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.
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.
Twelve-lead electrocardiogram in a patient with palpitations. Note deep symmetric T-wave inversions in the precordial leads. There are also T-wave abnormalities in the limb leads. In the absence of hypertension, these should raise suspicion of hypertrophic cardiomyopathy. Subsequent echocardiography and cardiac magnetic resonance imaging confirmed diagnosis of apical hypertrophic cardiomyopathy.
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.
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.
Midsystolic notching of the aortic valve (arrow) is indicative of dynamic left ventricular outflow obstruction.
Systolic anterior motion of mitral valve on M-mode echocardiography. The duration and extent of mitral–septal contact correlate with extent of outflow obstruction.
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.
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.
Steady-state free precession cine sequence still frame view of left ventricle (LV) and right ventricle (RV) showing significant asymmetric septal hypertrophy (S) compared to lateral wall (L). Note outstanding delineation of the LV blood to endocardial interface enabling accurate measurements of thickness of myocardial walls.
A still frame from a steady-state free precession short axis cardiac magnetic resonance study in a patient with suspected hypertrophic cardiomyopathy. There is severe asymmetric left ventricular (LV) hypertrophy involving the septum (S). Multiple papillary muscle heads are also noted in LV cavity. RV, right ventricle.
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.
Gadolinium-based delayed enhancement CMRI showing abnormal enhancement in multiple areas of the myocardium denoting fibrosis. Note the noncoronary predominant mid-myocardial distribution of hyperenhancement seen in nonischemic etiologies.
Bruder O, et al. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol
Maron MS, et al. Clinical profile and significance of delayed enhancement in hypertrophic cardiomyopathy. Circ Heart Fail
O'Hanlon R, et al. Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol
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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.
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).
Brockenbrough-Braunwald-Morrow sign. Following a premature ventricular beat, there is an increase in the gradient but a decrease in aortic and pulse pressure in hypertrophic cardiomyopathy during cardiac catheterization (double arrow).
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.
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
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.
Steady-state free precession left ventricular (LV) outflow tract view still frame showing marked LV myocardial hypertrophy with obliteration of apex in systole (arrow). Note characteristic “ace of spades” appearance of LV myocardium in systole. LA, left atrium.
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.
A: An example of a continuous wave Doppler signal across the left ventricle LV showing the mitral regurgitation signal and concomitant late peaking signal of midcavitary obstruction with a peak gradient of 41 mm Hg. B: A still frame left ventriculogram in a patient with severe mid ventricular HCM with apical aneurysm and outpouching.
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.
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.