A SUBJECT SEMINAR ON HYPERTROPHIC CARDIOMYOPATHY

1. Hypertrophic
cardiomyopathy
Dr. DEEPIKA.T
FIRST YEAR PG STUDENT
DEPARTMENT OF GENERAL MEDICINE
RRMCH, BENGALURU
MODERATOR
Dr. KRISHNA.M.V
HOD, DEPARTMENT OF GENERAL MEDICINE
RRMCH, BENGALURU

2. CONTENTS
 Introduction – Cardiomyopathy
HCM
 Definition & Background
 Historical Perspective
 Genetic Basis
 Morphology
 Pathophysiology
 Clinical Features
 Clinical Course
 Management
 Screening Strategies
 DD with Athlete’s heart

3. Cardiomyopathy
cardiomyopathy is defined as “disorders characterised by
morphologically and functionally abnormal myocardium in
the absence of any other disease that is sufficient, by itself, to
cause the observed phenotype”
Harrison's Principles of Internal Medicine, 20E (2018)
A myocardial disorder in which the heart muscle is
structurally and functionally abnormal, in the absence of
coronary artery disease, hypertension, valvular disease and
congenital heart disease sufficient to cause the observed
myocardial abnormality
ESC Working Group on Myocardial Pericardial Diseases (Elliott P et al. EHJ 2007)

4. ESC Working Group on Myocardial Pericardial Diseases (Elliott P et al. EHJ 2007)

5. Hypertrophic Cardiomyopathy

6. Definition
 Hypertrophic cardiomyopathy is defined as
left ventricular hypertrophy that develops in
the absence of causative hemodynamic
factors, such as hypertension, aortic valve
disease, or systemic infiltrative or storage
diseases
Harrison's Principles of Internal Medicine, 2OE (2018)

7. Background
 Hypertrophic cardiomyopathy is a genetic disorder
that is typically inherited in an autosomal dominant
fashion with variable penetrance and variable
expressivity
 HCM is the leading cause of sudden cardiac death in
preadolescent and adolescent .

8. 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 involves the
IVS, which results in a LVOT obstruction

9. Background
 Prevalence of HCM: 0.05-0.2% of the population
 Prevalence in North America, Africa and Asia is about
1:500
This occurrence is higher than previously thought,
suggesting a large number of affected but undiagnosed
people
 Approximately 25% of first-degree relatives of patients
with HCM show morphological evidence on 2D-echo
 Men: Women :: 2:1
 African-American : Caucasians :: 2:1

10. Historical Perspective
 First description of HCM by Teare in 1958
Found massive hypertrophy of ventricular septum in
small cohort of young patients who died suddenly
 First clinical diagnosis of HCM by Braunwald in the 1960s
 Alternative names
Idiopathic hypertrophic subaortic stenosis (IHSS)
Muscle subaortic stenosis
Hypertrophic obstructive cardiomyopathy (HOCM)

11. Genetic Basis
 Autosomal dominant inheritance with
incomplete penetrance
 More than nine different sarcomere genes
with over 1400 mutations have been
implicated, although ∼80% of patients have
a mutation in either MYH7 or MYBPC3
 Genetic basis of ventricular hypertrophy
does not directly correlate with prognostic
risk stratification

12.  At the level of sarcomere, mutations lead to
enhanced calcium sensitivity, maximal force
generation and ATPase activity
 Abnormal energetics and impaired relaxation
due to mutation and hypertrophy are seen.

13. Morphology
 Left Ventricular Hypertrophy
 Mitral Valve Apparatus
 Histopathology

14. Left Ventricular Hypertrophy
 Diverse patterns of asymmetric LV hypertrophy are
characteristic of HCM.
 Typically, one or more regions of the LV wall are of
greater thickness than other areas.
 A sharp transitions in thickness between adjacent
areas or noncontiguous patterns of segmental
hypertrophy, as well as extension into the right
ventricle.
 There is not a single “classic” morphologic form, and
virtually all possible patterns of LVH have been
reported, including normal LV wall thicknesses

15. Mitral Valve Apparatus
 There may be diverse alterations in valvular size and
shape and represent a primary morphologic
abnormality in HCM
 The valve may be as much as twice normal size from
elongation of both leaflets or segmental enlargement
of only the anterior leaflet or the midportion of the
posterior leaflet.

16. Histopathology
 Cardiac muscle cells show increased transverse
diameter and bizarre shapes, often maintaining
intercellular connections with several adjacent cells.
 Myocytes (and myofilaments) are arranged in chaotic,
disorganized patterns at oblique and perpendicular
angles.
 Abnormal intramural coronary arteries with thickened
walls (composed of increased intimal and medial
components) and narrowed lumen are present in
80%, most frequently within or close to areas of
replacement fibrosis, contributing to microvascular
ischemia and angina

17. Disorganized LV
architecture with
myocyte disarray.
Small-vessel disease;
remodeled intramural coronary
arteriole with thickened media
and narrowed lumen.
Replacement fibrosis, the
consequence of silent myocardial
ischemia and myocyte death.
Harrison's Principles of Internal Medicine, 19E (2015)

18. Pathophysiology
 The pathophysiology of HCM involves 4 interrelated processes:
Left ventricular outflow obstruction
Diastolic dysfunction
Myocardial ischemia

19. 1. LV outflow obstruction
 Long-standing LV outflow obstruction is a
major determinant for heart failure
symptoms and death in HCM patients
 Subaortic outflow obstruction is caused by
systolic anterior motion (SAM) of the mitral
valve – leaflets move toward the septum

20. LV outflow obstruction
 Explanations for the SAM of the mitral valve
1. Mitral valve is pulled against the septum by
contraction of the papillary muscles, which
occurs because of the valve's abnormal location
and septal hypertrophy altering the orientation
of the papillary muscles
2. Mitral valve is drawn toward the septum
because of the lower pressure that occurs as
blood is ejected at high velocity through a
narrowed outflow tract (Venturi effect)

21. LV outflow obstruction
 Physiological Consequences of Obstruction
Elevated intraventricular pressures
Prolongation of ventricular relaxation
Increased myocardial wall stress
Increased oxygen demand
Decrease in forward cardiac output

22. 2.Diastolic Dysfunction
Contributing factor in 80% of patients
Impaired relaxation
 Non uniform ventricular contraction
 High systolic contraction
 Diffuse ischemia causing stiffness.
Accounts for symptoms of exertional dyspnea
Increased filling pressures → increased
pulmonary venous pressure

23. 3. Myocardial Ischemia
Often occurs without atherosclerotic coronary artery
disease
Postulated mechanisms
Abnormally small and partially
obliterated intramural coronary arteries
as a result of hypertrophy
Inadequate number of capillaries for
the degree of LV mass and increased
myocardial oxygen consumption
Increased filling pressures
Resulting in subendocardial ischemia

24. Clinical presentation
 Dyspnea on exertion (90%), orthopnea, PND
 Palpitations (PAC, PVC, sinus pauses, AF, A
flutter, SVT and VT)
 Congestive heart failure (2o to increased filling
pressures and myocardial ischemia)
 Angina (70-80%)
 Syncope (20%), Presyncope (50%)
Outflow obstruction worsens with increased contractility
during exertional activities resulting in decrease in cardiac
output
Conditions of low preload, such as dehydration, and low
afterload, such as arterial vasodilatation, may lead to transient
hypotension and near-syncope
Secondary to arrhythmias

25. 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
degenerated into VF due to 2o
accessory pathway

26. Sudden Cardiac Death -
causes
Braunwald's Heart Disease- A Textbook of Cardiovascular Medicine 9th Ed

27. Physical Examination
Carotid Pulse
Bifid – rises quickly, then declines in midsystole
followed by a secondary rise in carotid pulsation
during late systole short upstroke & prolonged systolic
ejection
Jugular Venous Pressure
Prominent a wave – decreased RV compliance
Apical Impulse
Double apical impulse - forceful left atrial
contraction against a highly noncompliant left
ventricle
Triple apical impulse results from a late systolic
bulge that occurs when the heart is almost empty and
is performing near-isometric contraction

28. Physical Examination
Heart Sounds
S1 usually normal
S2 usually split but in severe cases
– paradoxically split
S3 indicate heart failure
S4 usually present due to
hypertrophy

29. Murmur
 Medium-pitch crescendo-decrescendo systolic
murmur along LLSB and apex and radiates to
suprasternal notch
 Dynamic maneuvers
Murmur intensity increases with
decreased preload
(i.e. Valsalva, standing, nitrates,
diuretics)
Murmur intensity decreases with
increased preload
(i.e. squatting, hand grip)

30. Diagnostic Evaluation
 Electrocardiogram
 Echocardiogram
 Catheterization
 Cardiac MR

31. ECG
 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.

32.  Abnormal ECG patterns are common in HCM patients
(up to 90% of probands) and may be present in
advance of the appearance of hypertrophy on
imaging. Criteria for LVH are usually present:
Increased precordial voltages and non-specific ST
segment and T-wave abnormalities (LVH strain).
 Deep, narrow “dagger-like” Q waves in the lateral and
inferior leads.
 Apical HCM - “giant T Wave Inversion” and no septal
Q waves
 An association exists between Wolf-Parkinson's
White and HCM

33. Left ventricular hypertrophy results in increased precordial voltages and non-
specific ST segment and T-wave abnormalities. Asymmetrical septal
hypertrophy produces deep, narrow (“dagger-like”) Q waves in the lateral
(V5-6, I, aVL) and inferior (II, III, aVF) leads.

34.  There is a subset of patients with phenotypic
expression of the disease by echocardiography that
has a normal ECG.
 Among 2,485 patients with an echocardiographic
evidence of HCM seen at the Mayo Clinic 135 (5.4%)
had a normal ECG. They had less severe phenotypic
expression of HCM.
(McLeod et al. JACC Vol. 54, No. 3, 2009)

35. 2-D echocardiography
Given its wide availability and relatively low cost, 2D
echocardiography is the initial imaging modality for the
diagnosis and management of HCM.
Abnormal systolic anterior leaflet motion of the mitral valve
LV hypertrophy
Left atrial enlargement
Diastolic dysfunction
Small ventricular chamber size
Septal hypertrophy with septal to free wall ratio greater than
1.4:1 (absolute septal wall thickness >15mm)
Decreased mid aortic flow
Partial systolic closure of the aortic valve in mid systole

36.  •Echocardiographic diagnostic criteria for
HCM:
Unexplained maximal wall thickness
(measured at end-diastole) ≥ 15 mm (or >2
standard deviation for age, height and gender)
in any myocardial segment
Septal/posterior wall thickness ratio of >1.3
in a nondilated ventricle and >1.5 in the setting
of systemic hypertension.

37. The different anatomic variants
in HCM

38. Braunwald's Heart Disease- A Textbook of Cardiovascular Medicine 9th Ed

39. When to use CMR?
 CMR should be integrated into the initial evaluation of
all patients if available.
 It is of greatest importance in the “ borderline
patient”: LV myocardium is not well visualized by the
echocardiogram
 The echocardiographic data are inconclusive
 The electrocardiogram is abnormal but the
echocardiogram is normal
 Members of high-risk families with non-diagnostic
findings on echocardiogram
 To differentiate HCM from other conditions including
amyloidosis, hypertensive heart disease and athlete’s
heart

40. Cardiac MRI
 Useful when echocardiography is questionable,
particularly with apical hypertrophy
 SAM of the mitral valve is clearly seen on cardiac
MRI
 Improvement in obstruction after septal ablation or
myomectomy can be demonstrated, as can the
location and size of the associated infarction, which
are useful for planning repeat procedures
 Cardiac MRI tagging identifies abnormal patterns of
strain, shear, and torsion in cases of HCM,
demonstrating significant dysfunction in hypertrophic
areas of the ventricle

41. Braunwald's Heart Disease- A Textbook of Cardiovascular Medicine 9th Ed

42.  Gadolinium contrast cardiac MRI -
differentiating HCM from other causes of
cardiac hypertrophy and other types of
cardiomyopathy such as, amyloidosis,
athletic heart, and Fabry’s disease
 Late gadolinium enhancement occurring in
HCM represents 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 of ventricular dilation toward
heart failure, thereby indicating a poorer
prognosis

43. Management
 Prevention of sudden cardiac death - ICD
 Medical Rx of Heart failure & AF
 Surgery
 Dual Chamber Pacing
 Alcohol Septal Ablation

44. Implantable Cardioverter
Defibrillators
Primary prevention in individuals with risk
factors such as
 Young Age
 Non-sustained Ventricular Tachycardia
 Severity of LV wall thickness
 Family History of Sudden Cardiac Death (age < 40y)
 Unexplained syncope
 Left Atrial Diameter
 Left Ventricular Outflow Tract Obstruction
 Hypotensive Blood Pressure Response to Exercise

45. Harrison's Principles of Internal Medicine, 19E (2015)

46. Braunwald's Heart Disease- A Textbook of Cardiovascular Medicine 9th Ed

47. Medical Therapy
 Beta-blockers
Increase ventricular diastolic filling/relaxation
Decrease myocardial oxygen consumption
Have not been shown to reduce the incidence of
Sudden Cardiac Death
 Verapamil
Augments ventricular diastolic filling/relaxation
 Disopyramide
Used in combination with beta-blocker
In the presence of persistent symptoms
Negative inotrope
 Diuretics in patients with fluid retention

48. Dual Chamber Pacing
 Proposed benefit:
Pacing the RV apex will decrease the
outflow tract gradient 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 as exercise capacity and oxygen
consumption are not improved
 No correlation has been found between pacing and
reduction of LVOT gradient

49.  severe medical refractory symptoms develop
in about 5% of patients , for whom surgical
myectomy or alcohol septal ablation may be
effective
 Neither procedure has shown to improve
outcome other than symptoms
 With both procedures, the most common
complication is the development of complete
heart block
Alcohol Septal Ablation

50. Harrison's Principles of Internal Medicine, 19E (2015)

51. Braunwald's Heart Disease- A Textbook of Cardiovascular Medicine 9th Ed

52. Differentiating from Athlete’s
heart
Unusual patterns of LVH
LV cavity < 45mm
Marked LA enlargement
Bizzare ECG patterns
Abnormal LV diastolic
filling
Family hostory of HCM
LV cavity > 55mm
Normal LV diastolic filling
Normal LA size
Male sex
Thickness decreases with
deconditioning
No Family hostory of HCM
Athlete’s
heart
HCM
LV
thickness
>15 mm
LV
thickness
<13 mm
Grey zone
13-15 mm
Favours HCM Favours Athlete’s heart

53. REFERENCES:
 Harrison’s principles of internal medicine
 ESC guidelines of cardiomyopathy
 Braunwald’s heart disease

54. thank you