name: Hypertrophic Cardiomyopathy
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-02-17T21:53:14Z'
synonyms:
- HCM
category: Complex
parents:
- Cardiovascular Disease
- Genetic Disorder
has_subtypes:
- name: Obstructive HCM
description: The thickened heart muscle obstructs blood flow out of the left
ventricle.
evidence:
- reference: PMID:38368032
supports: PARTIAL
snippet: Obstruction to left ventricular outflow occurs in approximately 60%
of patients.
explanation: The provided literature states that obstruction occurs in
approximately 60% of HCM patients, indicating that not all HCM cases are
obstructive. Thus, the statement that the thickened heart muscle obstructs
blood flow out of the left ventricle can be recognized as a subtype known
as obstructive HCM but does not apply to all HCM patients.
- reference: PMID:35555885
supports: PARTIAL
snippet: Left ventricular (LV) wall thickening, or LV hypertrophy (LVH), is
common and occurs in diverse conditions including hypertrophic
cardiomyopathy (HCM)...
explanation: The literature indicates that LV hypertrophy (LVH) occurs in
HCM alongside various conditions. However, it characterizes different
forms, not solely obstructive HCM, thereby acknowledging the partial
correctness of the subtype Obstructive HCM but not exclusively.
- reference: PMID:20560010
supports: SUPPORT
snippet: Left ventricular outflow tract obstruction (LVOTO) is one of the
defining features of hypertrophic cardiomyopathy (HCM)...
explanation: This specific literature confirms that left ventricular outflow
tract obstruction (LVOTO) is a defining feature of HCM, thereby supporting
the statement regarding the thickened heart muscle obstructing blood flow
out of the left ventricle.
- name: Non-Obstructive HCM
description: The heart muscle is thickened, but blood flow is not
significantly obstructed.
evidence:
- reference: PMID:34126727
supports: SUPPORT
snippet: Patients with non-obstructive HCM... According to the
characteristics of cardiac morphology and function shown by
echocardiography, the patients were divided into common type, dilated
type, restricted type and reduced ejection fraction type.
explanation: The reference describes non-obstructive hypertrophic
cardiomyopathy (HCM) as a subtype of HCM characterized by different
clinical subtypes based on cardiac morphology and function, supporting the
statement that non-obstructive HCM involves thickened heart muscle without
significant obstruction of blood flow.
- reference: PMID:35555885
supports: SUPPORT
snippet: Left ventricular (LV) wall thickening, or LV hypertrophy (LVH), is
common and occurs in diverse conditions including hypertrophic
cardiomyopathy (HCM)...Although various diseases share LV wall thickening
as a common feature, the histologic changes that underscore each disease
are distinct.
explanation: This reference supports the statement by acknowledging that
hypertrophic cardiomyopathy can include conditions with thickened heart
muscle where the histological features differ, indicating diverse subtypes
including non-obstructive forms.
prevalence:
- population: General Population
percentage: 0.2
evidence:
- reference: PMID:25814232
supports: PARTIAL
snippet: For the past 20 years, most data have supported the occurrence of
HCM at about 1 in 500.
explanation: 1 in 500 translates to 0.2%, which supports the statement.
However, the statement could be conflicting with the suggestion that HCM
might be more common than previously estimated.
- reference: PMID:34969871
supports: PARTIAL
snippet: Between 2010 and 2018, prevalence increased for ARVC by 180% and
HCM by 9%.
explanation: While the statement of HCM prevalence being 0.2% is
approximately correct, recognition of HCM prevalence seems to have
increased, indicating it could be more common now.
- reference: PMID:33623987
supports: PARTIAL
snippet: Currently, available estimates of prevalence and incidence of CMPs
are based on clinical data, collected with a wide variability in
population-source, and before the genetic testing evolved as a standard
diagnostic tool.
explanation: Prevalence estimates for HCM might vary based on the population
and advances in diagnostic tools, suggesting that 0.2% could be an
estimate but with existing variability.
progression:
- phase: Onset
evidence:
- reference: PMID:25897040
supports: SUPPORT
snippet: Myocardial fibrosis in HCM is a progressive phenomenon. Non-apical
phenotype and a higher LGE extent at CMR-1 are both associated with
greater LGE progression.
explanation: The literature supports that hypertrophic cardiomyopathy (HCM)
can progress over time, which implies progression from an initial onset
phase.
- reference: PMID:22158452
supports: SUPPORT
snippet: Progressive heart failure associated with left ventricular
remodeling and systo-diastolic dysfunction is one of the most severe
complications of hypertrophic cardiomyopathy (HCM).
explanation: The progression of hypertrophic cardiomyopathy (HCM) through
various stages, including an onset phase, is indicated by the reference to
progressive heart failure.
- reference: PMID:29111210
supports: SUPPORT
snippet: Hypertrophic cardiomyopathy (HC) has been characterized as a
generally progressive genetic heart disease...
explanation: The statement that HC is generally progressive suggests that
there is an initial onset phase followed by further disease progression.
- age_range: Adolescence-Adulthood
evidence:
- reference: PMID:29622585
supports: SUPPORT
snippet: In the subset of patients with serial imaging, statistically
significant increases in LGE, LV mass, and left atrial size were detected
over 2.5 years, indicating disease progression over time.
explanation: This study shows significant disease progression, including
increases in late gadolinium enhancement (LGE), left ventricular (LV)
mass, and left atrial size, indicating that hypertrophic cardiomyopathy
progresses over time from adolescence into adulthood.
- reference: PMID:29710196
supports: SUPPORT
snippet: Pediatric-onset HCM is rare and associated with adverse outcomes
driven mainly by arrhythmic events. Risk extends well beyond adolescence,
which calls for unchanged clinical surveillance into adulthood.
explanation: This study highlights that pediatric-onset HCM progresses into
adulthood and is associated with adverse outcomes, supporting continuous
clinical surveillance.
pathophysiology:
- name: Sarcomere Protein Mutations
description: Genetic mutations affecting the proteins of the cardiac sarcomere
lead to abnormal thickening of the heart muscle. The central biophysical
abnormality is sarcomere hypercontractility with increased myosin duty ratio
and power, resulting in impaired relaxation and elevated energetic cost of
contraction.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
locations:
- preferred_term: left ventricle
term:
id: UBERON:0002084
label: heart left ventricle
- preferred_term: interventricular septum
term:
id: UBERON:0002094
label: interventricular septum
cellular_components:
- preferred_term: sarcomere
term:
id: GO:0030017
label: sarcomere
- preferred_term: thick filament
term:
id: GO:0005863
label: myosin filament
- preferred_term: thin filament
term:
id: GO:0005865
label: striated muscle thin filament
biological_processes:
- preferred_term: muscle contraction
term:
id: GO:0006936
label: muscle contraction
- preferred_term: regulation of heart contraction
term:
id: GO:0008016
label: regulation of heart contraction
- preferred_term: ATP hydrolysis activity
term:
id: GO:0016887
label: ATP hydrolysis activity
evidence:
- reference: PMID:16416046
supports: SUPPORT
snippet: Hypertrophic Cardiomyopathy (HCM) is a relatively common primary
cardiac disorder defined as the presence of a hypertrophied left
ventricle... to date, 270 independent mutations in nine sarcomeric protein
genes have been linked to Familial Hypertrophic Cardiomyopathy (FHC)...
explanation: The reference discusses how mutations in sarcomeric protein
genes are linked to hypertrophic cardiomyopathy, which leads to heart
muscle thickening.
- reference: PMID:36797478
supports: SUPPORT
snippet: The most common form of genetic heart disease is hypertrophic
cardiomyopathy (HCM), which is caused by variants in cardiac sarcomeric
genes and leads to abnormal heart muscle thickening.
explanation: This reference directly states that HCM is caused by variants
in sarcomeric genes resulting in heart muscle thickening.
- reference: PMID:28645928
supports: SUPPORT
snippet: For example, increased myosin heavy chain (MHC) binding and ATP
utilization lead to the hypercontractile sarcomere in HCM...
explanation: This reference explains how specific mutations in sarcomeric
proteins lead to hypercontractility, a feature of muscle thickening in
HCM.
- reference: PMID:37060436
supports: SUPPORT
snippet: Recent advances in our mechanistic understanding of sarcomere
pathophysiology include high-resolution molecular models of sarcomere
components and the identification of the myosin super-relaxed state.
explanation: This reference details how understanding sarcomere function and
its pathophysiology relates to mutations leading to cardiomyopathy,
thereby supporting the statement about genetic mutations affecting
sarcomere proteins.
- name: Myocyte Disarray
description: Disorganization of heart muscle cells contributes to the
stiffness and dysfunction of the myocardium. Loss of physiological fiber
alignment and orientation creates structural abnormalities that impair
contractile efficiency and promote arrhythmogenic substrate.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
locations:
- preferred_term: ventricular myocardium
term:
id: UBERON:0002084
label: heart left ventricle
evidence:
- reference: PMID:33447843
supports: SUPPORT
snippet: Myocardial disarray is defined as disorganized cardiomyocyte
spatial distribution, with loss of physiological fibre alignment and
orientation.
explanation: The paper discusses how myocardial disarray is a typical
feature of hypertrophic cardiomyopathy (HCM), implying its role in
myocardial dysfunction.
- reference: PMID:7665141
supports: SUPPORT
snippet: Genes on five loci on separate chromosomes are responsible for a
familial disease in which all or part of the ventricular muscle undergoes
thickening with a histological picture of irregular hypertrophy and
disorganized arrangement of myocytes (disarray).
explanation: This indicates that myocyte disarray is a feature of the
disease, contributing to the thickening and impaired function of the
myocardium.
- reference: PMID:11040002
supports: SUPPORT
snippet: Within an individual heart the magnitude of hypertrophy correlated
with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002).
explanation: The correlation between hypertrophy, fibrosis, and disarray
supports the statement that myocyte disarray contributes to myocardial
dysfunction.
- name: Myocardial Fibrosis
description: Increased collagen deposition by interstitial cells contributes
to myocardial stiffness. Activation of TGF-beta and MAPK signaling pathways
promotes extracellular matrix remodeling and fibrosis, which is a
progressive phenomenon associated with greater disease severity.
cell_types:
- preferred_term: Interstitial Cells
term:
id: CL:4030031
label: interstitial cell
- preferred_term: cardiac fibroblast
term:
id: CL:0002548
label: fibroblast of cardiac tissue
locations:
- preferred_term: myocardial interstitium
term:
id: UBERON:0002084
label: heart left ventricle
biological_processes:
- preferred_term: extracellular matrix organization
term:
id: GO:0030198
label: extracellular matrix organization
- preferred_term: response to TGF-beta
term:
id: GO:0071559
label: response to transforming growth factor beta
cellular_components:
- preferred_term: extracellular matrix
term:
id: GO:0031012
label: extracellular matrix
evidence:
- reference: PMID:1414892
supports: SUPPORT
snippet: It appears that increased collagen production is mainly responsible
for the functional consequences of structural remodelling
explanation: The increased collagen production discussed here is consistent
with the contribution of interstitial cells to myocardial stiffness.
- reference: PMID:25573453
supports: SUPPORT
snippet: Tissue from cats with pre-clinical HCM also had a higher number of
neutrophils and a greater collagen content than the myocardium of normal
cats.
explanation: This study shows increased collagen deposition, contributing to
myocardial stiffness, aligning with the statement.
- reference: PMID:29522370
supports: SUPPORT
snippet: We conclude that myocardial macrophages play an important role in
the time-dependent increases in SPARC that enhance postsynthetic collagen
processing, insoluble collagen content, and myocardial stiffness and
contribute to the development of fibrosis.
explanation: The role of interstitial cells like macrophages in increasing
collagen content supports the statement.
- reference: PMID:12510171
supports: SUPPORT
snippet: The myocardial collagen matrix consists of a network of fibrillar
collagen which is intimately connected to the myocyte.
explanation: The mention of the collagen matrix supports the idea of
increased collagen deposition by interstitial cells contributing to
myocardial stiffness.
- name: Altered Calcium Handling
description: Increased myofilament calcium sensitivity and impaired diastolic
calcium removal lead to diastolic dysfunction and promote pro-hypertrophic
signaling. Altered calcium homeostasis contributes to both contractile
abnormalities and arrhythmogenic substrate.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
biological_processes:
- preferred_term: calcium ion transport
term:
id: GO:0006816
label: calcium ion transport
- preferred_term: regulation of cardiac muscle contraction
term:
id: GO:0055117
label: regulation of cardiac muscle contraction
cellular_components:
- preferred_term: sarcoplasmic reticulum
term:
id: GO:0016529
label: sarcoplasmic reticulum
locations:
- preferred_term: left ventricle
term:
id: UBERON:0002084
label: heart left ventricle
notes: Calcium dysregulation is a downstream consequence of sarcomere
mutations that impairs relaxation and triggers hypertrophic remodeling
- name: Mitochondrial Dysfunction
description: Elevated energetic cost of sarcomere hypercontractility leads to
mitochondrial stress and downregulation of energy metabolism pathways.
Impaired ATP production contributes to contractile dysfunction and cellular
remodeling.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
biological_processes:
- preferred_term: ATP metabolic process
term:
id: GO:0046034
label: ATP metabolic process
- preferred_term: oxidative phosphorylation
term:
id: GO:0006119
label: oxidative phosphorylation
cellular_components:
- preferred_term: mitochondrion
term:
id: GO:0005739
label: mitochondrion
locations:
- preferred_term: myocardium
term:
id: UBERON:0002084
label: heart left ventricle
notes: Energy metabolism dysfunction is a consistent finding across HCM
genotypes in tissue omics studies
- name: Left Ventricular Outflow Tract Obstruction
description: Asymmetric septal hypertrophy combined with systolic anterior
motion of the mitral valve creates dynamic obstruction to blood flow.
Venturi forces draw the mitral valve toward the septum, elevating wall
stress and contributing to ischemia and further hypertrophic remodeling.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
locations:
- preferred_term: interventricular septum
term:
id: UBERON:0002094
label: interventricular septum
- preferred_term: mitral valve
term:
id: UBERON:0002135
label: mitral valve
- preferred_term: left ventricular outflow tract
term:
id: UBERON:0016480
label: cardiac outflow tract
notes: Occurs in approximately 60% of HCM patients and is a defining feature
of obstructive HCM
phenotypes:
- category: Cardiovascular
name: Chest Pain
frequency: FREQUENT
evidence:
- reference: PMID:34533409
supports: SUPPORT
snippet: Hypertrophic cardiomyopathy (HCM) is a complex disease
characterized by thickening of the cardiac muscle. Common symptoms include
chest pain, shortness of breath, palpitations, fatigue and syncope
(fainting), which are often confused for other conditions.
explanation: This literature supports the statement as it lists chest pain
as a common symptom of Hypertrophic Cardiomyopathy.
phenotype_term:
preferred_term: Chest pain
term:
id: HP:0100749
label: Chest pain
- category: Cardiovascular
name: Dyspnea
frequency: FREQUENT
evidence:
- reference: PMID:29655822
supports: SUPPORT
snippet: Heart failure (HF), characterized by excessive exertional dyspnea,
is a common complication within the broad clinical spectrum of
hypertrophic cardiomyopathy (HCM).
explanation: The literature provided mentions that exertional dyspnea is
common in patients with hypertrophic cardiomyopathy, supporting the
statement that dyspnea is a common phenotype of HCM.
phenotype_term:
preferred_term: Dyspnea
term:
id: HP:0002094
label: Dyspnea
- category: Cardiovascular
name: Syncope
frequency: OCCASIONAL
notes: Often triggered by exertion
evidence:
- reference: PMID:29150126
supports: SUPPORT
snippet: Clinical manifestations of Hypertrophic Cardiomyopathy include
shortness of breath, chest pain, palpitations and syncope, which are
related to the onset of diastolic dysfunction, left ventricular outflow
tract obstruction, ischemia, atrial fibrillation and abnormal vascular
responses.
explanation: The excerpt directly states that syncope is a clinical
manifestation of hypertrophic cardiomyopathy.
- reference: PMID:36442670
supports: SUPPORT
snippet: 'Syncope in hypertrophic cardiomyopathy: Explaining the unexplained.'
explanation: Syncope is highlighted as a phenomenon occurring in individuals
with hypertrophic cardiomyopathy.
- reference: PMID:29761339
supports: SUPPORT
snippet: Syncope and presyncope-in addition to extremely variable cardiac
symptoms (dyspnea and angina)-are common.
explanation: The text explicitly mentions syncope as a common symptom in
hypertrophic cardiomyopathy patients.
phenotype_term:
preferred_term: Syncope
term:
id: HP:0001279
label: Syncope
- category: Cardiovascular
name: Arrhythmias
frequency: FREQUENT
evidence:
- reference: PMID:34969871
supports: SUPPORT
snippet: Study aims were to estimate the population-diagnosed prevalence of
cardiomyopathies and describe the temporal relationship between a
diagnosis of cardiomyopathy with HF and arrhythmia... Between 2010 and
2018, prevalence increased for ARVC by 180% and HCM by 9%.
explanation: The study indicates a relationship between hypertrophic
cardiomyopathy (HCM) and arrhythmias, supporting the statement that
arrhythmias are a common cardiovascular phenotype of HCM.
- reference: PMID:7201843
supports: SUPPORT
snippet: The patients with hypertrophic cardiomyopathy showed a significant
increase in supraventricular extrasystoles/24 hours, supraventricular
arrhythmias, high grade ventricular arrhythmia, and the number of patients
with more than 10 ventricular extrasystoles every 24 hours when compared
with the other groups.
explanation: This study directly assesses the prevalence and types of
arrhythmias in patients with hypertrophic cardiomyopathy, confirming that
arrhythmias are a common phenotype.
- reference: PMID:3158692
supports: SUPPORT
snippet: Frequent ventricular premature complexes, complex ventricular
ectopic activity and asymptomatic ventricular tachycardia are common to
both hypertrophic and dilated cardiomyopathy; in both conditions, sudden
death is a common occurrence.
explanation: This reference mentions common arrhythmic events in
hypertrophic cardiomyopathy, supporting the idea that arrhythmias are a
common cardiovascular phenotype in HCM.
phenotype_term:
preferred_term: Arrhythmias
term:
id: HP:0011675
label: Arrhythmia
- category: Cardiovascular
frequency: FREQUENT
name: Arrhythmias
notes: Abnormal heart rhythms are common. Can include atrial fibrillation and
ventricular arrhythmias.
sequelae:
- target: Palpitations
- target: Sudden Cardiac Death
evidence:
- reference: PMID:23124402
supports: SUPPORT
snippet: Hypertrophic cardiomyopathy is the most common genetic
cardiovascular disorder and the leading cause of sudden cardiac death in
the young. This article reviews the ventricular arrhythmias associated
with hypertrophic cardiomyopathy.
explanation: The reference confirms that hypertrophic cardiomyopathy is
associated with ventricular arrhythmias and is a leading cause of sudden
cardiac death.
- reference: PMID:28602671
supports: SUPPORT
snippet: Patients with HCM are predisposed to developing atrial fibrillation
(AF) due primarily to advanced diastolic dysfunction and left atrial (LA)
dilatation and remodelling.
explanation: The reference confirms that atrial fibrillation is common in
patients with hypertrophic cardiomyopathy.
- reference: PMID:29203161
supports: SUPPORT
snippet: Cardiac arrhythmias refer to any abnormality or disturbance in the
normal activation sequence of the myocardium and may be indicative of
structural heart disease and the cause of significant cardiovascular
complications and sudden cardiac death.
explanation: The reference discusses the role of arrhythmias in structural
heart disease, including hypertrophic cardiomyopathy, and their
association with significant cardiovascular complications and sudden
cardiac death.
- reference: PMID:11174912
supports: SUPPORT
snippet: Ventricular arrhythmias in the athlete generally occur in the
setting of structural heart disease that is genetically determined
(hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia,
anomalous coronary arteries) or acquired (coronary artery disease,
myocarditis, idiopathic dilated cardiomyopathies).
explanation: The reference confirms that ventricular arrhythmias are common
in hypertrophic cardiomyopathy, particularly in athletes.
phenotype_term:
preferred_term: Arrhythmias
term:
id: HP:0011675
label: Arrhythmia
- category: Cardiovascular
frequency: OCCASIONAL
name: Mitral Valve Regurgitation
notes: Thickened heart muscle can affect mitral valve function, causing
leakage.
evidence:
- reference: PMID:21909825
supports: SUPPORT
snippet: Elongation and pathological thickening of the mitral valve (MV) is
commonly seen in hypertrophic cardiomyopathy (HCM)... failure of either to
optimally adapt in this setting can result in mitral regurgitation.
explanation: The reference discusses the common occurrence of mitral valve
elongation and thickening in HCM, which can lead to mitral regurgitation.
- reference: PMID:35644869
supports: SUPPORT
snippet: 'RESULTS: Significant (more than mild) MR was a significant univariate
predictor of all the three LA strain values'
explanation: This study shows that mitral regurgitation (MR) is a
significant factor in patients with hypertrophic cardiomyopathy (HCM),
supporting the statement that thickened heart muscle can affect mitral
valve function, causing leakage.
- reference: PMID:37563454
supports: SUPPORT
snippet: However, the interplay between these conditions is increasingly
being recognized and they frequently coexist, as in the paradigmatic
examples of dilated cardiomyopathy and hypertrophic cardiomyopathy, which
are often complicated by the occurrence of mitral regurgitation.
explanation: The reference indicates that hypertrophic cardiomyopathy is
often complicated by mitral regurgitation, supporting the statement.
- reference: PMID:37574021
supports: SUPPORT
snippet: OHCM patients with MAC had a worse prognosis and more recurrent
mitral valve regurgitation than those without MAC after septal myectomy.
explanation: This study indicates that mitral valve regurgitation is a
complication in hypertrophic obstructive cardiomyopathy (OHCM), supporting
the statement.
- category: Systemic
frequency: OCCASIONAL
name: Fatigue
notes: Due to reduced cardiac output and efficiency.
evidence:
- reference: PMID:34533409
supports: SUPPORT
snippet: Common symptoms include chest pain, shortness of breath,
palpitations, fatigue and syncope (fainting)...
explanation: The reference mentions fatigue as a common symptom of
hypertrophic cardiomyopathy, supporting the statement that fatigue occurs
occasionally in this condition.
- reference: PMID:37715354
supports: SUPPORT
snippet: A 59-year-old man was referred for SSM as dyspnoea and low
threshold muscle fatigue associated to severe left ventricular outflow
obstruction...
explanation: The reference describes a patient with hypertrophic obstructive
cardiomyopathy experiencing muscle fatigue, aligning with the statement
that fatigue is occasionally observed due to reduced cardiac output and
efficiency.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Cardiovascular
name: Palpitations
frequency: FREQUENT
notes: Often associated with atrial fibrillation and ventricular arrhythmias
phenotype_term:
preferred_term: Palpitations
term:
id: HP:0001962
label: Palpitations
- category: Cardiovascular
name: Sudden Cardiac Death
frequency: OCCASIONAL
notes: Highest risk in young patients and those with sarcomere-positive
disease. Leading cause of sudden death in young athletes.
phenotype_term:
preferred_term: Sudden Cardiac Death
term:
id: HP:0001645
label: Sudden cardiac death
- category: Cardiovascular
name: Left Ventricular Hypertrophy
frequency: OBLIGATE
notes: Defining feature of HCM; often asymmetric with septal predominance
phenotype_term:
preferred_term: Left ventricular hypertrophy
term:
id: HP:0001712
label: Left ventricular hypertrophy
- category: Cardiovascular
name: Atrial Fibrillation
frequency: FREQUENT
notes: Due to advanced diastolic dysfunction and left atrial dilatation and
remodeling. Genotype-positive status associated with higher lifetime hazard.
phenotype_term:
preferred_term: Atrial fibrillation
term:
id: HP:0005110
label: Atrial fibrillation
biochemical:
- name: Troponin
presence: Elevated
context: During myocardial stress or damage
evidence:
- reference: PMID:24011925
supports: SUPPORT
snippet: The results demonstrated that hs-cTnT was elevated in a significant
number of our HCM patients; therefore, hs-cTnT can be introduced as a
valuable marker of myocardial injury in HCM patients.
explanation: This study observes and confirms that hypertrophic
cardiomyopathy (HCM) patients often have elevated levels of
high-sensitivity cardiac troponin T (hs-cTnT), indicating its utility as a
marker of myocardial injury.
- reference: PMID:15631686
supports: SUPPORT
snippet: More than 200 mutations in the cardiac sarcomeric proteins,
including myosin heavy and light chains, actin, troponin, tropomyosin,
myosin-binding protein-C, and titin/connectin, have been found to cause
various types of cardiomyopathy in human since 1990...
explanation: This study indicates that mutations in cardiac sarcomeric
proteins, including troponin subunits, are linked to various types of
cardiomyopathy, including hypertrophic cardiomyopathy, leading to
myocardial damage where elevated troponin can be expected.
diagnosis:
- name: Echocardiogram
notes: Shows left ventricular hypertrophy and outflow obstruction if present
evidence:
- reference: PMID:22948303
supports: SUPPORT
snippet: The evaluation of hypertrophic cardiomyopathy incorporates methods
based on the ultrasound image, which, along with MRI, allow recognizing
ventricular obstruction generating mechanisms, thus facilitating the
diagnosis and management of obstructive and latent obstructive forms.
explanation: The text indicates that echocardiographic imaging is crucial
for identifying left ventricular obstruction in hypertrophic
cardiomyopathy, supporting the statement about echocardiogram diagnosis.
- reference: PMID:37160197
supports: SUPPORT
snippet: This document provides an additional practical framework for
optimal image and measurement acquisition and guidance on how to tailor
the echocardiography examination for individuals with HCM.
explanation: This supports that echocardiogram (which includes ultrasound)
is a fundamental diagnostic tool for hypertrophic cardiomyopathy.
- reference: PMID:133253
supports: SUPPORT
snippet: Asymmetric septal hypertrophy was demonstrated in both obstructive
and nonobstructive HCM. In all cases of HCM studied, the thickness of the
interventricular septum was 1.4 cm or more (1.4-3.7 cm) ... A systolic
anterior movement of the mitral valve (SAM) was observed in obstructive
cases only and characterized by a large backward component in late systole
and an extreme approximation to the interventricular septum at its peak.
explanation: The echocardiographic study clearly demonstrates its
effectiveness in diagnosing features of HCM including left ventricular
hypertrophy and outflow obstruction.
- name: Electrocardiogram
notes: May show signs of left ventricular hypertrophy or arrhythmias
evidence:
- reference: PMID:32639329
supports: PARTIAL
snippet: In our study, only a few ECG voltage criteria used for the
detection of LVH in clinical practice showed an acceptable performance in
the HCM population.
explanation: While ECG can show signs of left ventricular hypertrophy, its
overall diagnostic accuracy in hypertrophic cardiomyopathy (HCM)
populations is limited.
- reference: PMID:37579849
supports: PARTIAL
snippet: Although the 12‑lead electrocardiogram (ECG) is abnormal in most
patients with hypertrophic cardiomyopathy (HCM), some present normal ECG.
explanation: The ECG can be useful for diagnosing HCM, but a normal ECG does
not rule out the condition.
- reference: PMID:23704850
supports: SUPPORT
snippet: Electrocardiogram typically shows repolarization changes and giant
(>10 mm), inverted T waves in the anterolateral leads.
explanation: Specific ECG patterns can be indicative of certain variants of
HCM.
- reference: PMID:30739754
supports: PARTIAL
snippet: The minimum check-up must include an electrocardiogram and a
transthoracic echocardiography, which will most of the time be completed
by magnetic resonance imaging.
explanation: While ECG is part of the diagnostic process, it alone may not
be sufficient for a conclusive diagnosis.
- reference: PMID:25060129
supports: SUPPORT
snippet: Attention is drawn to the finding that in many differing etiologies
of left ventricular hypertrophy ST-T-wave changes commonly referred to as
'strain'-pattern are a harbinger of an increased risk of malignant cardiac
arrhythmias and sudden death.
explanation: ECG changes such as ST-T wave abnormalities are relevant for
diagnosing LVH in the context of HCM.
genetic:
- name: MYH7
association: Pathogenic Variants
evidence:
- reference: PMID:38423942
supports: SUPPORT
snippet: 'Hypertrophic cardiomyopathy: New pathogenic variant in MYH7.'
explanation: The title of the referenced article explicitly indicates the
association of a pathogenic variant in MYH7 with hypertrophic
cardiomyopathy.
- reference: PMID:23905887
supports: SUPPORT
snippet: Genetic mutations can be identified in approximately 60% of
patients; these are commonest in genes that encode proteins of the cardiac
sarcomere.
explanation: While the specific mutations in MYH7 are not detailed in this
snippet, the article supports the general assertion that genetic
mutations, particularly in sarcomeric genes like MYH7, are common in
hypertrophic cardiomyopathy.
- reference: PMID:31735781
supports: SUPPORT
snippet: By NGS, we determined that these subjects with HCM symptoms carried
a missense heterozygous genetic mutation c.2632C>A (p.V878L) in the myosin
heavy chain 7 (MYH7) gene with an autosomal dominant pattern of
inheritance.
explanation: The article details a specific pathogenic variant (p.V878L) in
the MYH7 gene associated with hypertrophic cardiomyopathy.
- reference: PMID:36797478
supports: SUPPORT
snippet: The dominant-negative c.1208G>A (p.R403Q) pathogenic variant (PV)
in beta-myosin (MYH7) is a common and well-studied PV that leads to
increased cardiac contractility and HCM onset.
explanation: The article identifies the commonly studied pathogenic variant
(p.R403Q) in MYH7 which leads to hypertrophic cardiomyopathy.
- reference: PMID:30681346
supports: SUPPORT
snippet: Of 33 HCM genes, only 8 (24%) were categorized as definitive
(MYBPC3, MYH7, TNNT2, TNNI3, TPM1, ACTC1, MYL2, and MYL3).
explanation: The article categorizes MYH7 as one of the 'definitive' genes
associated with hypertrophic cardiomyopathy.
- reference: PMID:37565978
supports: SUPPORT
snippet: MYH7 variants cause hypertrophic cardiomyopathy (HCM),
noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM).
explanation: The article explicitly states that MYH7 variants cause
hypertrophic cardiomyopathy, reinforcing the genetic association.
- name: MYBPC3
association: Pathogenic Variants
evidence:
- reference: PMID:34180388
supports: SUPPORT
snippet: The proband carries a novel heterozygous nonsense variant of
MYBPC3:c.2731G > T (p.E911X) ... suggesting the functional damages to the
protein of MYBPC3.
explanation: The study identifies a novel pathogenic variant in MYBPC3
associated with hypertrophic cardiomyopathy.
- reference: PMID:24240729
supports: SUPPORT
snippet: The second wave started in 1995 by the discovery that mutations in
the gene encoding cMyBP-C cause hypertrophic cardiomyopathy (HCM).
explanation: This review discusses that mutations in MYBPC3 (which encodes
cMyBP-C) cause HCM.
- reference: PMID:37409452
supports: SUPPORT
snippet: The 2 sarcomere genes most commonly associated with hypertrophic
cardiomyopathy (HCM), MYBPC3 (myosin-binding protein C3)...
explanation: Study identifies MYBPC3 as a common gene associated with
hypertrophic cardiomyopathy.
- reference: PMID:35544052
supports: SUPPORT
snippet: Pathogenic variants associated with inherited cardiomyopathy ...
MYBPC3 ... were classified ...
explanation: This study includes MYBPC3 as one of the genes with pathogenic
variants associated with inherited cardiomyopathy.
- name: TNNT2
association: Pathogenic Variants
notes: Can present with relatively modest LVH but disproportionate arrhythmic
risk
evidence:
- reference: PMID:33588347
supports: SUPPORT
snippet: Variants were identified and annotated using in silico tools, and
further classified as pathogenic or benign according to the American
College of Medical Genetics and Genomics guidelines. Variants with
functional effects were identified...and TNNT2...
explanation: The study identifies pathogenic variants in TNNT2 among
patients with hypertrophic cardiomyopathy, supporting the genetic
association.
- reference: PMID:7665141
supports: SUPPORT
snippet: Genes on five loci on separate chromosomes are responsible for a
familial disease in which all or part of the ventricular muscle undergoes
thickening with a histological picture of irregular hypertrophy and
disorganized arrangement of myocytes (disarray). The three genes
identified so far encode for beta heavy chain myosin (chromosome 14),
troponin T (chromosome 1) and alpha tropomyosin (chromosome 15).
explanation: The study reveals that the troponin T gene (TNNT2) is one of
the implicated genes in hypertrophic cardiomyopathy.
- name: ALPK3
association: Pathogenic Variants
notes: Emerging gene; biallelic variants linked to pediatric-onset
cardiomyopathy, heterozygous variants show variable adult-onset HCM.
Involved in sarcomere and nuclear signaling.
- name: FHOD3
association: Pathogenic Variants
notes: Emerging gene; formin homology domain protein regulating actin
cytoskeleton. Variants perturb myofibrillogenesis and cytoskeletal
integrity, contributing to sarcomere remodeling.
- name: TRIM63
association: Pathogenic Variants
notes: Emerging gene; muscle-specific RING-finger protein (MuRF1) involved in
proteostasis. Loss- or gain-of-function variants may alter sarcomeric
protein turnover. Homozygous cases reported with severe remodeling.
- name: SVIL
association: Pathogenic Variants
notes: Emerging gene; supervillin is a cytoskeletal-membrane linker. Rare
variants recently reported in HCM cohorts, hypothesized to affect
sarcomere-cytoskeleton coupling. Associated with apical/septal phenotypes in
some populations.
environmental:
- name: None Applicable
evidence:
- reference: PMID:23692943
supports: WRONG_STATEMENT
snippet: Hypertrophic cardiomyopathy is a complex cardiovascular disorder
particularly sensitive to environmental changes and physiologic stress.
Warm weather and strenuous activity can be a dangerous combination for
people that have hypertrophic cardiomyopathy. Often sudden cardiac death
is the first symptom of the disorder.
explanation: The statement that hypertrophic cardiomyopathy is not
influenced by environmental factors is incorrect. Environmental factors
and physiological stress are significant factors in the management and
severity of hypertrophic cardiomyopathy.
treatments:
- name: Beta Blockers
description: Used to reduce heart rate and improve symptoms
evidence:
- reference: PMID:35450574
supports: SUPPORT
snippet: Beta-Blockers and Exercise Hemodynamics in Hypertrophic
Cardiomyopathy.
explanation: This reference discusses the use of beta-blockers in the
context of hypertrophic cardiomyopathy, which supports the statement that
beta-blockers are used to improve symptoms in this condition, though
details on heart rate reduction specifically may be implied but not
detailed.
- reference: PMID:21389910
supports: SUPPORT
snippet: Throughout the years, numerous medical treatments have been used to
achieve symptom control in these patients, and include medications such as
beta-blockers, calcium channel blockers, amiodarone, disopyramide, and
angiotensin receptor blockers.
explanation: The abstract directly mentions the use of beta-blockers to
control symptoms in hypertrophic cardiomyopathy, supporting the statement.
- reference: PMID:37850394
supports: SUPPORT
snippet: beta-Adrenergic receptor antagonists (beta-blockers) are the
first-line therapy for HCM. However, beta-blockers commonly selected for
this disease are often poorly tolerated in patients, where heart-rate
reduction and noncardiac effects can lead to reduced cardiac output and
fatigue.
explanation: This reference confirms that beta-blockers are a first-line
therapy for hypertrophic cardiomyopathy and are used for heart rate
reduction, supporting the statement.
- reference: PMID:25198737
supports: SUPPORT
snippet: Beta-blocker therapy is without doubt the treatment of choice for
patients with heart failure caused by hypertrophic cardiomyopathy, but the
dose needs to carefully titrated on an individual basis for maximum
benefit.
explanation: The reference highlights the use of beta-blockers in
hypertrophic cardiomyopathy to improve symptoms, aligning with the
statement.
treatment_term:
preferred_term: beta adrenergic agent therapy
term:
id: MAXO:0000186
label: beta adrenergic agent therapy
- name: Calcium Channel Blockers
description: Help to relax heart muscle and improve blood flow
evidence:
- reference: PMID:17162264
supports: SUPPORT
snippet: For symptomatic patients with non-obstructed disease medical
treatment with calcium channel blockers and beta-blockers is aimed to
improve heart failure symptoms, and ischemia. Verapamil is the most often
used, with likely benefit of relieving ischemia.
explanation: The literature supports that calcium channel blockers are used
to improve symptoms in hypertrophic cardiomyopathy patients, which implies
relaxing the heart muscle and improving blood flow.
- reference: PMID:3515244
supports: SUPPORT
snippet: The three approved calcium-channel blockers--nifedipine, verapamil
and diltiazem--have offered new treatments for angina.
explanation: Even though the focus is on angina, the acknowledged use of
calcium channel blockers reinforces their role in cardiovascular
conditions including HCM.
- reference: PMID:36044874
supports: SUPPORT
snippet: CCBs are effective antihypertensive drugs and a very good
therapeutic option for HTN LVH as they can cause reverse LVH remodeling.
explanation: The review suggests the effectiveness of calcium channel
blockers in treating hypertensive left ventricular hypertrophy (HTN LVH),
indicating a role in remodeling heart muscle, which aligns with improving
blood flow.
- reference: PMID:7004293
supports: SUPPORT
snippet: The negative inotropic effects of verapamil are valuable in
improving the symptoms and hemodynamic disturbances of hypertrophic
cardiomyopathy.
explanation: This directly supports the use of calcium channel blockers
(specifically verapamil) in hypertrophic cardiomyopathy by improving
symptoms and hemodynamics, which implies relaxing the heart muscle and
improving blood flow.
treatment_term:
preferred_term: calcium channel blocking agent therapy
term:
id: MAXO:0000434
label: calcium channel blocking agent therapy
- name: Septal Myectomy
description: Surgical removal of part of the thickened heart muscle
evidence:
- reference: PMID:38368037
supports: SUPPORT
snippet: Septal myectomy is a well-established procedure for septal
reduction in patients with obstructive hypertrophic cardiomyopathy (HCM)
who have not responded to medical treatment.
explanation: The literature directly confirms that septal myectomy is used
to surgically remove part of the thickened heart muscle in hypertrophic
cardiomyopathy patients.
- reference: PMID:31280832
supports: SUPPORT
snippet: Surgical myectomy was initially advocated only for patients with
symptoms refractory to maximal tolerated medical therapy.
explanation: This supports the usage of septal myectomy for removing
thickened muscle parts as a treatment for hypertrophic cardiomyopathy.
- reference: PMID:22687587
supports: SUPPORT
snippet: Treatments for hypertrophic cardiomyopathy are largely selected
based on patient symptoms and echocardiographic findings.
explanation: While this reference does not directly state septal myectomy,
it mentions treatment selection based on symptoms, which aligns with the
usage context of septal myectomy in other literature. Therefore, it
indirectly supports the use.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Alcohol Septal Ablation
description: Minimally invasive procedure to reduce obstruction by injecting
alcohol into a small artery that supplies the thickened heart muscle
evidence:
- reference: PMID:35710280
supports: SUPPORT
snippet: Over the past several decades, alcohol septal ablation has become
an established therapy for selected patients, in whom there is clinical
improvement in symptoms as well as objective functional capacity.
explanation: This reference supports the use of alcohol septal ablation as a
treatment for hypertrophic cardiomyopathy by describing improved clinical
outcomes and functional capacity.
- reference: PMID:36598161
supports: SUPPORT
snippet: There are several invasive therapies including proven therapies
such as alcohol septal ablation and septal myectomy.
explanation: This reference supports the use of alcohol septal ablation as a
proven therapy for hypertrophic cardiomyopathy.
- reference: PMID:10980888
supports: SUPPORT
snippet: Following balloon inflation and intracoronary myocardial contrast
echocardiography, ethyl alcohol is injected through the catheter lumen to
cause proximal interventricular septum infarction and relief of outflow
tract obstruction.
explanation: This reference supports the description of alcohol septal
ablation as a minimally invasive procedure to reduce obstruction by
injecting alcohol.
- reference: PMID:20973822
supports: SUPPORT
snippet: Alcohol septal ablation (ASA) has been shown to be an effective
treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM)
who are refractory to medical treatment.
explanation: This reference supports the effectiveness of alcohol septal
ablation in treating hypertrophic cardiomyopathy by injecting alcohol into
the septal artery.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Implantable Cardioverter Defibrillator (ICD)
description: Prevents sudden cardiac death in high-risk patients
evidence:
- reference: PMID:26002383
supports: SUPPORT
snippet: Nevertheless, several observational clinical studies have shown
that the ICD reliably terminates life-threatening ventricular
tachyarrhythmias in HCM, and is largely responsible for reducing HCM
mortality to 0.5% per year, by preventing SD and changing the natural
course of the disease.
explanation: This excerpt supports the statement by showing that ICDs
prevent sudden cardiac death in high-risk patients with hypertrophic
cardiomyopathy.
- reference: PMID:36396186
supports: SUPPORT
snippet: Implantable cardioverter-defibrillators are the mainstay of therapy
for prevention of sudden cardiac death in high-risk patients with
hypertrophic cardiomyopathy (HCM).
explanation: This excerpt also supports the statement by confirming that
ICDs are a primary treatment used to prevent sudden cardiac death in
high-risk HCM patients.
- reference: PMID:22687587
supports: SUPPORT
snippet: Risk of sudden death correlates with maximum left ventricular (LV)
wall thickness. Massive LV thickening of 30 mm or more is an indication
for primary prevention of sudden death with an implanted defibrillator.
explanation: This excerpt provides specific criteria for using ICDs as a
preventative measure in patients with significant hypertrophic
cardiomyopathy, further supporting the statement.
- reference: PMID:36134835
supports: SUPPORT
snippet: During follow-up of 4.8+/-3.4 years, there was no sudden cardiac
death, but 20.6% patients with implantable cardioverter-defibrillator had
at least one appropriate shock.
explanation: While the focus is on the outcome of ICD shocks, the lack of
sudden cardiac deaths among ICD patients aligns with the notion that ICDs
prevent sudden cardiac death in high-risk HCM patients.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
disease_term:
preferred_term: hypertrophic cardiomyopathy
term:
id: MONDO:0005045
label: hypertrophic cardiomyopathy
classifications:
harrisons_chapter:
- classification_value: cardiovascular disorder
- classification_value: cardiomyopathy
- classification_value: hereditary disease
references:
- reference: DOI:10.1016/j.cell.2025.01.011
title: Advances in the study and treatment of genetic cardiomyopathies
findings: []
- reference: DOI:10.1038/s44161-024-00505-0
title: Aficamten is a small-molecule cardiac myosin inhibitor designed to
treat hypertrophic cardiomyopathy
findings: []
- reference: DOI:10.1093/eurheartj/ehae421
title: 'Genetics of hypertrophic cardiomyopathy: established and emerging implications
for clinical practice'
findings: []
- reference: DOI:10.1186/s43044-024-00587-y
title: 'Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal
therapeutic approach with mavacamten, aficamten, and beyond'
findings: []
- reference: DOI:10.1186/s43044-025-00652-0
title: 'Cardiac myosin inhibitors: Efficacy, safety and future directions of aficamten
in hypertrophic obstructive cardiomyopathy'
findings: []
- reference: DOI:10.3390/biomedicines12030682
title: 'Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy:
A Glimpse into the Future'
findings: []
- reference: DOI:10.3390/biomedicines12122675
title: Hypertrophic Cardiomyopathy with Special Focus on Mavacamten and Its
Future in Cardiology
findings: []