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What is it?

Idiopathic hypertrophic sub aortic stenosis (IHSS) is a genetic disease characterized by marked hypertrophy of the left ventricle in the absence of chronic pressure overload (HTN, or aortic stenosis), involving specifically the interventricular septum and the left ventricular outflow tract. Also called hypertrophic obstructive cardiomyopathy (HOCM). Umbrella term: hypertrophic cardiomyopathy (HCM).

Epidemiology

  • Most common cause of sudden cardiac death in young athletes in the US.
  • Occurrence rate of 1 in 500.
  • Most common (Mendelian) genetic heart disease.
  • Presents after puberty (average age in mid-20s, but more and more in 40s and 50s).

Pathogenesis

  • Genetic abnormality of muscle cell proteins:
    • Autosomal dominant with variable penetrance (i.e. everyone who has the genes does not necessarily get the disease).
    • Most genes are for sarcomere proteins (Beta myosin heavy chain and myosin-binding protein C are most common). Currently, 11 or more causative genes with over 1400 mutations in genes encoding the thick or thin myofilament proteins of the sarcomere have been reported.
    • Most mutations lead to a single amino acid change.
    • These mutations cause myofibral disarray. Muscle cells are normally lined up linearly but in IHSS the muscle fibers are in disarray (i.e. in all different directions).
  • These abnormalities do not allow the heart muscle to contract properly.
  • Because of this, the heart compensates for this lack of effective contraction by hypertrophying (i.e. the cells get bigger).
  • Thus, the walls of the heart get bigger, and distinctive of this disease is that the inter ventricular septum becomes asymmetrically enlarged. The papillary muscles and mitral valve are deformed by the thickened septum, and thickening of the mitral valve leaflet also commonly occurs.
  • This hypertrophy can result in two major problems:
    • Since the walls of the ventricle are bigger, the chambers have become smaller. This leads to decreased ability of the heart to fill during diastole and thus the heart cannot pump enough blood forward to the systemic circulation during systole. This is termed DIASTOLIC heart failure.
    • Intermittent outflow obstruction:
      • The thickened septum causes a narrowing of the left ventricle outflow tract. In 75% of cases there is no obstruction. Ejection of blood through a narrowed outlet leads to the Venturi effect. Venturi forces pull anterior mitral leaflet toward septum during systole causing obstruction. This is called systolic anterior movement of mitral valve (SAM).
      • It is intermittent because it is dependent on how hard the heart muscle is working. If someone with this disease is exercising really hard and the heart rate is really fast, the diastolic period (the time when the heart fills with blood) is shorter so there is even less time to fill the ventricle. Since there is less blood in the ventricle the outflow tract becomes narrower and you get more obstruction. On the other hand, when the heart rate is slower, there is more time for the ventricle to fill in diastole so the outflow tract is widened by the blood, and there is less obstruction.

Diagnosis

1) History and physical

-Symptomatic vs. asymptomatic: Most patients have few or no symptoms

If a patient is symptomatic he/she may have dyspnea, syncope, angina, palpitations, dizziness, or sudden death

  • Dyspnea (most common symptom): Due to diastolic dysfunction. Blood backs up into the lungs because it cannot enter the chamber of the hypertrophied left ventricle. This causes fluid in the lungs and consequently dyspnea.
  • Palpitations: from arrhythmias that occur in IHSS such as premature atrial and ventricular beats, sinus pauses, atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular tachycardia. The arrhythmias occur due to fibrosis and myofibrillar disarray of the heart muscle.
  • Angina: due to more oxygen demand from thickened wall, than supply of oxygen available. Exacerbated during exertion.
  • Orthopnea/paroxysmal nocturnal dyspnea: observed in severe IHSS. Due to a combination of impaired diastolic function and subendocardial ischemia.
  • Dizziness: due to outflow tract obstruction and thus less blood flow to brain
  • Syncope/sudden death: due to ventricular arrhythmias that are caused by fibrosis and myofibrillar disarray

2) Physical Exam:

  • A murmur is usually the first clinical manifestation of the disease.
  • You will hear a systolic crescendo-decrescendo ejection murmur along the lower left sternal border, or apex, that increases with a decrease in preload (valsalva or standing up) or after load (anti-hypertensive medications) or decreases with an increase in preload (squatting) or afterload (clenching fist).
  • Can also hear S4 murmur due to non-compliance of left ventricle during diastole.
  • May also have accompanying MR murmur from systolic anterior motion of the mitral valve and significant LV outflow gradients.
  • A double peaked carotid pulse that occurs due to a quick rise, then fall (due to outflow tract obstruction) of blood flow through left ventricular outflow tract, then secondary rise of blood flow through the outflow tract.

3) Routine tests:

  • Labs: usually normal, but may have elevated BNP.
  • CXR: The cardiac silhouette ranges from normal to markedly increased in size. Left atrial enlargement can be observed especially when significant mitral regurgitation is present.
  • ECG: You can see LVH, left atrial abnormality, and left axis deviation. You may also see WPW with certain mutations, deep and broad Q waves in inferior and precordial lateral leads (likely related to gross septal hypertrophy rather than MI), and T wave changes.

4) Special tests:

  • Echocardiogram will show an increased septum: LV wall thickness ratio (> 1.5:1)
  • Cardiac MRI: especially useful when echo is questionable.
  • Cardiac catheterization: most accurate test to determine precise gradients of pressure across outflow tract.

5) Confirmatory tests

  • Genetic testing.
  • Cardiac muscle biopsy: Will show myofibral disarray.

Treatment

  • Asymptomatic patients
    • A significant number of patients will not have any symptoms and will have a normal life expectancy. However, these patients should still be counseled to avoid particularly strenuous activities and medications that decrease preload such as nitrates or diuretic blood pressure medications.

2) Medications

  • Medications are used to relieve symptoms: palpitations, dyspnea, angina, syncope
  • Beta blockers are considered first-line agents, as they can slow down the heart rate and allow for increased diastolic filling and decreased myocardial oxygen consumption. This reduces obstruction in outflow tract and ischemia respectively. Non-dihydropyridine calcium channel blockers such as verapamil and diltiazam can also be used.
  • Disopyramide: decreases contractility and SVT arrhythmias.
  • Amiodarone: the only agent proven to reduce the incidence and risk of cardiac sudden death. Very effective at converting atrial fibrillation and atrial flutter to sinus rhythm.

3) Surgical myomectomy

  • For patients who remain severely symptomatic despite medical therapy and/or with an outflow gradient of more than 50 mm Hg.
  • Involves removing a portion of the inter ventricular septum to widen the outflow tract.
  • Complications include possible death, arrhythmias, infection, incessant bleeding, septal perforation/defect, and stroke.

4) Alcohol septal ablation

  • Involves injection of alcohol into one or more septal branches of LAD.
  • The ablation is a “controlled heart attack” in which the part of the septum involved with the outflow tract is infarcted and subsequently contracts into a scar.
  • Less invasive but produces similar results to septal myomectomy.

5) Ventricular pacing

  • Pacemaker activates the inter ventricular septum before the ventricular free wall. This decreases the gradient across outflow tract.
  • Will also help treat arrhythmias.
  • Indications: 1) family history of sudden death 2) wall thickness > 30 mm. 3) unexplained syncope 4) history of ventricular arrhythmias

6) Cardiac transplant

  • For cases refractory to all treatments.

Natural history

  • The course of IHSS is extremely variable but in general the disease is progressive and there is usually a latency of 3 years between the discovery of a murmur and the manifestation of the first symptoms of the disease.
  • Occasionally symptoms actually diminish or disappear spontaneously with the passage of time.
  • About 1% per year suffer sudden cardiac death.

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