IHSS – Idiopathic Hypertrophic Subaortic Stenosis

Idiopathic hypertrophic subaortic stenosis (IHSS)

 

also called hypertrophic obstructive cardiomyopathy (HOCM), is a genetic form of hypertrophic cardiomyopathy (HCM)

 

Characterized by marked hypertrophy of the interventricular septum:

Reduces the diameter of the left ventricular outflow tract, leading to outflow tract obstruction

Overtime it leads to:

LVH and increased diastolic filling pressure

 

It is the most common (Mendelian) genetic heart disease, occurring at rate of approximately 1 in 500.

Autosomal dominant pattern of inheritance with variable penetrance leading to a high degree of phenotypic heterogeneity, which makes genetic testing implausible  

Monogenic disease where in 1 of the 13 genes lead to a single amino acid change in proteins that compose the sarcomere complex

 

Presents after puberty (Average in mid-20s, but increasingly seen in 40-50s)

Common in young athletes

May present with symptoms or sudden cardiac death (SCD)

 

Ordinarily, muscle cells line up linearly  

In IHSS, mutations lead to myofibrillar disarray (disorganization or haphazard arrangement of the muscle fibers).

Myocardium is unable to contract properly and the heart compensates for this lack of effective contraction by undergoing hypertrophy.

The walls of the heart thicken and the interventricular septum becomes asymmetrically enlarged leading to a narrowing of the left ventricle outflow tract.

 

Papillary muscles are deformed by the thickened septum and thickening of the mitral valve leaflet commonly occurs, as well.

 

Ejection of the blood through a narrowed outlet leads to a phenomenon known as the venturi effect:

Venturi forces pull anterior mitral leaflet toward septum during systole causing obstruction = systolic anterior movement of mitral valve (SAM).

 

Eventually, leads to diastolic heart failure through intermittent outflow obstruction Degree of obstruction is dependent on ionotropy and chronotropy:

During periods of strenuous exercise, HR incr → decr diastolic filling time (relaxation/filling) → decreased preload to the ventricle → narrowing of the outflow tract and incr obstruction

Note: paradoxically, when HR is decr/incr diastolic filling time → outflow tract expands and is less obstructed

Diagnosis

History – Most patients have few or no symptoms

• Dyspnea – diastolic dysfunction from LVH – back up into lungs
• Palpitations, syncope and sudden death – arrhythmias due to fibrosis and myofibrillar disarray
• Angina: Increased oxygen demand from thickened wall
• Orthopnea/paroxysmal nocturnal dyspnea – Due to impaired diastolic function and subendocardial ischemia (more severe dysfunction)

Physical Exam –

1. Precordium -apical impulse (parasternal lift)
2. Internal jugular pulse–prominent ”a” wave
3. Carotid pulse — bifid, or double peak, brisk wave
   1. Initial rapid ejection- mid-systolic (outflow tract) obstruction
   2. Secondary “decelerated rise” phase–partial AV (LV outflow) closure
4. Ausculation
   1. Murmur (typically the first clinical manifestation of disease)

1. Systolic Anterior Motion (SAM) of mitral valve – poor coaptation with mitral regurgitation
   1. Sound: Mid-systolic in apex radiating to the axilla
2. Turbulent flow through the outflow tract
   1. Similar to aortic stenosis
      1. Sound: Mid-systolic, crescendo-decrescendo, loudest at LLSB or apex
         1. Increases with: decreased preload (valsalva or standing up) or afterload (antihypertensives)
         2. Decreases with: increased preload (squatting) or afterload (clenching fist)

Extra heart sounds – S4 (non-compliance of left ventricle during diastole)

ECG

 

LVH, LA abnormality, LAD, deep & wide Q waves*, T wave changes

Certain mutations may exhibit WPW

*inferior and lateral precordial leads due to septal hypertrophy

Echocardiogram  

IV Septum: LV wall thickness ratio (> 1.5:1)

Other: Cardiac MRI, Catheterization, Genetic testing, BNP, Cardiac muscle biopsy

Treatments & approach:

 

• Asymptomatic

 

1. Significant number of patient will not have any symptoms and will have a normal life expectancy
2. Avoid
   1. Volume depletion = decreases outflow gradient, preventing SCD or tissue hypoperfusion
   2. Strenuous activity= increase cardiac inotropy and chronotropy, while decrease SVR, which decrease diastolic filling and decrease outflow
   3. Nitrates & diuretics–decrease SVR

 

• Symptomatic : palpitations, dyspnea, angina, syncope

 

1. Pharmacologic

 

• Beta blocker –1st line

 

1. Primarily non-vasodilating beta-blocker: Propranolol
2. Reduce cardiac chronotropy and ionotropy → improves diastolic filling, reduced outflow gradient, improves perfusion and subendocardium
3. May decrease ventricular stiffness
4. Can reduce physiologic outflow obstruction, dyspnea upon exertion, angina, ventricular arrhythmia.  
1. Non-dihydropyridine calcium channel blocker
   1. Verapamil, diltiazem
   2. Reduces cardiac chronotropy and ionotropy
   3. Improves diastolic filling, reduced outflow gradient, improves perfusion of subendocardium
2. Disopyramide — class I antiarrhythmic
   1. Decrease contractility and outflow gradients
   2. The only drug that Improves symptoms in those with outflow gradient at rest.
   3. Note: prolong QTc and anticholinergic side effects
3. Controversial
   1. ACE-inhibitor
   2. ARB
   3. Aldosterone
   4. Antiarrhythmics (i.e. Amiodarone)
1. Management of atrial fibrillation
   1. Most common arrhythmia: atrial fibrillation
      1. ~20%
      2. May reveals or worsens heart failure
   2. Management
      1. Unstable: DCCV
      2. Stable
         1. Rate control: Beta-blockers or Nondihydropyridine calcium channel blocker, if this fails
         2. Rhythm control: Amiodarone may help NSR
         3. If outflow obstruction: avoid digoxin
         4. Ablation: Recommended in certain
2. Electrophysiologic therapy
   1. Internal cardioverter defibrillator (ICD)
   2. The only non-surgical intervention proven to decrease mortality in those with appropriate risks (Note: heterogenous group, hard to identify who is at risk)
   3. Secondary prevention in those with a history of VFib and VTach
   1. Primary prevention
      1. Classical risk factor
         1. Family history of sudden death due  to HOCM
         2. Wall thickness >30mm
         3. Unexplained syncope
         4. History of ventricular arrhythmias
      2. HCM risk SCD
         1. Study to determine based factors involved in those at risk for SCD. Advocated ICD placement as primary prevention in those with >6%

1. Biventricular pacing
   1. May reduce outflow tract gradient
   2. Indicated for those who do not meet resynchronization criteria
      1. NYHAIII
      2. LVEF<35%
      3. QRS>120
      4. Seen improvement in all of these functions
1. Septal reduction
   1. Reserved for those who are severely symptomatic despite medical therapy and or with outflow gradient of >50mmHg

Myomectomy

Surgical resection of a portion of the interventricular septum, enlarging the outflow tract and improving gradients

First line reduction therapy – superior because it yields a larger outflow tracts on average

If performed successfully, survival rates are similar to those of the general public

Mitral valve surgery (i.e. repair, replacement) may be necessary

Percutaneous alcohol ablation

Injection of absolute alcohol into the first or largest of the septal perforating branch of LAD, creating a transmural infarct of the septum leading to reduced contractility and thickness of the proximal interventricular septum

Alternative therapy – less invasive, but with an increased risk of arrhythmia and 10-20% chance of permanent pacemaker

Suggested in patients with higher risk because they are older, have comorbidities or are averse to surgery

LV assist device

Experimental due to small LV cavity and current generation of LVADs

Heart transplantation

• Considered in those with HOCM and life-threatening arrhythmias or refractory heart failure
• Similar survival to those with Dilated CM, who are receiving transplant – borrowed their criteria:

Peak oxygen consumption and Minute ventilation – carbon dioxide production relationship (VE/VCO2) measured during cardiopulmonary exercise

 

SAM

https://www.youtube.com/watch?v=oblQE0LNbf8

https://www.youtube.com/watch?v=ICZmnCw0E5E