17 - Dilated and Hypertrophic Cardiomyopathies Flashcards
The heart is an electrical-mechanical transducer
What does this mean?
The heart converts electrical signal into a mechanical signal
CAD
VHD
CM
CAD - Coronary artery disease
VHD - valvular heart disease
CM - cardiomyopathy
Arrythmias are _______
Arrhythmias are electrical problems/SCD (sudden cardiac death)
Define cardiomyopathy
Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic; affects the LV and RV
- are either confined to the heart or a part of generalized systemic disorders, often leading to CVD (cardiovascular death) or progressive heart failure-related disability
Cardiomyopathy is defined by a _______
Cardiomyopathy is defined by a pathologically abnormal myocardium
What are the four major types of cardiomyopathies?
- Dilated (DCM)
- Hypertrophic (HCM)
- Restrictive (RCM)
- Arrhythmogenic RV (ARVC)
Label the types of cardiomyopathies based on the phenotype
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The classic ventricular remodeling that occurs with HCM (hypertrophic cardiomyopathy) results in ____________
The classic ventricular remodeling that occurs with HCM (hypertrophic cardiomyopathy) results in a normal sized left ventricular cavity with thickened ventricular walls (concentric LVH) and preserved systolic function and marked diastolic dysfunction (HFpEF)
HFpEF = Heart Failure with preserved ejection fraction
IMAGE SLIDE 7
The classic remodeling that occurs with DCM (dilated cardiomyopathy) results in __________
The classic remodeling that occurs with DCM (dilated cardiomyopathy) results in a globular shape of the heart, thinning of the left ventricular walls (eccentric LVH), overall decrease in systolic function and MR (HFrEF)
HFrEF = heart failure with reduced ejection fraction
Label the image:
SLIDE 8
SLIDE 8
The cytoplasm of cardiomyocyte contains sarcomeres which contain _______ filaments. Mutations in sarcomear genes lead to _____ and _____. Why?
The cytoplasm of cardiomyocyte contains sarcomeres which contain thin and thick filaments. Mutations in sarcomere genes lead to DCM and HCM. Why?
- Mutations lead to an inappropriate transcriptional response to mechanical stress
- Many of these nuclear membrane genes also induce cardiac conduction system disease
- Mutations in sarcomere genes lead to an ___________
- Many of these nuclear membrane genes also induce __________
- Mutations in sarcomere genes lead to an inappropriate transcriptional response to mechanical stress
- Many of these nuclear membrane genes also induce cardiac conduction system disease
What are 8 different causes of hypertrophic cardiomyopathy
- Pressure-overloaded LV eg HTN and/or moderate/severe AS
- Genetic Hypertrophic Cardiomyopathy (Sarcomeric mutations)
- Anderson-Fabry Cardiomyopathy
- Glycogen Storage Diseases (eg PRKAG2
- Danon’s Disease (LAMP2 mutations)
- Mitochondrial CM (eg MELAS)
- Drug-induced CM (eg Hydroxychloroquine)
- Undiagnosed CM
IMAGE SLIDE 31
In DMC the ____ gene encoding the giant protein ____ is mutated
In DMC the TTN gene encoding the giant protein Titin is mutated.
Titin’s amino terminus anchors in the Z band and its carboxy terminus ends in the M band. Titin interacts with both the thin and thick filaments
What is the function of Titin and how would a mutation in the TTN gene lead to DCM?
In DMC the TTN gene encoding the giant protein Titin is mutated.
Titin’s amino terminus anchors in the Z band and its carboxy terminus ends in the M band. Titin interacts with both the thin and thick filaments. Titin acts as a “biological spring” spanning half of the sarcomere and connecting the Z-disk to the M-line, with scaffold and signaling functions
Thick filament proteins are encoded by ____ and _____, two genes commonly linked to HCM
Thick filament proteins are encoded by MYH7* and *MYBPC3 , two genes commonly linked to HCM
Thick filament proteins are encoded by MYH7* and *MYBPC3 , two genes commonly linked to ____
Thick filament proteins are encoded by MYH7* and *MYBPC3 , two genes commonly linked to HCM
What gene mutations explain 75% of inherited HCM? What conclusion is drawn based on this?
Mutations in the genes encoding the thick filament components myosin heavy chain and myosin binding protein C (MYH7 and MYBPC3I) together explain 75% of inherited HCMs - leading to the observation that HCM is a disease of the sarcomere
What are the two most common types of cardiomyopathy (CM)?
Dilated (DCM) and hypertrophic (HCM)
Which two genes are implicated in HCM? What does this suggest about HCM?
MYH7
MYBPC3
- MYH7 encodes beta-myosin heavy chain
- MYBPC3 - myosin binding protein C
Suggests that HCM is sarcomeric in nature
glycogen accumulation in the heart is associated with ______
HCM
