Download Hypertrophic Cardiomyopathy

Hypertrophic
Cardiomyopathy
RAGHOTHAM PATLOLA, MD, FACC, FSCAI
INTERVENTIONAL CARDIOLOGIST
History
-
disease was first described in the 1950’s in England
the diagnosis was originally made based on physical
findings and M-mode echocardiography
clustering of disease in families, autosomal
dominant inheritance pattern
Pathogenesis
Macroscopic examination of the myocardium:
- the ventricular wall is thickened, preferentially
affecting the interventricular septum
– even when the hypertrophy is diffuse it is usually
asymmetrical, affecting some parts of the myocardium
more than others
- the ventricular cavity is
typically small
- the mitral valve often has
elongated leaflets and is
misshapen
Shirani J et. al, JACC 2000
Pathogenesis
Microscopic examination of the myocardium:
- myocyte hypertrophy and disarray
- myocardial fibrosis
– the myocardial interstitium has increased amount
of fibroblasts, fibrin and collagen
- smaller than normal intramural coronary arteries
Adapted from Shirani J et. al, JACC 2000
Pathogenesis
Focal distribution of myocyte disarray (to the left) adjacent to normal parallel alignment
of myocytes;
Adapted from: Varnavaa AM et al., Heart 2000;84:476-482
Reasons for ventricular hypertrophy
Myocardial hypertrophy frequently happens in conditions
causing increased afterload.
The ventricle is working against high pressure, or
“pumping” higher than normal volume.
Left ventricular hypertrophy:
- systemic hypertension
- aortic valve stenosis
Reasons for ventricular hypertrophy
Myocardial hypertrophy frequently happens in conditions
causing increased afterload.
Ventricle working against high pressure, or “pumping”
higher than normal volume.
Right ventricular hypertrophy:
- pulmonary hypertension
– asthma, COPD
– pulmonary thromboembolic disease
– primary pulmonary hypertension
- pulmonary valve stenosis
- left-to-right shunts (volume overload)
Reasons for ventricular hypertrophy
Myocardial hypertrophy frequently happens in conditions
causing increased afterload.
Ventricle working against high pressure, or “pumping”
higher than normal volume.
In these conditions:
- the hypertrophy is symmetric
- the ventricle eventually dilates as it cannot cope with
the pressure and/or volume overload
Hypertrophic Cardiomyopathy
- absence of high blood pressure or valvular stenosis
- left ventricular cavity usually small
- ventricular hypertrophy is asymmetric
- search for a genetic abnormality that might be causing
this disease
- mutation of b-myosin heavy chain, one of the proteins of
the myocardial sarcomere
Components of the Sarcomere
Adapted from: Spirito, P. et al. N Engl J Med 1997;336:775-785
Hypertrophic Cardiomyopathy
Adapted from: Spirito, P. et al. N Engl J Med 1997;336:775-785
Hypertrophic Cardiomyopathy
-
various degree of hypertrophy
various degree of obstruction
various age at presentation
various mortality risk
Hypertrophic Cardiomyopathy
Spirito, P. et al. N Engl J Med 1997;336:775-785
> 140
Pathophysiology
-
dynamic left ventricular outflow tract obstruction
mitral regurgitation
diastolic dysfunction
myocardial ischemia
cardiac arrhythmias
Adapted from: Nishimura, N Engl J Med 2004
1. Dynamic left ventricular outflow tract
obstruction
-
the original “classic” feature
we now know that it is absent in about half of the
patients, and the severity of the obstruction varies
greatly in those who do have it
The causes of obstruction:
- narrowed left ventricular outflow tract due to
hypertrophied interventricular septum
- anterior displacement of the mitral valve leaflets during
systole (SAM- systolic anterior motion of the mitral
valve).
1. Dynamic left ventricular outflow tract
obstruction
The severity of obstruction increases with:
- any maneuver that increases the force of contraction
- any maneuver that decreases filling of the ventricle
1. Dynamic left ventricular outflow tract
obstruction
The severity of obstruction increases with:
- any maneuver that increases the force of contraction
 exercise
 positive inotropic agents
- any maneuver that decreases filling of the ventricle
 volume depletion
 sudden assumption of upright posture
 tachycardia
 Valsalva maneuver
Nomenclature
Idiopathic Hypertrophic Subaortic Stenosis (IHSS)
Hypertrophic Obstructive Cardiomyopathy (HOCM)
Assymetric Septal Hypertrophy (ASH)
Muscular Subaortic Stenosis (MSS)
Hypertrophic Cardiomyopathy (WHO)
2. Mitral Regurgitation
-
non-coaptation of mitral leaflets in systole (at the time
when the mitral valve should be closed) due to
systolic anterior motion of the anterior mitral leaflet
(SAM)
-
structural abnormalities
of the mitral apparatus
3. Diastolic Dysfunction
-
the myocardium is stiff, non-compliant
the left ventricular diastolic pressure is elevated
the filling of the ventricle in diastole is impaired
the early diastolic filling phase (when most of the
filling occurs under normal conditions) is prolonged
and diminished and most of the filling occurs late in
ventricular diastole, during the atrial systole
-
many symptoms are a result of diastolic dysfunction
PAo systolic
LVEDP
SV
Volume
4. Myocardial ischemia
-
occurs in the absence significant stenosis of epicardial
coronary arteries
(i.e. coronary angiogram would be “clean”)
The mechanisms of ischemia include:
- supply/demand mismatch due to increased muscle
mass
- increased wall tension due to impaired relaxation
during diastole
- abnormal intramyocardial arteries
5. Arrhythmias
-
Paroxysmal supraventricular arrhythmias
- occur in 30-50%, result in shorter diastolic filling
time; patients have palpitations, shortness of
breath, may experience syncope
-
Atrial fibrillation
- 15-20%, poorly tolerated – not only is the time
for diastolic filling decreased, but patients loose
the “atrial kick”
-
Non-sustained ventricular tachycardia
- occurs during ambulatory monitoring in 25% of
patients
5. Arrhythmias
-
Sustained ventricular tachycardia/ventricular
fibrillation
– this is the lethal event for many patients with
hypertrophic cardiomyopathy
– it is more likely to happen during intense physical
exertion
Killer that claims four young lives each week
Daily Express - 31st August 2004
By Hilary Freeman
Parents call for action on sudden deaths - Jo Revill Health Editor
The Observer - 13th June 2004
Teenager collapses dancing with friends
Daily Mail - 17th May 2004
Unexpected tragedies
Cycling Weekly - 17th April 2004
Clinical Manifestations
The estimates of prevalence and mortality have
varied based on the source of data.
Originally thought to be rare (1 in 2000) and lethal
(3-6%/year)
vs.
Unselected population: 1 in 500 (0.2%)
Overall yearly mortality below 1%
Clinical Manifestations
• dyspnea
• fatigue
• decreased functional capacity
• angina pectoris
• dizziness
• syncope
• sudden cardiac death
• no symptoms
The severity of symptoms does not necessarily
correlate with the severity of outflow obstruction.
Physical Exam
• systolic murmur best heard between the apex and
left sternal border
- increases in intensity with maneuvers that
decrease preload (Valsalva, squatting to
standing position).
- does not radiate to the carotid arteries
• sustained apical impulse
• S4
• bisferiens pulse (carotids, femoral arteries)
Diagnostic Tests
• CXR – mostly normal
• routine blood-work – unremarkable
• EKG – usually shows marked LVH
• Echocardiogram – is the diagnostic test of choice
Echocardiogram
Typical features:
• asymmetric hypertrophy of the myocardium
(septal)
• LVOT obstruction – either resting, or provoked
(Valsalva, exercise, amyl-nitrate)
• systolic anterior motion of the anterior mitral valve
leaflet (SAM)
• mitral regurgitation
Nishimura, R. A. et al. N Engl J Med 2004;350:1320-1327
Morgensen et al., J Am Coll Cardiol, 2004; 44:2315-2325
Heart Catheterization
(not required for the diagnosis)
- systolic pressure gradient within the body of the
left ventricle (again, either resting or provoked)
- elevated left ventricular end-diastolic pressure
- elevated pulmonary capillary wedge pressure (LA
pressure) with a tall a-wave and v- wave (MR)
- “spike and dome” arterial tracing (pulsus bisferines
equivalent)
- Brockenbrough-Braunwald phenomenon –
increased gradient and decreased aortic
pressure in the beat following a ventricular
extrasystole
Adapted from: Nishimura, N Engl J Med 2004
Adapted from: Nishimura, N Engl J Med 2004
Natural History
- as viewed in the past:
most patients become symptomatic at an early age
in their teens, twenties and thirties, and are at a
significant risk for sudden cardiac death.
- what are we thinking in the age of wide-spread
echocardiography use:
- the disease may not become apparent till late,
60 years or older
- varied influence of the specific genetic mutation
- variable phenotypial penetrance
- variable mortality - less that 1%/year in
unselected population, in excess of 6%/year in
patients with high risk features
Natural History
Risk factors for cardiac death:
-
marked ventricular wall hypertrophy (>30mm)
young age at presentation (<14 years)
history of syncope
history of aborted cardiac arrest
family history of sudden cardiac death
certain genetic mutations
- sudden cardiac death
- progressive heart failure
- “burnt-out” hypertrophic cardiomyopathy
Management
- careful family history focused on sudden cardiac
death
- exercise testing to determine the presence of
exercise-induced LVOT gradient
- counseling regarding avoidance of strenuous
exercise, avoidance of dehydration
- instructions for prophylaxis against infective
endocarditis
- all first-degree family members should be
periodically screened with an echocardiogram –
yearly between ages 12-18, every 5 years
thereafter
- consider genetic testing
Treatment
No randomized clinical trials of medical therapy.
Three classes of negative-inotropic agents used, often in
combination.
Treatment
Beta-blockers
- first-line therapy, clinical improvement >50%
- negative inotropic effect decreases outflow gradient
- decreased myocardial demand results in reduced
ischemia
- prolonged diastolic filling time results in improved LV
filling as well as improved coronary perfusion
- may have an antiarrhythmic effect
- please NOTE that in hypertrophic cardiomyopathy, as
opposed to dilated cardiomyopathy, we are using betablockers for their negative inotropic effect
Treatment
Calcium-channel blockers
- useful in patients who do not tolerate beta-blockers,
- or in combination with beta-blockers
Disopyramide
- may be useful in some patients with a resting gradient
due to its strong negative inotropic effects
Non-Pharmacological Therapy
Surgical septal myectomy
- in patients that remain symptomatic (dyspnea or angina
limiting daily activities) despite maximal medical
therapy and have significant resting or provoked
outflow gradient
- the basal interventricular septum is excised which
“opens-up” the left ventricular outflow
Surgical Septal Myectomy
Nishimura, R. A. et al. N Engl J Med 2004;350:1320-1327
Non-Pharmacological Therapy
Surgical septal myectomy
- this procedure has been done since the 1960’s
- operative mortality is <1-2%
- most patients will have dramatic improvement in their
gradient as well as symptoms
- complications: complete heart block (3%), VSD (<1%),
AR (<1%)
Non-Pharmacological Therapy
Alcohol-induced septal ablation
- performed percutaneously in cardiac catheterization
laboratory
- 100% alcohol is injected into a septal perforator
- this results in infarction of the injected area
Alcohol-Induced Septal Ablation
Braunwald, E. N Engl J Med 2002;347:1306-1307
Alcohol-Induced Septal Ablation
Adapted from: Hypertrophic Cardiomyopathy, Cleveland Clinic Heart Center, clevelandclinic.org
Non-Pharmacological Therapy
Alcohol-induced septal ablation
- the gradient is reduced to <20mm Hg in 70-80%
- symptom relief is somewhat lower than with surgical
myectomy
- complications: mortality <1-2%, complete heart block
(10-30%), VSD, AR, ventricular fibrillation, myocardial
infarction of a larger territory
Non-Pharmacological Therapy
Dual-chamber pacemaker
- ventricular depolarization and contraction starting in the
RV apex may alter the outflow gradient and reduce
symptoms
- results of randomized trials have been neutral
- used in patients with significant symptoms who would
not tolerate surgical therapy
Non-Pharmacological Therapy
Cardiac transplantation
- reserved for patients who are severely symptomatic
despite maximal pharmacological as well as nonpharmacological therapy
- no significant residual gradient but severe disabling
diastolic dysfunction
- “burnt-out” hypertrophic cardiomyopathy now with
systolic dysfunction
Prevention of Sudden Cardiac Death
Implantable cardioverter-defibrillators
- indications are evolving
- considered in patients perceived to be at higher risk
for sudden cardiac death
- additional value of identifying the specific genetic
mutation for risk-stratification is being studied and
is likely to be used clinically in the near future
CAVEATS
- strenuous exercise, especially isometric, increases
the gradient and the probability of hemodynamic
collaps/ventricular arrhythmias/sudden cardiac
death
- dehydration, as well as marked peripheral
vasodilation can be life-threatening
CAVEATS
- atrial fibrillation is poorly tolerated and should be
addressed promptly in the setting of increased
symptoms and hypotension. The threshold to
perform electrical cardioversion should be low
- inotropes (dopamine, dobutamine, milrinone)
should be avoided in patients with hypertrophic
cardiomyopathy. In a hypotensive patient, fluids and
pure vasoconstrictors (phenylephrine) are to be
used