7 Hypertrophic Cardiomyopathy
Background
• Hypertrophic cardiomyopathy (HCM) is defined as the presence of left ventricular hypertrophy occurring in the absence of a cardiac or systemic disorder (e.g., valvular aortic stenosis or systemic hypertension).1
• Initially regarded as a rare disorder, the prevalence of HCM in the general population is now estimated to be approximately 1 in 500.
• HCM is a heterogeneous disorder with a spectrum of clinical findings, ranging from completely asymptomatic individuals to severely affected patients.
Overview of Echocardiographic Approach
• Echocardiography plays a vital role in the evaluation and management of patients with HCM (Box 7-1).
Step-by-Step Approach to the Evaluation of HCM
Step 1: Establish the Diagnosis of HCM
Step 2: Exclude Other Causes of Increased Wall Thickness
• Left ventricular hypertrophy caused by a genetic defect of the cardiac sarcomeric proteins needs to be distinguished from other important causes (Box 7-2).
Box 7-2 Differential Diagnosis of HCM on Echocardiography
Key Points
• The main categories in the differential diagnosis of left ventricular increased wall thickness are the following:
• Common causes of left ventricular hypertrophy are systemic hypertension and other conditions causing pressure-overload hypertrophy, such as valvular aortic stenosis, fibrous subaortic stenosis, and coarctation of the aorta.
• These non-monogenetic forms of left ventricular hypertrophy typically have a concentric (rather than asymmetrical) pattern of hypertrophy.
Athlete’s Heart3
• Wall thickness may be ≥ 13 mm (up to 15 to 16 mm) in 2% of elite athletes, raising the possibility of underlying mild HCM.
Storage Diseases4
• The intramyocardial accumulation or infiltration of abnormal metabolic products in various storage diseases may mimic HCM on echocardiography (Figure 7-1).
• Fabry’s disease is an X-linked recessive disorder of glycosphingolipid metabolism due to a deficiency of the lysosomal enzyme α-galactosidase A.
• Patients with Fabry’s disease may have multisystem involvement, especially of the skin, kidneys, nervous system, and heart.
• Mutations of genes regulating glycogen metabolism may also result in increased wall thickness on echocardiography.
• Mutations of the regulatory γ2 subunit of AMP-activated protein kinase (PRKAG2) gene cause a glycogen storage cardiomyopathy, which may be associated with ventricular preexcitation.
• Mutations of the lysosome-associated membrane protein 2 (LAMP2) gene (X-linked) cause Danon’s disease.
Key Points
• The prevalence of Fabry’s disease has ranged from 3% in all male patients with left ventricular hypertrophy to as much as 6% in male patients with presumed late-onset HCM (defined as diagnosis at age ≥ 40 years).
• In a cohort of 24 patients with increased wall thickness and ventricular preexcitation, mutations of the PRKAG2 and LAMP2 genes were detected in 29% and 17% of patients, respectively.
• Clinical features distinguishing patients with LAMP2 mutations from patients with HCM caused by sarcomeric gene mutations included the following: male sex, early onset of disease (<17 years of age), ventricular preexcitation on electrocardiography, severe concentric hypertrophy, and elevation of two serum enzymes: creatine kinase (CK) and alanine aminotransferase (ALT).
Infiltrative Cardiomyopathies
• Conditions such as cardiac amyloidosis or sarcoidosis are associated with increased wall thickness and may occasionally mimic HCM on echocardiography.
Septal Hypertrophy in the Elderly
• It may be difficult to distinguish between elderly patients with HCM and those with hypertensive heart disease.
• Terms that have been used to describe this finding are “sigmoid septum,” “septal bulge,” and “discrete upper septal hypertrophy.”
• It is controversial whether this finding should be considered a subtype of HCM or whether it represents a benign anatomic variant.
Step 3: Assess Pattern and Severity of Left Ventricular Hypertrophy
• 2D echocardiography can accurately detect and characterize the degree and extent of hypertrophy in patients with HCM.
Key Points
Anatomic Imaging
Acquisition
• Multiple transthoracic echocardiographic (TTE) views are necessary to assess the extent and severity of left ventricular hypertrophy (Figure 7-2).
• Measurements of the left ventricular wall segments (anteroseptal, inferoseptal, anterior, anterolateral, inferolateral, inferior) should be made in the parasternal short-axis views at the basal and midventricular levels.
• The apical septal, anterior, lateral, and inferior segments should be measured in the parasternal short-axis views at the apical level.
• Hypertrophied segments usually have either similar or slightly increased echogenicity in comparison with myocardial segments with normal wall thickness.
• In addition, diffuse bright echoes may be seen throughout the myocardium and may give a ground-glass appearance.
Analysis
• Septal involvement may be limited to the basal level or the hypertrophy may extend to the left ventricular apex.
Key Points
• Two different septal morphologic subtypes have been described:
• Young patients with HCM characteristically demonstrate the reverse septal curvature subtype, whereas older patients typically have the basal septal morphologic subtype.
• Patients with HCM and asymmetrical septal hypertrophy may have hypertrophy confined to the septum, or they commonly have hypertrophy of both the ventricular septum and the free wall (anterolateral wall segments).
• The distribution of hypertrophy can be in any pattern and can involve any myocardial segment (including the right ventricle).
• Other uncommon morphologic variants of HCM include asymmetrical apical HCM (predominant hypertrophy at the apical segments) and a concentric pattern of left ventricular hypertrophy.
• An ultrasound contrast agent should be administered when nonenhanced images are suboptimal for definitive diagnosis, such as in patients with suspected apical HCM.6
Severity of Left Ventricular Hypertrophy
• Since there is considerable variability in the thickness of the different septal and posterior wall segments in patients with HCM, the conventional calculations of left ventricular mass are not applicable in these patients.5
• Therefore, a number of echocardiographic indices have been developed to measure the distribution, extent, and/or burden of left ventricular hypertrophy.7
• Wigle’s score: Incorporates the degree of septal thickness at the basal anteroseptum, the extent of septal involvement, and the presence or absence of anterolateral wall involvement (Table 7-1).
• Wall thickness (Spirito-Maron) index: Obtained by adding the maximal wall thickness (at either the basal or midventricular level) of four left ventricular regions (anterior septum, posterior septum, lateral wall, and posterior wall).
• Maximal left ventricular wall thickness: The most clinically relevant measurement is the determination of the maximal thickness of all the left ventricular myocardial segments. The presence of massive left ventricular hypertrophy, defined as a wall thickness of ≥ 30 mm, has considerable implications for patients’ management and prognosis (see “Key Measurements for Predicting Prognosis in Patients with HCM” below).1
TABLE 7-1 EXTENT OF HYPERTROPHY ACCORDING TO ECHOCARDIOGRAPHIC POINT SCORE
| Extent of Hypertrophy | Points |
|---|---|
| Septal thickness, mm (basal third of septum) | |
| 15–19 | 1 |
| 20–24 | 2 |
| 25–29 | 3 |
| >30 | 4 |
| Extension to papillary muscles (basal two thirds of septum) | 2 |
| Extension to apex (total septal involvement) | 2 |
| Anterolateral wall extension | 2 |
| Maximum total | 10 |
Other Morphologic Subtypes of HCM
Apical HCM
Step 4: Determine if There Is LVOT Obstruction
• Studies of cohorts of patients with HCM have shown that approximately 25% of patients have LVOT obstruction at rest.
• One recent study has suggested that 70% of patients with HCM have either resting or provocable LVOT obstruction.
• Early M-mode echocardiographic studies demonstrated the abnormalities in morphology of the LVOT and in the mitral apparatus that contribute to the development of dynamic LVOT obstruction.
• Rapid early left ventricular ejection out of the LVOT also contributes to the development of SAM and LVOT obstruction.
• Morphologic features of HCM that contribute to SAM and LVOT obstruction include narrowing of the LVOT by the following:
Key Points
• Although the nature of the hydrodynamic forces on the anterior mitral leaflet remains controversial, it is believed that the distal anterior mitral leaflet is subjected to Venturi and/or drag forces.2
• Therefore, SAM occurs and the tip of the anterior mitral leaflet typically develops a sharp anterior and superior angulation, leading to mitral leaflet–septal contact in early to midsystole (Figure 7-4).
• Simultaneous cardiac catheterization and M-mode echocardiographic studies have shown that mitral leaflet–septal contact occurs almost simultaneously with the onset of the LVOT pressure gradient.
• Furthermore, there is a linear relationship between the time of onset of SAM and the severity of LVOT obstruction.
• SAM of the anterior leaflet leads to an interleaflet gap, which results in a posteriorly directed jet of mitral regurgitation (see Step 5 below).
Step 4A: Assess for the Presence of LVOT Obstruction at Rest
Anatomic Imaging
• Determine if there is SAM at rest (optimal views are parasternal long-axis view or apical views) (Figure 7-5).
• Three-dimensional echocardiography has provided some additional insight regarding the mechanism of SAM.8
• Three-dimensional echocardiography has been used to assess the LVOT area following invasive septal reduction therapy.
Physiologic Data
Acquisition
• Pulsed wave and continuous wave Doppler techniques are used to determine the pressure gradient across the LVOT in patients with HCM.
• Pulsed wave Doppler signals can be recorded sequentially from the left ventricular apex toward the outflow tract.
• Peak velocity increases as the sample volume approaches the site of contact between the anterior mitral leaflet and the septum.
Analysis
Key Points
• The peak gradient (ΔP) in the outflow tract can be estimated using the modified Bernoulli equation:
where V is peak velocity in the LVOT.
• By convention, patients with HCM are considered to have resting LVOT obstruction when the LVOT gradient measures ≥ 30 mm Hg.
• The characteristic continuous wave Doppler spectral profile of dynamic LVOT obstruction has an asymmetrical leftward concave shape (Figure 7-6).
• This results from a relative rapid initial rise in velocity followed by a more gradual increase in the outflow tract velocity to cause a peak in late systole, leading to a dagger-shaped configuration.
• There is an excellent correlation between the LVOT gradient determined by continuous wave Doppler measurements and by high-fidelity micromanometer recordings during cardiac catheterization.
Pitfalls
• There are important technical considerations in the performance and interpretation of Doppler studies in patients with HCM.
• Suboptimal continuous wave Doppler signals from the LVOT may be secondary to inadequate transthoracic echocardiographic windows or distortion of left ventricular geometry.
• Importantly, it is crucial to distinguish the high-velocity systolic signal coming from the outflow tract from the signal of the mitral regurgitant jet (see Figure 7-6).
• The spectral profile of mitral regurgitation has an earlier onset, a more abrupt initial increase in velocity, and a higher peak velocity than that of an outflow tract signal.
• Systolic jets with a peak velocity of greater than 5.5 m/s (i.e., LVOT gradient > 120 mm Hg) most likely represent mitral regurgitation.
• Orienting the transducer more medially and anteriorly away from the mitral regurgitant jet can help avoid contamination from the mitral regurgitant jet.
Step 4B: In Patients without Resting LVOT Obstruction, Determine if There Is Provocable LVOT Obstruction
• When there is HCM and a resting LVOT gradient of less than 30 mm Hg, patients should undergo investigations to assess for the presence of provocable LVOT obstruction.
• Determination of the existence of a provocable LVOT gradient is especially important in patients with exertional (or postprandial) symptoms, a history of presyncope or syncope, and/or a dynamic systolic murmur during bedside maneuvers.
Key Points
• Provocable LVOT obstruction is defined as a resting LVOT gradient of less than 30 mm Hg and a provocable LVOT gradient of ≥ 30 mm Hg.
• Several methods can be used in the echocardiography laboratory to elicit a provocable LVOT gradient in patients with HCM2:
• Valsalva maneuver:
• Assessment of SAM and LVOT gradient (by continuous wave Doppler measurement) is done at rest and then during the strain phase of the Valsalva maneuver.
• Disadvantages of this technique include the fact that some patients cannot perform a Valsalva and the fact that the LVOT Doppler signal may be obscured during the Valsalva maneuver.
• Exercise echocardiography:
• Exercise echocardiography is the method of choice since exercise most closely replicates physiologic stress.
• Furthermore, other relevant clinical data, such as the reproducibility of symptoms, exercise duration and capacity, blood pressure response with exercise, and/or oxygen consumption may also be obtained during exercise testing (also see “Additional Testing in Patients with HCM” below for further discussion of exercise testing).
• Upright exercise echocardiography is preferred to supine exercise (using a supine bicycle) since it most resembles upright typical physical activity in most patients.
Step 5: Assess the Mechanism of Mitral Regurgitation
• SAM of the anterior mitral leaflet results in failure of coaptation with the posterior mitral leaflet, creating a funnel-shaped gap through which mitral regurgitation can develop.
• The presence of a nonposterior jet of mitral regurgitation suggests intrinsic disease of the mitral leaflets (or mitral apparatus) independent of SAM.
Step 6: Assess Left Ventricular Diastolic Function
• Diastolic filling of the left ventricle is frequently compromised in HCM and may result in exertional dyspnea, elevated filling pressures, and progressive left atrial enlargement.
• These diastolic filling abnormalities, which are multifactorial in origin, include impairment in left ventricular relaxation and/or worsening left ventricular stiffness.
Step 6A: Measure Diastolic Filling Parameters and Determine E/e′ Ratio
Key Points
• The mitral inflow pattern typically demonstrates a prolonged isovolumic relaxation time (IVRT), reduced early rapid filling (E), a prolonged deceleration time (DT), and increased atrial filling (A) (Figure 7-7).
• Pulmonary venous inflow abnormalities may include systolic blunting, elevation of the pulmonary venous atrial reversal velocity, and an increased difference in duration between the pulmonary venous and mitral atrial filling velocities (Ar-A).
• However, studies of simultaneous echocardiographic and invasive hemodynamic assessments showed no significant correlation between filling pressures and various mitral inflow or pulmonary venous flow parameters.
• An integrated approach using a number of diastolic parameters is required in the assessment of diastolic filling in patients with HCM.
• Two echocardiographic techniques, tissue Doppler imaging and color M-mode, are useful for the estimation of left ventricular filling pressures in patients with HCM.
Tissue Doppler Imaging
Acquisition
• Tissue Doppler imaging of mitral annular motion is recorded in the apical 4-chamber view by placing a 5-mm sample volume at the septal and lateral corners of the mitral annulus.
Analysis
• The e′ velocities at the lateral and septal annulus are lower in patients with HCM (see Figure 7-7).
• A significant increase in e′, suggestive of improved left ventricular relaxation, was demonstrated in patients 6 months following septal ethanol ablation.
• The septal e′ has been shown to be an independent predictor of death and ventricular arrhythmias in children with HCM.
Step 6B: Determine Left Atrial Volume
• Mechanisms of left atrial enlargement include chronically abnormal ventricular filling pressures, elevated left atrial pressures, mitral regurgitation (secondary to SAM and independent mitral valve disease), and, possibly, atrial myopathy.
• 2D anteroposterior linear dimensions of the left atrium in the parasternal long-axis view fail to represent accurately true left atrial size.
• The left atrium from the parasternal long-axis view does not appreciate left atrial enlargement in the superior-inferior and medial-lateral dimensions.
• Measurement of the left atrial volume provides an estimation of the true size of the left atrial cavity.
Acquisition
• The left atrial volume indexed to body surface area (LAVI) should be obtained, as outlined by guidelines of the American Society of Echocardiography.5
• The biplane methods (area-length and Simpson’s method of disks) are very reproducible and are the recommended techniques for obtaining the left atrial volume.
Step 7: Assess Left Ventricular Systolic Function
• Overt left ventricular systolic dysfunction is usually defined as a left ventricular ejection fraction (LVEF) of less than 50% in this patient population.
Step 7B: Assess Myocardial Mechanics
• Myocardial strain imaging (derived from tissue Doppler imaging) allows for the assessment of regional myocardial function and myocardial deformation.
• Strain rate imaging has been shown to be useful in differentiating nonobstructive HCM from hypertensive heart disease.
• However, tissue Doppler–derived strain imaging has technical limitations due to its angle dependence and need for optimal alignment for Doppler measurements.
Key Points
Speckle Tracking Echocardiography (STE)
• Left ventricular contraction is characterized by complex deformation of the myocardium, including longitudinal myocardial fiber shortening, radial thickening, circumferential shortening, and left ventricular twist or torsion.8
• Speckle tracking (or 2D strain) echocardiography directly assesses myocardial motion from B-mode (2D) images and is not subject to angle dependence.
• This is a promising technique that may provide incremental information regarding subclinical systolic impairment in this patient population.
• Although speckle tracking evaluates myocardial function, there are significant differences between strain values across the 17 left ventricular segments.
• Therefore, the variation of regional strain across the left ventricle necessitates the use of site-specific normal ranges.
• In terms of rotational motion, STE allows for quantification of the twisting (or wringing) motion of the heart.
Step 8: Use Echocardiographic Data in the Management of Obstructive HCM
• The main classes of pharmacologic agents used in the treatment of obstructive HCM are beta blockers, disopyramide, and calcium channel blockers.
• Medical management in HCM is determined by symptomatic response and can be optimized using serial echocardiographic and Doppler studies.
• Important serial echocardiographic measurements include the assessment of SAM of the mitral valve and the degree of LVOT obstruction.
• Despite optimal medical therapy, patients may still have New York Heart Association Class III/IV symptoms and a significant LVOT gradient.
• Current options for invasive septal reduction therapy are septal ethanol ablation and surgical myectomy.
• Dual-chamber permanent pacing was previously advocated in drug-refractory symptomatic obstructive patients, but this technique is now infrequently performed because of the lack of long-term effectiveness of this procedure.
Septal Ethanol Ablation
• Septal ethanol ablation involves the selective injection of ethanol into a septal perforator branch of the left anterior descending coronary artery.
• The resulting septal branch occlusion causes an acute deterioration of basal septal function at the site of anterior mitral leaflet–septal contact, which abolishes SAM and the LVOT obstruction.
• This occlusion of the septal branch results in localized infarction of the basal septum, which leads to gradual focal septal thinning, widening of the LVOT, and progressive resolution of the LVOT obstruction.
• Intraprocedural transthoracic imaging has become essential for the guidance and monitoring of septal ethanol ablation (Figure 7-8).
• This procedure has traditionally been performed with the intra-arterial administration of an ultrasonic contrast agent into the target septal branch.
• Intra-arterial injection of a contrast agent allows for the specific localization of the vascular bed perfused by the individual septal perforator branch.
• The targeted vascular territory is the region of contact of the anterior mitral leaflet with the basal septum, which leads to LVOT obstruction.
• The site of leaflet-septal contact is identified by the zone of flow acceleration and color turbulence in the LVOT.
Key Points
• Contrast-guided echocardiography has been demonstrated to be safe and effective and results in fewer procedural complications.
• Because of recent concerns regarding the safety of ultrasonic contrast agents, the Food and Drug Administration of the United States has stated that the intracoronary use of ultrasonic contrast agents is contraindicated.6
• As an alternative, the use of agitated radiographic contrast agents is possible for the identification of the target septal branch, and it is associated with an acceptable degree of myocardial opacification.
• Echocardiographic and Doppler studies are beneficial in the serial noninvasive follow-up of patients after septal ethanol ablation.
• Multiple studies have documented a significant progressive reduction in the basal septal thickness, a decrease in the magnitude of the resting and provocable LVOT gradients, and an improvement in diastolic filling parameters in the 1 to 2 years following this procedure (Figure 7-9).
Surgical Myectomy
• Surgical resection of the hypertrophied subaortic myocardium widens the LVOT and decreases dynamic outflow tract obstruction.
• Echocardiography also plays an important role in detecting additional lesions requiring surgical management.
• Preoperative echocardiographic imaging in patients referred for surgical myectomy includes the evaluation of independent mitral valve disease and concomitant aortic valve disease, and the assessment of additional levels of obstruction (midventricular or right ventricular outflow tract).
• Intraoperative TEE guides the surgical intervention(s), assesses immediate results, and excludes important complications (e.g., creation of iatrogenic ventricular septal defect).
Key Points
• Intraoperative TEE enables careful assessment of the septal morphology (detailed interrogation of the depth, width, and length of the required myectomy), degree of SAM, and the mechanism and degree of mitral regurgitation (Figure 7-10).
• The length of septal hypertrophy is measured from the base of the right coronary cusp of the aortic valve.
• The targeted length of resection is 1 cm below the point of contact between the anterior mitral leaflet and the septum.
• The LVOT gradient can be measured by transgastric imaging in the long-axis view with the continuous wave Doppler beam aligned parallel to the LVOT.
• Following surgical excision, intraoperative TEE can provide real-time determination of the adequacy of the myectomy: the residual LVOT gradient and the degree of mitral regurgitation are reassessed prior to leaving the operating room (Figure 7-11).
• Monitoring with serial echocardiographic studies after the myectomy shows an immediate and persistent reduction in the magnitude of LVOT obstruction.
Selection of Invasive Septal Reduction Therapy
• There is significant controversy regarding the relative merits versus long-term risks of septal ethanol ablation, which was introduced in the 1990s, as compared with surgical myectomy, which has been performed since the 1960s and is regarded as the gold standard of invasive treatment in this condition.1
• In terms of the outcomes of septal ethanol ablation compared with myectomy, there have been a number of nonrandomized studies that have compared these two treatment strategies (Table 7-2).9
• There were no significant differences in short-term or long-term mortality between the ethanol ablation and myectomy cohorts.
• The major differences between patients undergoing ethanol ablation versus those undergoing myectomy were the following: (1) an increased need for permanent pacing following ethanol ablation and (2) a higher residual LVOT gradient following ethanol ablation.
• Both procedures need to be performed at centers with both technical and echocardiographic expertise.10
• Echocardiography is helpful in identifying additional abnormalities that favor the selection of myectomy over septal ethanol ablation:
Key Measurements for Predicting Prognosis in Patients with HCM
• However, in the last 2 to 3 decades, multiple long-term studies, especially from community-based cohorts, have shown that the overall prognosis of HCM is more benign.
• The most common mechanism of SCD in HCM appears to be the development of ventricular tachyarrhythmias originating from an abnormal myocardial substrate.
Key Points
• Risk stratification of patients with HCM has become increasingly important in the past decade since the prophylactic insertion of an implantable cardioverter-defibrillator (ICD) has been shown to be an effective tool in this patient population.1
• Clinical and echocardiographic data can provide important information regarding the long-term prognosis of patients with HCM.
• The risk factors that are considered to be potentially important (or regarded as minor risk factors) in the occurrence of SCD are the following1:
• One of the main challenges with identifying high-risk individuals in this patient population is that the positive predictive value of the “major risk factors” is actually relatively low, given that the incidence of SCD is low (Table 7-3).11
• Furthermore, the major risk factors have a fairly high negative predictive value (see Table 7-3)—thus the absence of these risk factors should be reassuring.
• Echocardiographic indices of prognosis have gained acceptance since they are noninvasive and reproducible.
• The only major risk factor identified by echocardiography is the maximal left ventricular wall thickness.
Left Ventricular Wall Thickness
• Two independent groups have demonstrated a direct association between the magnitude of the maximal left ventricular wall thickness and the risk of SCD in HCM.1
• In one multicenter study of 480 patients followed for 6.5 years, the risk of sudden death was 0 per 1000 person-years (95% confidence interval, 0 to 14.4) in patients with maximal left ventricular wall thickness ≤ 15 mm, whereas the risk of sudden death was 18.2 per 1000 person-years (95% confidence interval, 7.3 to 37.6) in patients with maximal left ventricular wall thickness ≥ 30 mm.12
• The cumulative 20-year risk of sudden death was almost 40% for patients with a wall thickness of ≥ 30 mm (Figure 7-12).
• In another study of 630 patients followed for nearly 5 years, there was a higher probability of sudden death with increasing wall thickness (relative risk per 5-mm increment was 1.31; 95% confidence interval, 1.03 to 1.66).
LVOT Obstruction
• In one study of over 1000 patients with HCM, the risk of death related to HCM was twofold higher in patients with a resting LVOT gradient of ≥ 30 mm Hg (Figure 7-13).13
• The risk of SCD in this study was also higher in patients with obstructive (resting LVOT gradient ≥ 30 mm Hg) versus nonobstructive HCM (relative risk of 2.1).
• However, the difference in the annual rate of sudden death between obstructive and nonobstructive patients was small (1.5% vs. 0.9%).
LV Systolic Dysfunction
• Terms used to denote systolic dysfunction in HCM include “dilated phase of hypertrophic cardiomyopathy,” “end-stage hypertrophic cardiomyopathy,” or “burnt-out hypertrophic cardiomyopathy.”1
• Systolic dysfunction is associated with wall thinning and cavity dilatation, and has been attributed to interstitial fibrosis, ischemia, infarction, and small vessel disease.8
Left Atrial Enlargement
• Left atrial enlargement, as determined by 2D echocardiographic measurements of the left atrial diameter, has been associated with an adverse long-term prognosis (increased risk of atrial fibrillation and increased risk of death).8
Additional Testing in Patients with HCM
Exercise Testing and Exercise Echocardiography
Provocable LVOT Obstruction
• All patients with presumed nonobstructive HCM should be tested for the presence of a provocable (or latent) LVOT gradient.
Key Points
• Patients who should be specifically targeted for exercise echocardiography include patients with the following:
• Upright exercise testing most accurately simulates physical stress and daily activities in patients with HCM.2
• Provocable LVOT obstruction elicited by exercise echocardiography is more reliable and reflective of symptomatology than provocable LVOT gradients elicited by the Valsalva maneuver or amyl nitrate inhalation.
Cardiovascular Magnetic Resonance Imaging in HCM
• Advances in cardiovascular magnetic resonance imaging (CMRI) have the following potential applications in patients with HCM2:
Diagnosis of HCM and Characterization of Hypertrophy
• Determination of the absolute wall thickness and the pattern of hypertrophy is important in the diagnosis of HCM.
• CMRI offers reliable imaging of the epicardial border of the myocardium in regions that often have poor echocardiographic visualization.
Key Points
• CMRI can appreciate full left ventricular myocardial thickness at wall segments that are traditionally difficult to visualize (e.g., anterolateral wall, apical region).
• In patients in whom there is a strong clinical suspicion of apical HCM and in whom the standard 2D echocardiographic study is nondiagnostic, subsequent testing with either contrast echocardiography or CMRI should be performed (Figure 7-14).
• CMRI is useful in differentiating cases of HCM from other cases of unexplained increased wall thickness, such as Fabry’s disease or cardiac amyloidosis.
• CMRI can also help demonstrate prominent trabeculations in the condition known as left ventricular noncompaction cardiomyopathy, which may help distinguish it from the apical form of HCM.
Identification of Fibrosis in HCM and Prognostication
• CMRI can be performed with the administration of gadolinium, which permits the detection and quantification of myocardial fibrosis in patients with HCM.2
• Following intravenous injection, gadolinium is temporarily deposited in the extracellular space of the myocardium.
• CMRI images with late gadolinium enhancement (LGE) show gadolinium deposition as bright or hyperenhanced.
• Areas within the myocardium with fibrosis or scarring are revealed by hyperenhancement of gadolinium (Figure 7-15).
• Multiple large studies have shown a variable but generally high prevalence of LGE in patients with HCM.
• The presence of LGE in patients with HCM has been associated with other risk factors for sudden death and with ventricular arrhythmias.
• The majority of recent studies have demonstrated that the presence of LGE is associated with an increased risk of adverse cardiovascular outcomes, although LGE was not found to be an independent predictor of SCD.14
1 Maron BJ, McKenna WJ, Danielson GK, et al. Clinical expert consensus document on hypertrophic cardiomyopathy: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2003;42:1687-1713.
2 Nagueh SF, Mahmarian JJ. Noninvasive cardiac imaging in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2006;48:2410-2422.
3 Maron BJ, Pelliccia A. The heart of trained athletes: Cardiac remodeling and the risks of sports, including sudden death. Circulation. 2006;114:1633-1644.
4 Arad M, Maron BJ, Gorham JM, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med. 2005;352:362-372.
5 Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: A report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440-1463.
6 Mulvagh SL, Rakowski H, Vannan MA, et al. American Society of Echocardiography Consensus Statement on the clinical applications of ultrasonic contrast agents in echocardiography. J Am Soc Echocardiogr. 2008;21:1179-1201.
7 Losi MA, Nistri S, Galderisi M, et al. Echocardiography in patients with hypertrophic cardiomyopathy: Usefulness of old and new techniques in the diagnosis and pathophysiological assessment. Cardiovasc Ultrasound. 2010;8:7.
8 Afonso LC, Bernal J, Bax JJ, Abraham TP. Echocardiography in hypertrophic cardiomyopathy: The role of conventional and emerging technologies. J Am Coll Cardiol Imag. 2008;1:787-800.
9 Agarwal S, Tuzcu EM, Desai MY, Smedira N, Lever HM, Lytle BW, Kapadia SR. Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;55:823-834.
10 Maron BJ, Dearani JA, Ommen SR, et al. The case for surgery in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;44:2044-2053.
11 McKenna WJ, Behr ER. Hypertrophic cardiomyopathy: Management, risk stratification, and prevention of sudden death. Heart. 2002;87:169-176.
12 Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342:1778-1785.
13 Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003;348:295-303.
14 Salerno M, Kramer CM. Prognosis in hypertrophic cardiomyopathy with contrast-enhanced cardiac magnetic resonance: The future looks bright. J Am Coll Cardiol. 2010;56:888-889.
1 Maron BJ, Maron MS, Wigle ED, Braunwald E. The 50-year history, controversy, and clinical implications of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: From idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009;54:191-200.
2 Drinko JK, Nash PJ, Lever HM, Asher CR. Safety of stress testing in patients with hypertrophic cardiomyopathy. Am J Cardiol. 2004;93:1443-1444.
3 Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation. 2006;114:2232-2239.
4 Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22:107-133.
5 Wang J, Buergler JM, Veerasamy K, Ashton YP, Nagueh SF. Delayed untwisting: The mechanistic link between dynamic obstruction and exercise tolerance in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2009;54:1326-1334.
6 Yang H, Woo A, Monakier D, et al. Left atrial enlargement in hypertrophic cardiomyopathy: The importance of left ventricular segmental hypertrophy and diastolic dysfunction. J Am Soc Echocardiogr. 2005;18:1074-1082.
7 Serri K, Reant P, Lafitte M, et al. Global and regional myocardial function quantification by two-dimensional strain. J Am Coll Cardiol. 2006;47:1175-1181.
This paper is the first major study of 2D strain imaging in patients with HCM.
8 Elliott PM, Gimeno JR, Thaman R, et al. Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy. Heart. 2006;92:785-791.
9 Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 2010;121:445-456.
10 Nagueh SF, Bierig M, Budoff MJ, et al. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with hypertrophic cardiomyopathy. Endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Magnetic Resonance, and Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr. 2011;24:473-498.
