Hypertrophic Cardiomyopathy

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Hypertrophic cardiomyopathy\: asymmetrical increase in left ventricular wall thickness not explained by abnormal loading
conditions; autosomal dominant inheritance with mutations in cardiac sarcomere protein genes.
Prevalence\: 1 in 500, most common in young adults; leading cause of sudden cardiac death in this age group.
Aetiology\: genetic condition a
binding protein C, cardiac troponin C); autosomal dominant inheritance.
Risk factors\: primarily family history.
Symptoms\: dyspnoea (90%), syncope/presyncope, chest pain, palpitations.
Clinical examination\: systolic ejection murmur, S4 heart sound, holosystolic murmur, double apical beat, lateral
displacement of apical pulse, prominent a wave.
Investigations\: ECG (LV hypertrophy, ST/T changes, Q-waves), ambulatory ECG, echocardiography (asymmetrical LV wall
thickening, LVOT obstruction), cMRI, cCT.
Management\: lifestyle advice (avoid dehydration/alcohol, weight loss), beta-blockers, CCBs, anticoagulation for AF, heart
failure management, ICD for secondary prevention, septal reduction therapy for LVOT obstruction.
Complications\: sudden cardiac death, arrhythmias, heart failure, infective endocarditis; risk factors for sudden death
include LV wall thickness, LA diameter, LVOT gradient, family history, NSVT, unexplained syncope, age.
Article 🔍
A comprehensive topic overview

Introduction

Hypertrophic cardiomyopathy is characterised by the presence of an asymmetrical increase in left ventricular wall
thickness, not solely explained by abnormal loading conditions (commonly hypertension and aortic stenosis).
1
It is typically inherited via autosomal dominant pattern with mutations in cardiac sarcomere protein genes.
Hypertrophic cardiomyopathy has an estimated prevalence of 1 in 500 and most commonly presents in young adults. It is
the leading cause of sudden cardiac death in this age group.
2

Aetiology

Hypertrophic cardiomyopathy is a primarily genetic condition a
beta-myosin heavy chain, myosin-binding protein C and cardiac troponin C, are structurally important in cardiac muscle.
3
However, the penetrance and expression of responsible genes vary, with complex presentations and sequela. Such
diversity in causal mutations and their expression results in an extremely heterogeneous range of phenotypes, each with a
di
Broadly speaking, hypertrophy is either secondary to functional and structural defects in myocytes or increased storage of
materials, such as glycogen.
4These mutations are commonly passed via autosomal dominant inheritance and these patients present with more severe
features of the disease.
Figure 1. A typical pedigree for autosomal dominant inheritance.
5
Disease characteristics
The primary feature of hypertrophic cardiomyopathy is asymmetrical left ventricular wall thickening, typically of the
septum. Thickening can be seen in any part of the ventricle.
Other pathological features include myocardial
coronary microcirculatory function.
Hypertrophic cardiomyopathy has a bimodal peak occurrence most commonly presenting in the third decade of life.
It is more common in men although the autosomal dominant inheritance pattern is without sex preference. However,
hypertrophic cardiomyopathy presents younger in women and they tend to be more symptomatic than men.

Risk factors

The only risk factor for hypertrophic cardiomyopathy (given it is a mostly inherited condition) is family history.

Clinical features

Most a
of hypertrophic cardiomyopathy is commonly incidental.
6
History
Typical symptoms of hypertrophic cardiomyopathy include\:
7
Dyspnoea (90%)\: due to left ventricular diastolic dysfunction and resultant pulmonary oedema.
Syncope and presyncope\: due to inadequate cardiac output (especially on exertion) or arrhythmias. Patients with
syncope are at high risk of sudden cardiac death.
Chest pain\: due to microvascular complications of the disease or mismatch between increased oxygen requirement of
the hypertrophied myocardium and reduced perfusion of coronary arteries due to impaired diastolic relaxation.
Palpitations\: due to arrhythmias, both supraventricular and ventricular in origin.
Other important areas to cover in the history include\:
Family history\: sudden cardiac death, unexplained heart failure, cardiac transplantation or implantable cardioverter-
de
Construction of a thorough pedigree can identify other family members at risk.
Clinical examinationIn patients with suspected hypertrophic cardiomyopathy, a thorough cardiovascular examination is required.Examination is often unremarkable and
cardiomyopathy include\:
Systolic ejection murmur loudest between the apex and left sternal border\: indicative of left ventricular out
obstruction (accentuated with Valsalva manoeuvre).
Fourth heart sound (S4) of atrial systole against a non-compliant ventricle.
Holosystolic murmur loudest at the apex or axilla\: indicative of mitral regurgitation.
Double apical beat of ventricular contraction and left atrial contraction against hypertrophic ventricle.
Lateral displacement of the apical pulse.
Splitting of the second heart sound.
Prominent a wave\: indicative of reduced right ventricular compliance with massive left ventricular hypertrophy.

Di

It is important to di
hypertension, aortic stenosis, athletic heart, and cardiac amyloidosis.
A detailed history is essential for making this distinction as well as a thorough review of past medical and family history.
Imaging, typically echocardiography, is also important for the exclusion of other di
Other less common di
Metabolic disorders (e.g. Anderson-Fabry disease, Pompe disease)
Primary mitochondrial disease
Neuromuscular disease (e.g. Friedreich’s ataxia)
Malformation syndromes (e.g. Noonan syndrome, LEOPARD syndrome)

Investigations

Bedside investigations
Relevant bedside investigations include\:
Blood pressure\: to exclude hypertension.
Electrocardiography (ECG)\: left ventricular hypertrophy manifests as increased voltages in precordial leads and non-
speci
dilatation.
Ambulatory electrocardiography (ECG)\: forms part of the initial risk assessment. Primary
asymptomatic non-sustained ventricular tachycardia (NSVT) and paroxysmal supraventricular arrhythmias (SVT).
Laboratory investigations
While there is no speci
other causes of ventricular dysfunction and potential precipitating factors.
Relevant laboratory investigations include\:
Full blood count\: to look for anaemia.
Urea and electrolytes\: for renal dysfunction.
Liver function tests\: for liver dysfunction.
Thyroid function tests\: thyroid disease can exacerbate left ventricular dysfunction.
NT-proBNP\: quantify the degree, if any, of heart failure.
Imaging
Echocardiography is the
Asymmetrical left ventricular wall thickness ≥15mm in one or more left ventricular myocardial segments in diastole, with
no other abnormal loading conditions, is suggestive of the diagnosis.
1Modalities of echocardiography include\:
Transthoracic echocardiography (TTE)\: is used to assess left ventricular wall thickness during diastole; left ventricular
out
left atrial enlargement and diastolic dysfunction. Images should be acquired at rest, during a Valsalva manoeuvre in
sitting and semi-supine positions and then standing if no left ventricular out
Exercise stress echocardiography\: indicated in symptomatic patients with no left ventricular out
identi
Transoesophageal echocardiography (TOE)\: indicated if images of left ventricular out
abnormalities are poorly visualised. Perioperative TOE is used to guide surgical strategy prior to septal myomectomy and
for detection of surgical complications.
Other relevant imaging investigations include\:
Cardiac magnetic resonance imaging (cMRI)\: should be considered as part of a thorough assessment if local resources
and expertise permit, however, it is not required for diagnosis. cMRI allows superior identi
and anterolateral hypertrophy and is, therefore, more likely to pick up apical hypertrophic cardiomyopathy as well as
other subtle markers of disease.
Cardiac computed tomography (cCT)\: consider in patients with poor echocardiography images and contraindications to
magnetic resonance imaging.
Specialist tests
Other specialist tests include\:
Cardiopulmonary exercise testing\: recommended in all patients and provides functional information about the patient’s
cardiac function. Useful in di
Electrophysiological testing\: indicated if proven persistent or recurrent supraventricular tachycardia or in patients with
ventricular pre-excitation.

Management

General lifestyle advice for all patients includes avoiding dehydration and alcohol, encouraging weight loss and safety
netting for symptoms of deterioration.
Angina
Beta-blockers and calcium channel blockers can be used in patients with prolonged or exertional angina-like chest pain
in the absence of signi
Safe use of oral nitrates relies on the exclusion of left ventricular out
cautiously.
1
Atrial
The prevalence of atrial
1
The two greatest predictors for paroxysmal or permanent atrial
diameter is ≥45mm, the patient should undergo 6 to 12 monthly, 48-hour ambulatory electrocardiogram monitoring to
exclude atrial
8
Management of atrial depends on the haemodynamic status of the patient\:
Haemodynamically unstable\: emergency direct current cardioversion
Haemodynamically stable\: beta-blockers or verapamil/diltiazem
Some important considerations for rate and rhythm control of atrial
Digoxin is not suitable in patients with left ventricular out
Flecainide should be avoided as it may prolong the QT interval
Anticoagulation is recommended in all patients with atrial
thromboembolic events. Continuation of lifelong anticoagulation, despite cardioversion and maintenance of sinus rhythm,
is also recommended.CHA DS -VASc scoring is not appropriate. HAS-BLED scoring can be used to evaluate a patient’s risk of bleeding.
8
2 2
Warfarin is the anticoagulant of choice. There is currently no data on the use of novel oral anticoagulants, and these,
therefore, are only indicated if warfarin is not tolerated.
Heart failure
Management of heart failure in patients with hypertrophic cardiomyopathy is divided depending on the patients’ ejection
fraction. In severe cases, cardiac resynchronisation therapy and cardiac transplant may be considered\:
Preserved ejection fraction\: reduce left ventricular diastolic pressure and improve left ventricular
blockers, verapamil or diltiazem and, if indicated, loop diuretics.
Reduced ejection fraction\: a threshold ejection fraction of \<50%, given the preservation of cavity size in patients with
hypertrophic cardiomyopathy, is recommended when considering renin-angiotensin-aldosterone system inhibition.
9
Below this threshold, management with diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or
angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) is recommended in keeping with
heart failure guidelines.
Cardiac transplantation can be considered in patients with NYHA functional class III or IV symptoms, refractory to medical
management and without left ventricular out
Implantable cardioverter-de
An implantable cardioverter-de
ventricular tachycardia or ventricular
haemodynamic instability.
Primary prevention with an implantable device is considered within a clinical context alongside risk factors for sudden
cardiac death.
1
Left ventricular out
Left ventricular out≥30mmHg. Gradient ≥50mmHg is
the threshold at which left ventricular out
Investigation of LVOTO is initially with 2D and Doppler echocardiography at rest, Valsalva and on standing. Further
management depends on the peak provoked tract gradient.
If on exercise stress echocardiography the out
\<50mmHg, medical therapy is the mainstay of treatment.
10
The purpose of medical therapy is to improve exercise tolerance, improve symptoms and improve left ventricular diastolic

Medications include vasodilating beta-blockers initially, followed by disopyramide, if QTc within normal limits, or verapamil,
if beta-blockers are ine1
Low-dose loop diuretics may improve dyspnoea.
If symptoms of left ventricular out
be considered. The two main procedures are ventricular septal myomectomy or septal alcohol ablation.
Indications for septal reduction therapy are\:
Left ventricular out≥50mmHg
New York Heart Association (NYHA) grade III or IV
Recurrent exertional syncope despite medical treatment
If myomectomy and septal alcohol ablation are contraindicated, dual-chamber, biventricular pacing has been shown to
improve quality of life and functional capacity in selected patients.
12
Follow-up
All patients with unexplained hypertrophic cardiomyopathy should receive genetic counselling including testing of
degree relatives.
Patients should have an annual follow-up with ambulatory ECG monitoring.Complications
Complications of hypertrophic cardiomyopathy include\:
13
Sudden cardiac death
Arrhythmias\: supraventricular (especially atrial
Heart failure
Infective endocarditis
Risk factors for sudden death
Although the annual rate of sudden cardiac death in patients with hypertrophic cardiomyopathy is estimated at less
than 1%, some speci
14
The risk for sudden cardiac death can be estimated based on the following factors\:
1
Maximal left ventricular wall thickness
Left atrial diameter
Maximal left ventricular out
Family history of sudden cardiac death
Non-sustained ventricular tachycardia
Unexplained syncope
Age
HCM Risk-SCD is a validated prediction tool used for sudden cardiac death risk in hypertrophic cardiomyopathy.

References

European Society of Cardiology. 2 0 1 4 E S C G u i d e l i n e s o n d i a g n o s i s a n d m a n a ge m e n t o f h y p e r t r o p h i c c a r d i o m y o p a t h y .
Published August 2014. Available from\: [LINK]
Circulation. P r e v a l e n c e o f h y p e r t r o p h i c c a r d i o m y o p a t h y i n a ge n e r a l p o p u l a t i o n o f y o u n g a d u l t s . Published August 1995.
Available from\: [LINK]
National Library of Medicine (US). Genetics Home Reference. F a m i l i a l H y p e r t r o p h i c C a r d i o m y o p a t h y . Published May 2020.
Available from\: [LINK]
Circulation Research. H y p e r t r o p h i c C a r d i o m y o p a t h y \: G e n e t i c s , P a t h o g e n e s i s , C l i n i c a l M a n i f e s t a t i o n s , D i a g n o s i s , a n d
T h e r a p y . Published September 2017. Available from\: [LINK]
Figure 1. Wikimedia. A t y p i c a l p e d i g r e e f o r a u t o s o m a l d o m i n a n t i n h e r i t a n c e . License\: [CC-BY-SA]. Available from\: [LINK]
The Lancet. H y p e r t r o p h i c c a r d i o m y o p a t h y . Published August 2012. Available from\: [LINK]
Medscape. H y p e r t r o p h i c C a r d i o m y o p a t h y C l i n i c a l P r e s e n t a t i o n . Published January 2016. Available from\: [LINK]
Arrhythmia and Electrophysiology Review. A t r i a l
April 2017. Available from\: [LINK]
JACC\: Heart Failure. C l i n i c a l s p e c t r u m a n d m a n a g e m e n t o f h e a r t f a i l u r e i n h y p e r t r o p h i c c a r d i o m y o p a t h y . Published May
2018. Available from\: [LINK]
European Society of Available from\: [LINK]
Cardiology. I n v e s t i g a t i o n o f l e f t v e n t r i c u l a r o u t
American Heart Journal. T h e r a p e u t i c e
p a t i e n t s w i t h h y p e r t r o p h i c c a r d i o m y o p a t h y . Published February 1992. Available from [LINK]
Global Cardiology Science and Practice. C a r d i a c p a c i n g i n p a t i e n t s w i t h h y p e r t r o p h i c o b s t r u c t i v e c a r d i o m y o p a t h y .
Published August 2018. Available from\: [LINK]
Patient.info. H y p e r t r o p h i c C a r d i o m y o p a t h y . Published August 2017. Available from\: [LINK]European Society of Cardiology. P r e v e n t i o n o f s u d d e n d e a t h i n h y p e r t r o p h i c c a r d i o m y o p a t h y \: b r i d g i n g t h e ga p s i n
k n o w l e d g e . Published July 2016. Available from\: [LINK]

Reviewer

Dr Chih Wong
Consultant Cardiologist

Related notes

Acute Coronary Syndrome (ACS)
Acute Heart Failure
Atrial Fibrillation (AF)
Atrioventricular Block
Brugada Syndrome

Test yourself

Contents

Introduction
Aetiology
Risk factors
Clinical features
Source\: geekymedics.com