Hypertrophic cardiomyopathy

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HYPERTROPHIC
CARDIOMYOPATHY
(HCM)
Dr. Michael Kapeliovich MD, PhD
11.11.2021

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Elliott et al. Eur Heart J 2008; 29:270

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CARDIOMYOPATHIES
Hypertrophic cardiomyopathy (HCM)
Dilated cardiomyopathy (DCM)
Restrictive cardiomyopathy
Arrhythmogenic right ventricular dysplasia
Unclassified
Elliott et al. Eur Heart J 2008; 29:270

4.

Circulation 2020; 142: e558-e631

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Eur Heart J 2014;35:2733-79

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HCM - Definition
HCM – a disease state in which morphologic
expression is confined solely to the heart.
It is characterized predominantly by LVH in the
absence of another cardiac , systemic or
metabolic disease capable of producing
hypertrophy in a given patient .
For this patient a disease-causing sarcomere (or
sarcomere-related) variant is identified, or
genetic etiology remains unresolved.

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Sarcomere
Tolkatchev et al. Progr Molec Biol and Translational Science 2019

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HCM - Diagnosis
• In adult pt is established by imaging (Echo, CMR)
showing a maximal end diastolic wall thickness >15
mm anywhere in left ventricle, in the absence of
another cause of hypertrophy.
• Limited hypertrophy (13-14 mm) can be diagnostic
when present in family members of a pt with HCM or
in conjunction with positive genetic test.
• For children there is a need to adjustment for body
size and growth.

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HCM : differential diagnosis
• Systemic disorders including various metabolic and multiorgan
syndromes:
RASopathies*, mitochondrial myopathies, glycogen/lysosomal
storage disease, Fabry, amyloid, sarcoid, hemochromatosis,
Danon cardiomyopathy
• Hypertension
• CAD
• Athletes heart
• Valvular and subvalvular aortic stenosis
--------------------* A group of rare genetic conditions caused by mutations in genes of the
Ras-MAPK pathway

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Etiology
• Variants of 1 of 8 or more genes encoding proteins of
the cardiac sarcomere (or sarcomere-related
structures) are implicated in causing LVH.
• Among pts with HCM ~30-60% have identifiable
pathogenic or likely pathogenic genetic variant.
• Among pts with HCM and pathogenic sarcomere
gene variant the 2 most common genes are beta
myosin heavy chain 7 (MYH7) and myosin binding
protein C3 (MYBPC3) identified in 70% of variantpositive pts

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Etiology
• Other genes (TNNI3, TNN2, TPM1, MYL2,
MYL3, ACTC1) each account for a small
proportion of pts (1-5%).
• Within these genes >1500 variants are
recognized.
• Each offspring of an affected family member
has a 50% chance of inheriting the variant.

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Pathophysiology
Dynamic LVOT obstruction
Mitral regurgitation
Diastolic dysfunction
Myocardial ischemia
Arrhythmias
Autonomic dysfunction
HF

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Diagnostic methods
• Cardiac anamnesis and family history including
3 generations
• Physical examination
• Echocardiography
• CMR
• Cardiac CT
• Heart rhythm assessment
• Angiography and invasive hemodynamic assessment
• Exercise stress testing

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Dynamic LVOT obstruction

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Left ventricular outflow tract obstruction (LVOTO)
• Either at rest or with provocation is present in ~75%
of HCM pts
• Peak LVOT gradient > 30 mm Hg is indicative of
obstruction
• LVOT gradient (resting or provoked) > 50 mm Hg in
pts with drug refractory symptoms considered an
indication for septal reduction therapy (SRT)

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Left ventricular outflow tract obstruction (LVOTO)
• Provocative maneuvers :
- standing
- Valsalva
- amyl nitrite inhalation
- exercise

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Left ventricular outflow tract obstruction (LVOTO)
• Two principal mechanisms:
1) septal hypertrophy with narrowing of LVOT
abnormal blood flow displacement of
mitral valve leaflets anteriorly
2) anatomic alterations in MV apparatus
(longer leaflets, anterior displacement of
papillary muscles)

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Left ventricular outflow tract obstruction (LVOTO)
• Adverse effects:
- high LV systolic pressure
- exacerbation of LVH
- myocardial ischemia
- prolongation of LV relaxation
- reduction of stroke volume
- increased risk of HF
- associated with reduced survival

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Left ventricular outflow tract obstruction (LVOTO):
treatment
• Beta-blockers - 1st line therapy
• Non-dihydropyridine calcium channel blockers (CCB):
diltiazem, verapamil
• Disopyramide* for pts not responding to BB or CCB
• Septum reduction therapy (SRT) - for pts who remain
severely symptomatic despite optimal medical
therapy
-----------------* a) may enhabce AV-node conduction rapid rhythm during A-Fib
b) anticholinergic effect

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Left ventricular outflow tract obstruction (LVOTO):
treatment
• Acute hypotension in pts with obstructive HCM medical emergency ;
Rx: IV vasoconstrictors (phenylephrin + beta-blocker)
• In pts with signs of HF low dose diuretics could be
used, while aggressive diuresis may decrease
preload and augment LVOTO

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Left ventricular outflow tract obstruction (LVOTO): treatment
• Septal reduction therapy (SRT) - for pts who remain severely
symptomatic despite optimal medical therapy
1) septal myectomy
2) alcohol septal ablation
- less effective in pts with high resting gradients (>100 mm Hg)
and extreme septal hypertrophy (>30 mm)
- greater risk of conduction block requiring permanent
pacemaker
- greater risk of residual obstruction and repeat intervention
(7-20%)
- advantageous in pts with frailty or comorbid conditions which
increase risk of surgical myectomy

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Nonobstructive HCM

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Management of HF in HCM

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Management of HF in HCM

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Management of HF in HCM

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Myocardial ischemia
• Mismatch between myocardial oxygen supply and
demand
- myocardial hypertrophy
- microvascular dysfunction
- impaired coronary flow reserve
- medial hypertrophy of intramural arterioles
- hyperdynamic systolic function
- LVOTO with high intracoronary pressure
- myocardial bridging

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Arrhythmias and SCD

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Atrial fibrillation
Anticoagulant Rx
1) HCM pts with clinical A-Fib

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Atrial fibrillation
Anticoagulant Rx
2) HCM pts with subclinical A-Fib >24 hours

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Atrial fibrillation
Anticoagulant Rx
3) HCM pts with subclinical A-Fib >5min , but
<24 hours

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Atrial fibrillation
Rate control

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Atrial fibrillation
Rhythm control

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Atrial fibrillation
Drugs for rhythm control
- sotalol
- amiodarone
- disopyramide (efficacy in A-Fib is not well established)
- class 1c (propafenon, flecainide) not recommended in
pts with structural disease, but is safe in pts with ICD
- dofetilide

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Atrial fibrillation
Rhythm control

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Ventricular arrhythmias

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Ventricular arrhythmias

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Ventricular arrhythmias

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SCD: risk assessment and prevention
• HCM is the most common cause of SCD in young
people in North America
• Among pts with HCM younger at higher risk for SCD
than older pts
• Major clinical risk factors help to stratify pts
according to level of risk and to identify those most
likely to benefit from primary ICD therapy
• Risk score is available , but it’s performance is not
very good
• SCD assessment at initial visit and repeated every 1-2
years is recommended

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HCM sudden cardiac death risk stratification: clinical risk
factors

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HCM sudden cardiac death risk stratification
• Family Hx of sudden death from HCM
- < 50 years old
- 1st degree relative
- other relative (generally 2nd degree, but multiple
SCDs in tertiary relatives should be also consider
relevant

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HCM sudden cardiac death risk stratification
• Massive LVH
- wall thickness > 30 mm in any segment within
chamber by Echo or CMR imaging
- > 28 mm in individual pts
- for pediatric pts with HCM threshold for wall
thickness is not well established: max wall
corresponds to z-score > 20 and > 10 mm seems
reasonable

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HCM sudden cardiac death risk stratification
• Unexplained syncope
- > 1 unexplained episodes of acute transient loss of
consciousness, unlikely to be of neurogenic
(vasovagal) etiology
- not attributable to LVOTO
- especially occurring within 6 months of evaluation;
events beyond 5 years in the past have little
significance

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HCM sudden cardiac death risk stratification
• HCM with LV dysfunction
- systolic LV dysfunction with EF < 50% by Echo or
CMR imaging

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HCM sudden cardiac death risk stratification
• LV apical aneurysm
- apical aneurysm defined as a discrete
thin-walled dyskinetic or akinetic segment of
the most distal portion of the LV chamber,
independent of size

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HCM sudden cardiac death risk stratification
• Extensive LGE on MRI imaging
- diffuse and extensive LGE, representing fibrosis,
either quantified or estimated by visual inspection
- comprising > 15% of LV mass
- not established in children

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HCM sudden cardiac death risk stratification
• NSVT on ambulatory monitoring
- runs are frequent (> 3)
greater weight
- long (> 10 beats)
- fast (> 200 bpm)
- occurring over 24-48 hr of monitoring
- for pediatric pts a VT rate that exceeds the
baseline sinus rate by 20% is considered significant

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Patient selection for ICD

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Patient selection for ICD

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Patient selection for ICD

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Elliott et al. Eur Heart J 2014;35:2733-79

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Genotype-positive, phenotype-negative

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Lifestyle considerations for patients with HCM

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Thank you for attention

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Backup slides