HYPERTROPHIC CARDIOMYOPATHY

✓ Medically ReviewedDISEASEID: MDBT0162🚨 TRIAGE: URGENTICD-10: I42.2

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Definition

CLINICAL DEFINITION

Hypertrophic cardiomyopathy (HCM) is a primary genetic myocardial disorder characterised by left ventricular hypertrophy (LVH) that develops in the absence of causative haemodynamic factors (such as hypertension or valvular disease). The hypertrophy is typically asymmetric, predominantly involving the interventricular septum, and is associated with myocardial fibre disarray and interstitial fibrosis.

IN PLAIN ENGLISH

Hypertrophic cardiomyopathy is an inherited condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood. This thickening can sometimes block blood flow out of the heart or cause dangerous irregular heartbeats.

COMMON MISCONCEPTION / WHAT IT DOES NOT MEAN

Hypertrophic cardiomyopathy is NOT the same as the left ventricular hypertrophy caused by chronic high blood pressure or aortic stenosis, which are secondary adaptive responses to increased workload. It is also distinct from athletic heart syndrome, where physiological hypertrophy occurs without the pathological myocyte disarray or genetic mutations seen in HCM.

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Word Breakdown

hyper-

=excessive, above normal (from Greek 'hyper')

cardio-

=heart (from Greek 'kardia')

-myopathy

=disease of muscle (from Greek 'mys' = muscle, 'pathos' = disease)

Literal Meaning: Disease of the heart muscle characterised by excessive thickening

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Abbreviations

HCM=Hypertrophic Cardiomyopathy — the standard clinical abbreviation

HOCM=Hypertrophic Obstructive Cardiomyopathy — historical term for the obstructive phenotype

LVOT=Left Ventricular Outflow Tract — key anatomical site for obstruction in HCM

SAM=Systolic Anterior Motion — of the mitral valve, a key mechanism of LVOT obstruction

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Synonyms & Variants

Hypertrophic Obstructive Cardiomyopathy›Asymmetric Septal Hypertrophy›Idiopathic Hypertrophic Subaortic Stenosis›

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Category-Specific Context

As a disease, hypertrophic cardiomyopathy represents a primary genetic disorder of the sarcomere, distinct from secondary hypertrophy. It encompasses a broad phenotypic spectrum ranging from asymptomatic non-obstructive variants to severe obstructive physiology with heart failure or life-threatening ventricular arrhythmias.

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Clinical Context & Usage

CLINICAL SETTINGS

Cardiology Outpatient ClinicEmergency DepartmentGenetics Counselling ServiceSports Medicine ClinicIntensive Care Unit

USAGE & DOCUMENTATION NOTES

In clinical documentation, HCM is frequently subtyped by the presence or absence of left ventricular outflow tract (LVOT) obstruction, typically defined as a resting or provoked gradient ≥30 mmHg. Clinicians often document the maximal wall thickness (e.g., 'asymmetric septal hypertrophy with maximal thickness 22 mm') and the presence of systolic anterior motion (SAM) of the mitral valve. Genetic testing results and family screening status are routinely included in the problem list.

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Primary Causes & Pathophysiology

PATHOPHYSIOLOGY

Hypertrophic cardiomyopathy is primarily caused by autosomal dominant mutations in genes encoding sarcomeric proteins, most commonly beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). These mutations lead to impaired sarcomere function, increased myocardial energy demand, and compensatory hypertrophy. The histological hallmark is myocyte disarray, where cardiac muscle fibres lose their normal parallel alignment and are interspersed with interstitial fibrosis. This structural disorganisation impairs diastolic relaxation, leading to a stiff, non-compliant left ventricle and elevated filling pressures. In the obstructive phenotype, asymmetric septal hypertrophy combined with systolic anterior motion (SAM) of the anterior mitral valve leaflet creates a dynamic left ventricular outflow tract (LVOT) obstruction, which worsens with decreased preload or increased contractility.

PRIMARY CAUSES

Sarcomeric gene mutations (e.g., MYH7, MYBPC3)

Autosomal dominant mutations alter sarcomere structure and function, triggering compensatory myocyte hypertrophy, disarray, and interstitial fibrosis.

De novo genetic mutations

Spontaneous mutations in sarcomeric genes occur in patients with no family history, accounting for a significant minority of isolated HCM cases.

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Epidemiology

Prevalence:Affects approximately 1 in 500 to 1 in 200 individuals in the general population based on recent epidemiological and genetic cohort studies, making it one of the most common inherited cardiovascular disorders.

Age Group:Can be diagnosed at any age from infancy to late adulthood; however, phenotypic expression and clinical recognition most commonly occur during adolescence and young adulthood.

Sex Predilection:Equal

Geographic Distribution:Globally distributed across all ethnic and geographic populations, as the causative sarcomeric mutations are found worldwide without a single predominant regional founder effect.

Red Flags & Triage ★

TRIAGE LEVEL

🚨 URGENT

DO NOT MISS — LIFE-THREATENING PRESENTATIONS

Syncope or pre-syncope during exertion in a young patient — raises high suspicion for dynamic LVOT obstruction or malignant ventricular arrhythmias, requiring urgent echocardiography and Holter monitoring to assess sudden cardiac death risk
New-onset atrial fibrillation in a patient with HCM — significantly increases the risk of thromboembolism and necessitates immediate initiation of systemic anticoagulation regardless of the CHA2DS2-VASc score

URGENT EVALUATION TRIGGERS

Exertional syncope or near-syncope — requires urgent evaluation for arrhythmias or severe LVOT obstruction
Sustained palpitations or documented non-sustained ventricular tachycardia (NSVT) on ambulatory monitoring — prompts urgent risk stratification for sudden cardiac death and consideration of an implantable cardioverter-defibrillator (ICD)
Acute chest pain with dynamic ECG changes — requires evaluation to distinguish from acute coronary syndrome, as myocardial ischaemia can occur in HCM due to microvascular dysfunction

Contraindications & Precautions

CONTRAINDICATIONS

Vasodilators (e.g.
nitrates
dihydropyridine calcium channel blockers) — contraindicated in obstructive HCM as they reduce afterload and worsen the dynamic LVOT gradient
High-intensity competitive sports — generally restricted in patients with high-risk features for sudden cardiac death
though recent guidelines allow individualised shared decision-making for some
Positive inotropes (e.g.
digoxin
dobutamine) — contraindicated in obstructive HCM as increased contractility exacerbates LVOT obstruction

SPECIAL PRECAUTIONS

Diuretics must be used cautiously to manage congestion
as excessive volume depletion reduces preload and can severely worsen dynamic LVOT obstruction
Beta-blockers and non-dihydropyridine calcium channel blockers (verapamil) are preferred for symptom control
but must be titrated carefully to avoid severe bradycardia or heart block
First-degree relatives require cascade screening with echocardiography and genetic counselling
as the condition is autosomal dominant

Complications

DOWNSTREAM CLINICAL COMPLICATIONS

Sudden cardiac death (SCD) — primarily due to ventricular tachyarrhythmias arising from areas of myocyte disarray and fibrosis
Left ventricular outflow tract (LVOT) obstruction — dynamic gradient causing exertional dyspnoea
angina
and syncope
Atrial fibrillation — resulting from left atrial enlargement secondary to chronic diastolic dysfunction and elevated filling pressures
Progressive heart failure — either with preserved ejection fraction (diastolic heart failure) or
in the 'burnt-out' phase
systolic dysfunction with wall thinning
Thromboembolism — particularly stroke
secondary to undetected or poorly managed atrial fibrillation

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Confused With (LASA & DDx) ★

LEXICAL (LASA) — SIMILAR NAMES

Hypertensive Heart Disease

Both present with left ventricular hypertrophy on echocardiogram; however, hypertensive heart disease is secondary to chronic pressure overload, whereas HCM is a primary genetic sarcomere disorder.

Athlete's Heart

Both feature increased left ventricular wall thickness; athlete's heart is a physiological adaptation to exercise that regresses with detraining, unlike the pathological hypertrophy of HCM.

CLINICAL DIFFERENTIAL DIAGNOSES (DDx)

Aortic Stenosis

Key Distinguishing Feature: Presents with a systolic murmur and LVH, but echocardiography reveals a calcified, stenotic aortic valve rather than asymmetric septal hypertrophy and SAM.

Cardiac Amyloidosis

Key Distinguishing Feature: Causes increased wall thickness but typically presents with a 'sparkling' granular appearance on echo, low voltage on ECG, and systemic signs of amyloid deposition.

Fabry Disease

Key Distinguishing Feature: An X-linked lysosomal storage disorder that causes concentric LVH; distinguished by systemic features (angiokeratomas, neuropathy) and reduced alpha-galactosidase A activity.

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Clinical Pearls

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The murmur of obstructive HCM behaves oppositely to aortic stenosis: it increases in intensity with manoeuvres that decrease preload or afterload (such as the Valsalva manoeuvre or standing) and decreases with squatting or leg elevation.

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Mavacamten, a first-in-class cardiac myosin inhibitor, has recently emerged as a targeted therapy for symptomatic obstructive HCM. It reduces the need for septal reduction therapy by directly addressing the underlying sarcomeric hypercontractility, though it requires strict echocardiographic monitoring to avoid reducing the ejection fraction below 50%.

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An apical variant of HCM (Yamaguchi syndrome) may be missed on standard echocardiography; cardiac MRI or contrast echocardiography is often required to visualise the characteristic 'spade-like' left ventricular cavity and deep T-wave inversions on ECG.

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Sudden cardiac death risk stratification relies on validated models such as the ESC HCM Risk-SCD calculator. This tool incorporates factors like maximal wall thickness, family history of SCD, unexplained syncope, non-sustained VT, and left atrial size, rather than relying on a single isolated feature to guide ICD implantation.

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Example Usage & SOAP

CLINICAL SENTENCE

"The patient is a 24-year-old male with known hypertrophic obstructive cardiomyopathy, presenting with worsening exertional dyspnoea and a resting LVOT gradient of 55 mmHg on echocardiography, which increases to 90 mmHg with Valsalva."

IN A SOAP NOTE

S: 32-year-old female with known HCM reports increased exertional chest tightness and lightheadedness over the past month. Denies frank syncope or palpitations. O: BP 118/75 mmHg, HR 68 bpm regular. Harsh crescendo-decrescendo systolic murmur heard best at the left lower sternal border, increases with standing. ECG shows LVH with deep T-wave inversions in lateral leads. Echo reveals asymmetric septal hypertrophy (max thickness 21 mm) with SAM of the mitral valve and a resting LVOT gradient of 42 mmHg. A: Symptomatic obstructive hypertrophic cardiomyopathy. Symptoms likely driven by dynamic LVOT obstruction and diastolic dysfunction. P: 1. Increase bisoprolol to 5 mg daily to improve diastolic filling and reduce LVOT gradient. 2. Avoid dehydration and heavy exertion. 3. Repeat Holter monitor to screen for NSVT. 4. Refer to specialised HCM clinic for consideration of septal reduction therapy if refractory to medical therapy.

DIFFERENTIAL DIAGNOSIS CONTEXT

Differential for unexplained left ventricular hypertrophy: (1) Hypertrophic cardiomyopathy — suggested by asymmetric septal thickening, family history, and myocyte disarray; (2) Hypertensive heart disease — suggested by long-standing poorly controlled hypertension and concentric LVH; (3) Cardiac amyloidosis — suggested by low ECG voltage despite thick walls, heart failure with preserved ejection fraction, and systemic features; (4) Fabry disease — suggested by concentric LVH, neuropathic pain, angiokeratomas, and reduced alpha-galactosidase A levels.

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Classifications & Scoring

SCORING TOOL

ESC HCM Risk-SCD Calculator

Validated clinical tool to estimate the 5-year risk of sudden cardiac death in patients with HCM. Incorporates age, maximal wall thickness, left atrial size, LVOT gradient, family history of SCD, non-sustained VT, and unexplained syncope to guide ICD implantation decisions.

Clinical Calculator ↗

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Prognosis

SHORT-TERM OUTCOME

Most patients remain asymptomatic or mildly symptomatic for decades with a normal life expectancy; however, those with severe LVOT obstruction or refractory symptoms may require septal reduction therapy to improve functional status within months.

LONG-TERM PROGNOSIS

Overall long-term survival is similar to the general population for the majority of patients. However, a subset faces an increased risk of sudden cardiac death, progressive heart failure, or thromboembolic events, necessitating lifelong risk stratification and surveillance.

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References & Coding

ICD-10 DIAGNOSTIC CODE

I42.2

LITERATURE CITATIONS & GUIDELINES

[1]Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2020;76(25):e261-e318.

[2]Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3627-3639.

[3]Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM). Lancet. 2020;396(10252):759-769.

MEDICAL DISCLAIMER — This content is intended for educational purposes and qualified healthcare professionals only. Always refer to current clinical diagnostic criteria, institutional protocols, and official guidelines. Medobo is not responsible for clinical decisions made based on this content.