Hypertrophic Cardiomyopathy Flashcards
What is HCM?
The most common genetic cardiac disease defined as left ventricular hypertrophy in the absence of abnormal loading conditions
How many people does it affect?
1 in 500
What level of hypertrophy is needed to be classed as HCM?
There has to be a septal thickness of >15mm, but symptoms usually arise at 20-30mm
What causes HCM?
- 60% of people have an autosomal dominant mutation of their sarcomeric proteins
- 5-10% are caused by inherited metabolic disorders or neuromuscular disease
- Certain drugs can also induce HCM e.g Tacrolimus and Doxorubicin
What are the main proteins that are affected?
- Beta Myosin Heavy Chain (Most prevalent)
- Cardiac Troponin T
- Myosin Binding Protein C
What features are present in Beta Myosin Heavy Chain Mutation?
It is most frequently caused by an Arg403Gln polymorphism and causes early onset disease, extensive hypertrophy and higher incidence of SCD
What affects phenotype?
Genetics, but is also affected by factors such as lifestyle, co-existent hypertension and environmental factors.
So there can be wide phenotypic heterogeneity even with the same polymorphism
What are the microscopic features of HCM?
- Hypertrophied myocytes-bizarre shapes with multicellular connections
- Myocyte disarray may be widely distributed and increased disarray is associated with greater risk of SCD
- Small intramural coronary arteries with thicker walls resulting in ischaemia of myocardium (causes impaired vasodilatory capabilities and bursts of myocardial ischaemia which leads to myocyte death and formation of automaticity-generating fibrotic tissue)
- Expanded interstitial collagen = arrhythmogenic-a source of primary re-entrant arrhythmias because of altered electrical properties and disordered refractory periods
* microscopic features are visible in hypertrophied and non-hypertrophied myocardium
What are the macroscopic features of HCM?
- Very variable
- Most patients show diffuse hypertrophy but 1/3 have hypertrophy limited to a single segment
- Asymmetrical hypertrophy
- Hyperdynamic LV and SAM with LVOTO
- Mitral valve malformations e.g increased size due to leaflet elongation, greater flexibility (contributes to SAM) and direct insertion of papillary muscles on to leaflets (Shows deeper congenital malformation)
What is the venturi effect?
If there is a constriction in a vessel, the blood has to move through it quicker to maintain blood flow and this sets up a pressure gradient-high pressure on the outside (aortic lumen) and low pressure on the inside (left ventricular outflow tract)
What is Systolic Anterior Motion of the Mitral Valve?
In HCM, the ventricular septum becomes hypertrophied so the left ventricular outflow tract narrows and a venturi effect is set up. The low pressure in the LVOT because of the venturi effect pulls the anterior leaflet of the mitral valve towards it during systole which narrows the LVOT even more and generates a viscious cycle
How many HCM patients are affected by LVOTO and SAM?
30-60%
Can be life-threatening as it can reduce ejection fraction, predisposes to AF which increases risk of fatal arrhythmia via aberrancy, and can cause mitral regurgitation so severe it can virtually inhibit cardiac output
What are the typical ECG findings of HCM?
Left Ventricular Hypertrophy: Large S wave in V1, Large R wave in V5/6 >35mm
Dagger-like T waves
P-mitrale (P waves are delayed between the two atria because of hypertrophy)
What are the symptoms of HCM?
- Shortness of breath, especially during exercise
- Palpitations
- Chest pain
- Fainting
Diagnostic tools of HCM:
Symptoms, ECG, Examination, ECHO, Genetic Testing*
