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Hypertrophic
cardiomyopathy
Frank and Mehta
Definition
• The term cardiomyopathy is purely descriptive, meaning disease of the
heart muscle
• Hypertrophic cardiomyopathy (HCM) is a disease in which the heart
muscle (myocardium) becomes abnormally thick — or hypertrophied. This
thickened heart muscle can make it harder for the heart to pump blood.
Hypertrophic cardiomyopathy may also affect the heart's electrical system
• In most people, hypertrophic cardiomyopathy doesn't cause severe
problems and they're able to live a normal life. In a small number of
people with hypertrophic cardiomyopathy, the thickened heart muscle can
cause symptoms such as shortness of breath, problems in the heart's
electrical system resulting in life-threatening arrhythmias and sudden
cardiac death. Hypertrophic cardiomyopathy is the most common cause of
heart-related sudden death in people under 30
The myocardial disarray
•
Microscopic examination of the heart muscle shows that it is
abnormal. The normal alignment of muscle cells is absent and
this abnormality is called myocardial disarray. This disarray
can contribute to an irregular heartbeat (arrhythmia) in some
people.
• Synonyms: HOCM, IHSS and
muscular sub-aortic stenosis
• 1 in 500 of the UK population
suffers from the disease
• Note that thickening of LV wall
resembling HCM occurs in other
disease states: Noonan’s
syndrome, Mitochondrial
myopathies, Friedreich
ataxia,metabolic
disorder,Anderson-Fabry
disease,LV-non compaction and
cardiac amyloidoses.
Hypertrophy
Differential diagnosis
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HCM
Can be asymmetric
Wall thickness: > 15 mm
LA:
> 40 mm
LVEDD :
< 45 mm
Diastolic function: always
abnormal
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Athletic heart
Concentric & regresses
< 15 mm
< 40 mm
> 45 mm
Normal
Stimulus
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Unknown
Disorder of intracellular calcium metabolism
Neural crest disorder
Papillary muscle malpositioned and
misoriented
Genetics and molecular diagnosis
• Mandelian autosomal dominant trait.
• Mutations in any of the 10 genes, each encoding protein component of
cardiac sarcomere
• Beta-myosin heavy chain(first identified) chromosome 14. Myosin-binding
protein C and cardiac troponin T comprise more than half genotyped
patients to date. Regulatory and essential myosin light chains, titin, alphatropomyosin, alpha-actin, cardiac troponin I and alpha –myosin heavy
chain account for fewer cases.
http://genepath.med.harvard.edu/~seidman/cg3/
genetic basis
Symbol
Gene
Mutations
HCM
DCM
MYH7
betacardiac
Myosin
Heavy
Chain
194
13
list
MYBPC3
cardiac
MyosinBinding
Protein C
149
1
list
TNNT2
cardiac
Troponin
T
31
6
list
TNNI3
cardiac
27
Troponin I
1
list
TPM1
alphaTropomyo 11
sin
2
list
ACTC
cardiac
alphaActin
7
2
list
MYL2
cardiac
Regulator
y Myosin
Light
Chain
10
0
list
MYL3
cardiac
Essential
Myosin
Light
Chain
5
0
list
434
25
total mutations
• Phenotypic expression of HCM(LVH) is product not only of casual
mutation, but also of modifier genes and environmental factors.
• Increased risk of atrial fibrillation in HCM identified with beta-myosin
heavy chain Arg 663 His mutation. Not all the individuals harbouring the
gene defects will express clinical features of HCM.(note silent mutations).
• Substantial LV modelling with spontaneous LVH occurs associated with
accelerated body growth and maturation(adolescence )
Pedigree
• autosomnal dominant
• passed on from affected
males and females
• The disease does not
skip generations
Variants of HCM
Most common location: subaortic , septal, and ant. wall.
• Asymmetric hypertrophy (septum and ant. wall): 70 %.
• Basal septal hypertrophy: 15- 20 %.
• Concentric LVH: 8-10 %.
• Apical or lateral wall: < 2 % (25 % in Japan/Asia): characteristic giant Twave inversion laterally & spade-like left ventricular cavity: more benign.
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The major abnormality of the heart in HCM is an
excessive thickening of the muscle. Thickening
usually begins during early adolescence and
stops when growth has finished, ie late teens to
early twenties. It is uncommon for thickening to
progress after this age
The left ventricle is almost always affected, and
in some patients the muscle of the right
ventricle also thickens.
It can be seen from Figure that the hypertrophy
is usually greatest in the wall separating the left
and right chambers of the heart (the septum).
The muscle thickening in this region may be
sufficient to narrow the outflow tract . In some
patients this thickening is associated with
obstruction to the flow of blood out of the heart
into the major blood vessel, the aorta.
• In some cases of asymmetric
septal hypertrophy, obstruction
to the outflow of blood from the
heart may occur, as shown here.
The mitral valve touches the
septum, blocking the outflow
tract. Some blood is leaking back
through the mitral valve (mitral
regurgitation)
The variants
Pathophysiology of HCM
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Dynamic LV outflow tract obstruction
Diastolic dysfunction
Myocardial ischemia
Mitral regurgitation
Arrhythmias
Pathophysiology
• Left ventricular outflow tract gradient
• ↑ with decreased preload, decreased
afterload, or increased contractility.
• Venturi effect: anterior mitral valve leaflets &
chordae sucked into outflow tract →
↑ obstruction, eccentric jet of MR in mid-late
systole.
Left ventricular outflow tract
gradient
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Approximately 25% of patients with HCM have a dynamic systolic pressure
gradient in the left ventricular outflow tract caused by contact between the mitral
valve leaflet(s) and the interventricular septum under resting conditions
Outflow tract gradient in excess of 30 mmHg is an important cause of symptoms.
Some authors believe that the gradient is simply a consequence of high velocity
flow through the aortic valve, and hence does not represent a real obstruction to
cardiac output.
However, if the gradient is greater than 50 mmHg, the percentage of systolic
volume ejected before the beginning of SAM is greatly reduced and this is
probably responsible for patients' symptoms when severe, outflow tract gradient
can cause dyspnoea, chest pain, syncope, and predisposes to the development of
atrial arrhythmias ; it is also an independent predictor of disease progression and
adverse outcome, including sudden death
Physical examination
Maneuvers that ↓ end-diastolic volume
(↓ venous return & afterload, ↑ contractility)
• Vasodilators
• Inotropes
• Dehydration
• Valsalva
• Amyl nitrite
• Exercise
→ ↑ HCM murmur
General considerations for natural
history and clinical course
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Clinical presentation in any phase from infancy to old age.variable clinical course
25 % of cohort achieve normal longevity.
Course of many patients may be punctated by adverse clinical events: sudden
cardiac death, embolic stroke, and consequences of heart failure
Progressive symptoms largely of exertional dyspnea, chest pain, impaired
conciousness, syncope near-syncope or pre-syncope: depending on functionality
of LV systole, progression to advanced congestive heart failure(end-stage phase!)
with LV remodelling and systolic dysfunction, complications attributable to AF,
including embolic stroke.
Triad: DOE(per exclusionem), angina, presyncope/syncope
Sustained V-Tach and V-Fib: most likely mechanism of syncope/ sudden death.
Dependant on atrial kick: CO ↓ by 40 % if A. Fib present.
Note poor prognosis in case of male patient, yonger age family Hx. For sudden
death, Hx. Of syncope, exercise induced hypotention(worst)
Brockenbrough response
• In PVC: augmented preload, increased
contractibility, in HCM worsening of LVOT
obstruction increase in pressure gradient.
• Normal subjects following PVC shows a
proportional increase in Ao systolic and LV
systolic pressures.
Management
• The first step in developing a treatment plan is to
demonstrate whether or not a dynamic left ventricular
outflow tract obstruction is present.
• Physical examination should reveal a dynamic outflow tract
murmur often accompanied by a bifid carotid impulse.
• The treatment of hypertrophic obstructive cardiomyopathy
has been divided into pharmacologic therapy versus more
invasive procedures (dual-chamber pacing, catheter-based
septal ablation, and septal myectomy)
Pharmacologic Therapy
• the goal of medications in hypertrophic cardiomyopathy is to
blunt these catecholamine-induced phenomena
• Drugs, which suppress contractility (negative inotropic agents)
and suppress heart rate (negative chronotropic agents), have
been the mainstays of therapy.
• Beta-adrenergic receptor blockers, calcium entry blockers, and
disopyramide have been the drugs of choice.
• Since most patients have symptoms only with exertion, the
resting gradient should not be used as assessment of efficacy
of medical therapy. The calcium channel blockers are a good
alternative if a beta-blocker cannot be tolerated.
Dual-Chamber Pacing
• In the patient with sinus rhythm, the normal activation and contraction
sequence of the left ventricle results in the base of the heart commencing
contraction prior to the apical portion.
• This results in septal contraction which projects into the left ventricular
outflow tract with subsequent left ventricular outflow obstruction.
• Pacing the ventricle from the right ventricular apical lead position allows
the apical segments to contract prior to the basal segments and helps with
ventricular emptying before the outflow obstruction can occur.
• Chronic pacing may result in remodeling of the ventricle, such that there
is widening of the left ventricular outflow tract to further decrease the
gradient.
• Dual-chamber pacing of both the atrium and the ventricle is necessary for
synchronization of atrial and ventricular contraction
• The gold standard for symptomatic relief in patients with hypertrophic
obstructive cardiomyopathy is septal myectomy. Via an aortotomy, the
ventricular septum is debulked at the basal and mid-ventricular levels.
Additional muscle is usually removed from the anterior wall as well. This
results in immediate enlargement in left ventricular outflow tract and
abolishment of the gradient in most cases . In addition, if mitral
regurgitation is secondary to the distortion of the mitral valve leaflets
from the systolic anterior motion, the mitral regurgitation is also
abolished. All of this results in a significant decrease in filling pressures
and a significant improvement in diastolic filling of the heart.
Echocardiographic still
frames from the
parasternal long-axis. The
left images were obtained
prior to surgical myectomy,
while the right images
were obtained after
myectomy in the same
patient. The bottom
images are magnified
views of the left ventricular
outflow tract. Note the
surgical "bite" from the
septum and enlargement
of the outflow tract. Ao =
aortic root, LA = left atrium,
LV = left ventricle.
• It is important to recognize that the ideal
patient for septal myectomy has idiopathic
hypertrophy localized to the basal ventricular
septum.
Echocardiographic still
frames from the apical
long-axis. Note the
massively enlarged
papillary muscle inserting
directly into the anterior
mitral leaflet (arrows). The
left image is a diastolic
frame and the right image
is a systolic frame. There is
obstruction caused by the
hypertrophied papillary
muscle at the mid-cavity
level in this patient. LA =
left atrium, LV = left
ventricle, RV = right
ventricle.
Non-Surgical Septal Ablation
Echocardiographic still frames
(systole) from the parasternal
long-axis. The image on the
left is prior to catheter-based
septal ablation, while the right
image was obtained at followup 3 months after the
procedure. Note the systolic
anterior motion of the mitral
valve causing obstruction in
the baseline image, which is
abolished due to akinesis of
the septum at follow-up
(arrows). Ao = aortic root, LA =
left atrium, LV = left ventricle.
• Recent interest has been generated with a catheter-based
therapy-septal ablation. With this procedure, installation of
ethyl alcohol is performed through a PTCA balloon catheter
and carefully selected septal perforator branches. This results
in a localized myocardial infarction of the basal septum. There
have been cases where intractable ventricular fibrillation has
occurred during the procedure. Large ventricular septal
defects resulting in death have occurred. Also, there have
been reported cases where the alcohol diffuses through
collateral circulation to involve the entire wall, resulting in a
large anteroapical myocardial infarction.
HCM Patients Without
Obstruction
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The activation of the local (myocardial tissue) renin-angiotensin cascade (RAS) has
been reported in HCM and other hypertrophic ventricles. Inhibition of the tissue
RAS via intracoronary infusions of ACE inhibitor can improve diastolic properties.
However, systemic administration has not been widely studied. Caution must be
taken prior to commencing therapy with antagonists of RAS (ACE inhibitor,
angiotensin receptor blocker, etc.) that the patients have no resting or inducible
outflow gradient. The afterload reduction that is produced by these agents can
exacerbate the obstructive tendency, and counteract any gains made in diastolic
function. Drugs, which slow or blunt the heart rate, can facilitate left ventricular
filling by maintaining an adequate diastolic filling period. Additionally, low-dose
diuretics can be useful adjuncts in non-obstructive HCM. A novel surgical
technique has been developed for patients with severely limiting dyspnea and
apical HCM. Debulking of the apical myocardium results in a larger ventricular
cavity and improved operating compliance at end-diastole
Prevention of Sudden Death in
HCM
• Patients who have been resuscitated from cardiac arrest or have sustained
ventricular tachycardia are clearly at increased risk.
• secondary prevention of sudden death with implantable defibrillator
appears to be efficacious
• Primary prevention of sudden is much more difficult. HCM with one or
more first-degree relatives who have had SCD would appear to be a great
risk. Those with the most severe forms of hypertrophy have also been
reported to harbor increased risk. Other factors such as nonsustained
ventricular tachycardia, syncope in young patients, perfusion defects,
hypotensive response to exercise, etc., have also been studied in HCM.
The approach to place ICDs in patients with prior cardiac arrest, sustained
ventricular tachycardia, or a significant family history of sudden death
should be considered.
References
• http://www.cardiovascularultrasound.com/content/6/1/19
• http://www.escardio.org/guidelines-surveys/escguidelines/GuidelinesDocuments/guidelines-HCM-FT.pdf
• http://www.mayoclinic.com/health/hypertrophiccardiomyopathy/DS00948/DSECTION=risk-factors
• http://www.mayoclinic.org/hypertrophiccardiomyopathy/physiciansguide.html