Hypertrophic cardiomyopathy

1
Hypertrophic cardiomyopathy

• Frank and Mehta

2
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

3
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.

4

• 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 Noonans
  syndrome, Mitochondrial myopathies, Friedreich
  ataxia,metabolic disorder,Anderson-Fabry
  disease,LV-non compaction and cardiac amyloidoses.

5
Hypertrophy
6
Differential diagnosis

• HCM

• Athletic heart

• Can be asymmetric
• Wall thickness gt 15 mm
• LA gt 40 mm
• LVEDD lt 45 mm
• Diastolic function always abnormal

• Concentric regresses
• lt 15 mm
• lt 40 mm
• gt 45 mm
• Normal

7
Stimulus

• Unknown
• Disorder of intracellular calcium metabolism
• Neural crest disorder
• Papillary muscle malpositioned and misoriented

8
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,
  alpha-tropomyosin, alpha-actin, cardiac troponin
  I and alpha myosin heavy chain account for fewer
  cases. http//genepath.med.harvard.edu/seidman/cg
  3/

9
genetic basis
10

• 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 )

11
Pedigree

• autosomnal dominant
• passed on from affected males and females
• The disease does not skip generations

12
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 lt 2 (25 in
  Japan/Asia) characteristic giant T-wave
  inversion laterally spade-like left ventricular
  cavity more benign.

13

• 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.

14

• 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)

15
The variants
16
(No Transcript)
17
Pathophysiology of HCM

• Dynamic LV outflow tract obstruction
• Diastolic dysfunction
• Myocardial ischemia
• Mitral regurgitation
• Arrhythmias

18
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.

19
Left ventricular outflow tract gradient

• 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

20
Physical examination

• Maneuvers that ? end-diastolic volume
• (? venous return afterload, ? contractility)
• Vasodilators
• Inotropes
• Dehydration
• Valsalva
• Amyl nitrite
• Exercise
• ? ? HCM murmur

21
(No Transcript)
22
General considerations for natural history and
clinical course

• 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)

23
(No Transcript)
24
(No Transcript)
25
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.

26
(No Transcript)
27
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)

28
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.

29
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

30

• 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.

31
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.
32

• It is important to recognize that the ideal
  patient for septal myectomy has idiopathic
  hypertrophy localized to the basal ventricular
  septum.

33
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.
34
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 follow-up 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.
35

• 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.

36
HCM Patients Without Obstruction

• 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

37
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.

38
(No Transcript)
39
References

• http//www.cardiovascularultrasound.com/content/6/
  1/19
• http//www.escardio.org/guidelines-surveys/esc-gui
  delines/GuidelinesDocuments/guidelines-HCM-FT.pdf
• http//www.mayoclinic.com/health/hypertrophic-card
  iomyopathy/DS00948/DSECTIONrisk-factors
• http//www.mayoclinic.org/hypertrophic-cardiomyopa
  thy/physiciansguide.html