Back to Book/course

Clinical Echocardiography

0% Complete
0/64 Steps
  1. Introduction to echocardiography and ultraound imaging
    12 Chapters
  2. Principles of hemodynamics
    5 Chapters
  3. The echocardiographic examination
    3 Chapters
  4. Left ventricular systolic function and contractility
    11 Chapters
  5. Left ventricular diastolic function
    3 Chapters
  6. Cardiomyopathies
    6 Chapters
  7. Valvular heart disease
    8 Chapters
  8. Miscellaneous conditions
    5 Chapters
  9. Pericardial disease
    2 Chapters
Section Progress
0% Complete

Hypertrophic cardiomyopathy (HCM): from pathophysiology to echocardiography

Hypertrophic cardiomyopathy is a genetic disorder that causes left ventricular hypertrophy under normal loading conditions. Hypertrophic cardiomyopathy should not be confused with hypertrophy caused by increased loading conditions. Increased ventricular load is mostly caused by systemic hypertension or aortic stenosis. In hypertension, the increased systemic resistance makes it more difficult for the ventricle to eject blood into the aorta during systole. In aortic stenosis, there is increased resistance in the aortic valve itself, due to the reduced area of the valvular orifice. Both aortic stenosis and hypertension result in increased ventricular load, which the ventricle counteracts by developing hypertension.

Hypertrophic cardiomyopathy implies left ventricular hypertrophy under normal loading conditions.

It is fundamental to distinguish hypertrophic cardiomyopathy from hypertrophy caused by increased loading conditions. The latter is far more common and the conditions may coexist. A significant percentage of the population has hypertension, and aortic stenosis is also more common than hypertrophic cardiomyopathy (especially among elderly). Patient characteristics and the degree of hypertrophy can be used to distinguish hypertrophic cardiomyopathy from hypertrophy caused by loading conditions. In the presence of increased loading conditions, one should suspect hypertrophic cardiomyopathy if the degree of hypertrophy is disproportional to the load (i.e., if hypertrophy is more pronounced than the load could reasonably explain). The probability of hypertrophic cardiomyopathy is inversely related to age, such that the younger the patient presenting with hypertrophy, the more likely a genetic etiology.

The genetic mechanisms underlying hypertrophic cardiomyopathy are complicated and some gene variants may only cause hypertrophy under certain loading conditions (i.e in the presence of increased load). Thus, some cases of hypertrophic cardiomyopathy may be the result of a disproportionate response to increased ventricular loading.

The presence of systemic hypertension or aortic stenosis does not rule out hypertrophic cardiomyopathy.

Epidemiological aspects of hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy is equally common among men and women. The prevalence in a Western population is approximately 0.2%. Hypertrophic cardiomyopathy is one of the most common causes of cardiac arrest and sudden cardiac death (SCD) among young individuals. Among athletes, hypertrophic cardiomyopathy is the most common cause of sudden cardiac death. Therefore, current screening recommendations for athletes emphasize on measures to detect hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is the most common cause of sudden cardiac death among athletes, and one of the most common causes of sudden cardiac death among young individuals.

Echocardiography in hypertrophic cardiomyopathy (HCM)

The hypertrophy is generally asymmetric, i.e its distribution in the left ventricular myocardium varies. Septal hypertrophy, apical hypertrophy and hypertrophy of the left ventricular free wall are common. General hypertrophy is less common.

Hypertrophic cardiomyopathy causes concentric hypertrophy

Hypertrophic cardiomyopathy causes concentric hypertrophy, which means that the generated myocardium allocates space in the ventricular cavity. In concentric hypertrophy, left ventricular volume is reduced, which means that the ejection fraction (EF) must increase to produce sufficient stroke volumes (Figure 1). Although the ventricular volume is reduced by concentric hypertrophy, it may still be normal when compared to reference values.

Figure 1. Types of left ventricular hypertrophy. Left ventricular volume is reduced in concentric hypertrophy. Eccentric hypertrophy results in increased ventricular volume.
Figure 1. Types of left ventricular hypertrophy. Left ventricular volume is reduced in concentric hypertrophy. Eccentric hypertrophy results in increased ventricular volume.

The opposite of concentric hypertrophy is eccentric hypertrophy, which is common among athletes. Eccentric hypertrophy is characterized by hypertrophy of the outer myocardial layers, which does not reduce left ventricular volume. Athletes typically exhibit increased ventricular volume and slightly reduced ejection fraction. The athlete’s heart is capable of maintaining cardiac output at lower ejection fractions due to the fact that they generate large stroke volumes.

Definition of hypertrophic cardiomyopathy

To diagnose hypertrophic cardiomyopathy, the following two measurements are made in the parasternal long-axis view (PLAX) or parasternal short-axis view (PSAX):

  • Septal thickness
  • Inferolateral wall thickness

If either exceeds 15 mm, there is hypertrophy. If the hypertrophy is not explained adequately by hypertension or aortic stenosis, hypertrophic cardiomyopathy is likely.

Athletes often display pronounced physiological hypertrophy, which can be difficult to differentiate from cardiomyopathy. Likewise, storage disorders and mitochondrial diseases can cause wall thickening, which may be difficult to differentiate from hypertrophic cardiomyopathy. The following features can be used to distinguish cardiomyopathy from the differential diagnoses:

  • A hyperdynamic left ventricle suggests cardiomyopathy.
  • Severe septal hypertrophy suggests cardiomyopathy.
  • Obstruction in LVOT suggests cardiomyopathy.
  • A small left ventricle suggests cardiomyopathy.

Table 1 presents a comprehensive list of conditions that may mimic HCM/HOCM (adapted from Marian et al [1]).

Table 1. Phenocopy Conditions for Hypertrophic Cardiomyopathy

Phenotype Phenotypic Clue
AMPK-mediated glycogen storage Normal or reduced left ventricular systolic function, pre-excitation pattern
Pompe disease Autosomal recessive, multiorgan disease, pre-excitation pattern
Anderson–Fabry disease X-linked, multisystem also involving skin, kidney, and peripheral nerves
Danon disease X-linked dominant, proximal muscle weakness, intellectual disability, short PR on ECG, elevated CK levels
Amyloidosis Low QRS voltage, other organ involvement, subendothelial LGE
Kearns–Sayre syndrome Multisystem disease
Friedreich ataxia Autosomal recessive, neurodegeneration
Myotonic dystrophy Myotonia, muscular dystrophy, cataract, and frontal baldness
Noonan/LEOPARD syndromes (rasopathies) Congenital heart defects, lentigines, Café-au-lait spots
Neimann–Pick disease Autosomal recessive neurodegenerative disease
Refsum disease Retinitis pigmentosa, peripheral neuropathy, and ataxia
Deafness Autosomal dominant deafness

CK = creatine kinase; LGE late gadolinium enhancement.

Hypertrophic obstructive cardiomyopathy (HOCM)

In hypertrophic cardiomyopathy, it is important to clarify whether the hypertrophy causes a narrowing of the left ventricular outflow tract (LVOT). Approximately 65% of patients with hypertrophic cardiomyopathy have obstruction in LVOT, a condition referred to as hypertrophic obstructive cardiomyopathy (HOCM).

HOCM with systolic anterior motion (SAM)

The obstruction in LVOT is caused by septal hypertrophy. When the septum bulges into the LVOT, hemodynamics change in the outflow tract, which leads to the anterior leaflet of the mitral valve being sucked into the LVOT. As a result, the outflow tract is obstructed. The motion of the anterior leaflet of the mitral valve is called systolic anterior motion (SAM). Thus, obstruction of the LVOT is due to hypertrophy of the septum and subsequent SAM (Figure 2).

Figure 2. Systolic anterior motion (SAM) of the anterior leaflet of the mitral valve causes obstruction of the LVOT. SAM is typically accompanied by mitral regurgitation (MR), with posteriorly directed jet. CW = continuous wave doppler.

If SAM is pronounced, the anterior leaflet may touch the septum during systole. Subsequently, a pronounced obstruction can lead to closure or flutter of the aortic valve during systole.

Mitral regurgitation is a byproduct of SAM (Figure 2).

Figure 3. Continuous wave (CW) doppler in the LVOT in (A) obstruction due to SAM and septal hypertrophy and (B) aortic stenosis.
Figure 3. Continuous wave (CW) doppler in the LVOT in (A) obstruction due to SAM and septal hypertrophy and (B) aortic stenosis.

Continuous wave (CW) doppler is used to detect obstruction in the LVOT (Figures 2 & 3). The spectral curve is characterized by a slow acceleration, which distinguishes it from the Doppler signal in aortic stenosis (Figure 3).

Note that SAM typically causes the mitral valve regurgitation jet to involve the LVOT. It is important to place the Doppler cursor correctly in the LVOT in order to avoid unintentional recording of the mitral valve regurgitation jet. Video 1 shows HOCM with SAM.

Video 1. HOCM with SAM.

Obstruction in the LVOT is affected by left ventricular filling. The less the filling, the more pronounced the obstruction. This implies that hypovolemia and tachycardia (both lead to diminished ventricular filling) cause increased obstruction in the LVOT. Valsalva maneuver also reduces left ventricular filling (obstruction in LVOT can be provoked by performing Valsalva maneuver).

SAM causes mitral regurgitation (MR)

As mentioned above, hypertrophic cardiomyopathy with SAM is generally accompanied by mitral valve regurgitation (MR) with a posteriorly directed jet.

Apical and midventricular hypertrophy

In midventricular hypertrophy, obstruction may be observed midventricularly, which is detected using continuous wave (CW) Doppler (Figure 4A). In apical hypertrophy, thickened myocardium is seen in the apex. This gives the cavity a pointed appearance, as demonstrated in Figure 4B. Patients with apical hypertrophic cardiomyopathy exhibit T-wave inversion in the precordial leads (V1-V6) on ECG.

Figure 4. Apical and midventricular hypertrophic cardiomyopathy.
Figure 4. Apical and midventricular hypertrophic cardiomyopathy.

Diastolic function in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy leads to impaired diastolic function, i.e the relaxation of the left ventricle is impaired, resulting in prolonged deceleration time (DT) and reduced E/A ratio. The deceleration time is prolonged because it takes longer to equalize the pressure difference between the left atrium and the ventricle. This is explained by the fact that left ventricular compliance is reduced in hypertrophic cardiomyopathy.

Sudden Cardiac Death (SCD) in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is one of the most common causes of sudden cardiac arrest among young people. Cardiac arrest can strike any individual with hypertrophic cardiomyopathy. It should be noted, however, that the incidence of sudden cardiac arrest is very low among people with HCM/HOCM.

Patients with hypertrophic cardiomyopathy who have experienced circulatory arrest or malignant ventricular arrhythmias are unlikely to benefit from beta-blockers or antiarrhythmic drugs. The most effective treatment is an ICD (Implantable Cardioverter Defibrillator). Table 2 shows risk factors for cardiac arrest in hypertrophic cardiomyopathy.

Table 2. Risk factors for sudden cardiac arrest in cardiomyopathy

Known riskfactors
Previous cardiac arrest (“aborted SCD”)
Family history of sudden cardiac arrest
Previous syncope
History of ventricular tachycardia
Severe hypertrophy
Probable riskfactors
LVOT obstruction
Abnormal blood pressure reaction during exercise
Early onset of symptoms


SAM also occurs in individuals who do not have HOCM. Individuals who have left ventricular hypertrophy may develop SAM in the setting of hypovolemia.

Below follows supplementary material intended for readers interested in the genes causing HCM. Refer to Marian et al for details (1).

Established causal genes for HCM

Established causal gene HCM (large families)

Gene Protein Function
MYH7 β-Myosin heavy chain ATPase activity, force generation
MYBPC3 Myosin-binding protein C Cardiac contraction
TNNT2 Cardiac troponin T Regulator of actomyosin interaction
TNNI3 Cardiac troponin I Inhibitor of actomyosin interaction
TPM1 α-Tropomyosin Places the troponin complex on cardiac actin
ACTC1 Cardiac α-actin Actomyosin interaction
MYL2 Regulatory myosin light chain Myosin heavy chain 7–binding protein
MYL3 Essential myosin light chain Myosin heavy chain 7–binding protein
CSRP3 Cysteine- and glycine-rich protein 3 Muscle LIM protein (MLP), a Z disk protein

Likely causal genes for HCM (small families)

Gene Protein Function
FHL1 Four-and-a-half LIM domains 1 Muscle development and hypertrophy
MYOZ2 Myozenin 2 (calsarcin 1) Z disk protein
PLN Phospholamban Regulator of sarcoplasmic reticulum calcium
TCAP Tcap (telethonin) Titin capping protein
TRIM63 Muscle ring finger protein 1 E3 ligase of proteasome ubiquitin system
TTN Titin Sarcomere function

Genes associated with HCM (small families and sporadic cases)

ACTN2 Actinin, α2 Z disk protein
ANKRD1 Ankyrin repeat domain 1 A negative regulator of cardiac genes
CASQ2 Calsequestrin 2 Calcium-binding protein
CAV3 Caveolin 3 A caveolae protein
JPH2 Junctophilin-2 Intracellular calcium signaling
LDB3 Lim domain binding 3 Z disk protein
MYH6 Myosin heavy chain α Sarcomere protein expressed at low levels in the adult human heart
MYLK2 Myosin light chain kinase 2 Phosphorylate myosin light chain 2
NEXN Nexilin Z disc protein
TNNC1 Cardiac troponin C Calcium-sensitive regulator of myofilament function
VCL Vinculin Z disk protein


Marian et al – Hypertrophic Cardiomyopathy Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy (2017).

4.3/5 (6 Reviews)
error: Contact us for permission to use contents. Permission will be granted for non-profit sites.

Join our newsletter and get our free ECG Pocket Guide!

ECG pocket guide

Start learning ECG & echo now!