Genetics,
Clinical and Pathophysiology
Apical hypertrophic cardiomyopathy (ApHCM) was first described in Japan by Sakamoto et al.
as a novel cardiac condition characterized by an ace-of-spades configuration of the left ventricular cavity,
apical hypertrophy,
and giant negative T waves.
ApHCM is seen as a variant of global hypertrophic cardiomyopathy in which act particular genetic factors.
It presents often a congenital autosomal dominant aetiology.
Recent studies suggest the association with genetic mutations in ACTC1,
TPM1,
MYBPC3 and MYH7.
Symptoms include chest pain,
palpitations,
dyspnea,
light-headedness and syncope,
that usually appear in advanced stages,
when it has already established a situation of failure.
In fact the structural modifications (fibers disarray,
fibrosis) lead to an alteration in relaxation,
until the diastolic dysfunction,
with increase the pressure in the ventricle,
in the atria and in the pulmonary circulation,
with the onset of dyspnea.
The increase in pressure and atrial dimensions can lead to atrial fibrillation,
which predisposes to stroke.
The chest pain of ApHCM is caused by myocardial ischemia due both to increased oxygen consumption of myocardial hypertrophy and to myocardial hypertrophic pressure on vessels,
reducing the flow.
Unlike the other forms,
LV outflow tract obstruction and mitral regurgitation are rare,
but we can find other features as midventricular obstruction with cavity obliteration and apical aneurysm formation.
Diagnosis
According to more recent guidelines we can diagnosis of HCM in presence of maximal LV wall thickness ≥15 mm,
in the absence of other causes that can determine myocardial hypertrophy (arterial hypertension,
aortic stenosis).
The wall thickness is considered borderline when it is between 13 to 14 mm.
Actually,
any wall thickening could be compatible with HCM,
in fact many of HCM’s cases have family members with sarcomeric mutation,
but without clinical manifestation (“genotype positive/phenotype negative”).
In addition,
about one third of patients have wall thickening in a small portion of the left ventricle and normal LV mass.
In 1981,
BJ Maron published a four types classification,
and one of this is LV apical hypertrophy.
Hypertrophy confined predominantly to the LV apex (only the apical 4 segments and the apical cap according to the 17-segment guidelines of the American Society of Echocardiography) with maximal apical wall thickness of ≥15 mm or a ratio of maximal apical to posterior wall thickness ≥1.3 at end-diastole,
in absence of systemic hypertension,
confirmed the diagnosis of ApHCM.
Typically,
echocardiography is the first imaging modality used in the evaluation of cardiomyopathy.
Though it is few accurate in the measurement of wall thickening and in the identification of small focal areas of hypertrophy,
because of suboptimal imaging from poor acoustic windows,
or when hypertrophy is concerning to regions of the LV myocardium not well visualized by echocardiography,
particularly at the apex.
Thus CMR,
with a native better contrast between the blood pool and myocardium, allows a more precise evaluation of LV wall thickness,
also in the familiar screening,
either to do more accurate diagnosis.
In approximately 60% of patients who are subjected to genetic testing,
this is negative or ambiguous.
In these cases,
CMR can provide other features,
as myocardial crypt,
elongated mitral valve leaflets,
expanded extracellular space with T1 mapping and LGE,
identifying those subjects to follow over time,
which may be at risk of the disease's clinical conversion.
We can distinguish three types of ApHCM:
- Pure form,
exclusive apical involvement;
- Mixed form,
the thickening affects predominantly the apex with extension to the contiguous segments,
such as midventricular or base;
- Form with midventricular hypertrophy,
hypertrophy affects the apex and the non-contiguous segments with predominance of midventricular.
All these forms may develop apical aneurysms (Figure 6).
Left Ventricular Apical Aneurysms
Patient with ApHCM may developed an apical aneurysm in 10-20% of the case.
For some Authors it is considered part of the natural history of the disease,
as the chronic increase of filling pressure intra-chamber can cause subsidence of apical wall,
particularly in the apex.
In fact,
patients with the midventricular obstruction variant of ApHCM are significantly more likely to develop an apical aneurysm,
compared to those without an intracavitary gradient.
Before the application of CMR to HCM,
this group of patients had been underdiagnosed,
because the echocardiography not reliably small or moderate sized aneurysms.
Some studies have shown association with increased cardiovascular mortality.
Contrast-enhanced CMR has demonstrated that the aneurysm rim is composed predominantly of fibrosis that extends into the septum and free wall.
It represents a focus for ventricular tachycardia or ventricular fibrillation with increased risk of arrhythmic sudden death (SDA).
In addition,
aneurysm-level flow alterations could favour the LV thrombus formation,
also with the risk of thromboembolic stroke.
For this reason,
the patients with this phenotype may raise important management implications with consideration for implantable cardioverter defibrillator (ICD) therapy,
as well as systemic anticoagulation for stroke prevention.
Differential diagnosis
Athlete’s heart:
An important condition to differentiate is hypertrophy due to cardiomyopathy from that due to physical training.
Some athletes may suffer from hypertrophic cardiomyopathy,
and this can makes harder the diagnosis.
Therefore,
the CMR can help to distinguishes these conditions.
Usually,
the finding of focal pattern of hypertrophy is typical of HCM.
Also,
the physical deconditioning is another factor to be taken into account.
After a period of systemic deconditioning,
the wall thickness regresses more than 2 mm supports a diagnosis of athlete’s heart,
while the persistence of wall thickening despite deconditioning supports a diagnosis of HCM.
The analysis of LGE can add useful elements,
in fact areas of LGE are features which are present in half past of patients with HCM,
but not in athlete’s heart; so,
the presence of LGE in athletes favours a diagnosis of HCM,
while the absence not exclude HCM.
Arterial hypertension:
CMR can help in differentiation between HCM and hypertrophy due by arterial hypertension.
The pattern of hypertrophy after a prolonged period of systemic hypertension is more concentric type,
instead,
in HCM is more commonly asymmetric.
Furthermore,
the regression of hypertrophy after treatment with antihypertensive favours diagnosis of hypertensive cardiomyopathy.
Another feature as LV outflow obstruction due to typical SAM,
support diagnosis of HCM,
rarely seen in hypertensive cardiomyopathy.
Risk Stratification for SDA
HCM represent a pathological entity at risk to develop adverse events as sudden death.
Fortunately,
it is a condition that occurs in a few patients,
(annual incidence for cardiovascular death of 1–2%,
with SCD,
heart failure and thromboembolism),
but it is important to assess a prevention strategy.
Patients with ApHCM was seen to have a lower risk of complications than other phenotypes,
however the presence of apical aneurysm,
with scarring,
favours the occurrence of arrhythmias such as sustained ventricular tachycardia or ventricular fibrillation that may result in SDA.
Risk stratification for SDA is much important in the management of HCM,
in order to select the patients who should implant an implantable cardioverter-defibrillators (ICD).
The ICD is the only therapeutic measure allowing to prevent SDA.
However,
efficacy of the ICD strategy for SD prevention is highly dependent on the selection of patients who really can benefit of this measure.
Trials have shown that implantation of an ICD for primary and secondary prophylaxis can reduce mortality.
In according to the recent European Society of Cardiology (ESC) guidelines and ACCF/AHA Guideline,
concerning the risk stratification for sudden death (SD) there are several risk factors taken into account,
and some are different from a guideline to another.
Among the risk factors we have age,
maximum left ventricular wall thickness,
left atrial diameter,
left ventricular outflow tract obstruction,
and other factors as the LGE extension and presence of apical aneurysms.
These are all factors where the CMR play a key-role in the right risk stratification,
particularly on the LGE extension.
In patients with HCM and evidence of LGE on CMR,
there are increased rates of non-sustained ventricular tachycardia on ambulatory Holter monitoring compared with patients without LGE,
raising the concept that LGE reflecting myocardial fibrosis,
which represents a substrate for generation of malignant ventricular arrhythmias.
This can be explained if we consider that in the patient with HCM,
there is a chronic microvascular ischemia,
with progressive loss of myocytes that are replaced by fibrous tissue.
However,
in the guidelines the LGE is not considered as an important risk factor,
because an association with SDA didn’t show (more than 50% of individuals with HCM have areas of LGE).
Thus,
recent studies has seen a prognostic role by percentage of extension of the areas.
In fact,
an extension of LGE ≥15% of LV mass demonstrate a 2-fold increase in adverse event risk in those patients otherwise considered to be at lower risk,
with an estimated likelihood for adverse events of 6% at 5 years.
The relative risk increases of 40% every 10% extra of LGE extension.
Definitely,
the LGE by CMR is an important parameter to consider,
especially in cases of doubt.
Strain analyses
In recent years,
the analysis of myocardial strain is becoming a key role in the representation of cardiac function,
better than ejection fraction,
that is generally predictive of outcomes in heart failure.
Most patients with HCM have normal or hyperdynamic regional and global systolic function,
but after the advent of strain analysis software,
systolic and diastolic function abnormalities have proven that they are an expression of myofiber disarray,
fibrosis,
and perturbations in cellular physiology/bioenergetics.
Decreased myocardial strain is known to be associated with extensive myocardial fibrosis.
Echocardiography speckle tracking (TSE) is a method already validated.
Several studies have shown the decreased of strain in hypertrophic segments,
particularly the reduction of global longitudinal strain (GLS),
the most robust and reproducible of the LV deformation parameters,
is associated with outcome in HCM.
CMR has emerged as the reference standard for the evaluation of biventricular morphology and function.
Recently,
CMR-feature tracking has been validated how method against traditional myocardial tagging method.
There are still few studies about the use of the tracking feature in HCM.
Recently,
Smith et all,
have demonstrated that feature tracking on CMR images can detect global and segmental differences in a population of children,
adolescents,
and young adults with HCM.
They have encountered patients with phenotypic HCM had decreased GLS compared with controls while circumferential and radial strains did not differ.
In addition,
segments with hypertrophy had reduced radial and longitudinal strains compared with controls,
whereas segments without hypertrophy had greater radial and circumferential strains compared with controls.
According to these data,
in our case we have seen reduction specially of global longitudinal strain (GLS),
to a lesser extent global circumferential strain (GCS),
while the global radial strain (GRS) appared normal.
During segmental analysis we found low values in hypertrophic segment in the apex,
and high values of radial strain in basal not hypertrophied segments.