Cardiomyopathies Flashcards
describe the structure of the myocardium
- Thickest layer of the heart
- Composed of cardiac muscle
- Specialised structure with specific characteristics that allow the cells to carry out their functions
describe the structure of the cardiomyocyte and what its role is
role
- regulation of muscle contraction
structure
- Sarcomere consists of around 20 proteins
- There are many other accessory proteins that make connections between the myocytes and the extracellular matrix
what is meant by the term cardiomyopathy
- This is a general term for diseases of heart muscle, where walls of the heart chambers have become stretched, thickened or stiff. This affects the hearts ability to pump blood around the body
- Any disease of the myocardium that cannot be explained by coronary artery narrowing or abnormal loading ventricles
- Focused on disorders that arise within the tissue itself, cardiomyocytes or extracellular matrix
what is a primary cardiomyopathy
- Disease is chiefly confined to the heart
- Primary cardiomyopathies – have genetic, mixed (genetic and nongenetic) or nongentic(acquired) causes and are confined solely to the heart
what is a secondary cardiomyopathy
- Affect the heart as part of a systemic disease (e.g. amyloidosis, hemochromatosis or sarcoidosis)
what is the classification of cardiomyopathies
Historically, cardiomyopathy was separated into 3 categories - hypertrophic, dilated, and restrictive categories.
NOW
- Familial/genetic – occurrence in more than one family member.
- Non familial/non genetic – primary case/absence of disease in other family members.
what where the 3 categories of cardiomyopathies (3 main subtypes as well)
- hypertrophic
- dilated
- restrictive categories
what are the subtypes of cardiomyopathy
- Hypertrophic cardiomyopathy (HCM)
- Dilated cardiomyopathy (DCM)
- Restrictive cardiomyopathy (RCM)
- Arrhythmogenic right ventricular cardiomyopathy (ARVC)
- Unclassified cardiomyopathy
what are the most common cardiomyopathies
- HCM and DCM are the most common
what is dilated cardiomyopathy (DCM)
- Dilated cardiomyopathy phenyotype is mainly characterized by enlargement (dilation) of the chambers and decreased contractile (systolic) function usually in the left side
- Ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease
- Right ventricular dilation and dysfunction may or may not be present
what are the causes of dilated cardiomyopathy
- idiopathic
- familial
Inflammatory
- infectious (especially viral)
- non infectious
- connective tissue disorders
- permpartum cardiomyopathy
- Sarcodosis
Toxic
- chronic alcohol consumption
- chemotherapeutic agents
metabolic
- hypothyroidism
- chronic hypocalcameia
neuromuscular
- muscular or myotonic dystrophy
describe familia forms of dilated cardiomyopathy
In about 35% of patient’s genetic mutations can be identified that usually involve proteins that are part of
- Sarcolemma
- Cytoskeleton
- Sarcomere
- Mitochondrion
- Nuclear membrane
what is the histopathology of dilated cardiomyopathy
- Changes in the structure, composition or cardiomyocytes leading to a remodelling of the myocardium
- Distinctive phenotype shows a patch work left ventricle where cardiomyocytes are interspersed with necrotic and fibrotic patches and intermittent calcifications
- there is more fibrotic parts of the heart
what are the pathophysiology of dilated cardiomyopathy
- Myocyte injury causes a decrease in contractility which causes a decrease in stroke volume which causes a decrease in cardiac output
what are the compensation mechanisms that are activated for the decrease in CO in dilated cardiomyopathy
- this can cause activation of the sympathetic activity
- which causes an increase in contractility which will increase stroke volume and thus cardiac output and thus maintain blood pressure
- and it also causes an increase int he heart rate which maintains blood pressure - renin- angiotensin system is activated this
- causes vasoconstriction which increases the TPR which matains blood pressure
- it increases venous returns to the heart which causes an increase in preload this leads to an increase in stroke volume and therefore an increase in cardiac output and blood pressure being maintained
- it also causes aldosterone to increase which leads to salt and water retention - increase in antidiuretic hormone
- this causes an increase in blood volume which leads to venous return to the heart being increased and thus prealod increase this leads to an increase in stroke volume and therefore an increase in cardiac output and blood pressure being maintained
what are the detrimental effects of the compensation of dilated cardiomyopathy
- Vasoconstriction causes increased venous return to the heart which increases the preload, but this also increases afterload and makes it more difficulty for the LV to eject blood which can lead to hypertrophy
- Angiotensin II and aldosterone contribute directly to pathogenic cardiac remodelling, it causes vasoconstriction which increases venous return to the heart which increases preload and thus afterload and makes it difficult for LV to eject blood
what are the signs and symptoms of dilated cardiomyopathy
- Decreased cardiac output – tiredness and fatigue
- Pulmonary oedema – Dyspnoea/Crackles
- Ascites and peripheral oedema (in legs, ankles)
- Enlarged heart – leftward displacement of apical beat and possibly a third heart sound (indicates poor systolic function)
- Mitral regurgitation – regurgitation of blood back into the left atrium
- Palpitations – this is caused by arrhythmias
what diagnostic test would you perform on someone suspected with dilated cardiomyopathy
- Signs/Symptoms/Family history
- A physical exam
- Blood tests
- An electrocardiogram (ECG)
- A chest X-ray – enlarged cardiac silhouette
- An echocardiogram – ultrasound to image heart
- An exercise stress test
- Cardiac catheterization
- A CT scan
- An MRI
how do you treat dilated cardiomyopathy
- MEDICATION TO CONTROL HEART FAILURE SYMPTOMS:
• beta-blockers – to control heart rate.
• anti-coagulants - to reduce the chance of blood clots forming
• Diuretics – to reduce the build-up of the fluid
• ACE inhibitor or an Angiotensin II Receptor Blockers (ARBs) - lower blood pressure - PREVENTION AND TREATMENT OF ARRTHYMIAS:
• Medication to control arrhythmia and possibly blood thinners to prevent blood clots.
• Pacemaker - implanted to control the rhythm of the heart
• Implantable cardioverter defibrillators or ICDs to control the rhythm and shock the heart if it goes out of normal rhythm. - CARDIAC SURGERY/TRANSPLANTATION:
• Surgery to remove areas of heart muscle if it affects blood flow from the heart.
• A very small number of people may need a heart transplant (a heart from a donor).
describe what hypertrophic cardiomyopathy is
Depending on the area and amount of thickening, the volume of the ventricle may be normal, or may be reduced.
If septal thickening predominates this may cause left ventricular outflow tract obstruction or mitral valve dysfunction.
HCM generally affects the left ventricle, and, particularly the septum – but it can also affect the right ventricle
what is hypertrophic cardiomyopathy caused by
- caused by a single genetic mutation
- often inherited as an autosomal dominant trait
what is the most frequent cause of sudden death in young people
Hypertrophic cardiomyopathy is the most frequent cause of sudden death in young people (including trained athletes) and can lead to functional disability from heart failure and stroke.
The majority of affected individuals probably remain undiagnosed and many do not experience greatly reduced life expectancy or substantial symptoms.
what is the gene mutation in hypertrophic cardiomyopathy
- Mutations in 13 sarcomeric proteins have been associated with HCM – the most commonly affected are myosin-binding protein C and β-myosin heavy chain.
- Mutations in β-myosin heavy chain gene (β-MyHC) were the first to be identified in HCM and cause 30% of all cases.
- In cardiac and skeletal muscle cells, the β-myosin heavy chain forms part of larger protein called type II myosin.
- The heavy chains each have two parts: a head region and a tail region. The head region - the motor domain, interacts actin.
- Most mutations are in the motor domain of myosin however, disease-causing mutations in the rod region have also been identified
what are the two parts of the B-myosin heavy chain
The heavy chains each have two parts: a head region and a tail region. The head region - the motor domain, interacts actin.
what are the most common mutations in hypertrophic cardiomyopathy
- Mutations in 13 sarcomeric proteins have been associated with HCM – the most commonly affected are myosin-binding protein C and β-myosin heavy chain.
- Myosin-binding protein C - a thick filament-associated protein – function still disputed but thought to have a role in the regulation of cross bridge cycling.
describe the histology of hypertrophic cardiomyopathy
A: asymmetrical subaortic septal hypertrophy.
B: the asymmetrical septal hypertrophy.
C: In the area of thickened muscle, the muscle cells can appear disorganized (or in ‘disarray’). Myocardial disarray at histology
what are the symptoms of hypertrophic cardiomyopathy
There is wide variation in the symptoms of HCM, with some people having few or no symptoms, to people who have very severe symptoms
• Palpitations – caused by arrhythmias.
• Chest pain – reduced oxygen levels getting to the heart.
• Dizziness or fainting – reduced oxygen levels or blood flow to the brain.
• Breathlessness (or dyspnoea) – pulmonary oedema, making it harder to breathe.
• Tiredness – reduced cardiac output.
how would you diagnose someone with hypertrophic cardiomyopathy
- Medical history
- Physical exam
- ECG
- Exercise ECG tests
- Holter monitoring
- Echo echocardiogram
- MRI scan
how would you treat someone with hypertrophic cardiomyopathy
- Medication
- Devices
- Surgery
what is the most lethal form of cardiomyopathy
restrictive cardiomyopathy
how is restrictive cardiomyopathy characterised
Alterations in tissue flexibility in the absence of changes in ventricular myofibrillar arrangement and gross abnormalities.
RCM is, therefore, characterized by increased stiffness of the myocardium that causes increased pressure in one or both ventricles.
Ventricular relaxation is impaired and the atria then enlarge in response to the increased pressure in some patients.
what causes RCM
- fibrosis or scarring of endomyocardium
2. Infiltration of myocardium by an abnormal substance
It can also be genetic and run in families.
what are the genetic causes of RCM
- Recently mutations in the sarcomeric protein troponini I were associated with a familial form of the disease, it is now recognized as the primary disease causing mutation in familial RCM
- Mutations in other sarcomeric proteins such as cardiac desmin, a-cardiac actin, and B-MyHc as well as mutations that have been implicated in HCM have been described in RCM patients
what can cause secondary restrictive cardiomyopathy
Secondary restrictive cardiomyopathy caused by cardiac amyloidosis – misfolding amyloid deposits
what are signs and symptoms of restrictive cardiomyopathy
- Decreased cardiac output - fatigue (tiredness)
- Systemic congestion
- Jugular venous distension
- Peripheral oedema
- Arrhythmias - Palpitations
- Possible conduction block
- Signs of congestive heart failure may also be present e.g. pulmonary crackles etc.
how is RCM diagnosed
- Medical history
- Phyiscal exam
- ECG/chest X ray
- CT and MRI
- Poor prognosis except when the underlying cause can be treated
what causes Arrhythmogenic right ventricular cardiomyopathy (ARVC)
ARVC is inherited in an autosomal-dominant or recessive pattern
Mutations in proteins that comprise the cardiac desmosome account for most inherited cases of ARVC. Disruptions in desmosome stability cause structural and functional alterations and are associated with cardiomyocyte apoptosis.
what is the histology of ARVC
Adipose and fibrotic tissue that replace cardiomyocytes are a hallmark of ARVC, primarily in the right ventricle
- Left ventricular is also involved in the later stages of the disease
The right ventricle enlarges as myocyte loss progresses, causing a reduction in blood volume pumped from the heart and arrhythmias
