Echocardiographic diagnosis of the different phenotypes of hypertrophic cardiomyopathy
Parato et al. Cardiovascular Ultrasound
Echocardiographic diagnosis of the different phenotypes of hypertrophic cardiomyopathy
Vito Maurizio Parato 0
Valeria Antoncecchi 2
Fabiola Sozzi 1
Stefania Marazia 5
Annapaola Zito 4
Maria Maiello 3
Pasquale Palmiero 3
on behalf of Italian Chapter of ISCU
0 Cardiology Unit and EchoLab of Emergency Department, Madonna del Soccorso Hospital, Politecnica delle Marche University , 3-7, Via Manara, San Benedetto del Tronto-Ascoli Piceno 63074 , Italy
1 Cardiology Unit, University Policlinico Hospital , Milan , Italy
2 Cardiology Unit, Sarcone Hospital , Terlizzi, Bari , Italy
3 ASL BR, Health Center , Districtual Cardiology, Brindisi , Italy
4 Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari , Bari , Italy
5 Cardiology Unit, Giannuzzi Hospital , Manduria , Italy
Hypertrophic Cardiomyopathy (HCM) is an inherited cardiovascular disorder of great genetic heterogeneity and has a prevalence of 0.1 - 0.2 % in the general population. Several hundred mutations in more than 27 genes, most of which encode sarcomeric structures, are associated with the HCM phenotype. Then, HCM is an extremely heterogeneous disease and several phenotypes have been described over the years. Originally only two phenotypes were considered, a more common, obstructive type (HOCM, 70 %) and a less common, non-obstructive type (HNCM, 30 %) (Maron BJ, et al. Am J Cardiol 48:418 -28, 1981). Wigle et al. (Circ 92: 1680-92, 1995) considered three types of functional phenotypes: subaortic obstruction, midventricular obstruction and cavity obliteration. A leader american working group suggested that HCM should be defined genetically and not morphologically (Maron BJ, et al. Circ 113:1807-16, 2006). The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases recommended otherwise a morphological classification (Elliott P, et al. Eur Heart J 29:270-6, 2008). Echocardiography is still the principal tool for the diagnosis, prognosis and clinical management of HCM. It is well known that the echocardiographic picture may have a clinical and prognostic impact. For this reason, in this article, we summarize the state of the art regarding the echocardiographic pattern of the HCM phenotypes and its impact on clinical course and prognosis.
Hypertrophy; Cardiomiopathy; Echocardiography
Hypertrophic Cardiomyopathy (HCM) is an inherited
cardiovascular disease and its prevalence is estimated to
be one case per 500–1000 among the general population.
Hundred mutations in more than 27 genes are
associated with the HCM phenotype; most of them encode for
sarcomeric structures, while only 5–10 % of HCM patients
show other genetic mutations or non genetic causes .
For this reason HCM can be mainly meant as a
sarcomeric disease, with myocardial fibers disarray as its
In 2006, the American Heart Association Working
Group  suggested that HCM should be defined
genetically and not morphologically.
Subsequently, the European Society of Cardiology
Working Group on Myocardial and Pericardial Diseases
recommended a morphological classification  including
non- sarcomeric forms of HCM. The key point of this
latter approach is that clinical evaluation of patients more
often starts with the finding of a hypertrophied heart
rather than a genetic mutation.
For these reasons, in this article, we review the
echocardiographic pattern of the principal HCM phenotypes.
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Differential diagnosis of cardiac hypertrophy
Several heart diseases may present with hypertrophy
Rapezzi et al.  recently published a review article
summarizing how clinical, electrocardiographic and
echocardiographic features can suggest, in this setting,
a specific aetiology for hypertrophy.
Metabolic disorders and congenital syndromes are
usually diagnosed very early in lifetime but some types of
amyloidosis and Anderson-Fabry disease are frequently
discovered in adulthood and cardiac hypertrophy
sometimes could be the first clue.
Amyloidosis is often suggested by the presence of
pericardial effusion and a ground-glass appearance of
myocardium with the involvement of both ventricular
chambers, interatrial septum and AV valves tissue.
Storage and infiltrative diseases (e.g. Anderson-Fabry,
Danon and Pompe diseases) are commonly associated
with severe concentric LVH. In Noonan Syndrome the
obstruction of right ventricular outflow can be detected.
For these reasons it is very important to make a correct
differential diagnosis between HCM and other heart
diseases presenting with hypertrophy.
The HCM diagnosis
HCM diagnosis is based on the presence of
hypertrophied left ventricle in the absence of other disorders
that could be responsible for it, such as pressure
overload diseases (mainly arterial hypertension and aortic
ECG is an essential tool to make a suspicion of HCM.
In 75 % to 95 % of HCM patients the ECG shows changes
in the form of left ventricular hypertrophy .
Twentyfive percent of patients exhibit a left anterior hemiblock or
a left bundle branch block . The configuration of
hypervoltage and giant negative T waves is typical for apical
forms, and pseudoinfarct Q waves are typical for
obstructive forms . Peripheral low voltage suggests a storage
disease or cardiac amyloidosis . A normal ECG does
not exclude the presence of HCM but can suggest a mild
manifestation of the disease.
Even if cardiac magnetic resonance (CMR) ability, in the
assessment of HCM, is improving , especially for
intramyocardial fibrous tissue or scar detection using
delayedenhancement imaging, echocardiography remains the
principal tool for the diagnosis and morphological
characterization of HCM.
≥15 mm in adults;
>12–15 mm in relatives;
The HCM diagnosis requires the absence of other
cardiac or systemic diseases susceptible to producing a
similar degree of hypertrophy .
All ventricular walls should be analysed at multiple
levels but measurements have to be done in end-diastole
, preferably in short axis view .
In 1995, Klues HG  said that in hypertrophic
cardiomyopathy, the distribution of left ventricular
hypertrophy is characteristically asymmetric and particularly
heterogeneous, encompassing most possible patterns of
wall thickening, from extensive and diffuse to mild and
segmental, and with no single morphologic expression
considered typical or classic. A greater extent of left
ventricular hypertrophy is associated with younger age.
The greatest wall thickness measured at any site in the
LV chamber at end diastole is regarded as the maximal
wall thickness and a marker of the magnitude of LV
hypertrophy. Maron MS et al.  found a non-linear
and parabolic relation between greater LV wall thickness
and NYHA class. Therefore, marked symptoms were
most commonly associated with moderate degrees of LV
hypertrophy (wall thickness of 16 to 24 mm) but less
frequently with extreme hypertrophy (>30 mm) or mild
hypertrophy (<15 mm).
Beyond the accurate evaluation of hypertrophy
distribution and entity, ultrasounds allow the characterization
of left ventricle (LV) systolic and diastolic function, left
atrium (LA) volume, left ventricle outflow tract (LVOT),
right ventricle outflow tract (RVOT), mid-ventricular
obstruction (MVO), apical morphology, mitral valve
(MV) + systolic anterior movement (SAM) and pulmonary
Although a genetic-echocardiographic pattern
relationship has not been confirmed , according to some
studies [12–14], the septum contours could suggest
specific HCM genotypes. In particular a reverse curvature
was found to be predictive of MYH7/myofilament
Several new echo-techniques have been applied to HCM
An hypertrophy confined to the apex or to the
anterolateral wall could be missed and sometimes the use of
contrast agents for cavity opacification is necessary, as
like as for the detection of apical aneurysms and clots
[15, 16, 17].
Three-dimensional echocardiography (3DE) is supposed
to be more accurate in the mass quantification but there
are still few data about its routine use in clinical practice
Strain rate imaging, obtained either by Tissue Doppler
Imaging (TDI) and Speckle Tracking Echocardiography
(STE), is emerging as a useful tool to differentiate HCM
from hypertensive cardiomyopathy since more
remarkable reductions in strains were demonstrated in HCM
patients comparing to the other [18, 19].
Longitudinal strain analysis by STE enables early
detection of left ventricular (LV) contraction abnormalities in
patients with preserved ejection fraction. Yang H. et al.
 found that patients with HCM have abnormalities in
myocardial mechanics that are related to the site of
abnormal myocardial hypertrophy. They showed that
apical HCM and septal HCM have common mechanical
abnormalities. Longitudinal strain is lower,
circumferential strain is higher, and twist is apically displaced. The
extent of these abnormalities and their regional
expressions vary according to the degree of hypertrophy in every
segment. However, some abnormalities are present even
in segments with relatively normal wall thickness, likely
because of underlying disarray or fibrosis in segments
without marked thickening. These findings validate the
concept that abnormalities in function are related to the
site and degree of hypertrophy.
In Maron’s classification phenotypes , by using
global longitudinal strain (GLS), Reant P. et al. 
demostrated that a lower GLS values correlate with
several prognostic markers (higher LV mass, higher LV
filling pressures, abnormal blood pressure response
during exercise test), reflect a more intrinsic myocyte
dysfunction than other markers and allow earlier
detection of LV systolic function abnormalities, while EF is
usually preserved in HCM. They demonstrated also that
type III pattern of Maron’s classification  (septum + at
least a part of LV free wall) exhibits a worse profile than
other patterns, with a significantly lower GLS values.
At the moment there are not reproducible data to
provide specific cut-off for strain measures in HCM
LV untwisting, assessed by speckle tracking
echocardiography (STE), may be a novel parameter for
evaluating LV relaxation. Van Dalen B. et al.  found
delayed untwisting to be a rather uniform characteristic
of patients with HCM regardless of the extent and site
of LV hypertrophy, which is in agreement with the
results of a study published by Spirito and Maron .
But they found also an important influence of the
pattern of hypertrophy on LV twist in HCM, which
provides further insight into the pathophysiology of this
Potential misdiagnosis may also occur in athletes’ left
ventricle hypertrophy (LVH). In these cases the
distinction between physiological and pathological hypertrophy
has important consequences for the participation in
strenuous physical activities.
Differential features include LV cavity dilation in athlete’s
heart and the presence of LA enlargement in HCM .
HCM patients still have impaired systolic and diastolic
function on Tissue Doppler Imaging (TDI) analysis,
whereas athletes typically demonstrate normal or
supranormal TDI velocities. Finally athlete’s hypertrophy tends
to revert stopping training for some months.
Echocardiography is also important for patients’
followup, prognostic evaluation  and therapeutic management
since Trans-Thoracic Echocardiography (TTE) or
TransEsophageal Echocardiography (TEE) are recommended to
guide alcohol septal ablation and surgical myectomy
Finally echocardiography is fundamental in the clinical
screening of HCM patients’ relatives .
The 2008 ESC-Guidelines on Stress-Echocardiography,
published by Sicari R , recommended the use of
dypiridamole test in HCM patients in order to evaluate
the coronary flow reserve, using PW-doppler on LAD
However, since 2009 Maron MS  supported an
emerging role for CMR in the contemporary evaluation
of patients with HCM.
In this article we review the state of the art of the
HCM echocardiographic diagnosis focusing on the
echocardiographic patterns of the more common phenotypes.
Left ventricle diastolic dysfunction
Abnormalities of diastolic function can be observed in
about 80 % of patients with HCM, regardless of the
morphological phenotype . The diastolic dysfunction
is a physio-pathological aspect of great value in HCM
patients, both for the earliness of the onset, for the
explanation of the severity of symptoms and for
informations on prognosis.
The LV diastolic dysfunction is the result of regional
diastolic abnormalities of variable magnitude, and it is
accentuated by an asynchrony of relaxation. Its degree
appears poorly correlated with the extent of hypertrophy.
Alterations can affect both early and end phase of the
Several parameters have been validated to study the
diastolic function. Among them: mitral flow doppler
analysis, tissue doppler velocities, left atrium size and
function. Simple and repeatable indices are represented
by the iso-volumetric relaxation time (IRT), usually
elongated, and the deceleration time (DT) of E-diastolic
wave. The analysis of the pulmonary venous flow
doppler pattern provides additional data that can be
interpreted and become useful in the clinical management of
the patient, since the atrial reversal velocity and its
duration have a significant correlation with LV
enddiastolic pressure .
Following the Finocchiaro et al. recommendations ,
in HCM patients LV filling must be assessed by pulsed
doppler at the level of the mitral opening tips. The pattern
of LV filling is classified as follows. Restrictive filling
pattern: in the presence of E-deceleration time <120 ms or
of E/A wave ≥ 2 associated with E-deceleration time ≤
150 ms. Abnormal relaxation: E/A <1 associated with
Edeceleration time >220 ms. Normal (or ‘pseudonormal’):
intermediate filling pattern. It should be measured the
peak of myocardial early diastolic velocity at the lateral
mitral annulus (lateral E’) and transmitral to tissue
doppler imaging (TDI) early diastolic velocity ratio (E/E’;
using tissue Doppler imaging). The LA and right atrial
(RA) volumes must be measured in systole just before the
mitral valve opening, using a monoplane area-length
method. According to the ASE guidelines, diastolic
dysfunction is defined in the presence of severe LA
dilation [indexed left atrial volume (LAVi) > 40 mL/m2],
increased E/E’ (>15), reduced E’ velocity (<8 cm/s) and a
restrictive pattern .
Diastolic dysfunction equally affects patients with HCM
regardeless of the distribution of hypertrophy and it’s
associated with various clinical and echocardiographic
variables such as LV obstruction .
Diastolic dysfunction is a large contributor to the
HCM patho-physiology and it is a major trait of the
The distribution of the ventricular and septal wall
thickening in HCM varies widely. Ventricular hypertrophy can
be focal or diffuse, asymmetrical or concentric, obstructive
In HCM, diastolic dysfunction is independent from
the morphological pattern. The main correlates of
diastolic dysfunction are LV obstruction, age, degree of
hypertrophy and mitral regurgitation .
Some studies have noted a statistical significance
correlations between E/e’ ratio and LV filling pressures. This is
present in a large range of annular velocities, including
patients with a lateral annular e’ velocity >8 cm/sec . But
a recent study conducted by Geske JB et al.  noted a
modest correlation in patients with HCM between
severely impaired LV relaxation and markedly reduced
annular velocities. Other clinical researches show that the E/
e’ ratio correlates with exercise tolerance in adults 
and in children  with HCM. In addition, septal e’
velocity appears to be an independent predictor of death and
ventricular dysrhythmia in children with HCM .
LA size and more accurately its volume, provide
important prognostic information in HCM [32, 33]. LA
enlargement in HCM has multifactorial origins: the
severity of mitral regurgitation, the presence of diastolic
dysfunction and possibly atrial myopathy . The
assessment of LA function via Doppler echocardiographic
techniques has been performed by indirect methods using
mitral flow and pulmonary venous inflow signals and LA
volumes using 2D and 3D echocardiography during the
different atrial phases [26, 32–34].
Other indirect measures of LA function have included
the calculation of LA ejection force and kinetic energy,
which are increased in patients with obstructive HCM and
are reduced (though not normalized) after relief of
obstruction . Strain imaging of the LA allows for more
direct assessment of LA function. Longitudinal strain of
the LA by tissue Doppler and 2D speckle-tracking during
all three atrial phases was assessed in HCM. LA strain
values are reduced in patients with HCM compared with
those with secondary LV hypertrophy .
HCM is an extremely heterogeneous disease and several
phenotypes have been described over the years [37–39].
Originally only two phenotypes of HCM were considered:
a more common, obstructive type (HOCM, 70 %) and a less
common, non-obstructive type (HNCM, 30 %) [37, 40].
In 1981, Maron BJ  published a four types
classification. Type I: hypertrophy involving the basal septum;
type II: hypertrophy involving the whole septum; type
III: hypertrophy involving septum, anterior, and
anterolateral walls; type IV: LV apical hypertrophy (Fig. 1).
Nowadays, this classification, based on hypertrophy
distribution, is probably the most popular .
In 1995 Wigle ED et al., after a long debate, 
considered three types of functional phenotype: subaortic
obstruction, midventricular obstruction and cavity
Syed IA et al.  considered at least five major
anatomic subsets based on the septal contour, as well as
the location and extent of hypertrophy: reverse
curvature, sigmoidal septum, neutral contour, apical form,
Reverse curvature septum HCM shows a predominant
mid-septal convexity toward the left ventricular (LV)
cavity with the cavity itself often having an overall crescent
shape. Dynamic subaortic obstruction may be present in
this form usually with systolic anterior motion (SAM) of
the mitral leaflets and turbulent flow in the outflow tract.
Sigmoid septum HCM shows a generally ovoid LV
cavity with the septum being concave to the LV cavity
and a prominent basal septal bulge. Subaortic
obstruction is present in this form usually with SAM of the
mitral leaflets and a posteriorly directed jet of mitral
Neutral septum HCM shows an overall straight septum
that is neither predominantly convex nor concave toward
the LV cavity. Subaortic obstruction is less present.
Apical HCM shows a predominant apical distribution
of hypertrophy. Myocardial delayed enhancement is seen
Fig. 1 The four phenotypes of Maron’s classification (1981) (from reference 21)
in the LV apex at the site of maximal hypertrophy in this
Mid-ventricular HCM shows predominant hypertrophy
at the mid-ventricular level. In this form a thinned and
dyskinetic apical pouch is also present. Obstruction is at
the level of the papillary muscles. No mitral SAM.
Myocardial delayed enhancement may be seen in the
dyskinetic apical pouch.
The most common HCM morphology is reverse
curvature and it is most associated with identifiable
HCMassociated gene mutations .
Recently, Helmy SM  proposed a classification
including four different patterns which show a good
correlation with clinical and ecg presentation (Table 1).
Considering these classifications, we summarize the
echocardiographic features of the most common phenotypes.
Table 1 Helmy’s four-patterns classification. (Modified from ref. 38)
Septum and adjacent
but not apical hypertrophy
Apical in combination with
other LV segments’ hypertrophy
Apical hypertrophy alone
The diagnosis is defined by a septal-to-posterior
diastolic wall thickness ratio ≥ 1.3  (or ≥1.5 in hypertensive
patients) (Fig. 2A).
It corresponds to reverse curvature and sigmoid
septum of Syed’s classification .
False positives may be due to: 1) the presence of a
right ventricular moderator band or LV tendon that may
result in overestimation of septal thickness; 2) the
presence of a sigmoid septum in an elderly patient (often
inaccurately reported as ASH) which may be also
associated with the presence of SAM.
Hypertensive patients who have had an inferior
myocardial infarction often mimic the ASH pattern of HCM. In
this setting, the septal/posterior wall ratio may exceed 1.5
simply because the septum is mildly hypertrophied and the
posterior wall is thinned as a result of the prior infarct .
The Asymmetric Septal Hypertrophy pattern may occur
with or without left ventricle outflow tract (LVOTO).
Left Ventricle Outflow Tract Obstruction (LVOTO)
The presence of resting obstruction is defined as a peak
LVOT gradient >30 mmHg. It has prognostic significance
in HCM as a predictor of the risk of sudden cardiac death
(SCD) and progression to heart failure . LVOTO arises
due to narrowing of the LVOT by septal hypertrophy,
anterior displacement of the mitral apparatus and systolic
anterior motion (SAM) of the mitral anterior leaflet. The
presence of a subaortic membrane and mitral valve
abnormalities should be excluded .
It has been demonstrated that a steeper LV to aortic
root angle is a predictor of LVOTO, irrespective of basal
septal thickness .
Most patients with HCM do not exhibit significant
resting LVOTO but a dynamic gradient occurs in 25–30 % of
patients, with the resulting pressure gradient being highly
variable and strongly influenced by central blood volume
and contractile state .
Fig. 2 a PLAX view demonstrating the asymmetrical hypertrophy of the interventricular septum over the posterior wall with a ratio >1.3.
b Massive septal hypertrophy characterized by a septal diastolic thickness > 30 mm. c Massive septal hypertrophy with RVOT obstruction by
the projection of the massively hypertrophied interventricular septum into the right outflow tract. d MOHC with the ‘hourglass’ shaped left
ventricle consisting of two different chambers: the proximal and the distal chamber
For this reason, all symptomatic patients without
evidence of a resting gradient should be investigated for
dynamic LVOTO either by Valsalva manoeuvre and
Exercise stress echocardiography is recommended in
symptomatic patients if bedside manoeuvres fail to induce
LVOTO ≥50 mmHg. Pharmacological provocation with
Dobutamine is not recommended, as it is not
physiological and can be poorly tolerated .
The use of glyceryl trinitrate (GTN) is also an option
to unmask latent obstruction. Sublingual GTN is
administered with the patient supine and evidence of a
gradient should be assessed 5–10 min later in a standing
position, as the resulting reduction in preload may reveal
an intra-ventricular gradient.
Systolic Anterior Motion (SAM) of the mitral valve
Systolic anterior motion (SAM) of the mitral valve was
first described as a feature of HCM in the late 1960’s,
and, although initially thought to be diagnostic of
HCM, it has now been showed in many other
conditions (including patients with no other evidence of
cardiac disease). We know that ∼ 30–60 % of patients
with HCM present with SAM and, in 25–50 % of these,
left ventricular outflow tract obstruction (LVOTO) is
Marked systolic anterior motion of mitral valve
(with prolonged mitral-septal contact) is more
common in patients with diffuse and extensive
hypertrophy involving two to four left ventricular segments
than in patients with only one hypertrophied
The presence of SAM is then not pathognomonic for
HCM and may also occur with:
The haemodynamic consequences of SAM include the
prolongation of the ejection time and the reduction of
stroke volume. Coaptation of the mitral leaflets may be
disrupted resulting in mitral regurgitation.
The presence of SAM is documented using M-mode
echocardiography and is characterized by mid-systolic
notching of the aortic valve and contact of the anterior
mitral valve leaflet/chordae with the septum. Its severity can
be inferred from the duration of leaflet/chordal contact
with the septum, being mild if contact occurs for <10 % of
systole, and severe if >30 % of systole  (Fig. 3).
SAM of the mitral valve in hypertrophic
cardiomyopathy (HCM) has generally been explained by a Venturi
effect related to septal hypertrophy, causing outflow
tract narrowing and high velocities. Patients with HCM,
however, also have primary abnormalities of the mitral
apparatus, including anterior and inward or central
displacement of the papillary muscles, and leaflet
elongation. These findings have led to the hypothesis that
changes in the mitral apparatus can be a primary cause
of SAM by altering the forces acting on the mitral valve
and its ability to move in response to them. Despite
suggestive observations, however, it has never been
prospectively demonstrated that such changes can
actually cause SAM .
Massive septal hypertrophy
It is a rare HCM phenotype characterized by a septal
diastolic thickness ≥ 30 mm (Fig. 2B). It is usually
associated with a LVOTO but a RVOT obstruction may also
occur with the projection of the massively hypertrophied
interventricular septum into the right outflow tract
(Fig. 2C). This pattern is associated with an higher risk
of arrhythmic sudden death .
Spirito P . and colleagues have suggested that severe
left-ventricular hypertrophy (wall thickness ≥30 mm)
alone is sufficient to warrant ICD therapy .
Fig. 3 PLAX M-mode of SAM documented by the contact of the
anterior mitral valve leaflet/chordae with the septum
Elliot P . found that the excellent survival in the
40 % of patients with a wall thickness of 30 mm or more
and no other clinical risk factors shows that a wall
thickness of this magnitude cannot by itself be used as
justification for implantation of an ICD in patients with
hypertrophic cardiomyopathy. Nor does it support the
assertion that the absence of massive hypertrophy can
be used to reassure patients. This study does, however,
suggest that wall thickness may be a useful risk marker
when it is included in a broader clinical risk assessment
that takes into account other established risk factors
such as family history, symptoms, the presence of
arrhythmia, and exercise blood pressure responses.
Asymmetric posterior LV wall hypertrophy
In 1991, Lewis JF and Maron BJ  described a
subgroup of patients with hypertrophic cardiomyopathy
characterized by an unusual morphologic pattern in
which there is marked and often asymmetric thickening
of the posterior left ventricular free wall (Fig. 4H). The
left ventricular outflow tract is narrowed because of
anterior displacement of the mitral valve within the
small left ventricular cavity. Systolic anterior motion of
the mitral valve is usually present. The clinical profile of
these patients included outflow obstruction, severe and
early symptoms usually refractory to medical therapy
and requiring surgical approach.
Midventricular Obstructive Hypertrophic Cardiomyopathy
MOCH is a rare phenotype with a prevalence of 1 % of
all HCM cases .
It is characterized by an atypical intraluminal stenosis of
the left ventricle. Hypertrophy is detectable only in the mid
portion of the left ventricle and involves the papillary
muscles, resulting in a systolic obstruction of the mid-ventricle
This pattern shows smaller LV diastolic volumes and a
muscular apposition of the septum and LV free wall able
to produce a pressure gradient (PG) . The
continuouswave Doppler echocardiography reveals PG with
abnormally high flow velocities across the obstruction.
Usually a midventricular PG toward the base occurs in
systole whereas a PG toward the apex is detectable in
diastole . However there may be a paradoxical jet
flow from the apex toward the base during the left
ventricular isovolumetric relaxation and the early diastolic
filling period and also a jet flow toward the apex during
Diastolic function is usually severely impaired for this
phenotype and septal E/e’ is higher in severely
symptomatic patients indicating higher estimated LV filling pressure.
The ‘hourglass’ shaped left ventricle consists of two
different chambers: the proximal and the distal chamber.
Fig. 4 e 3DTTE imaging of LV apical aneurysm (from ref. 36). f TTE imaging of non massive apical HCM picture. g TTE imaging of massive apical
HCM characterized by a systolic cavity obliteration. h Asymmetric LV posterior wall hypertrophy (from ref. 59)
The proximal chamber is an enlarged cavity, with thinned
walls and an inferior-basal septum bulging (Fig. 2D). The
distal chamber usually is an apical aneurism.
This form is present in the Syed’s classification .
Left ventricle apical aneurism
LV apical aneurysm may be defined as a discrete
thinwalled dyskinetic or akinetic segment of the most distal
portion of the chamber with a relatively wide
communication to the LV cavity . The incidence of concealed
apical aneurysm with mid-ventricular cavity obliteration
is approximately 1–2 % of all HCM cases . The
echocardiographic assessment of the aneurism should
include: size (max length or width), dyskinetic/akinetic
pattern, thin rims and transmural (and often more
extensive) myocardial scarring identified by late gadolinium
enhancement on CMR. Specific complications are more
common in association with large or medium rather than
with small aneurysms and they consist of: sudden death,
LV systolic dysfunction, progressive heart failure
symptoms, embolic stroke by LV apical thrombus [16, 17–52].
Diagnostic accuracy for LV apical aneurysm is 57 % for
echocardiography (more for medium/large in just 2
dimensions provided by 2D-aneurism), 80 % for
echocardiography with the use of a contrast agents (Fig. 4E) and
100 % for CMR .
3D-TTE indeed, can provide a more comprehensive
assessment of the apical aneurysm as compared to
2DTTE, which provides at any given time only a thin slice of
a structure being studied . With 3D-TTE, the entire
extent of the aneurysm can be contained in the 3D dataset
so that it could be more fully studied using multiple cross
sections at any desired angulation. Measurements in 3
dimensions, including the azimuthal dimension (z axis), allow
to assess the volume of the aneurysm, that it is not possible
to measure in just 2 dimensions provided by 2D-TTE. This
would allow a more accurate monitoring of the progression
of the aneurysm over time. A more comprehensive
assessment of thrombus is also possible  (Fig. 4E).
RVOT obstruction in MOHC
HCM should be considered as an extensive process
involving both the left and the right sides of the heart.
As previously stated, RVOT obstruction may coexist
with massive hypertrophy and LVOTO but it could also
occasionally be isolated [16, 54–56]. It may be present also
in MOHC forms .
Isolated apical HCM (Helmy’s pattern 4)  is a rare
variant in the non-Japanese population ranging from
1 % to 2 % [6, 57].
It is a rare phenotype in which the hypertrophy is
confined to the LV apex with an apical wall thickness
≥15 mm and a ratio of maximal apical to posterior wall
thickness ≥1.5 on 2D-echo .
This form is reported in the Syed’s classification .
There are some special features of HCM with apex
involvement: first, when the apex is involved, ECG
evidence of LV hypertrophy is virtually always
detectable. In Helmy’s study it was present in 100 % of
patients with patterns 3 and 4 .
Non massive apical HCM
Apical involvement (with a end-diastolic thickness <
30 mm) may be in combination with other LV segments’
hypertrophy (Helmy’s pattern 3 ).
This form is generally judged to have a favourable
outlook, with a very low risk of developing obstruction
or apical aneurysm (Fig. 4F).
Patients usually are asymptomatic and the diagnosis is
made following routine ECG .
Massive apical HCM
The massive hypertrophy of the LV apex is known as
It is characterized by a systolic cavity obliteration at
TTE assessment  (Fig. 4G).
It is associated to the risk of aneurism formation
probably because of a micro-vascular myocardial
ischemia causing myocardial scarring. In a previous study,
32 % of patients with apical aneurysm had distal
hypertrophy alone .
Mild hypertrophy phenotypes
The categories of patients with mild hypertrophy and of
patients with non-diagnostic morphological
abnormalities (ie. abnormal myocardial strain, systolic anterior
motion or elongation of the mitral valve leaflets and
abnormal papillary muscles) pose specific and often
difficult clinical problems. These features can represent a
HCM fenotype that although apparently is a mild form
of the disease but in fact it is not without risks.
In 2009, Maron MS et al. , using Cardiac Magnetic
Resonance (CMR), concluded that patterns of LV
hypertrophy are usually not extensive in HCM, involving <50 %
of the chamber in about one-half the patients, and are
particularly limited in extent in an important minority.
Contiguous portions of anterior free wall and septum
constituted the predominant region of wall thickening,
with implications for clinical diagnosis .
Coppini R et al.  noted several differences in the
echocardiographic evaluation between thick and
thinfilament mutation forms.
Patients with thin–filament mutations had lesser
maximal wall thickness values than thick filament and
more often show atypically distributed hypertrophy
including concentric and apical patterns with the lower
prevalence of resting LVOT obstruction. Thin–filament
patients have smaller LV mass index and lower LVEF(%).
Patients with thick-filament HCM presented a classic
asymmetric LVH involving the basal septum and anterior
Coppini R  showed a correlation between
thinfilament gene mutation and clinical phenotype/outcome.
In adult HCM patients, thin-filament mutations are
associated with increased risk of LV disfunction and heart
failure compared with thick-filament disease, whereas
arrhytmic risk in both is comparable. Triphasic LV filling
is particularly common in thin-filament HCM, reflecting
profound diastolic dysfunction.
Levine RA  demonstrated that that primary
structural changes in the mitral valve and its supporting
structures and their relation to the outflow tract, as
observed in patients with HCM, can cause SAM in the
absence of significant septal hypertrophy.
SAM appears to be determined by two factors: the ability
of the leaflets to move anteriorly (papillary muscle
displacement causing slack and increased residual leaflet length)
and their interposition into the outflow stream by anterior
displacement, determining the direction of this motion.
Leaflet slack can permit prolapse (excess superior and
posterior motion) or SAM (excess superior and anterior
motion), depending on how the papillary muscles shift the
orientation of the leaflets relative to the outflow. All these
findings can be assessed by echocardiography .
The impact of different echo-patterns of
hypertrophy on clinical course and prognosis
The main questions of this article are the following: 1)
why is it important to know the type of hypertrophy? 2)
What is the clinical impact or prognostic implication of
different types of hypertrophy?
The impact of different patterns of hypertrophy on
clinical course/prognosis of HCM patients has generated
We reported some cases in which the
echocardiographic pattern may impact significantly on the clinical
course and prognosis.
1. The clinical impact and prognosis of the ASH is
related to LVOTO development, especially when a
SAM of mitral valve leaflets is present. The LVOTO
increases the risk of evolution to the end stage
echo-pattern  when small cavity regresses and
evolves into a picture similar to that of a dilated
cardiomyopathy, with decreased LV systolic function
and a dilated left ventricle. Interventricular and
intraventricular delays are commonly present in
patients with ASH-HCM, despite the absence of
conduction abnormalities on the electrocardiogram,
and appear to correlate to the degree of septal LVH
and the presence of LV outflow obstruction. A study of
123 patients with HCM found that an intraventricular
delay ≥45 ms predicted an increased risk for ventricular
tachyarrhythmias an sudden cardiac death at 5-years
follow-up (85.5 % sensitivity; 90.4 % specificity; positive
predictive value: 66.9 %; negative predictive value:
96.7 %; test accuracy: 88.8 %) .
The treatment of this form is aimed to relieve the
subaortic PG, decreasing symptoms and improving
2. The massive hypertrophy pattern, with a wall thickness
≥30 mm, may be associated with an higher risk of
sudden death when it is considered together with other
risk factors [48, 28]. Recently, O’Mahony C proposed a
novel clinical risk prediction model for sudden cardiac
death in hypertrophic cardiomyopathy, including the
magnitude of hypertrophy .
3. The clinical impact of asymmetrical LV posterior
wall hypertrophy is related to outflow obstruction
often producing severe and early symptoms usually
refractory to medical therapy and requiring surgical
4. The clinical impact and prognosis of MOHC form
is related to the specific complications due to apical
aneurysm formation. They are more common in
association with large or medium rather than with
small aneurysms and consist of: sudden death, LV
systolic dysfunction, progressive heart failure
symptoms, embolic stroke by LV apical thrombus
[16, 17, 51–53].
5. Non massive apical form has a modest clinical impact and a favorable prognosis while the massive form is associated to the risk of aneurism formation .
6. Mild and atypically distribuited hypertrophy (usually due to thin-filament mutations) are associated with an increased risk of LV disfunction and heart failure compared with thick-filament disease .
It is very important to know and recognize particular
echo-features of each HCM phenotype in order to plan
the correct treatment and to improve patients’ quality of
life and survival.
Echocardiography is still the principal tool for the
diagnosis, prognostic assessment and clinical management of
HCM. New techniques, such as 3D-TTE and strains
curves analysis, are improving their sensibility and
specificity. Two-dimensional strain is a simple, rapid, and
reproducible method to early detection of abnormalities in
patients with HCM and apparently normal left ventricular
In this review-article we demonstrate that
echocardiographic pattern of the different phenotypes impacts
significantly on the clinical course and prognosis of the
HCM, hypertrophic cardiomyopathy; HOCM, hypertrophic obstructive
cardiomyopathy; HNCM, hypertrophic non-obstructive cardiomyopathy; LVH,
left ventricle hypertrophy; ECG, electrocardiogram; CMR, cardiac magnetic
resonance; 2D, two-dimensional; LV, left ventricle; NYHA, New York heart
association; LA, left atrium; LVOT, left ventricle outflow tract; SAM, systolic
anterior movement; MVO, mid-ventricular obstruction; 3DE, 3-dimensional
echocardiography; TDI, tissue doppler imaging; STE, speckle tracking
ecocardiography; GLS, global longitudinal strain; EF, ejection fraction; TTE,
trans-thoracic echocardiography; TEE, trans-esophageal echocardiography;
ESC, European society of cardiology; PW, pulsed wave; LAD, left anterior
descending; IRT, isovolumetric relaxation time; DT, deceleration time; RA, right
atrium; ASE, American society of echocardiography; LAVi, left atrial volume
indexed; ASH, asimmetrical septal hypertrophy; LVOTO, left ventricle outflow
tract obstruction; SCD, sudden cardiac death; GTN, glyceryl trinitrate; RVOT,
right ventricle outflow tract; ICD, implantable cardioverter defibrillator; MOHC,
midventricular obstruction hypertrophic cardiomyopathy; PG, pressure gradient;
3D-TTE, three dimensional trans-thoracic echocardiography; 2D-TTE, two
dimensional trans-thoracic echocardiography; 3D, three dimensional; LVEF,
left ventricle ejection fraction
Figures processing: Andrea Giovanni Parato.
VA analyzed the published works on phenotypes classifications. FS was a
major contributor in writing the manuscript. SM analyzed the published
works on echocardiography applied to HCM. AZ collected the figures and
tabs. MM and PP worked on the references searching and english form.
All authors read and approved the final manuscript.
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