Chapter 23. Hypertrophic Cardiomyopathy

Note: Not all criteria are needed for diagnosis of hypertrophic cardiomyopathy.

• Asymmetric hypertrophied nondilated ventricle with septal to posterior wall end-diastolic thickness ≥ 1.3 cm not explained by other etiologies.
• Ejection murmur that increases with Valsalva with or without concomitant mitral regurgitation murmur and preserved aortic second sound.
• Increased gradients causing obstruction across left ventricular outflow tract and/or mid ventricle with characteristic late peaking “dagger”-shaped Doppler velocity profile.
• Mitral systolic anterior motion with varying degree of mitral regurgitation.
• Midsystolic aortic valve closure.
• Impaired diastolic function with decrease in tissue Doppler (early diastolic velocity [E′]) and longitudinal strain.

Definition & Prevalence

Hypertrophic cardiomyopathy (HCM) is a disorder of the myocardium caused by mutations of the sarcomere or sarcomere-associated proteins. It mainly manifests as symmetric or asymmetric left ventricular hypertrophy (LVH) > 1.5 cm (Figure 23–1) in a nondilated ventricle unexplained by other cardiac or systemic causes of hypertrophy (see Table 23–1 for differential diagnosis of LVH). HCM has numerous alternate names such as idiopathic hypertrophic subaortic stenosis (IHSS) or asymmetrical septal hypertrophy (ASH). However, HCM is the widely preferred term for this condition as segmental hypertrophy can occur in any segment of the ventricle, not just the septum. Coexistent right ventricular (RV) hypertrophy and RV outflow obstruction occur less commonly in biventricular involvement.

HCM is relatively common (1 in 500) in the general population with about 750,000 people affected in the United States. Although it is the most common cause of sudden death in the young (< 35 years old) in North America, most people afflicted with HCM live a normal life. Contrary to the long mistaken notion that HCM was a uniformly fatal disease associated with a shortened life span, HCM patients may live well into their sixth to eighth decades, with patients older than age 90 with HCM being reported. Moreover, the first clinical recognition of HCM may occur when patients are in their sixth to eighth decade of life; usually these patients have milder forms of the disease with the most serious complications being uncommon after age 60. The natural history of HCM can take many paths: sudden cardiac death, symptomatic HCM heart failure, end-stage cardiomyopathy, atrial fibrillation, and stroke. However, if intervened upon in a timely manner, HCM can potentially have no effect on normal longevity.

Genetics & Histopathology

The genetics of HCM involve an autosomal dominant pattern of inheritance, with 60–70% of patients having an affected family member. HCM is more common in males than females. Common genes affected include β-myosin heavy chain, myosin binding protein C, troponin I, and troponin T, but numerous others have been described. Mutations of the sarcomeric proteins lead to histopathologic evidence of myocardial disarray, which then leads to pathologic hypertrophy and patchy fibrosis of the myocardium. Intramural vessels are also frequently abnormal in HCM with thrombotic obliteration causing ischemia, which may propagate fibrosis regardless of presence of epicardial coronary disease. The genetic basis of ventricular hypertrophy does not always correlate with prognosis. Patients with tropomyosin mutations have only a mild degree of ventricular hypertrophy, with little or no left ventricular (LV) outflow tract obstruction, but they still carry a disproportionately high risk for sudden death.

Phenotype of Hypertrophic Cardiomyopathy

The extent and location of hypertrophy in HCM are highly variable. Asymmetric hypertrophy is most common (septal 90%, midventricular 1%, posteroseptal and lateral wall 1%, apical 3%, symmetric 5%). ASH is defined as septal-to-posterior wall ratio > 1.3 and, in hypertensive patients, > 1.5. Massive hypertrophy > 30 mm is a risk factor for sudden death. Abnormal mitral valve and its apparatus are commonly seen in HCM. Elongated mitral leaflets and abnormal/anteriorly displaced papillary muscles and direct insertion of chordae tendineae or papillary muscles to anterior mitral leaflet can be seen (Figure 23–2). All these factors may contribute to outflow obstruction.

The following processes contribute to the pathophysiology of HCM.

1. Abnormal diastolic function

2. Outflow tract obstruction

3. Mitral regurgitation

4. Myocardial ischemia

5. Arrhythmias

6. Abnormal autonomic function

Diastolic Dysfunction

Diastolic filling abnormalities, invariably present in almost all patients with HCM, may precede hypertrophy, and as it worsens, an increased dependence on atrial contribution to ventricular filling occurs. Thus arrhythmias, like atrial fibrillation, are poorly tolerated by patients with HCM and should be promptly treated with sinus rhythm preferentially restored if feasible. Mitral inflow parameters demonstrate varying degrees of dysfunction, most commonly impaired relaxation, whereas restrictive filling patterns are less common but manifest in advanced disease states. Myocardial abnormalities documented by tissue Doppler, speckle tracking echocardiography-based strain, and LV twist and torsion abnormalities have been demonstrated in HCM. Figure 23–3 demonstrates impaired relaxation in mitral inflow, delayed propagation slope on color M-mode, and abnormal tissue Doppler, all indicative of diastolic dysfunction in a patient with HCM.

Outflow Obstruction

HCM can be broadly categorized into obstructive and nonobstructive types based on presence or absence of gradient (Figure 23–4). About two-thirds of patients with HCM have outflow tract obstruction manifesting as resting or provocable gradient of ≥ 30 mm Hg. However, only 25–30% of patients demonstrate obstruction at rest. Simple maneuvers such as the Valsalva maneuver, standing, or administration of amyl nitrite can provoke or exacerbate outflow tract obstruction and gradients and should be a routine part of clinical and echocardiographic evaluation when HCM is suspected (Table 23–2, Figure 23–5). Outflow obstruction can contribute to exercise intolerance, angina, syncope, and decreased survival. Patients with obstructive HCM are at higher risk of adverse events (heart failure and death) than those without obstruction. The combination of hypertrophied septum bulging into LV outflow tract and abnormal mitral valve motion in systole (systolic anterior motion [SAM]) contribute to outflow obstruction.

Although the exact cause of SAM is debated, two perspectives exist. One is a causal mechanism of SAM precipitated by chordal slackening/anterior displaced mitral valve apparatus leading to “drag forces,” and the other implicates SAM as a consequence of Venturi effect of accelerated flow across the left ventricular outflow tract (LVOT) (Figure 23–6). The severity of obstruction and timing of SAM onset are linearly related. An important caveat is that SAM can be seen in non-HCM states, such as a hyperdynamic small-ventricle, volume-depleted state, post mitral valve repair, and as a nonspecific finding confined to the chordal apparatus (chordal SAM). Thus, although patients in many different pathophysiologic states may exhibit HCM physiology (gradients, SAM), this does not equate to a diagnosis of HCM.

Mitral Regurgitation

The main etiology of mitral regurgitation (MR) in HCM is malcoaptation of the mitral leaflets secondary to SAM. SAM-related MR is posteriorly directed starting in mid-late systole (Figure 23–7). If a nonposterior jet of MR is seen, then intrinsic mitral valve disease should be suspected. Concomitant primary mitral valve disease is reported in about 20% of patients with HCM (mitral valve prolapse, ruptured chordae, mitral annular calcification, and anomalous or anteriorly displaced papillary muscle) (see Figure 23–2). If SAM is relieved by either myectomy or septal ablation, posterior MR tends to resolve or diminish. Nonposterior MR may require surgical repair or replacement of the valve, which may be one reason why surgical myectomy is favored over ablation as a treatment strategy for HCM.

A comprehensive echocardiography assessment of MR is important in HCM. The assessment of peak outflow gradients can be challenging in some patients with HCM in the setting of MR due to contamination of both jets (Figure 23–8). Careful observation of jet profile, coexistent inflow profile, and evaluation of peak gradients from different windows will help to differentiate outflow gradients from MR.

Myocardial Ischemia

The combination of significant LVH with or without outflow obstruction sets the stage for substantial increase in myocardial oxygen demand and can precipitate angina secondary to myocardial ischemia in HCM. Angina has been reported in approximately 30% of HCM patients, although ischemic perfusion defects on myocardial perfusion imaging can be present in a large majority of patients with HCM. Although epicardial coronary disease may cause angina/perfusion defects, a supply-demand mismatch in conjunction with abnormal microvasculature is likely the major contributor.

Abnormal Autonomic Tone

About 25% of HCM patients demonstrate abnormalities of autonomic function, which if present, portend a poorer prognosis. Abnormalities with exercise, such as systolic drop in blood pressure of ≥ 20 mm Hg, or failure to augment blood pressure can occur from factors such as outflow obstruction and inappropriate vasodilatation despite an appropriate increase in cardiac output.

Physical Examination

A general exam is not helpful in diagnosing HCM except when associations with other diseases such as Friedrich ataxia or Noonan syndrome are present. The cardiovascular clinical exam findings of HCM are usually striking unless there is no obstruction at rest. Radial pulse is of brisk character. There is a characteristic brisk carotid upstroke with an abrupt deceleration due to obstruction. The apical impulse is described as bifid and sustained due to the initial powerful contraction followed by obstruction and then by continued contraction of the left ventricle. A systolic thrill may be felt. The first and second heart sounds are normal. An S4 may be heard due to atrial contraction against a noncompliant left ventricle.

The systolic murmur in HCM is a harsh crescendo-decrescendo heard all over the precordium but usually is not transmitted to the carotids. The murmur increases in intensity with Valsalva, standing, and inhalation of amyl nitrite, due to a drop in preload and decrease in LV cavity size and vasodilation (amyl nitrite), which can worsen outflow obstruction. The murmur intensity decreases with squatting and passive leg raising. A second murmur of mid-late MR can be heard, induced by SAM of mitral valve. The combination of powerful ejection followed by obstruction and subsequent mitral insufficiency can be aptly described as the “eject-obstruct-leak” triad of hypertrophic obstructive cardiomyopathy (HOCM). The key differentiation of HCM murmur is from aortic stenosis (AS). However, the pulse of AS is low amplitude and slow (parvus et tardus) compared to brisk in HCM. Ejection click (with bicuspid etiology) and aortic regurgitation murmur are more common in AS and not typically seen in HCM. Aortic second sound is abnormal in AS and normal in HCM. Finally, AS murmur decreases with Valsalva in contrast to HCM murmur, which increases.

Diagnostic Tests

Electrocardiogram

More than 90% of patients with HCM exhibit 12-lead electrocardiography (ECG) abnormalities. Such abnormalities can precede echocardiographic findings and become more prevalent as age increases. Common abnormalities include LVH with strain, prominent Q waves, left atrial enlargement, and left axis deviation. ST elevation or depression or T-wave inversions can also be seen. Specific patterns such as deep symmetric T-wave inversions in lateral precordial leads (suggestive of apical variant HCM) are also well recognized (Figure 23–9). In general, ECG abnormalities are present in > 80% of obstructed HCM compared to approximately 50% in nonobstructive types of HCM. Preexcitation patterns are also seen in some patients with HCM, and atrial fibrillation has been documented in up to 25–30% of elderly HCM patients.

Echocardiogram

Echocardiography (echo) plays an integral role in diagnosis, follow-up, and management of patients with HCM. Abnormalities can be demonstrated on M-mode echo; two-dimensional (2D) echo; color, pulsed and continuous wave, and tissue Doppler; and strain imaging. Key findings of HCM by echo include the following.

M-Mode

Midsystolic notching of aortic valve is seen in HCM (Figure 23–10). SAM of mitral valve can also be assessed, and extent of SAM and SAM-septal contact distance as a marker of severity can be assessed (Figure 23–11). RV and LV septal and posterior wall thickness and chamber sizes can be determined.

2d Echo

Asymmetric septal hypertrophy is the most common pattern, although other patterns can be seen (see Figure 23–1). RV hypertrophy may also be present. Because echo can underestimate or miss hypertrophy confined to the lateral wall and apex, comprehensive multiple nonforeshortened views of LV are needed. Echo contrast imaging can be useful to assess apical variant HCM. Mitral valve abnormalities can be seen as described previously. SAM can be assessed, and all chamber sizes can be evaluated. Recently enlarged left atrium (indexed volume > 34 mL/m2) has been shown to be an independent adverse prognosticator in HCM. A nonspecific increased backscatter of hypertrophied myocardium causing a “ground-glass” appearance can be seen. However, this is not specific for HCM and can be seen in other infiltrative diseases.

Doppler

Pulsed wave and continuous wave Doppler assessment is integral in establishing the level of outflow obstruction and peak gradients, respectively. The modified Bernoulli equation (4V2) is used to determine peak gradient. The classic late peaking “dagger-shaped” velocity profile can be seen when outflow obstruction is present (see Figure 23–4). A peak gradient of > 30 mm Hg is considered as evidence for resting outflow obstruction. Gradients should be assessed at rest and with provocation by Valsalva or standing (see Figure 23–5B). If echo features suggest HCM but no obstruction is demonstrable at rest or Valsalva, exercise echo with peak/immediate postexercise gradient assessment could unmask HOCM (latent obstruction). Color Doppler and continuous wave Doppler can be used to comprehensively assess severity and mechanism of MR. It is important to reliably distinguish the MR signal from the LVOT obstruction signal to avoid overestimation of severity of outflow obstruction. Diastolic function and tissue Doppler abnormalities of myocardial function should be assessed. In particular, recent studies have shown that average E′ velocities by tissue Doppler of < 13.5 cm/s predicted genotype-positive HCM with a sensitivity of 75% and specificity of 86%. Reduced longitudinal peak systolic deformation (strain) averaged across all walls < 10.6% (in absolute value) predicted HCM with a sensitivity of 85% and specificity of 100% and helped differentiate it from hypertensive LVH. A combination of septal/posterior wall ratio > 1.3 and systolic strain assessment yields a predictive accuracy for HCM of 96%. The estimation of filling pressures using E/E′ at best correlates moderately with invasive wedge pressure measurements, although low E′ in itself has independent adverse prognostic value in HCM. Delayed untwisting of LV has been demonstrated by torsion analysis using speckle tracking techniques, again reflecting diastolic dysfunction-related abnormalities seen in HCM.

Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance imaging (CMRI) is rapidly becoming a key component in enhancing diagnostic accuracy, morphology, and more importantly, prognostication due to tissue characterization of fibrosis in HCM. With its superior spatial resolution and indefinite choice of imaging planes, it has demonstrated enhanced accuracy in assessing HCM features and identifying patterns of hypertrophy not well seen on echocardiography. Approximately 6% of patients missed by echo (mainly anterolateral hypertrophy) are diagnosed with HCM by CMRI, and 57% of apical aneurysms missed by echo are identified on CMRI in the apical variant. Assessment of LV mass and end-diastolic wall thickness is more accurate with CMRI than echo. Figures 23–12 and 23–13 show CMRI delineation of septal hypertrophy in HCM.

CMRI also provides superb assessment of mitral valve apparatus morphologic abnormalities and gives unparalleled assessment of the right ventricle. However, echo is superior to CMRI in the functional assessment of severity of obstruction and diastolic function assessment. The presence of patchy myocardial fibrosis in HCM detected by late gadolinium enhancement techniques in CMRI is increasingly recognized as an adverse prognosticator for arrhythmias and mortality. Characteristic patterns include delayed enhancement detected at RV insertion points into the left ventricle, although multiple areas of fibrosis can be seen in the left and/or right ventricle with predominance in the hypertrophied zones of the ventricle (Figure 23–14). CMRI is also excellent to evaluate success of interventions, such as surgical myectomy or percutaneous alcohol septal ablation. It can be used to assess extent of procedural success and scar formation following septal ablation. Most recently, CMRI has been used to characterize presence of “myocardial crypts” or recesses in different areas of the myocardium in phenotype-negative but genotype-positive family members of probands with HCM. Whether these represent early manifestations of an HCM phenotype yet to develop remains to be established, as does any long-term significance.

Cardiac Computed Tomography Angiography, Cardiac Nuclear Perfusion Imaging, and Positron Emission Tomography

Cardiac computed tomography angiography (CCTA), cardiac nuclear perfusion imaging, and positron emission tomography (PET) are not routinely used in assessment of HCM but may be useful in select cases. Retrospective gated CCTA can provide LV function assessment apart from LV morphology and coronary anatomy. It can also accurately delineate septal perforator course noninvasively as a road map for septal ablation. Single-photon emission computed tomography (SPECT) and PET can demonstrate characteristic intense uptake of radioisotope in hypertrophied zones of myocardium and also demonstrate perfusion abnormalities mainly related to microvascular flow reserve abnormalities in HCM Quantitative PET-determined coronary flow reserve abnormalities along with ischemic perfusion defects have been shown to predict adverse outcomes in HCM in limited studies. However, there is no evidence that routine CCTA or PET adds incremental information in diagnostic accuracy or risk stratification to warrant routine use in all patients with HCM.

Cardiac Catheterization

Echo with Doppler forms the crux of diagnosis of HCM, and invasive hemodynamics is usually not necessary. However, if clinical and echo findings are discrepant or the exact severity of obstruction cannot be accurately determined by echo, then catheterization may be needed. A carefully conducted study with continuous documentation of pullback gradients will outline the level and severity of obstruction. A classic “spike and dome” arterial pulse waveform can be recorded representing the rapid ejection followed by sudden obstruction. Pulmonary capillary wedge pressure may be elevated, reflecting high filling pressures from diastolic dysfunction, stiff ventricle, and noncompliant atrium. Depending on the severity of MR, a prominent “v” wave can be recorded. Also the Brockenbrough-Braunwald-Morrow sign can be demonstrated by inducing premature ventricular beats. Following a ventricular extrasystole, an increase occurs in LV systolic pressure, decrease in ascending aortic pressure, and increase in gradient. Importantly, a drop in pulse pressure is seen in HCM compared to AS where pulse pressure does not change (Figure 23–15).

Exercise Echocardiography

Exercise echocardiography is recommended to provoke obstruction, which is either absent or minimal at rest (< 30 mm Hg), particularly in patients with features of nonobstructive HCM. Furthermore, exercise can unmask abnormal hemodynamic responses such as failure to augment systolic blood pressure or a drop in systolic blood pressure with exercise. Other abnormal signs with exercise include poor exercise capacity, ventricular arrhythmias, ST depression, and/or ischemic wall motion abnormalities (regardless of presence of epicardial disease). Exercise echocardiography has a class 2A indication in the 2011 American College of Cardiology/American Heart Association (ACC/AHA)'s HCM guidelines for evaluation of provocable gradients and exercise hemodynamics. Symptomatic patients with HCM with gradients at rest or with provocation ≥ 50 mm Hg usually require therapy (medical and/or invasive), and hence, exercise testing is not indicated in such patients. However, once medical therapy is maximized in patients with HOCM, repeat exercise echocardiography may be helpful to reevaluate symptoms, exercise hemodynamics, and effects of medical therapy on reduction of outflow obstruction/gradients. Although dobutamine can induce outflow obstruction and gradients, it is not recommended for testing in HCM as it can provoke a similar response even in normal individuals.

Genetic Testing

The most practical current application for genetic testing in HCM is screening of asymptomatic family members of patients with HCM. If a known mutation exists in HCM patients, focused genetic testing can be done for that mutation in the family. If genetic testing is unyielding, surveillance imaging may be needed. Adolescents and athlete family members should undergo echo annually, and nonathlete family members should undergo echo every 5 years.

Diagnostic Considerations in Hypertrophic Cardiomyopathy Variants

Apical HCM

This form of HCM is more frequently reported in the Asian populations and is associated with deep symmetric T-wave inversions in the anterior precordial leads (see Figure 23–9). Echo reveals a predominant pattern of hypertrophy distributed toward the apex with relative sparing of the base, although concomitant basal hypertrophy may also be present. In conjunction with the normal contractility, the marked narrowing of the hypertrophied apex in systole produces the “ace of spades” appearance on echo. Apical variant HCM can be missed in echo due to foreshortened views or poor visualization of hypertrophy with low-frequency transducers. Use of higher frequency transducers, color Doppler to delineate full extent of blood flow, and contrast echo can overcome these limitations. CMRI is an excellent alternative to echo and is a superior technique to diagnose apical HCM due to lack of any limitations that occur with echo (Figure 23–16). In general, isolated apical HCM is devoid of outflow obstruction, and these patients have a more benign prognosis than the classical HCM patients.

Midventricular HCM

This variant involves predominant hypertrophy of the mid ventricle, resulting in midcavitary obstruction and separation of the ventricle into two compartments in systole. Flow acceleration and obstructive gradients can be demonstrated in the mid ventricle where most obstruction exists, although concomitant outflow obstruction may be present. Abnormal early diastolic color flow can be seen during isovolumic relaxation due to differential intraventricular pressure gradients across the obstruction. Coexistent hypertension may exacerbate midventricular hypertrophy. In the pure midventricular HCM, SAM may be absent and no outflow obstruction may be detected. Continuous wave Doppler can delineate maximal obstructive midventricular gradients (Figure 23–17A). Long-standing obstruction in mid ventricle can cause apical necrosis with aneurysm formation due to chronic subendocardial ischemia (Figure 23–17B). This subset of patients is more prone to ventricular arrhythmias and thrombus formation. CMRI is an excellent technique to demonstrate these apical aneurysms, which can often be missed by echo.

Hypertensive HCM in the Elderly

First described in the 1980s, this entity is increasingly recognized more frequently given the growing population of elderly patients with hypertension. Whether this represents a variant of HCM or mimics the physiology of HCM is still debated. Most patients have a long history of hypertension, small hypertrophied ventricles, narrow LVOT with mitral annular calcification, and some anterior displacement of the mitral annulus. This constellation can set the stage for acceleration of flow, SAM, and outflow obstruction, although midventricular obstruction may also be present. Treatment is similar to HCM with regard to relief of outflow obstruction with negative inotropic drugs and adequate control of hypertension. Avoidance of excessive diuresis and preload reduction is also a key component.

End-Stage HCM

Seen in < 5% of patients, end-stage HCM features ventricular dilation, advanced diastolic dysfunction, and a course predominated with symptoms of systolic and diastolic heart failure. Medical treatment consists of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, β-blockers, diuretics, and spironolactone, as well as nonpharmacologic strategies such as implantable cardioverter-defibrillator (ICD) and biventricular pacing if indicated. In refractory cases, heart transplantation should be considered. Survival after heart transplantation in HCM is comparable to the general population.

The therapeutic strategies in HCM can be divided into pharmacologic and nonpharmacologic strategies.

Pharmacologic Strategies

Pharmacologic therapy for HCM is focused on decreasing inotropy, augmenting diastolic filling time, and reducing dynamic outflow obstruction. Resting gradients are not useful to gauge effectiveness of therapy. Negative inotropic agents such as β-blockers and rate-slowing calcium channel blockers can help diminish gradients and outflow obstruction in HOCM and also decrease myocardial oxygen demand. High doses, such as 200 mg of propranolol or metoprolol or 240–360 mg of verapamil or diltiazem, may be effective. Caution should be used when high resting outflow gradients are present when initiating verapamil because peripheral vasodilatation may occur, leading to syncope. Disopyramide, a class Ia antiarrhythmic agent with potent negative inotropic effect, can be used as an adjunct to standard therapies. Amiodarone, which has β-blocking properties, has been shown to have a favorable effect on prognosis in selected patients with HCM. Pure vasodilators (eg, dihydropyridines, nitrates, hydralazine) should be avoided. β-Agonists and digoxin may worsen obstruction by augmenting contractility and should be avoided. Excessive diuresis should also be avoided because it may exacerbate obstruction, although diuretics will be needed to relieve pulmonary congestion in the setting of pulmonary edema. Exercise echocardiography can be used to assess efficacy of treatment and decrease provocable gradients on therapy. In nonobstructive variants of HCM, treatments can be targeted for diastolic dysfunction with judicious use of diuretics as needed for elevated filling pressures. In advanced HCM with dilated and dysfunctional ventricles (“burnt out” or end-stage HCM), standard heart failure therapies are indicated as discussed earlier. Atrial fibrillation occurs in 25–30% of elderly patients with HCM, is poorly tolerated, and requires electrical cardioversion and/or aggressive rate control. HCM patients with atrial fibrillation are at high risk for stroke and should receive anticoagulation therapy. Radiofrequency ablation can be offered to some patients with drug-refractory atrial fibrillation. Finally, if the HCM patient continues to remain symptomatic despite medical treatment, more aggressive nonpharmacologic therapies should be explored regardless of degree of residual outflow obstruction.

Nonpharmacologic Therapies

Nonpharmacologic strategies include surgical septal myectomy, alcohol septal ablation, and dual-chamber pacing.

Surgical Septal Myectomy

Septal myectomy is widely regarded as the best treatment for HCM with regard to relief of outflow obstruction. In brief, the procedure involves removal of the basal portion of the ventricular septum to enable a wider outflow tract for exit of blood, thus relieving outflow obstruction. Modifications of this procedure include wider zones of resection of the ventricular septum up to the level of papillary muscles, resection and/or reimplantation of abnormal papillary muscle heads, and mitral valve repair or replacement if needed for associated primary mitral valve disease. Mortality rate for isolated myectomy is < 0.5% in experienced centers, with > 90% of patients experiencing symptomatic relief. Complications occur in < 1% and include heart block, ventricular septal defect, aortic regurgitation, and conduction delays, most commonly left bundle branch block.

Alcohol Septal Ablation

The basic principle underlying alcohol septal ablation is to identify a septal perforator branch (usually from the left anterior descending coronary artery) that supplies the hypertrophied portion of the basal septum and inject absolute ethanol (1–3 mL) via a percutaneous approach and induce a local transmural infarction in that zone (usually an overage of 10% of the overall LV wall). This has been shown to reduce outflow gradient and concomitant MR similar to myectomy. An immediate fall in outflow gradient is observed with successful septal ablation in > 90% of patients. Continued improvement may be seen over ensuing months as the scar forms and retracts and the outflow tract widens. Preprocedural determination of limited zone of supply of the perforator branch to the obstructing portion of septum is crucial and is achieved usually with injection of echo contrast agents selectively during angiography into the septal branch. If the contrast agents light up adjacent areas of the heart or right ventricle portion of the septum, alcohol should not be infused. Ideal candidates for this procedure usually include older patients whose comorbidities preclude surgical myectomy. The likelihood of permanent pacemaker implantation is four to five times higher with septal ablation than with myectomy. Massive septal hypertrophy is unlikely to benefit from septal ablation. The hemodynamic and functional improvement over 3–5 years has been shown to be similar overall for septal ablation and myectomy. Similarly, there appears to be no difference in the medium-term incidence of sudden cardiac death (SCD) or all-cause mortality between myectomy and septal ablation. However, the incidence of sustained ventricular arrhythmias and SCD after septal ablation is reported at 3–10% (regardless of underlying HCM risk) in contrast to myectomy, which has much a lower incidence of sustained ventricular arrhythmias (0.2–0.9%/year). Thus, long-term follow-up studies comparing the two techniques are required to conclusively decide whether the scar created with septal ablation carries long-term risk of SCD.

Dual-Chamber Pacing

The physiologic principle underlying dual-chamber pacing (DDD) is the induction of asynchronous contraction of the septum induced by RV pacing. This causes the septum not to bulge into the outflow tract in early-mid systole and thus decreases the outflow obstruction and gradients. However, DDD pacing is now considered to be of not much benefit because most symptomatic improvement reported by patients in initial studies has been deemed to be a placebo effect in subsequent randomized trials. Nevertheless, it could be considered as a treatment option in selected elderly patients above 65 years old or in those who already have an ICD in place where a trial of pacing can assess whether there is gradient reduction and symptom improvement. However, there is no benefit from DDD pacing in reducing risk of SCD, and it has no role in nonobstructive HCM. Figure 23–18 summarizes all treatment options as well as genetic counseling recommendations for HCM.

Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy

A subset of patients with HCM is at increased risk of SCD (1%/year). The only effective prevention strategy against SCD for these patients is an ICD. Although ICD recommendations for secondary prevention are usually straightforward, the decision as to when to recommend ICD in a primary prevention setting is challenging. Existing evidence suggests a 4%/year ICD intervention rate when used for primary prevention in appropriate high-risk patients. Some of the risk factors for SCD in patients are provided below to help guide decisions in identifying the high-risk patient who may need close follow-up and/or ICD therapy as part of primary prevention.

In the list below, the first nine risk factors for SCD are considered established risk factors. The 2011 ACC/AHA's HCM Guidelines consider ICD implantation reasonable (Class 2A Level of Evidence C) for risk factors indicated with an asterisk.

1. Young (age < 30 years)

2. Massive septal hypertrophy (> 30 mm)*

3. Family history of sudden death*

4. Nonsustained ventricular tachycardia on Holter or exercise-induced nonsustained ventricular tachycardia and other SCD risk markers*

5. Sustained ventricular tachycardia or supraventricular tachycardia

6. Certain gene mutations (Arg403Gln)

7. Recurrent unexplained syncope with HCM*

8. Bradyarrhythmias (occult conduction system disease)

9. Inappropriate blood pressure response (failure to increase by at least 20 mm Hg systolic or a drop of 20 mm Hg systolic with exercise) and other SCD risk markers*

10. Severity of LVOT obstruction (conflicting evidence)

11. Late gadolinium enhancement with CMRI (emerging evidence, not established risk factor)

12. LV apical aneurysm (limited evidence)

Hypertrophic Cardiomyopathy and Athlete's Heart

Physiologic LV remodeling with LVH mimicking HCM can sometimes be seen in athletes, which makes decision making regarding pathologic versus physiologic LVH challenging. Borderline increase in LV thickness (13–15 mm) is usually seen in elite/endurance athletes (long-distance cycling, cross-country skiing, rowing), but LV thickness > 15 mm should raise concern for HCM. Women athletes seldom develop LV thickness > 12 mm, beyond which pathologic hypertrophy should be suspected. Echo plays a key role in helping differentiate physiologic from pathologic hypertrophy. Normal- to small-sized ventricle, diastolic function impairment, tissue Doppler and strain abnormalities, and abnormal mitral valve apparatus all favor HCM. Cardiopulmonary exercise testing may also help because athletes will have high levels of VO2max with excellent exercise capacity compared to HCM, where these parameters will be impaired. CMRI may also help as a complementary imaging modality to make more accurate estimations of LV wall thickness, cavity size, and presence of delayed enhancement. Despite all of these potential parameters used for differentiation between these two entities, sometimes conclusive diagnosis may be elusive and a period of deconditioning for 3 months may be needed with repeat assessment of LV wall thickness/mass. There will be regression of LV thickness and mass in physiologic but not pathologic hypertrophy. Athletes with HCM should not participate in high-intensity or contact sports regardless of whether they have obstruction. However, they can participate in light to moderate intensity sport activity (eg, golf).

Special Considerations in Hypertrophic Cardiomyopathy

Endocarditis Prophylaxis

Current ACC/AHA guidelines do not recommend routine antibiotic prophylaxis for HOCM patients unless prior history of endocarditis exists. Overall risk of endocarditis is considered low in HCM unless significant outflow obstruction and abnormal mitral valve structure coexist.

Pregnancy and HCM

Asymptomatic HCM is not a contraindication for pregnancy but requires counseling prior to planning and careful observation during pregnancy. Pregnant HCM patients stable on β-blockers can have these continued with monitoring of fetus for bradycardia. Severely symptomatic HCM patients who are pregnant require high-risk obstetrics/cardiology care. Pregnancy is discouraged for HCM patients with heart failure due to high maternal and fetal morbidity and mortality.