4. Hypertrophic CARDIMYOPATHY_103149.pdf

GGG

1. Hypertrophic
Cardiomyopathy

2. Case
17 years oldmale professional basketball player with no
known past medical history collapses on the playing floor
during practiceandsubsequentlyarrests.Hehadbeen
having some exertional dyspnea for a few months prior to
this incident but it did not affect his activity level.Hewas
was
no
told growing up that he had a “heart murmur” that
neverformallyinvestigated.Hewastaking
medications, and there was noamilyory of cardiac
disease in his family.An autopsy laterrevealed that the
patient had hypertrophic cardiomyopathy.
f hist

3. Background
Hypertrophiccardiomyopathyisagenetic
disorderthatistypicallyinheritedinan
autosomaldominantfashionwithvariable
penetrance and variable expressivity
Thediseasehascomplexsymptomatologyand
potentially devastatingconsequencesfor patients
and their families
HCMistheleadingcauseofuddencardiac
death in preadolescentand adolescent children
s

4. Background
The hallmark of the disorder is myocardial
hypertrophy that is inappropriate, often
asymmetrical and occurs in the absence of an
obvious inciting hypertrophy stimulus
This hypertrophy can occur in any region of the
left ventricle but frequently involvesIVS,
which results in an obstruction of flowhrough
the LVOT
the
t

5. Background
Prevalence of HCM: 0.05-0.2% of the
population

This occurrence is higher than previously thought, suggesting a
large number of affected but undiagnosed people
Morphologic evidence of disease is found by
echocardiography in approximately 25% of first-degree
relatives of patients with HCM
Men and African-Americans affectedbyalmost 2:1
ratio over women and Caucasians
Global disease with most cases reptedfrom USA,
Canada, Western Europe, Israel, & Asia
Maron BJ et al. Circulation. Aug 15 1995;92(4):785-9
or

6. Historical Perspective
HCM wasinitially described by Teare in 1958
Foundmassive hypertrophy of ventricular septuminsmall
cohortof young patients who died suddenly
Braunwald was the first to diagnose HCM
clinically in the 1960s

Many names for the disease
Idiopathic hypertrophic subaortictenosisIHSS)
Muscle subaortic stenosis
Hypertrophic obstructive cardiomyopathy (HOCM)
s (

7. Genetic BasisofHCM
Autosomal dominant inheritance
pattern
>450 mutations in 13 cardiac
sarcomere & myofilament
(myosin heavy chain, actin,
tropomyosin, and titin) related
genes identified
Genotype specific risks for
mortality and degree of
hypertrophy
Genetic basis of ventricular
hypertrophy does not directly
correlate with prognostic risk
stratification
Alcalai et al.J Cardiovasc Electrophysiol 2008;19:104-110.

8. GeneticsofHCM
Alcalai et al. J Cardiovasc Electrophysiol 2008;19:105.

9. Patterns

10. Pathophysiologyof HCM
The pathophysiology of involves 4 HCM

Interrelated processes:
Left ventricular outflow
Diastolic dysfunction
obstruction

Myocardial ischemia
Mitral regurgitation

11. LV Outflow Obstruction in HCM
Long-standingLV outflowobstructionisa
majordeterminantforheartfailuresymptoms
and death in HCM patients
Subaorticoutflowobstructioniscausedby
systolic anteriormotion(SAM)ofthemitral
valve – leaflets move toward theeptums

12. LV Outflow Obstruction in HCM
Explanations for the SAM of the mitral valve
Mitral valve is pulled against the septum by contraction1.
of the papillary muscles, which occurs because of the
valve's abnormallocation andseptalhypertrophy
altering the orientation of the papillary
muscles
Mitral valve is pushed against the septumbecause of its2.
abnormal position in the outflow tract
Mitral valve is drawn toward theum se of the3.
lower pressure that occursblood ted at high
velocity
effect)
throughanarrowedoutflowtract (Venturi
as
sept
isej
ec
ec
au

13. LV Outflow Obstruction in HCM
Physiological Consequences of Obstruction
Elevated intraventricular pressures
Prolongation of ventricular relaxation
Increased myocardial wall stress
Increased oxygen demand
Decrease in forward cardiac out put

14. FreedomfromHCMrelateddeaths
Maron MS et al. NEJM. 2003;348:295.

15. Pathophysiologyof HCM
The pathophysiology of HCMinvolves 4
interrelated processes:
Left ventricular outflow
Diastolic dysfunction
obstruction

Myocardial ischemia
Mitral regurgitation

16. Pathophysiologyof HCM
Diastolic Dysfunction
Contributing factor in 80% of patients
Impaired relaxation
High systolic contraction load
Ventricular contraction/relaxation not uniform


Accounts for symptomsxertional dyspnea
Increased filling pressures increasedlmonaryvenous
pressure
ofe
pu

17. Pathophysiologyof HCM
The pathophysiology of HCMinvolves 4
interrelated processes:
Left ventricular outflow
Diastolic dysfunction
obstruction

Myocardial ischemia
Mitral regurgitation

18. Pathophysiology of HCM
Myocardial Ischemia
Often occurs without atherosclerotic coronaryartery
disease
Postulated mechanisms
Abnormally small and partially obliterated intramural
coronary arteries as a result of hypertrophy
Inadequate number of capillaries fore degree of LV
mass and increased myocardialxygen consumption
Increased filling pressures
Resulting in subendocardial ischemia
o
th

19. Pathophysiologyof HCM
The pathophysiology of HCMinvolves 4
interrelated processes:
Left ventricular outflow
Diastolic dysfunction
obstruction

Myocardial ischemia
Mitral regurgitation

20. Pathophysiology of HCM
Mitral Regurgitation
Resultsfromthesystolic anteriormotionofthe
mitral valve
Variations in leaflet length (posterior/anterior leaflet
lengthmismatch) –restricttheabilityofthe
posterior leaflet to follow the anterior leaflet and to
coapt effectively resulting in MR
Severity of MR directly proportionao LV outflow
obstruction
Results in symptoms of dyspnea, orthopnea in HCM
patients
l t

21. Clinical Presentation
Dyspnea on exertion (90%), orthopnea, PND
Palpitations(PAC,PVC,sinuspauses,AF,Aflutter,
SVT and VT)
Congestive heart failure (2
o
to increased fillingpressures
and myocardial ischemia)
Angina (70-80%)
Syncope (20%), Presyncope (50%)


Outflowobstructionworsenswith increasedcontractility
during exertionalactivitiesltingindecreaincardiac
output
Secondary to arrhythmias
resu se

22. Clinical Presentation
Sudden cardiac death
HCM is most common cause of SCD in young
people, including athletes
Can be the first manifestation
Most common cause is arrhythmias esp. VF either


denovo or AF degeneratedntoF2
o
accessory
pathway
iV

23. Physical Examination
Carotid Pulse
Bifid – rises quickly, then declines in midsystole followed
by a secondary rise in carotid pulsation duringlate systole
short upstroke & prolonged systolic ejection
Jugular Venous Pulse
Prominent a wave – decreased RV compliance
Apical Impulse
Doubleapical impulse-forcefulleftatrialcontraction
against a highly noncompnt l tricle
Triple apical impulse results from alate systolic bulge that
occurs when the heart is almost empty and is performing
near-isometric contraction
liaeftven

24. Physical Examination
Heart Sounds
S1usually normal
S2usually split but in severe stenosis – paradoxicallysplit
S3indicate heart failure
S4usually present due to hypertrophy
Murmur
Medium-pitch crescendo-decrescendo systolic murmur
along LLSB and apex and radiates to suprasternal notch
Dynamic maneuvers
Murmur intensity increases withcreased preload
(i.e. Valsalva, standing, nitrates, diuretics)
Murmur intensity decreases with increased preload
(i.e. squatting, hand grip)
de

26. Physical Examination
Holosystolic murmur at the apex and axilla of
mitral regurgitation is heard in patients with
systolic anterior motion of the mitral valveand
significant LV outflow gradients
Diastolic decrescendo murmur of aortic
regurgitation is heard in 10% of patients,

although mild aortic regurgitation can be
detected by Doppler echocardiography in 33%
of patients

27. DiagnosticEvaluation
Electrocardiogram
Echocardiogram
Catheterization
Cardiac MRI



28. ElectrocardiograminHCM
LVH with nonspecific ST/T wave abnormalities
Left or right axis deviation, LAE, Conduction abnormalities
Abnormal and prominent Q wave in the anterior precordial and lateral limb leads
A fib with preexitation implies poor prognosis
Findings on Holter monitoring include APC’s VPC’s, sinus pauses, wandering atrial pacemaker,
atrial tachycardia, AF/flutter and nonsustained ventricular tachycardia.

29. Echocardiography in HCM
2-D echocardiography is diagnostic for HCM
Abnormal systolic anterior leafletmotion of themitralvalve
LV hypertrophy
Left atrial enlargement
Diastolic dysfunction
Small ventricular chamber size


Septal hypertrophy with septal tofree wall ratio greater than
1.4:1 (absolute septal wall thicknes>15mm)
SAM of anterior and rarely perior mitral valve leaflet and
mitral regurgitation
Decreased mid aortic flow
Partial systolic closure of the aortic valve in mid systole
ost
s

35. Cardiac MRI in HCM
Useful when echocardiography is questionable, particularly with
apical hypertrophy
Cines loops typically show obstruction and velocity mapping is
useful in the assessment of peak velocities
SAM of the mitral valve is clearly seen on cardiac MRI
Improvementinobstructionafterseptalablationor
myomectomy can be demonstrated, as can the location and size
of the associated infarction, which areuseful forplanning repeat
procedures
Cardiac MRI tagging identifies abnormaltterns ain, shear,
andtorsion incasesofHCM, demonstratingsignificant
dysfunction in hypertrophic areas of the ventricle
pa ofstr

36. Cardiac MRI in HCM
Gadolinium contrast cardiac MRI - differentiating HCM from
othercausesofcardiachypertrophyandothertypesof
cardiomyopathy such as, amyloidosis, athletic heart, and Fabry’s
disease
LategadoliniumenhancementoccurringinHCMrepresents
myocardial fibrosis
The greater the degree of late gadolinium enhancement, the more
likely that the particular HCM patient has 2 or more risk factors
for sudden

death
More likely the patient has or will develop progression ofventricular
dilation toward heart failure, thereby indicing apoorer prognosis
Most patients with HCM have no gadolinium enhancement
Common benign pattern is 2 stripes running along the junction of the
right ventricle insertion into the left ventricle
at

40. Apical HCMbyEcho&CMR
•64 female with CP
palpitation
•ECG – extensive T wave
inversion
•Echo – akinetic apex &
diastolic dysfunction
•Cine CMR – confirmed
clinical suspicion of apical
HCM
&

41. High riskHCM
•33 male with HCM
family history
of
sudden death
•Cine CMR shows
HCM with ASH
•After gadolinium
extensive late
enhancement
•Patient was offered
ICD
and
an

42. Cardiac Catheterization
Diagnosticcardiac catheterizationisusefultodeterminethe
degreeofLVOTobstruction,cardiachemodynamics,the
diastolic characteristics of the left ventricle, LV anatomy and
coronary anatomy
Reserved for situations when invasive modalities of therapy, such
as a pacemaker or surgery, are being considered

Therapeutic cardiaccatheterizationinterventions,include
transcatheter septal alcohol ablation
The arterial pressure tracing foundn cdiac catheterization
may demonstrate a "spike and dome"nfiguration
o
co
ar

43. Cardiac Catheterization
Approximately one fourth of patients demonstrate
pulmonary hypertension - usually mild
Enhancing ofLVOT gradient in post PVC
Results in characteristic change recorded on arterial pressure
tracing - exhibits a pulse pressure that fails to increase as

expected or actually decreases (theso-called Brockenbrough-
Braunwald phenomenon)
One of the more reliable signs of dynamicstruction of the
LVOT, intensity of murmur also incr sedea
ob

44. CardiacCatheterization
•LV gram shows hypertrophiedLV
•MR secondarytoSAMofmitral
valve
•The LV cavityis oftensmall and
systolic
resulting
ejectionistypicallyvigorous,
invirtualobliterationofthe
ventricular cavity at end systole
•Intientswithical involvement,
the extensive hertrophymay convey a
spade-like configuronotheleft
ventricular angiogram
pa
yp
ap
atit

45. DiseaseProgressioninHCM
ACC Consensus Document. J Am Coll Cardiol.2003;42(9):1693.

46. Sudden CardiacDeathinHCM
Most frequent in young
adults <30-35 years old
Primary VF/VT
Tend to die during or
just following vigorous
physical activity
Often is1
st
clinical
manifestation
HCM is most
cause of SCD
of disease
common
among
J Am Coll Cardiol. 2003;42(9):1693.
young competitive
athletes

47. SCDin CompetitiveAthletes
Maron B. Atlas of Heart Diseases. 1996

48. NaturalHistory of
HCM
Heart Failure Atrial Fibrillation 
Only 10-15%progressto Prevalent in up to30% of 
NYHA III-IV older patients
Only 3% will become
truly end-stage with
systolic dysfunction
Dependent on atrial kick –
CO decreases by 40% if AF
present
 
Endocarditis utonomicsfunction
4-5% of HCM patients 5% of H atients
Usually mitral valve ociatedwith poor
affected prognosis
A


2
Ass
D
CM
y
p

49. Influence of Gender &
Race
Women often remain under diagnosed and are
clinical recognized after they develop more
pronounced symptoms
1
HCM clinically under recognized in African-
Americans
Most athletes with SCD due tHCare
undiagnosed African-Americans
2
Olivotto I et al. J Am Coll Cardiol 2005;46:480.
1
2
Maron BJ et al. J Am Coll Cardiol 2003;41:974.
o

50. TreatmentofHCM
Medical therapy
Device therapy
Surgical septal myomectomy
Alcohol septal ablation



51. ACC Consensus Document. J Am Coll Cardiol. 2003;42(9):1693.

52. Medical Therapy
Beta-blockers
Increase ventricular diastolic filling/relaxation
Decrease myocardial oxygen consumption
Have not been shown to reduce the incidenceofSCD
Verapamil
Augments ventricular diastolic filling/relaxation
Disopyramide
Used in combination with beta-blocker
Negative inotrope
Diuretics

53. Dual-Chamber Pacing
Proposed benefit:
Pacing the RV apex will decrease the outflow tractgradient
by decreasing projection of basal septum into LVOT
Several RCTs have found that the improvement in
subjective measures provided by dual-chamber pacing

is likely a placebo effect
Objective measures such asxercise capacity and
oxygen consumption are not improved
No correlation has been found between pacing and
reduction of LVOT gradient
e

54. SurgicalSeptalMyectomy
Nishimura RA et al. NEJM. 2004. 350(13):1320.

55. ·- I
Journal of the Americ-an College of
Cariliology
Vol. 46, No. 3,
2005C 2005 by the American College of Cardiology
Foundation
ISSN 0735-
1097/05/£30.00Published by Elsevier
Inc.
doi:
10.1016/j.jacc.2005.02.090
Hypertrophic and Dilated Cardiomyopathy
Long-Term Effects of SurgicalSepta!
Myectomy on Survival in Patients With
Obstructive Hypertrophic Cardiomyopathy
Steve R. Ommen, MD, FACC* Barry J. Maron, MD, FACC,*:j: Iacopo Olivotto, MD,§
Martin S. Maron, MD,JJ Franco Cecchi, MD,§ Sandro Betocchi, MD, FACC,�]
Bernard J. Gersh, MB, CHB, DPHJL, FACC,* Michael J. Ackerman, MD, PHD, FACC,*
Robert B. McCully, MB, CHB, FACC,* Joseph A. Dearani, MD,t Hartzell V. Schaff MD, FACC;r
Gordon K. Danielson, MD, FACC,t A. Jamil Tajik, MD, FACC,* Rick A. ishimura, MD, FACC*
Rochester and Minneapolis, Minnesota; Ftorence and Naples, Italy; and Boston, Massachusetts
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56. Journal of the Americ-an College of Cariliology Vol. 46, N<
C 2005 by the American College of Cardiology Foundation ISSN 0735-
1097/tPublished by Elsevier Inc. doi:
10.1016/j.jacc.20
Hypertrophic and Dilated
Cardiomyo1
Long-Term Effects of Surgical Septa!
Myectomy on Survival in Patients With
Obstructive Hypertrophic Cardiomyopathy
Steve R. Ommen, MD, FACC* Barry J. Maron, MD, FACC,*:j: Iacopo Olivotto, MD,§
Martin S. Maron, MD,JJ Franco Cecchi, MD,§ Sandro Betocchi, MD, FACC,�]
Bernard J. Gersh, MB, CHB, DPHJL, FACC,* Michael J. Ackerman, MD, PHD, FACC,*
Robert B. McCully, MB, CHB, FACC,* Joseph A. Dearani, MD,t Hartzell V. Schaff MD, FACC;r
Gordon K. Danielson, MD, FACC,t A. Jamil Tajik, MD, FACC,* Rick A. ishimura, MD, FACC*
Rochester and Minneapolis, Minnesota; Ftorence and Naples, Italy; and Boston, Massachusetts
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57. J Am Coll Cardiol 1999;34(1):191-6.

58. Alcohol Septal Ablation

59. AlcoholSeptalAblation
Before After

60. Pre Alcohol Septal Ablation

61. Post Alcohol Septal Ablation

62. Alcohol Septal Ablation
Successful short-term outcomes
LVOT gradient reduced from a mean of 60-70 mmHgto
<20 mmHg
Symptomatic improvements, increased exercise tolerance
Long-term data not available yet
Complications


Complete heart block
Large myocardial infarction
No randomized efficacy trialst forcohol septal
ablation vs. surgical myectomy
yeal

63. Overall survival:
93.5% at 2 yrs, 88%
at 4 yrs
Circulation. 2008; 18(2): 131-9.

64. EfficacyofTherapeuticStrategies
Nishimura et al. NEJM. 2004. 350(13):1323.

65. Coil Embolization
Case report of 20 patients
with drug-refractory HCM
Occlude septal perforator
branches
NYHA functional class and
peak oxygen consumption
improved at 6 months
Significant reduction in
septum thickness by echo
European Heart Journal 2008;29:350.

66. Implantable Cardioverter
Defibrillators in HCM
Primary & SecondaryPrevention

67. Appropriate discharges in
23% of patients
Rate of appropriate
discharges of 7% per year
Of 21 patients for which
intracardiac electrograms
were available, 10 shocks for

F
CDs in
ry
VT, 9 shocks for V
Suggested role for I
primary & seconda
prevention of SCD
Maron BJ et al. NEJM 2000;342:365-73.

68. Risk Stratification – ICDs
Primary Prevention Risk Factors for SCD
Premature HCM-related sudden death inmorethan
1 relative
History of unexplained
syncope

Multiple orprolonged NSVT on Holter
e response texercise
How manyrisk factors warrant ICD placement?
 Hypotensive blood press
 Massive LVH
ur o

69. Multicenter registry study
with 506 pts from 1986-2003
Average age 41 years old
35%pts - primary
prevention received ICDs
had 1 risk factor
Primary Outcome:
appropriate ICD

interventions terminating
VF/VT
J Cardiovasc Electrophysiol 2008;19(10).

70. 3500 asymptomatic elite
athletes (75% male), mean
age 20.5 +/- 5.8 years, no
family hx of HCM
12-lead ECG, 2D-Echo
53 athletes (1.5%) had


LVH
3 athletes (0.08%) had
ECG and echo features

of
HCM
J Am Coll Cardiol. 2008;51(10):1033-9.

71. HCMvs.Athlete’sHeart
Circulation 1995;91.

72. Future Directions
Identification of additional causativemutations
Risk stratification tools
Determining more precise indications for ICDs
Defining most appropriate role for alcohol
septal ablation
?Gene therapy

73. ThankYou!