Hypertrophic cardiomyopathy diagnostic testing

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org]; ; Caitlin J. Harrigan [mailto:charrigan@perfuse.org]; Martin S. Maron, M.D.; Barry J. Maron, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.

Overview
A diagnosis of hypertrophic cardiomyopathy is based upon a number of features of the disease process. While there is use of echocardiography, cardiac catheterization, or cardiac MRI in the diagnosis of the disease, other important factors include ECG findings and if there is any family history of HCM or unexplained sudden death in otherwise healthy individuals.

Stress Test
===2011 ACCF/AHA Guideline Recommendations: Stress Testing ===

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Class IIa
1. Treadmill exercise testing is reasonable to determine functional capacity and response to therapy in patients with HOCM. (Level of Evidence: C)

2. Treadmill testing with monitoring of an ECG and blood pressure is reasonable for SCD risk stratification in patients with HOCM. (Level of Evidence: B)

3. In patients with HOCM who do not have a resting peak instantaneous gradient of greater than or equal to 50 mm Hg, exercise echocardiography is reasonable for the detection and quantification of exercise-induced dynamic LVOT obstruction. (Level of Evidence: B)}}

Electrocardiogram
Large septal q waves may be present reflective of the septal hypertrophy. In the Yamaguchi variant of apical hypertrophic cardiomyopathy there may be deeply inverted T waves in precordial leads V2-V6 and II, III, aVL (see example).



===2011 ACCF/AHA Guideline Recommendations: Electrocardiography ===

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Class I
1. 1. A 12-lead ECG is recommended in the initial evaluation of patients with HOCM. (Level of Evidence: C)

2. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring is recommended in the initial evaluation of patients with HOCM to detect ventricular tachycardia (VT) and identify patients who may be candidates for ICD therapy. (Level of Evidence: B)

3. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring or event recording is recommended in patients with HOCM who develop palpitations or lightheadedness. (Level of Evidence: B)

4. A repeat ECG is recommended for patients with HOCM when there is worsening of symptoms. (Level of Evidence: C)

5. A 12-lead ECG is recommended every 12 to 18 months as a component of the screening algorithm for adolescent first-degree relatives of patients with HOCM who have no evidence of hypertrophy on echocardiography. (Level of Evidence: C)

6. A 12-lead ECG is recommended as a component of the screening algorithm for first-degree relatives of patients with HOCM. (Level of Evidence: C)

Class IIa
1. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring, repeated every 1 to 2 years, is reasonable in patients with HOCM who have no previous evidence of VT to identify patients who may be candidates for ICD therapy. (Level of Evidence: C)

2. Annual 12-lead ECGs are reasonable in patients with known HOCM who are clinically stable to evaluate for asymptomatic changes in conduction or rhythm (i.e., AF). (Level of Evidence: C)

Class IIb
1. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring might be considered in adults with HOCM to assess for asymptomatic paroxysmal AF/atrial flutter. (Level of Evidence: C)}}

Echocardiography
Echo with doppler is the primary procedure used to diagnose hypertrophic cardiomyopathy. There is a prolonged isovolumic relaxation time, reduced peak E velocity, prolonged deceleration time, increased peak A velocity, and decreased E/A ratio as compared to normal controls.

Proper examination should evaluate :

 * Left ventricular asymmetric hypertrophy
 * Parasternal long axis shows relationship of the septal hypertrophy and the outflow tract


 * Left ventricular diastolic dysfunction
 * LV inflow across the mitral valve
 * LA inflow in the pulmonary vein
 * Myocardial Doppler tissue velocity
 * Isovolumetric relaxation time


 * Dynamic outflow tract obstruction
 * SAM (systolic anterior motion) of the mitral leaflet
 * Mid-systolic closure of the aortic valve
 * Late peaking, high velocity flow in the outflow tract
 * Variability of obstruction with maneuvers (exercise, amyl nitrate inhalation, and post-PVC beats)


 * Doppler Techniques
 * Use continuous wave doppler to measure the systolic flow velocity in the LV outflow tract and mid-cavity (both at rest and during maneuvers such as the Valsalva maneuver or during dobutamine administration.

Because of the turbulent, high-velocity jet in the left ventricular outflow tract (LVOT), the anterior mitral leaflet moves anteriorly in systole, exacerbating the outflow tract obstruction, and promoting mitral regurgitation. The following images show classic systolic anterior motion (SAM) of the mitral valve leaflets:

On parasternal long-axis view

On parasternal short-axis view

===2011 ACCF/AHA Guideline Recommendations: Echocardiography ===

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Class I
1. A TTE is recommended in the initial evaluation of all patients with suspected HOCM. (Level of Evidence: B)

2. A TTE is recommended as a component of the screening algorithm for family members of patients with HOCM unless the family member is genotype negative in a family with known definitive mutations. (Level of Evidence: B)

3. Periodic (12 to 18 months) TTE screening is recommended for children of patients with HOCM, starting by age 12 years or earlier if a growth spurt or signs of puberty are evident and/or when there are plans for engaging in intense competitive sports or there is a family history of sudden cardiac death. (Level of Evidence: C)

4. Repeat TTE is recommended for the evaluation of patients with HOCM with a change in clinical status or new cardiovascular event. (Level of Evidence: B)

5. A transesophageal echocardiogram (TEE) is recommended for the intra-operative guidance of surgical myectomy. (Level of Evidence: B)

6. TTE or TEE with intracoronary contrast injection of the candidate’s septal perforator(s) is recommended for the intra-procedural guidance of alcohol septal ablation. (Level of Evidence: B)

7. TTE should be used to evaluate the effects of surgical myectomy or alcohol septal ablation for obstructive HOCM. (Level of Evidence: C)

Class IIa
1. TTE studies performed every 1 to 2 years can be useful in the serial evaluation of symptomatically stable patients with HOCM to assess the degree of myocardial hypertrophy, dynamic obstruction, and myocardial function. (Level of Evidence: C)

2. Exercise TTE can be useful in the detection and quantification of dynamic LVOT obstruction in the absence of resting outflow tract obstruction in patients with HOCM. (Level of Evidence: B)

3. TEE can be useful if TTE is inconclusive for clinical decision making about medical therapy and in situations such as planning for myectomy, exclusion of sub-aortic membrane or mitral regurgitation secondary to structural abnormalities of the mitral valve apparatus, or in assessment for the feasibility of alcohol septal ablation. (Level of Evidence: C)

4. TTE combined with the injection of an intravenous contrast agent is reasonable if the diagnosis of apical HOCM or apical infarction or severity of hypertrophy is in doubt, particularly when other imaging modalities such as CMR are not readily available, not diagnostic, or are contraindicated. (Level of Evidence: C)

5. Serial TTE studies are reasonable for clinically unaffected patients who have a first-degree relative with HOCM when genetic status is unknown. Such follow-up may be considered every 12 to 18 months for children or adolescents from high-risk families and every 5 years for adult family members. (Level of Evidence: C)

Class III (No Benefit)
1. TTE studies should not be performed more frequently than every 12 months in patients with HOCM when it is unlikely that any changes have occurred that would have an impact on clinical decision making. (Level of Evidence: C)

2. Routine TEE and/or contrast echocardiography is not recommended when TTE images are diagnostic of HOCM and/or there is no suspicion of fixed obstruction or intrinsic mitral valve pathology. (Level of Evidence: C)}}

===2011 ACCF/AHA Guideline Recommendations: Detection of Concomitant Coronary Disease ===

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Class III (No Benefit)
1. Routine SPECT MPI or stress echocardiography is not indicated for detection of silent CAD-related ischemia in patients with HOCM who are asymptomatic. y artery disease|low likelihood of CAD]] to rule out possible concomitant CAD. (Level of Evidence: C)}}

Late Myocardial Enhancement
Late myocardial enhancement has been associated with myocardial fibrosis and may allow for earlier detection of hypertrophic cardiomyopathy than is currently available with echocardiography and ECG.


 * Choudhury et al studied 21 patients with previously diagnosed hypertrophic cardiomyopathy . They noted:
 * Late myocardial enhancement following gadolinium administration in a patchy intramyocardial distribution.
 * Typically occurred in the hypertrophied regions, predominantly in the middle third of the ventricular wall in a patchy, multi focal distribution.
 * If enhancement occurred, it occurred at the junctions of the intraventricular septum and right ventricular free wall.


 * Moon et al looked at whether the extent of hyperenhancement on MR in patients with HCM would be associated with the risk of heart failure and sudden death The study involved 53 patient were selected for presence or absence of an increased clinical risk of sudden death and/or progressive adverse left ventricular remodeling.
 * Myocardial hyperenhancement was present in 79% of patients.
 * They found no evidence of abnormal myocardium on non-contrast images.
 * There was more hyperenhancement in patients with progressive disease than without.
 * There was greater hyperenhancement in patients with ≥ 2 risk factors for sudden death.
 * Patients with diffuse hyperenhancement had ≥ 2 risk factors for sudden death vs patients with confluent hyperenhancement.

Of note, other investigators have discovered that in carriers without signs of hypertrophy on EKG or echocardiography, Cardiac MR can detect the presence of crypts in the LV wall which may progress to hypertrophy.

Left Ventricular Hypertrophy
MR is helpful in visualizing the asymmetric thickening of the interventricular septum in patients with HCM. However, it may be more helpful than other forms of imaging to differentiate the variant types of hypertrophic cardiomyopathy.

Mitral Regurgitation and Systolic Anterior Motion
MR can be helpful in evaluating the extent of systolic anterior motion of the mitral valve.

Obstruction
MR can be help visualize turbulence in left ventricular outflow tract created by obstruction in patients with obstructive hypertrophic cardiomyopathy.

===2011 ACCF/AHA Guideline Recommendations: Cardiac Magnetic Resonance ===

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Class I
1. CMR imaging is indicated in patients with suspected HOCM when echocardiography is inconclusive for diagnosis. (Level of Evidence: B)

2. CMR imaging is indicated in patients with known HOCM when additional information that may have an impact on management or decision making regarding invasive management, such as magnitude and distribution of hypertrophy or anatomy of the mitral valve apparatus or papillary muscles, is not adequately defined with echocardiography. (Level of Evidence: B)

Class IIa
1. CMR imaging is reasonable in patients with HOCM to define apical hypertrophy and/or aneurysm if echocardiography is inconclusive. (Level of Evidence: B)

Class IIb
1. In selected patients with known HOCM, when sudden cardiac death risk stratification is inconclusive after documentation of the conventional risk factors, CMR imaging with assessment of late gadolinium enhancement (LGE) may be considered in resolving clinical decision making. (Level of Evidence: C)

2. CMR imaging may be considered in patients with LV hypertrophy and the suspicion of alternative diagnoses to HOCM, including cardiac amyloidosis, Fabry disease, and genetic phenocopies such as LAMP2 cardiomyopathy. (Level of Evidence: C)}}

Cardiac CT
Echocardiographic findings reflect the clinical and anatomic findings described above, e.g. LVH, diastolic dysfunction, MR, LA enlargement, elevated PAP.

Characteristic of obstructive HOCM is systolic anterior motion of the mitral valve (SAM). The anterior leaflet is pulled toward the LVOT during systole via the Venturi effect, leading to obstruction, a gradient and MR.

===2011 ACCF/AHA Guideline Recommendations: Detection of Concomitant Coronary Disease ===

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Class I
1. Coronary arteriography (invasive or computed tomographic imaging) is indicated in patients with HOCM with chest discomfort who have an intermediate to high likelihood of CAD when the identification of concomitant CAD will change management strategies. (Level of Evidence: C)

Class IIa
1. Assessment of coronary anatomy with computed tomographic angiography (CTA) is reasonable for patients with HOCM with chest discomfort and a low likelihood of CAD to assess for possible concomitant CAD. (Level of Evidence: C)}}

Positron Emission Tomography
Positron Emission Tomography (PET) studies have demonstrated that coronary flow reserve is reduced in patients with HCM. Those patients who subsequently died had a greater reduction in coronary flow reserve at baseline. It has been hypothesized that this ischemia may mediate in part the higher risk in sudden cardiac death.

===2011 ACCF/AHA Guideline Recommendations: Detection of Concomitant Coronary Disease ===

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Class IIa
1. Assessment of ischemia or perfusion abnormalities suggestive of CAD with single photon emission computed tomography (SPECT) or positron emission tomography (PET) myocardial perfusion imaging (MPI; because of excellent negative predictive value) is reasonable in patients with HOCM with chest discomfort and a low likelihood of CAD to rule out possible concomitant CAD. (Level of Evidence: C)

Class III (No Benefit)
1. Assessment for the presence of blunted flow reserve (microvascular ischemia) using quantitative myocardial blood flow measurements by PET is not indicated for the assessment of prognosis in patients with HOCM. (Level of Evidence: C)}}

Cardiac Catheterization
Upon cardiac catheterization, catheters can be placed in the left ventricle and the ascending aorta, to measure the pressure difference between these structures. In normal individuals, during ventricular systole, the pressure in the ascending aorta and the left ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or with HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta, with the left ventricular pressure higher than the aortic pressure. This gradient represents the degree of obstruction that has to be overcome in order to eject blood from the left ventricle.

The Brockenbrough–Braunwald–Morrow sign is observed in individuals with HCM with outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In individuals with aortic stenosis, after a premature ventricular contraction (PVC), the following ventricular contraction will be more forceful, and the pressure generated in the left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve represents, the post-PVC ascending aortic pressure will increase as well. In individuals with HCM, however, the degree of obstruction will increase more than the force of contraction will increase in the post-PVC beat. The result of this is that the left ventricular pressure increases and the ascending aortic pressure decreases, with an increase in the LVOT gradient.



While the Brockenbrough–Braunwald–Morrow sign is most dramatically demonstrated using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine physical examination as a decrease in the pulse pressure in the post-PVC beat in individuals with HCM.

Electrophysiologic study
The prognostic value of electrophysiologic testing in the absence of spontaneous, sustained ventricular tachycardia is limited, and in fact, the study itself may be dangerous. Sustained ventricular tachyarrhythmias, predominantly rapid polymorphic ventricular tachycardia, have been induced in 27 to 43 percent of patients with HCM at electrophysiologic study, but their prognostic significance is controversial. The predictive value of asymptomatic nonsustained ventricular tachycardia is also limited. Paced electrogram fractionation in hypertrophic cardiomyopathy may helpful in determining which patients are at risk for ventricular fibrillation.

The absence of inducible, sustained monomorphic ventricular tachyarrhythmias, absence of nonsustained ventricular tachycardia on ambulatory ECG, and no history of impaired consciousness (i.e., cardiac arrest or syncope) identified a subset (22 percent) of patients with HCM with a low (<1 percent) risk for sudden cardiac death.

Guideline Resources
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy