient with the potential hazards of a prosthesis and long-term need for systemic anticoagulation. Further, studies have shown that compared to septal myectomy alone, mitral valve replacement in patients with obstructive HCM is associated with an increased risk of perioperative (univariate odds ratio 12) and late mortality. ^, Thus, mitral valve replacement in patients with obstructive HCM should be reserved for patients with rheumatic or severe myxomatous or degenerative disease that is not amenable to repair. ^,

Additional surgical considerations

Associated intrinsic mitral valve disease.

Other structural abnormalities of the mitral valve besides those typically associated with obstructive HCM exist in approximately 7% of patients undergoing surgical treatment of obstructive HCM. ^, Mitral valve repair is feasible in 60% to 80% of these patients using conventional reparative techniques, especially if the pathology is simple leaflet prolapse due to ruptured chordae tendineae, ^, ^, but there are special considerations in patients with HCM. First, exposure of the mitral valve through a standard left atriotomy may be compromised by the anterior displacement of the hypertrophied left ventricle Second, the use of an undersized annuloplasty, especially a complete ring prosthesis, to reinforce leaflet repair may predispose to SAM and residual LV outflow tract obstruction. If anuloplasty is necessary, a flexible band on the posterior anulus is preferred.

Anomalous papillary muscles.

Wigle and colleagues first described the insertion of a papillary muscle into the body of the anterior leaflet in a patient with HCM and LV outflow tract obstruction. Although uncommon, anomalous papillary muscles are important surgically. As seen in Fig. 19.21 , those that insert into the body of the anterior leaflet of the mitral valve can narrow the outflow tract and contribute to LV outflow tract obstruction. In conjunction with septal myectomy, such anomalous muscles should be excised with care not to disrupt any associated chordal attachments to the anterior leaflet. Surgical awareness is important as these anomalies are not readily identified on preoperative TTE or intraoperative transesophageal imaging.

A cross-section of a heart showing a type 1 anomalous papillary muscle. A double-headed arrow marks the obstruction point between the thick septum and the abnormal muscle. Thediagram shows a long-axis cross-sectional view of a human heart focusing on the internal structures of the left ventricle. The heart walls are depicted in shades of pink and red representing thick cardiac muscle with the interventricular septum appearing significantly hypertrophied or thickened. Positioned within the ventricular cavity is a type I anomalous papillary muscle which appears as an elongated muscular structure extending toward the top of the chamber. A small double-headed arrow is placed in the narrow gap between the thickened interventricular septum and this anomalous papillary muscle to identify the specific site of left ventricular outflow tract obstruction. Below the ventricle a small section of yellow tissue with purple and red circular vessels while the aortic root and mitral valve structures are shown at the top right of the ventricle. The diagram effectively communicates how the proximity of the oversized septum to the abnormally placed papillary muscle creates a physical bottleneck that restricts the flow of blood as it exits the heart. — • Figure 19.21

Ablation for atrial fibrillation.

Atrial fibrillation is common in patients with HCM and is reported preoperatively in 20% of patients undergoing septal myectomy. Ablation for atrial fibrillation during surgical septal reduction is expected to reduce arrhythmia recurrence late after operation and reduce the risk of embolic stroke. Selection of ablation method depends on arrhythmia burden and severity of associated symptoms as well as experience of the surgical team. ^, For patients with only minor symptoms and few episodes of paroxysmal arrhythmia, pulmonary vein isolation with amputation or occlusion of the LA appendage may be adequate. The more complete lesion set described by Cox ^, is preferred for patients with long-term persistent atrial fibrillation and for patients who are highly symptomatic with atrial fibrillation. Methods of surgical ablation for atrial fibrillation are described in detail in Chapter 15 .

Midventricular cavitary obstruction.

Midventricular obstruction is less common than subaortic obstruction in HCM and has a different pathophysiologic mechanism. It is caused by narrowing of the mid ventricle during systole with apposition of the septum and papillary muscles. In untreated patients, midventricular obstruction may have a worse prognosis than the more common phenotype. ^, Secondary mitral valve regurgitation is uncommon, but there is a wide spectrum of phenotypes, and some patients will have both subaortic obstruction (with SAM of the mitral leaflets) as well as midventricular obstruction. Further, patients with midventricular obstruction may develop apical aneurysms (see next paragraph) that can lead to ventricular arrhythmias or thromboembolism. Midventricular obstruction has been relieved through a transaortic approach, but in most patients, midventricular myectomy is most easily performed through a transapical incision. The contact lesion on the septum and the opposing papillary muscle guides excision of the septum.

Apical aneurysms.

Repair of apical aneurysms includes excision of the aneurysm wall coupled with midventricular and apical myectomy to eliminate an intracavitary gradient. In one series of 44 patients with HCM undergoing apical aneurysm repair, underlying pathophysiology was nonobstructive apical HCM (ApHCM) in 17 patients (39%), HCM with midventricular obstruction in 16 (36%), and a combination of ApHCM and midventricular obstruction in 11 (25%). Rarely, an apical aneurysm with midventricular obstruction will be associated with SAM-mediated subaortic LV outflow tract obstruction. The aneurysmectomy site is closed in a linear fashion, and patch repair is unnecessary.

Heart failure associated with small LV diastolic volume.

Apical myectomy has been proposed to treat severely symptomatic patients with ApHCM and small LV end-diastolic volume. ^, ^, Through an incision in the apex of the left ventricle lateral to the LAD coronary artery, excision of ventricular septal muscle at the apex and midventricular levels is performed with the objective of increasing LV end-diastolic volume and improving LV compliance. Postoperative hemodynamic studies have demonstrated a significant ( P <.002) decrease in LV end-diastolic pressure, an increase in LV diastolic volume index, and an increase in stroke volume. ^, Transapical myectomy for ventricular enlargement is reserved for patients with advanced heart failure symptoms for whom cardiac transplantation is the only other surgical option.

Special features of postoperative care

Management of hemodynamics and cardiac rhythm

The patient is cared for with the principles and protocols described in Chapter 4 . Marked LVH reduces ventricular compliance to such an extent that LA pressures of 16 to 18 mmHg may be required early postoperatively for adequate preload. Beta-adrenergic receptor agonists such as isoproterenol and dopamine should be avoided in most patients because they increase heart rate and myocardial contractility and may increase residual outflow tract gradient. Similarly, hypovolemia and drugs that reduce systemic vascular resistance, such as nitrovasodilators, should be used cautiously to avoid reducing LV volume and exaggerating any residual gradient.

Atrial fibrillation may be poorly tolerated, so measures should be taken to reduce its probability of occurrence and to treat it aggressively if it develops. This can be best accomplished using β-adrenergic receptor blocking agents (e.g., metoprolol) and amiodarone.

Implanting a cardioverter defibrillator

Patients with obstructive HCM and a history of cardiac arrest or ventricular tachycardia or fibrillation should be considered for an ICD for secondary prevention of SCD. If the device is implanted during hospitalization for septal myectomy, the procedure is usually performed on the third or fourth day postoperatively. An ICD may also be indicated for primary prevention in patients considered at high risk for SCD. Recognized risk factors for SCD include a family history of sudden death from HCM, massive LV wall thickness (>30 mm in any segment by echocardiography or CMR), unexplained syncope unlikely to be neurocardiogenic or attributable to LV outflow tract obstruction, LV systolic dysfunction (ejection fraction <50%), LV apical aneurysm independent of size, extensive late gadolinium enhancement on CMR imaging, and nonsustained ventricular tachycardia on ambulatory monitoring.

There is debate regarding the importance of LV outflow tract obstruction on the risk of SCD, but the presence of an outflow tract gradient is included as a continuous, weighted variable in the risk calculator endorsed by the European Society of Cardiology. Further, in a study of HCM patients with ICDs, McLeod and colleagues reported that the average annualized event (appropriate ICD discharge) rate was 4.3%/year in the nonmyectomy group, compared with 0.24%/year following myectomy ( P =.004).

Various algorithms and risk calculators may be useful in the decision for ICD implant in the general population of patients with HCM, ^, but there are few studies that address how SCD risk is affected following relief of LV outflow tract obstruction. One report found that occurrence of SCD following septal myectomy was less than predicted and suggested refinement in guidelines for ICD implant in postoperative patients.

Results

Early (Hospital) death

In contemporary practice, hospital mortality for isolated septal myectomy performed in specialized HCM centers is 2.6% but ranges from 0.9% in centers performing 10 or more procedures per year to 3.7% in programs performing one to five operations annually ( Fig. 19.22 ). Lower case volume, in addition to older age, preoperative dialysis dependence, and mitral valve replacement, were incremental risk factors for mortality. Perioperative mortality has remained somewhat higher with concomitant CABG and valve replacement. As emphasized by Maron and colleagues, it is appropriate to cite these low mortality statistics to current candidates for myectomy rather than to quote older, obsolete data.

A bar graph shows early mortality percentages by average annual septal myectomy cases with values ranging from 0.9 to 5.9 percent. The bar graph displays Early mortality following septal myectomy on the vertical y axis, with percentages graduated from 0 to 20. The horizontal x-axis categorizes hospitals by their Institutional volume of procedures per year, with four categories: 1, 2 to 4, 5 to 9, and greater than or equal to 10. For centers performing only 1 procedure per year, the bar indicates a high mortality rate of 15.6 percent. This rate drops sharply to 6.2 percent for centers performing 2 to 4 procedures per year and continues to decrease to 3.8 percent for those performing 5 to 9 procedures. The final bar shows that for high-volume centers performing 10 or more procedures annually, the mortality rate is at its lowest at 0.8 percent. A dashed horizontal line is drawn across the graph at the 1 percent mark to emphasize that only the highest volume centers achieve a risk of death below this threshold. The data clearly demonstrates a strong inverse correlation between surgical experience at an institutional level and the risk of early postoperative death for this specific heart procedure. — • Figure 19.22

Time-related survival

Information on survival late after septal myectomy now extends beyond 20 years. In a 2005 report by Ommen and colleagues, 10-year survival of 289 patients with obstructive HCM undergoing septal myectomy was 83%, similar to that of an age- and sex-matched US population and to the survival of HCM patients without obstruction. In a 2019 report of 2506 patients undergoing transaortic septal myectomy for obstructive HCM ( Fig. 19.23 ) , 20-year survival was approximately 50%. Survival of both males and females was similar to age- and sex-matched populations through the first decade postoperatively, but the comparative survival of females declined beyond 10 years. However, female sex was not an independent risk factor for reduced late survival after septal myectomy after adjusting for important baseline prognostic factors, including age, symptomatic status at presentation, and severity of obstructive physiology and diastolic dysfunction. There is no difference in survival following septal myectomy among patients stratified by genetic status.

A pair of survival graphs, labeled unadjusted and adjusted, shows male and female survival percentages over twenty-five years after surgery. The pair of survival graphs shows unadjusted and adjusted curves for male and female patients. The vertical axis shows survival percentage ranging from 0 to 100, and the horizontal axis shows years from surgery ranging from 5 to 25. In the upper unadjusted graph, the male curve starts near 100 and declines gradually to about 50 at twenty-five years, while the female curve lies slightly lower throughout the same period. In the lower adjusted graph, both male and female curves follow nearly parallel downward slopes from 100 to about 60 at twenty-five years, with reduced separation between them. Both graphs show shaded bands around each curve representing confidence intervals. — • Figure 19.23

Data from other surgical series estimate 5-year survivals that range from 84% to 96% and 10-year survivals from 71% to 88%. Schulte and colleagues reported 88% 10-year and 72% 20-year survival in a group of 364 patients. Woo and colleagues reported similar 10- and 20-year survival (83% and 68%, respectively) among 338 adult patients. Late survival is higher in patients undergoing isolated myectomy than in those undergoing combined procedures.

Modes of death

In current practice, only approximately 25% of patients with HCM ultimately die due to their disease, and the prevalence of HCM-related death is greatest in patients less than age 30 years. But late cardiac modes of death are more common in patients who have undergone septal myectomy, presumably due to more advanced disease. In one large study of 398 patients who died late following septal myectomy, cardiac-related deaths occurred in 224 (56%) patients, but HCM was identified as the primary cause of death in 64. Other modes of death included those from coronary artery disease (n = 64), stroke (n = 23), other cardiomyopathy (n = 20), and heart failure (n = 15). Noncardiac deaths occurred in 174 (44%). Gene-positive status was not associated with mortality. With the availability of ICDs and associated protocols for implant, lower risk of SCD may improve postoperative survival in the future. ^,

Incremental risk factors for premature death

Older age at operation is a risk factor for early and late death. ^, ^, However, many elderly patients not only survive but have marked hemodynamic and symptomatic improvement. ^, The addition of mitral valve replacement to myectomy is a risk factor for late death. ^, ^, Other risk factors following septal myectomy include coronary artery disease, ^, preoperative atrial fibrillation, concomitant procedures, ^, development of complete heart block, ^, and preoperative presence of pulmonary artery hypertension ( Fig. 19.24 ).

A pair of survival graphs shows fifteen-year survival by right ventricular systolic pressure groups below 35, 35 to 49, and 50 or more millimeters of mercury. The pair of survival graphs shows unadjusted and adjusted curves comparing patient survival by right ventricular systolic pressure levels. The vertical axis shows survival percentage from 40 to 100, and the horizontal axis shows follow up time in years from 0 to 15. In the unadjusted graph, three survival curves are labeled less than 35, 35 to 49, and 50 or more millimeters of mercury, with the lowest curve representing the highest pressure group. The chi-square value is 39.28, and the P value is less than 0.001. In the adjusted graph, the same three groups show similar separation with the chi-square value 9.85 and P value 0.007. Both graphs include shaded regions representing 95 percent confidence intervals around each curve. — • Figure 19.24

Myocardial changes

Surgical reduction of LV outflow tract obstruction has secondary benefits on cardiac structure. Deb and colleagues demonstrated a substantial decrease in LV mass and mass index assessed by TTE following septal myectomy. This favorable reverse remodeling occurred early after operation and persisted beyond two years. Successful myectomy also leads to a reduction in LA enlargement. Menon and colleagues reported a significant ( P <.0001) decrease in LA volume index among 32 young patients after septal myectomy, and this reduction correlated closely with a decrease in the severity of MR ( P =.04). More recently, Nguyen and colleagues found that both LV mass and LA volume index decreased significantly following septal myectomy for obstructive HCM. In this study, the decrease in LA volume occurred early after operation, likely as a response to lower LA pressure due to gradient relief and abolishing of MR; further late reduction in LA volume suggests continued reverse remodeling. The decrease in its volume following septal myectomy may account for the finding that risk of new-onset atrial fibrillation late postoperatively is substantially reduced.

Additional hemodynamic benefits of septal myectomy have been documented. In a study by Monteiro and colleagues, LV diastolic filling, determined by mitral inflow Doppler velocity signals, was substantially improved postoperatively. In a cardiac catheterization study reported by Yang and colleagues, septal myectomy improved LV diastolic function as evidenced by reductions in LV diastolic time constant (Tau), average LA pressure, and pulmonary artery pressure. Provocation of dynamic LV outflow tract obstruction not only increases outflow gradient but also causes reduction in LV stroke volume. As seen in Fig. 19.25 , septal myectomy restores the ability to augment stroke volume following a premature ventricular beat, which may be an important mechanism of symptomatic improvement after operation.

A pair of bar graphs labeled preoperative and postoperative shows stroke volume in aortic stenosis and obstructive hypertrophic cardiomyopathy at rest and provoked. The pair of bar graphs labeled preoperative and postoperative shows stroke volume measured in milliliters on the vertical axis from 0 to 150 and grouped by condition on the horizontal axis as aortic stenosis and obstructive hypertrophic cardiomyopathy. Each group has two bars for at rest and provoked states. In the preoperative graph, aortic stenosis shows higher stroke volume than obstructive hypertrophic cardiomyopathy. In the postoperative graph, both groups show an increase in stroke volume, with aortic stenosis remaining higher. Single asterisks indicate P less than 0.05, and double asterisks indicate P less than 0.01 above comparison lines. — • Figure 19.25

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Tags: Hartzell V. Schaff, Kirklin/Barratt-Boyes Cardiac Surgery

Apr 21, 2026 | Posted by drzezo in CARDIAC SURGERY | Comments Off

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