The concept of the hereditary nature of HCMP is universally recognized. IN
literature, the term “family
hypertrophic cardiomyopathy. ” Most (at least 60%) of all
cases of the disease are heritable, with the main type being
inheritance is autosomal dominant at varying degrees
penetrance and with a 50% risk of transmission to descendants [13, 14, 16].
The remaining cases are due to denovo mutations, but seemingly sporadic
cases when the patient has no relatives who have HCMP or have
myocardial hypertrophy, may appear due to incomplete
penetrance of the disease in parents or, less commonly, with
autosomal recessive inheritance.
HCMP is a genetically heterogeneous disease, the cause
which are about 1500 mutations described to date
several genes encoding proteins of the heart sarcomere and some
non-sarcomeric proteins [13, 14, 15, 16]. A typical picture of the disease
regarded as genetically determined heart disease
To date, 11 protein components are known that perform
contractile, structural or regulatory functions whose defects
observed with HCMP (table. 1). Moreover, in each gene there are many defects
may be the cause of the disease (polygenic multiallelic
Table 1. The main genetic determinants of HCMP
65-85% of all mutations
About 15 – 20% of all mutations
beta myosin heavy chain
myosin binding protein C
– essential and regulatory myosin light chain
– cardiac troponin I
– alpha myosin heavy chain
In general, in patients with mutations in sarcomeric protein genes, the disease
manifests earlier, and a higher frequency of marital
accumulation of HCMP and sudden cardiac death [17, 18]. They also
there is a tendency to more pronounced hypertrophy, microvascular
dysfunction and myocardial fibrosis .
Some mutations in genes
sarcomeric proteins may have a more serious prognosis
[20, 21, 22]. Up to 5% of individuals are carriers of several mutations in
sarcomeric protein genes, and they tend to have earlier
manifestations and a more severe phenotype, and prognosis .
The genetic defects described in HCMP are characterized by high
population specificity, varying degrees of penetrance,
the severity of morphological and clinical manifestations. To the most
Common causes of disease in Western Europe and the USA include
mutations in the heavy chain genes of beta-myosin and myosin-binding protein C,
in each population, the contribution of various genes to the incidence of
The Russian population is characterized by significant national and
genetic heterogeneity. Its formation was influenced
various ethnogenetic processes occurring on the vast
geographic space for centuries including
numerous migrations, mixing, and integration.
Mutations in the b-MHC gene
play an important role in the etiology of HCM in Russian patients, but this
far from the only gene responsible for the development of the disease. For
determining the strategy for DNA diagnosis of HCM in Russia is necessary
identify the role of other candidate genes and identify more
unknown loci etiologically associated with the development of the disease.
5 to 10% of adult cases develop as a result of others
diseases, including hereditary metabolic and neuromuscular
diseases, chromosomal abnormalities and genetic syndromes [23, 24].
A number of hereditary metabolic disorders and diseases of accumulation,
usually manifesting in childhood and young adulthood
imitate the phenotype and clinical picture of HCMP.
conditions predominantly having systemic manifestations are considered
as a syndrome, including signs of myocardial hypertrophy. In this
the group includes mitochondrial disorders, hereditary
metabolic diseases: Anderson-Fabry disease, glycogenosis;
diseases caused by mutations in genes encoding regulatory
2 AMP-activated protein kinases (PRKAG2) or X-linked
lysosome-associated membrane protein encoding gene (LAMP2,
Danone’s disease); malformation syndromes: LEOPARD, Noonan syndromes,
Church; neuromuscular diseases (Friedreich’s ataxia) [25, 26, 27,
28, 29]. Some patients suffer from non-genetic diseases,
which can mimic hereditary forms, for example, amyloidosis
hearts [30, 31].
In addition, each of the pathologies has its own characteristics. So,
a disease associated with a mutation in the PRKAG2 gene is often accompanied by
Wolf-Parkinson-White Syndrome (WPW) .Application of terms such as
“Mitochondrial HCMP” is recognized as unacceptable, preferred
is the wording of the diagnosis: for example, “Noonan syndrome with LVH.”
Long-term use of certain medications (anabolic
steroids, tacrolimus, hydroxychloroquine) may cause LVH, although
in this case, a thickening of the LV wall is rarely observed? 1,5 cm [32, 33].
Genetic defect realized under the influence and in the conditions
environment, leads to the formation of the main substrate of the disease,
HCMP – severe myocardial hypertrophy with specific
The pathophysiology of HCMP is determined by a complex set of interconnected
links, the main of which are: outflow tract obstruction
left ventricle (VLH), diastolic dysfunction (DD), mitral
regurgitation (MR), myocardial ischemia, electrophysiological disorders and
arrhythmias, features of autonomic regulation of blood circulation (Fig.
The hypercontractile state of the myocardium is characteristic in normal or
a reduced LV cavity up to its obliteration into the systole.
intracardiac hemodynamics with HCMP are very diverse and determine
a wide range of clinical manifestations: shortness of breath, pain,
arrhythmias, pre- and syncope, high likelihood of SCD,
decreased exercise tolerance other manifestations.
1.2.2. Left ventricular outflow tract obstruction
Depending on the presence or absence of a systolic gradient
pressure in the cavity of the left ventricle, HCMP divided into obstructive and
non-obstructive, which determines the clinical picture and has an important
practical value when choosing treatment tactics [3, 4].
According to the severity of the gradient of obstruction (Gr. D), three
hemodynamic subgroups: gradient at rest? 30 mmHg. Art. in
rest (the so-called basal obstruction); labile obstruction,
characterized by significant spontaneous fluctuations
intraventricular gr. D for no apparent reason; latent obstruction,
which is called only when loaded and provocative
pharmacological tests (in particular, by inhalation of amyl nitrite, when taken
nitrates or intravenous administration of isoproterenol).
VTLZ obstruction occurs due to anterior systolic
the movement of the cusps of the mitral valve and systolic contact of the cusps with
MJP [34, 35]. Mechanical resistance in VTLZh creates the conditions for
increased ejection rate during early systolic exile
blood from the left ventricle, anterior systolic movement of the anterior sash
mitral valve (PSD MK) and its mid-systolic contact with
MJP resulting from a suction effect or phenomenon
Also, cutting, mis-oriented papillary
the muscles pull the mitral valve, the valves of which also have
excess length, towards MZHP that leads to reduction already
narrowed VTLZH and causes or aggravates its obstruction. Inevitable
a consequence of the displacement of the mitral leaflet is an overload of the LP and MR,
the severity of which is directly proportional to the severity of obstruction.
VTLH obstruction is an additional hemodynamic cause
development of drug dilatation.
VTLZ obstruction leads to complex cardiac abnormalities
hemodynamics, including an increase in systolic pressure in the cavity
ventricle, lengthening the period of relaxation of the chambers, increase
diastolic pressure in the left ventricle, MR, myocardial ischemia, decrease
cardiac output. The obstruction of VTLZH with GKMP is dynamic
nature, varies depending on the degree of load and contractility
myocardium, ventricular volume, state of afterload.
pressure in VTLZH is noted during physical exertion, an increase in strength
heart rate and prescribing drugs with positive inotropic
effect when conducting a Valsalva test. Severity of obstruction
decreases with an increase in LV preload (increase in volume
circulating blood, raising the lower limbs), with a decrease
myocardial contractile function and the appointment of drugs with a negative
The contact of the anterior mitral valve leaflet with MJP,
observed in almost all patients with obstructive HCMP, leads to
violation of her movement. As a result of chronic trauma of the anterior sash
in contact with MJP in diastole in patients with HCM
compaction and thickening of it, as well as the corresponding endocardial
In addition to subaortic obstruction, in patients with HCMP with hypertrophy,
mainly in the middle third of the MJP described middle ventricular
obstruction, when a muscle-type constriction is created between the septum and
back papillary muscle. Obstructive type of disease with severe
intraventricular pressure gradient leads to increased stress
LV walls, LV myocardial ischemia, to cardiomyocyte death and development
Subaortic gradient and associated elevation
intraventricular pressure reflect true mechanical
VTLH resistance and are pathophysiologically and prognostically
important factors in patients with HCMP.
- Causes of Hypertrophic Cardiomyopathy
- 1.3. Ep >Currently observed ubiquitous increase in the number of registered cases of this pathology due to introducing modern methods into practice diagnosis, and probably in connection with a true increase in the number of patients with HCMP. Various studies in North America, Europe, Asia and Africa give the frequency of unexplained LV hypertrophy among adults [45, 46, 47].
Causes of Hypertrophic Cardiomyopathy
Among the causes of HCMP, doctors call the family hereditary factor. Defective inherited genes can encode the synthesis of myocardial contractile protein. There is a chance of gene mutation due to external influences. Other possible causes of hypertrophic cardiomyopathy are:
- hypertensive disorders;
- diseases in the lungs;
- ischemic disease;
- severe stress;
- biventricular heart failure;
- rhythm disturbance;
- excessive physical exertion;
- age after 20 years.
The pathological condition is most often provoked by gene mutations. They lead to the fact that the heart muscle abnormally thickens. Also, in patients, the position of muscle fibers in the organ changes. Violation of the synchronous contraction of cells occurs, due to which heart rhythm failures develop.
Hypertension, ischemia, congenital malformations and other pathologies that usually cause such problems are not related to the development of hypertrophy in the left ventricle.
For the development of this disease, there are 2 reasons:
- Hereditary transmission of the disease. As a result, the genes responsible for coding myocardial contractile proteins mutate.
- Acquired. In this case, hypertrophic cardiomyopathy is caused due to spontaneous gene mutation. Such a mutation can occur under the influence of both external and internal factors. Unfortunately, so far medicine is not able to accurately determine the mechanism of the development of the disease, as well as factors influencing it. Which makes it difficult to correctly predict.
Hypertrophic cardiomyopathy is a heart disease, the main sign of which is a thickening of the ventricular wall. In most diagnosed cases, the left ventricle suffers. In medical practice, a thickening of the myocardium of more than 1,5 cm is considered the main symptom of the disease. Especially if this occurs against the background of the impossibility of relaxing the walls of the ventricles.
Given that this disease passes almost without symptoms, and it is possible to predict its development, based on the person’s heredity, it makes sense to undergo a preventive examination. Especially if a person has or had relatives with heart disease. Thus, you can manage to start treatment in a timely manner.
1.3. Ep >Currently observed
ubiquitous increase in the number of registered
cases of this pathology due to
introducing modern methods into practice
diagnosis, and probably in connection with
a true increase in the number of patients with HCMP. Various
studies in North America, Europe, Asia and Africa
give the frequency of unexplained LV hypertrophy among adults [45, 46,
Many indicate an age-dependent pattern of occurrence,
which is significantly lower among patients under the age of 25 years .
According to recent studies, the prevalence of typical
the phenotype of the disease in the general population in different countries of the world is
higher than previously thought, and ranges from 0,3 to 0,5 per 100000
per year [48, 49, 50].
So in the US, at least 600 people
have signs of this pathology. Despite genetic heterogeneity
different populations of HCMP are equally often detected in cohorts
the population of different countries and continents, of different races [48, 51]. At
lack of domestic epidemiological studies can
suggest at least 300 patients with HCM in Russia.
Depending on the localization of the pathological process, hypertrophy can be observed in the left and right ventricle. But most often the first variant of the course of the disease is revealed.
Left ventricular lesion is asymmetric. This is a more common pathology that affects the entire ventricular septum or its basal parts. This type of hypertrophy can be observed in the apex of the heart, posterior or anterolateral wall. A symmetrical shape is also found, but it is rare.
- hypertrophic obstructive cardiomyopathy;
- hypertrophic non-obstructive cardiomyopathy.
The development of the disease occurs in several stages:
- Н and the first myocardium is moderately thickened no more than 2 cm.
- The middle stage is characterized by the appearance of discomfort in the heart during physical exertion. This is due to a 25 mm thickening.
- The third stage is accompanied by attacks of angina pectoris, shortness of breath, an increase in muscle more than 2,5 cm.
- In the fourth stage, blood circulation is significantly impaired, there is a high probability of sudden death.
Hypertrophic changes in the heart muscle can equally occur in both men and women. The disease is most often inherited. Half of the people whose immediate relatives suffered from the problem observe the same pathological processes.
Today there is no unified classification of HCMP.
In this case, the family (family history) and sporadic forms of the disease are distinguished.
The morphological principle suggests a separation depending on the location and severity of hypertrophy (Table 2) .
Table 2. Classification of HCMP depending on the location of hypertrophy (ED Wigle)
I. LV hypertrophy:
A) Asymmetric hypertrophy, including:
– apical (apical) hypertrophy
– hypertrophy of the free lateral or posterior part of the breast
B) Symmetric (concentric) hypertrophy
II. Right ventricular hypertrophy (rarely in combination with LV hypertrophy)
Possible options: hypertrophy of the basal, anterior, anterolateral, posterior part of the MJP, diffuse hypertrophy of the MJP.
– obstructive (obstructive HCMP): pressure gradient in VTLZh
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