Albree Tower-Rader
Milind Desai
I.Introduction. Hypertrophic cardiomyopathy (HCM) is generally defined as the presence of left ventricular (LV) hypertrophy (LVH) of a nondilated LV in the absence of another cardiac or systemic disease which could explain the degree of LVH. There are many causes of LV wall thickening; however, these diseases can typically be identified by a history of significant hypertension or severe aortic stenosis, or due to multisystem organ involvement (e.g., skeletal muscle weakness in Danon disease; Table 10.1).
TABLE 10.1 Differential Diagnosis of Left Ventricular Wall Thickening |
Long-standing hypertension |
Athlete’s heart |
Aortic stenosis |
Amyloidosis |
Mitochondrial disease |
Fabry disease |
Friedreich ataxia |
Danon disease |
Noonan syndrome |
Pompe disease |
Whereas there are many alternative names for HCM, including idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and muscular subaortic stenosis, the World Health Organization recommends that HCM should be used because it does not imply that LV outflow tract (LVOT) obstruction is an invariable component of the disease. HCM is a heterogenous disease with a spectrum including patients who are asymptomatic with or without obstruction, who develop heart failure symptoms, angina, or arrhythmias, and who suffer from sudden death.
II.Clinical Presentation
A.Natural history
1.The histologic features of HCM are disarray of cell-to-cell arrangement, disorganization of cellular architecture, and fibrosis. The most common sites of ventricular involvement are, in decreasing order, the septum, apex, and mid-ventricle. One-third of patients have wall thickening limited to one segment.
2.The prevalence of HCM is ~1 in 500 in the general population, and it appears to be inherited. It is a leading cause of sudden death among athletes aged <35 years.
B.Signs and symptoms
1.Heart failure. Symptoms, which include dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, and fatigue, are largely a consequence of two processes: elevated LV diastolic pressure caused by diastolic dysfunction and dynamic LV outflow obstruction.
a.Events that accelerate heart rate, decrease preload, shorten diastolic filling time, increase LV outflow obstruction (i.e., exercise and tachyarrhythmias), or worsen compliance (i.e., ischemia) exacerbate these symptoms.
b.Between 5% and 10% of patients with HCM progress to severe LV systolic dysfunction, characterized by progressive LV wall thinning and cavity enlargement.
2.Myocardial ischemia. Myocardial ischemia occurs in obstructive and nonobstructive HCM.
a.The clinical presentation is similar to that of ischemic syndromes in persons without HCM. Patients with HCM may have abnormal electrocardiograms (ECGs) at baseline (e.g., inferior q-waves, T-wave inversions) with changes which can be seen in ischemic syndromes. Nuclear stress testing (thallium perfusion or positron emission tomography) has shown that patients with HCM may have reversible or fixed perfusion defects in the absence of epicardial coronary artery disease.
b.The incidence of concomitant atherosclerotic coronary artery disease is estimated to be ~20%. Thus, mismatch of supply and demand because of thickened vessels and small vessel disease from increased collagen deposition in the intima and media is considered to be the most likely pathophysiology of ischemia. Contributing factors include the following:
(1)Small vessel coronary disease with decreased vasodilator capacity
(2)Elevated myocardial wall tension as a consequence of delayed diastolic relaxation time and obstruction to LV outflow
(3)Decreased capillary-to-myocardial fiber ratio
(4)Decreased coronary perfusion pressure
3.Syncope and presyncope are usually a consequence of diminished cerebral perfusion caused by inadequate cardiac output. These episodes are commonly associated with exertion or cardiac arrhythmia.
4.Sudden cardiac death (SCD). Risk of SCD is low and <1% per year.
a.HCM is the most common cause of SCD in children and young adults (age < 30 years). Although risk extends into mid-life, rates are lower even with significant risk factors (see Section VI.C.4.b). Patients with SCD often have no or minimal symptoms prior. Approximately 60% of deaths occur during periods of inactivity; the remaining deaths occur after vigorous physical exertion.
b.SCD events are generally accepted to be due to sustained ventricular tachyarrhythmias. Proposed arrhythmogenic mechanisms include myocardial disarray and fibrosis, silent ischemia associated with microvascular coronary artery disease, and high sympathetic drive.
III.Physical examination
A.Inspection of the jugular venous system may reveal a prominent a-wave that indicates hypertrophy and lack of compliance of the right ventricle. A precordial heave, representing right ventricular (RV) strain, can be found in persons with concomitant pulmonary hypertension.
B.Palpation
1.The apical precordial pulse is usually laterally displaced and diffuse. LVH may cause a presystolic apical impulse or palpable fourth heart sound (S4). A three-component apical impulse may occur, with the third impulse resulting from a late systolic bulge of the left ventricle.
2.The carotid pulse has been classically described as bifid. This rapid carotid upstroke followed by a second peak is caused by a hyperdynamic left ventricle.
C.Auscultation
1.S1 (first heart sound) is usually normal and is preceded by S4.
2.S2 (second heart sound) can be normal or paradoxically split as a result of the prolonged ejection time of patients with severe outflow obstruction.
3.The harsh, crescendo–decrescendo systolic murmur associated with HCM is best heard at the left sternal border. It radiates to the lower sternal border but not to the neck vessels or axilla.
a.The intensity and duration of the murmur vary with maneuvers which affect preload and afterload which can be used to differentiate it from other systolic murmurs (Table 10.2). During periods of increased venous return, the murmur is of shorter duration and is less intense. In the underfilled ventricle and during periods of increased contractility, the murmur is harsh and of a longer duration.
TABLE 10.2 Effects of Maneuvers or Pharmacologic Intervention to Differentiate Murmur of Hypertrophic Cardiomyopathy from Aortic Stenosis |
||||
Maneuver |
Physiologic Effect |
HCM |
AS |
MR |
Valsalva and standing |
Decreases VR, SVR, and CO |
↑ |
↓ |
↓ |
Squat and handgrip |
Increases VR, SVR, and CO |
↓ |
↑ |
↑ |
Amyl nitrite |
Increases VR; Decreases SVR and LV volume |
↑ |
↑ |
↓ |
Phenylephrine |
Increases SVR and VR |
↓ |
↑ |
↑ |
Extrasystole |
Decreases LV volume |
↑ |
↓ |
No change |
Post-Valsalva release |
Increases LV volume |
↓ |
↑ |
No change |
AS, aortic stenosis; CO, cardiac output; HCM, hypertrophic cardiomyopathy; LV, left ventricular; MR, mitral regurgitation; SVR, systemic vascular resistance; VR, venous return; ↓, decrease; ↑, increase.
(1)The concomitant murmur of mitral insufficiency can be differentiated because of its holosystolic, blowing quality that radiates to the axilla.
(2)A soft, early, decrescendo, diastolic murmur of aortic insufficiency is found in ~10% of patients with HCM.
IV.Genetic aspects of HCM. HCM is caused by genetic mutations of sarcomere genes typically inherited in an autosomal dominant manner. To date, HCM has been linked to over 1,400 different mutations in at least 11 genes (Table 10.3); however, not all mutations have the same evidence for pathogenicity, and a probable disease-causing mutation is identified in ~50% of cases currently. Of patients with positive genetic testing, mutations are most commonly found in the genes for β-myosin heavy chain (MYH7) and myosin-binding protein C (MBPC3).
TABLE 10.3 Molecular Genetics of Hypertrophic Cardiomyopathy |
||
Gene |
Protein |
Frequency (%) |
|
Thick Filament |
||
MYH7 |
β-Myosin heavy chain |
15–25 |
MYL2 |
Regulatory myosin light chain |
<2 |
MYL3 |
Essential myosin light chain |
<1 |
|
Thin Filament |
||
TNNT2 |
Cardiac troponin T |
<5 |
TNNI3 |
Cardiac troponin I |
<5 |
TPM1 |
α-Tropomyosin |
<5 |
ACTC1 |
α-Cardiac actin |
<1 |
|
Intermediate Filament |
||
MYBPC3 |
Myosin-binding protein C |
15–25 |
HCM genotype does not necessarily imply that subjects will have the phenotypic traits of HCM because variable penetrance exists, and environmental factors and modifier genes affect whether a particular subject will manifest HCM phenotypically. Current guidelines recommend genetic counseling for patients with known HCM and screening with or without genetic testing for first-degree relatives of patients with HCM. It is reasonable to perform genetic testing in the index patient with HCM to aid in identifying first-degree relatives at risk for HCM. Patients who are genotype-positive, phenotype-negative should undergo periodic screening based on age and clinical status (see Section VII.E).
It is uncertain whether patients with positive genetic testing for a pathogenic mutation have an increased risk for heart failure or SCD.
V.Diagnostic testing
A.Electrocardiogram. Although most patients have electrocardiographic evidence of disease, there are no specific changes that are pathognomonic for HCM. Common electrocardiographic findings in HCM are listed in Table 10.4. These abnormalities do not correlate with disease severity.
TABLE 10.4 Electrocardiographic Findings in Hypertrophic Cardiomyopathy |
Evidence of right and left atrial enlargement |
Q-waves in the inferolateral leads |
Voltage criteria for large negative precordial T-waves (associated with Yamaguchi or apical HCM) |
Left-axis deviation |
Short PR interval with slurred upstroke |
HCM, hypertrophic cardiomyopathy.
B.Echocardiography is the preferred diagnostic method because of its high sensitivity and low-risk profile. It allows characterization of the site and mechanism of obstruction. Careful assessment for conditions that cause increased wall thickness (aortic or subaortic stenosis, hypertension, infiltrative diseases, etc.) should also be performed.
1.M-mode and two-dimensional echocardiographic findings in HCM are listed in Table 10.5. Close evaluation of the extent of hypertrophy should be performed given the role of septal thickness in risk stratification for SCD.
TABLE 10.5 Two-Dimensional, M-Mode, and Doppler Echocardiographic Findings in Hypertrophic Cardiomyopathy |
Maximal left ventricular diastolic wall thickness >15 mm |
Asymmetric left ventricular hypertrophy (septal > posterior wall thickness) |
Systolic anterior motion of the mitral valve |
Small left ventricular cavity |
Resting gradient > 30 mm Hg |
Provocable gradients > 50 mm Hg |
Septal immobility |
Normal or increased motion of the posterior wall |
Premature closure of the aortic valve |
Reduced rate of closure of the mitral valve in mid-diastole |
Mitral valve prolapse with regurgitation |
2.Doppler echocardiography enables recognition and quantification of dynamic LVOT obstruction as well as the response to various maneuvers.
a.Approximately one-fourth of patients with HCM have a resting pressure gradient between the body and LVOT; approximately half of the patients with normal LVOT gradients at rest will have provocable gradients.
b.The diagnosis of HCM with obstruction is based on resting peak instantaneous gradient >30 mm Hg. These gradients correlate directly with the time of onset and duration of contact between the mitral leaflet and the septum, as occurs during systolic anterior motion (SAM) of the mitral leaflet. The earlier and longer the contact occurs, the higher the pressure gradient is.
(1)Inducing obstruction and, therefore, gradients, in patients believed to have latent obstruction, can be accomplished with substances (e.g., amyl nitrite) or maneuvers (e.g., Valsalva maneuver and exercise) that decrease LV preload or increase contractility. The use of dobutamine is not recommended because it can provoke increased LVOT gradients in normal patients.
c.Recognition of mitral regurgitation (MR)
(1)Approximately 60% of patients with HCM have structural abnormalities of the mitral valve, including increased leaflet area, elongation of leaflets, and anomalous insertion of papillary muscles directly into the anterior mitral leaflet.
(2)When there is no leaflet abnormality, the degree of MR is directly related to the severity of obstruction and lack of leaflet coaptation.
C.Exercise stress testing. Exercise stress echocardiography testing provides significant information regarding functional capacity, exercise-induced symptoms, and prognosis.
1.Quantification of patient functional capacity
2.Determination of presence of provocable LVOT obstruction and correlation with symptoms
3.Prognostication with blood pressure, heart rate, and rhythm response to exercise
D.Magnetic resonance imaging (MRI). Advantages of MRI in the evaluation of HCM include excellent resolution, lack of radiation, inherent contrast, three-dimensional imaging, and tissue characterization. Disadvantages are cost, length of study, and exclusion of patients with contraindications to exposure to magnetism, such as patients with implantable cardioverter–defibrillators (ICDs) or pacemakers.
1.Detection of LVH missed by echocardiography, specifically in the anterolateral and basal LV free walls
2.Myocardial scar, often found in patients with HCM, can be detected as delayed hyperenhancement with gadolinium contrast MRI. More recent studies suggest that the amount of hyperenhancement may be a predictor of SCD.
3.Improved identification of MR, SAM, abnormal papillary muscles, and diastolic dysfunction
4.Differentiation from alternative causes of increased LV wall thickness such as Fabry disease and amyloidosis.
E.Cardiac catheterization is most commonly used for defining coronary anatomy before procedures for septal reduction or MR, or for the evaluation of ischemic symptoms. Invasive hemodynamic assessment may also be used to assess for provocable obstruction for symptomatic patients without obstruction on noninvasive imaging. The characteristic findings of HCM during hemodynamic assessment are listed in Table 10.6 and illustrated in Figure 10.1.
TABLE 10.6 Hemodynamic Findings during Cardiac Catheterization |
Subaortic or mid-ventricular outflow gradient on catheter pullback |
Spike-and-dome pattern of aortic pressure tracinga |
Elevated right and left ventricular end-diastolic pressures |
Elevated pulmonary capillary wedge pressure |
Increased V-wave on wedge tracingb |
Elevated pulmonary arterial pressure |
aA consequence of outlet obstruction.
bMay result from either mitral regurgitation or elevated left atrial pressure.
FIGURE 10.1 Severe increase in the left ventricular (LV) aortic gradient in the beat after a premature ventricular contraction (PVC) (Brockenbrough–Braunwald–Morrow sign) because of an increase in contractility and decrease in afterload during the post-PVC beat.
1.Patients with normal epicardial coronary arteries may have myocardial bridges, phasic narrowing during systole, reduced coronary flow reserve, or systolic reversal of flow in the epicardial vessels.
2.Left ventriculography usually reveals a hypertrophied ventricle, prominent septal bulge, nearly complete obliteration of the ventricular cavity during systole, SAM, and MR. The spadelike appearance of the ventricular cavity is confined to ventricles with apical involvement.
VI.Management strategies
A.Goals of management. Management of patients with HCM is focused on two major goals: (1) treating symptoms of systolic and/or diastolic heart failure, arrhythmias, angina, and presyncope or syncope and (2) preventing sudden death. The etiologies of symptoms in HCM are multifactorial and include LVOT obstruction, diastolic dysfunction, ischemia, arrhythmias, and MR. Consequently, therapy varies among patients and is designed to target individual symptoms and mechanisms. See Figure 10.2 for a simplified treatment algorithm.
FIGURE 10.2 Management algorithm for hypertrophy cardiomyopathy. DDD, dual pacing for both chambers, dual-chamber activity sensing, and dual response; HCM, hypertrophic cardiomyopathy. (Adapted from Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. Circulation. 2011;124:e783–e831. Reprinted with permission from Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. Circulation. 2011;124(24):e783–e831. Copyright © 2011 American Heart Association, Inc.)
B.Medical therapy. General principles for medical therapy focus on medications which have negative inotropic and chronotropic properties and thus improve diastolic filling and decrease myocardial demand. Care should be taken to avoid medications which decrease preload because this can worsen LVOT obstruction.
1.β-blockers are considered first-line therapy for both obstructive and nonobstructive HCM. Despite the fact that they have not been shown to decrease mortality, they do improve symptoms and exercise tolerance. β-Blockers with additional α-blocking properties, such as carvedilol and labetalol, should be avoided because of their additional vasodilatory properties.
a.The mechanism of action of β-blockers is inhibition of sympathetic stimulation brought about by the negative inotropic and chronotropic properties of the drugs. β-Blockers diminish myocardial oxygen requirements and augment diastolic filling, which mitigate angina and the detrimental effects of LV outflow obstruction, respectively.
2.Calcium channel blockers (CCBs) are considered to be second-line agents that are also effective in reducing the common symptoms of HCM in patients who are unresponsive or intolerant to treatment with β-blockers.
a.CCBs have a negative inotropic effect and reduce the heart rate and blood pressure. They may also have beneficial effects on diastolic function by improving rapid diastolic filling, although possibly at the expense of higher LV end-diastolic pressures. The beneficial effects seem to be limited to the nondihydropyridines verapamil and diltiazem. Dihydropyridine CCBs (nifedipine, amlodipine) should be avoided because of their significant vasodilatory effects (see below).
b.Nondihydropyridines can have unpredictable vasodilatory effects and should be administered cautiously to patients with considerable outlet obstruction and elevated pulmonary pressures.
3.Disopyramide, a class Ia antiarrhythmic agent, may be an effective alternative or adjunct to β-blocker and CCB therapy. Its strong negative inotropic qualities coupled with its ability to suppress ventricular and supraventricular arrhythmias make it an effective treatment when marked outflow obstruction or arrhythmias are manifested. Potential disadvantages are anticholinergic properties, accumulation in patients with hepatic or renal dysfunction, the possibility of augmenting atrioventricular (AV) nodal conduction in the presence of atrial fibrillation, and waning hemodynamic effects with time. It is because of these significant side effects that disopyramide is typically used in a very symptomatic patient when a more definitive procedure is being planned, such as surgical myectomy or alcohol septal ablation. It is not considered to be a long-term treatment for HCM.
4.Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have an unclear role in HCM. Previously they were avoided because of the potential for peripheral vasodilation, and a recent randomized control trial demonstrated no benefit with losartan versus placebo in slowing progression of disease.
5.Diuretics should be used cautiously for symptom reduction in the setting of pulmonary edema because high filling pressures are often necessary because of the stiff ventricle, and overdiuresis may reduce LV size and increase obstruction.
6.Digoxin should be avoided because of potential worsening of the LVOT obstruction secondary to the positive inotropic effect.
7.Phenylephrine, a pure α-agonist that causes vasoconstriction, can be considered in cases of refractory hypotension unresponsive to intravenous fluids. Pressors with positive inotropic effects, such as norepinephrine, dopamine, and dobutamine, can provoke LVOT obstruction and should be avoided.
C.Nonpharmacologic treatment is typically reserved for those patients with symptoms despite optimal medical therapy. Patients with symptomatic obstruction and resting or latent gradient of ≥50 mm Hg despite optimal medical treatment are candidates for septal myectomy or alcohol septal ablation. Younger patients with gradients >75 mm Hg and low surgical risk should be considered for septal myectomy even in the absence of symptoms. With severe symptomatic, nonobstructive HCM, cardiac transplantation remains the only option.
1.Septal myectomy of HCM has been performed for more than 50 years and is the procedure of choice for patients with symptomatic obstructive HCM despite maximal medical therapy.
a.When performed by an experienced surgeon, septal myectomy is considered the most definitive treatment and is associated with a mortality rate of <1% to 2%. It is effective in improving symptoms, resting LVOT gradients, MR, and filling pressures. After myectomy, survival is comparable to the general population when matched by age and gender.
b.Concomitant surgery to address obstruction because of abnormal papillary muscle attachment, mitral valve regurgitation not improved following septal myectomy, or atrial fibrillation with a maze procedure may be performed allowing for a more comprehensive approach compared with alcohol septal ablation.
2.Alcohol septal ablation—essentially a controlled infarction of the septum—is an alternative to septal myectomy generally used in patients who are not candidates for surgical myectomy. There are no randomized control trials comparing myectomy and septal ablation.
a.Technique. In the cardiac catheterization laboratory, a guidewire is advanced through the left main trunk to probe the first or second septal perforator or both. An angioplasty catheter is placed in the proximal portion of the septal branch for vessel isolation. Ultrasonic contrast agents are infused in the cannulated perforator to define the area at risk for infarction. Infusion of 1 to 4 mL of absolute alcohol causes infarction in the zone of septal myocardium served by the cannulated septal branch. In most centers, a temporary ventricular pacing catheter is placed into the RV apex before performing the ablation, in order to manage any transient conduction abnormalities.
b.Results. In the majority of patients, there is a marked immediate decrease in the LVOT gradient. This gradient response is thought to be triphasic: immediate reduction (because of stunning), early reappearance, and sustained fall by 3 months after the procedure (because of remodeling). Within this initial period, most patients attain satisfactory symptomatic relief. Risks of the procedure include high-grade AV block with subsequent pacemaker implantation, coronary dissection, large anterior wall myocardial infarction, pericarditis, and electrical instability of the scar that forms as a result of the infarction.
3.Dual-chamber pacing was previously used in hopes of alleviating symptoms by altering the timing of septal contraction; however, this was not shown to be beneficial in trials. Dual-chamber pacing should only be considered in patients with medically refractory symptoms who are not candidates for septal reduction therapy.
4.Special management considerations
a.Atrial fibrillation occurs in up to a third of patients with HCM and can worsen heart failure symptoms and increase risk of thromboembolic stroke. Loss of atrial systole and decreased diastolic filling times because of rapid ventricular rates can lead to acute hemodynamic decompensation and pulmonary edema because of LV diastolic dysfunction. Risk of stroke is ~0.8% per year and all patients with HCM-associated atrial fibrillation should be on anticoagulation therapy unless contraindicated.
(1)Acute paroxysms of atrial fibrillation are best managed with prompt cardioversion with transesophageal echocardiogram to exclude atrial thrombus. The 2014 ACC/AHA/HRS Guidelines for the Management of Patients with Atrial Fibrillation state that disopyramide and amiodarone are reasonable for maintenance of sinus rhythm, whereas it is uncertain whether other class III agents, such as dofetilide, sotalol, and dronedarone, should be used given the paucity of safety data. Some recommend reserving their use for patients with ICDs.
(2)Chronic atrial fibrillation may be well tolerated if the heart rate is controlled with β-blockers or calcium channel antagonists.
(3)Maze or radiofrequency ablation. For patients who do not tolerate atrial fibrillation and cannot be maintained in sinus rhythm with antiarrhythmic medications, catheter ablation, maze, or AV nodal ablation and implantation of a dual-chamber pacemaker may be an option.
b.Risk stratification for sudden death and subsequent ICD implantation for primary prevention of SCD in high-risk patients continues to be one of the more challenging aspects for the management of patients with HCM. Table 10.7 lists the established factors for risk stratification. Additional risk factors (e.g., scar burden as determined by late gadolinium contrast on MRI) continue to be evaluated.
TABLE 10.7 Risk Factors for Sudden Cardiac Death |
Established Risk Markers for Secondary Prevention |
Previous cardiac arrest |
Sustained ventricular tachycardia |
Established Risk Markers for Primary Prevention |
Prolonged or repetitive episodes of nonsustained ventricular tachycardia on Holter monitor |
Left ventricular wall thickness >30 mm |
Family history of SCD in first-degree relative |
Failure to increase blood pressure by ≥20 mm Hg with exercise |
Syncope without other attributable cause |
Risk Modifiers |
Late gadolinium enhancement on cardiac MRI |
Left ventricular apical aneurysm |
MRI, magnetic resonance imaging; SCD, sudden cardiac death.
(1)The decision to implant an ICD should be individualized by taking into consideration patient risk factors as well as age. The frequency of annual ICD-related complications in patients with HCM is 4%. Patients who are younger at the time of implantation are at higher lifetime risk for complications (e.g., infection, inappropriate ICD discharge) because of the longer length of device implantation.
(2)Patients with a history of cardiac arrest and sustained ventricular arrhythmias should be strongly considered for an ICD. In this group, the annual rate of appropriate ICD discharge is ~10%.
(3)Selection of patients for ICD implantation as primary prevention based on one or more risk factors for SCD is difficult and must be individualized. In the primary prevention group, the annual rate of appropriate ICD discharge is about 4%. Current guidelines state that it is reasonable to consider ICD implantation in patients with a family history of SCD or multiple risk factors. The HCM Risk-SCD calculator was recently developed to estimate risk for SCD and has been validated in small population studies, although a larger validation study is ongoing.
VII.Special Considerations
A.Athlete’s heart
1.Differentiating HCM from hypertrophy of athletes. Failure to diagnose HCM places an athlete at undue risk for sudden death whereas incorrect labeling of HCM often leads to irrational treatments, unnecessary fears, and inappropriate recommendations concerning exercise. Diagnostic uncertainty is greatest when maximal diastolic LV wall thickness exceeds the upper limit of normal (12 mm) but is less than the defined lower limit of expected hypertrophy (15 mm) for HCM and in the absence of SAM and LV outflow obstruction.
a.Characteristics that substantiate the diagnosis of HCM include unusual patterns of hypertrophy, an LV end-diastolic diameter of <45 mm, septal thickening >15 mm, left atrial enlargement, abnormal diastolic function, family history of HCM, and abnormal LV filling.
b.Findings more consistent with physiologic LVH in an athlete are LV end-diastolic diameter >45 mm, septal thickening <15 mm, left atrial size <4 cm, and a decrease in LV thickness with deconditioning.
c.Cardiometabolic stress testing can be useful to distinguish between patients with physiologic LVH and HCM. A peak Vo2 >50 mL/kg/min or >120% predicted maximum Vo2 differentiates athlete’s heart from HCM.
d.Should differentiation still not be possible, the patient should stop training and over several months ventricular hypertrophy will typically regress if physiologic, but persist in HCM.
2.Participation in sports. HCM is the most common cause of sudden death in young athletes. The American College of Cardiology Bethesda Conference and European Society of Cardiology recommend prohibiting athletes with HCM from participating in competitive high school and college sports because of increased risk of SCD during intense exercise. These recommendations remain in force after medical or surgical intervention.
a.Athletes with HCM with or without obstruction who are <30 years should not participate in competitive, aerobically demanding sports.
b.Participation in recreational sports should take into consideration the intensity of the activity (with the resulting fluctuations in hemodynamics) and the danger to the individual should impaired consciousness occur.
B.Infective endocarditis (IE)
1.Prophylaxis. Guidelines on the prevention of IE published by the American Heart Association in 2007 question the practice of treating patients with HCM with antibiotics prior to dental procedures and recommend against it except in the setting of prior endocarditis. Given the catastrophic consequences of endocarditis in patients with HCM, routine antimicrobial prophylaxis for IE should be weighed on an individual basis.
C.Yamaguchi or apical HCM
1.Clinical presentation. Patients experience chest pain, dyspnea, fatigue, and, in rare instances, sudden death.
2.Prevalence. Within Japan, apical HCM constitutes 25% of all cases of HCM. Outside Japan, only 1% to 2% of cases are associated with isolated apical hypertrophy.
a.An ECG reveals giant negative T-waves in the precordial leads and LVH (Fig. 10.3).
FIGURE 10.3 Electrocardiogram (ECG) in an apical hypertrophic cardiomyopathy (HCM, Yamaguchi). The classic ECG for apical HCM has deep anteroapical T-wave inversions.
b.Echocardiographic findings include the following:
(1)Localized hypertrophy in the distal left ventricle beyond the origin of the chordae tendineae
(2)Wall thickness in the apical region of at least 15 mm or a ratio of maximal apical to posterobasal thickness >1.5
(3)Exclusion of hypertrophy in other parts of the ventricular wall
(4)No LVOT obstruction or gradient
c.MRI demonstrates localized hypertrophy to the cardiac apex. MRI is useful in the care of patients with poor echocardiographic windows.
d.Cardiac catheterization reveals a spadelike configuration of the LV cavity at end diastole and apical end-systolic LV cavity obliteration.
4.Prognosis is favorable compared with that associated with other forms of HCM.
5.Management. Therapeutic efforts are limited to management of diastolic dysfunction with β-blockers and calcium channel antagonists.
D.HCM among the elderly
1.Clinical presentation. In addition to the signs and symptoms of other forms of HCM, hypertension is more common with HCM in the elderly population.
2.Incidence. Although the incidence is unknown, HCM among the elderly is probably more common than expected.
3.Genetic aspects. Reports have suggested that the delayed expression of mutations in the gene for cardiac myosin-binding protein C may play an important role in HCM in the elderly.
4.Echocardiographic findings for elderly patients (65 years or older) are compared to findings for young patients (40 years or younger) as follows:
a.Common findings
(1)LVOT gradient, both provocable and at rest
(2)Asymmetric hypertrophy
(3)SAM of the mitral valve
b.Differences pertaining to the elderly
(1)Less hypertrophy
(2)Less RV involvement
(3)Ovoid versus crescentic left ventricle
(4)Prominent septal bulge (i.e., sigmoid septum)
(5)More acute angle between the aorta and septum as the aorta uncoils with age
5.Prognosis. Favorable compared with patients who present at a younger age
6.Management. Similar to that of other HCM patients
E.Screening of family members
1.Serial 12-lead ECG and transthoracic echocardiogram are recommended every 12 to 18 months in first-degree relatives of HCM patients starting at age 12 during adolescence because of the propensity of HCM to worsen during growth spurts.
2.Because of the possibility of late-onset phenotypic expression, screening of first-degree relatives should continue into middle age, but the frequency of screening can be scaled back to a minimum of every 5 years once full growth has been obtained.
3.If genetic testing reveals a mutant HCM gene in the offspring, the high penetrance of the mutation imparts a >95% lifetime risk of developing clinical and/or phenotypic evidence of disease. These gene-positive offspring should continue with serial examinations.
4.First-degree relatives that are mutation negative have no risk of developing HCM and do not need further screening.
ACKNOWLEDGMENTS: The authors acknowledge the contributions of Drs. Eiran Gordeski, Mark Robbins, A. Thomas McRae III, and Anthony Hart to prior editions of this chapter.
Landmark Articles
Agarwal S, Tuczu EM, Desai MY, et al. Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;55(8):823–834.
Caselli S, Maron MS, Urbano-Moral JA, et al. Differentiating left ventricular hypertrophy in athletes from that in patients with hypertrophic cardiomyopathy. Am J Cardiol. 2014;114:1383–1389.
Lever HM, Karam RF, Currie PS, et al. Hypertrophic cardiomyopathy in the elderly: distinctions from the young based on cardiac shape. Circulation. 1989;79:580–589.
Maron BJ, Nishimura RA, McKenna WJ, et al. Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy: a randomized, double-blind, crossover study (M-PATHY). Circulation. 1999;99:2927–2933.
Vriesendorp PA, Schinkel AF, Liebregts M, et al. Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Circ Arrthythm Electrophysiol. 2015;8(4):829–835.
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