Cardio Flashcards
Sinus Node
specialized group of cells in
the right atrium that generates impulses that
coordinate the pumping of blood
Arrhythmia
Abnormal Heart Beat
Bradycardia
excessively slow heartbeat
Tachycardia
Excessively rapid heartbeat
V-fib
ventricles quiver
rather than pumping blood
ECG/EKG
A
study used to record the electrical
activity of the heart using electrodes
attached to the skin
P wave:
Represents atrial
activation
PR interval
Represents
the time from onset of atrial
activation to onset of
ventricular activation
QRS complex:
Represents
ventricular activation
QRS duration
Duration of
ventricular activation
ST-T wave:
Represents
ventricular repolarization
QT interval
Duration of
ventricular activation and
recovery.
Holter monitor
portable device that
records the electrical activity of the heart
over a period of time (at least 24 hours)
Cardiac stress test
measures the
heart’s ability to respond to external
stress (exercise or drugs) using an EKG
in a controlled setting
Echocardiogram
A test that uses
ultrasounds waves
to visualize that
heart
Color Doppler (echos)
used to visualize abnormal
communications between the left and right side of the
heart, leaking of blood through the valves, and if the
valves are opening properly.
Transthoracic echocardiogram (TTE)
Non-invasive technique
Most common form of echocardiogram
Transesophageal echocardiogram (TEE)
A probe containing an ultrasound transducer is
passed into the patient’s esophagus for visualization
of the heart
Clearer images
Ejection Fraction
measurement of the
blood ejected from the left ventricle with
each heart beat
normal ejection fraction
50% or higher
Heart catheterization
Invasive test that
involves the insertion of a catheter into a
chamber or vessel of the heart for
evaluation or other procedures
Reasons for Heart catheterization
Pulmonary arterial pressure or myocardial biopsy
Pacemaker
An electronic device
implanted to provide electrical impulses to
regulate the heartbeat
Reasons for a pacemaker
Used in individuals with a slow heart rate or problem
with the heart’s electrical conduction system
Automatic implantable cardioverter
defibrillator (ICD)
An electric device that
is implanted to monitor for and correct
cardiac arrhythmia
Reasons for an ICD
Used in individuals at risk for sudden cardiac death
Syncope
fainting, brief loss of
consciousness caused by temporary lack
of oxygenated blood
Palpitations
Feelings or sensations that
the heart is pounding/racing or skipped/
stopped beats. May represent a normal or abnormal heart
rhythm
Sudden Cardiac death
Death from an abrupt loss of heart
function
• Within 1 hour of the onset of cardiac symptoms
• Natural, rapid, unexpected
Symptoms: chest pain, palpitations, dizziness,
lightheaded, syncope
• 25-50% - no prior heart medical history
Survival rate of sudden cardiac death
Only an 8 percent survival rate
Coronary heart disease and heart attack
Multifactorial disease (with a few rare exceptions) • Risk factors - Family history (strongest independent risk factor) - Sedentary lifestyle - Smoking - Obesity - High-fat diet
Familial Hypercholesterolemia
Significant elevations in total serum
cholesterol and LDL cholesterol early in
life
FH risks
Xanthomas
Atheromas
Elevated risk for CAD and myocardial infarction
Xanthomas
yellowish cholesterol-rich material in tendons or
other body parts
Atheromas
accumulation of debris containing cholesterol in the artery walls (plaques)
FH inheritance
AD - homozygotes have earlier age of onset and more severe disease
Genes for FH
LDL recepter gene (LDLR)
ApoB-100
others
Benefits of genetic testing for familial
hypercholesterolemia
- Early screening for elevated cholesterol levels
* Risk-factor modification before onset of disease
Locus heterogeneity
Mutations in different genes causes a similar
phenotype
Allelic heterogeneity
Different mutations within the same gene cause a
similar phenotype
Phenotypic heterogeneity
Different mutations within the same gene cause
different phenotypes
Cardiomyopathy
Diseases of the heart muscle
(myocardium)
Can lead to heart failure (swelling of
lower extremities, dyspnea – shortness of
breath), risk for arrhythmia, stroke, and
sudden cardiac death
Dilated cardiomyopathy
• Most common type
• Usually occurs in adults
• Muscle that makes up the left ventricle stretches
and becomes thinner, spreads to the right
ventricle and atria
• Dilated heart chambers cannot pump blood
efficiently (systolic dysfunction – ejection
fraction less than 50%)
Hypertrophic cardiomyopathy
• Affects all ages
• Muscle cells enlarge causing ventricular walls to
thicken and stiffen
• Ventricle cannot adequately relax and fill with
blood
• Can result in sudden cardiac arrest, arrhythmia,
chest pain, dizziness, fatigue, syncope, shortness
of breath, or fainting
Restrictive cardiomyopathy
- Mostly occurs in older adults
- Scar tissue replaces normal heart muscle
- Ventricles become stiff and rigid
- Blood flow in the heart is reduced
- Can lead to heart failure or arrhythmias
Arrhythmogenic Right Ventricular Dysplasia
ARVD
• Often affects teens or young adults
• Muscle tissue in the right ventricle dies and is replaced
with scar tissue
• Disrupts the heart’s electrical signals and causes
arrhythmias
• Palpitations and fainting after physical activity
GENETIC
Most common reason for referral for heart transplant
Dilated cardiomyopathy (DCM)
Mutations in _ are the most common known cause of DCM
TTN (TITAN)
TNNT2
DCM gene. TNNT2 mutations may be associated with earlyonset
and aggressive disease, but late onset has
also been reported.
Phenotype: DCM with conduction system
disease
• LMNA: DCM with arrhythmias like atrial
fibrillation, risk of sudden cardiac death, often
require a pacemaker
- Mutations in LMNA also cause Emery-Dreifuss
muscular dystrophy
- Can present as cardiomyopathy alone, skeletal
myopathy alone, or both
• SCN5A
X-linked transmission of DCM genes
DMD (Duchenne) and TAZ (Barth syndrome)
Hypertrophic Cardiomyopathy
Left ventricular hypertrophy without
another predisposing cardiac condition
(like aortic stenosis and long-standing
hypertension)
Symptoms of HCM
• Shortness of breath (particularly with exertion), chest pain, palpitations, and syncope • May be asymptomatic • Can lead to heart failure • Can lead to sudden cardiac death
Diagnosis of HCM
• Echocardiogram, electrocardiogram, physical
exam and history
• Heart tissue sample
• Genetic testing
HCM Genes
60-70% caused by mutations in sarcomere genes
• Autosomal dominant
• Pathologic feature: myocyte hypertrophy and
disarray
MYH7 and MYBPC3 are the big ones!!
Mutations in _ and _ each make up to 40% of HCM
MHY7 and MYPBC3
MYH7 mutations are association with:
younger age of diagnosis, more severe
hypertrophy, and nearly complete
penetrance, but variable survival.
Other “HCM” genes
PRKAG2 and LAMP2 and GLA
• Result in metabolic storage disease of the
myocardium
• Mutations in PRKAG2 may result in WolffParkinson-White
(WPW) syndrome with or
without HCM
• Mutations in LAMP2 result in Danon disease, an
x-linked disorder with cardiomyopathy, muscle
weakness, variable intellectual disability
LAMP2
Mutations in LAMP2 result in Danon disease, an
x-linked disorder with cardiomyopathy, muscle
weakness, variable intellectual disability
PRKAG2
Mutations in PRKAG2 may result in WolffParkinson-White
(WPW) syndrome with or
without HCM
GLA
GLA
• Results in Fabry disease, x-linked, associated
with left ventricular hypertrophy, may be limited
to the heart
RAS MAPK pathway genes
Other HCM genes. ~20% of individuals with Noonan syndrome develop HCM
Non-Compaction Cardiomyopathy (NCCM)
- Usually seen as Left Ventricular noncompaction
(LVNC) - Approximately 70% of LVNC is inherited
- Wide range of age of onset
• Adult form = average age of onset is 40yo
• Congenital form = average age of onset is 6yo
Heart formation
- Embryonic development of the heart is
very complex - The myocardium is the muscle of the
heart and starts off as a spongy layer
• Starts off as trabecular fibers and recesses
(spaces)
- Between weeks 5 and 8, this spongy
material compacts
• The recesses disappear or become capillaries
• If the myocardium does not compact as tightly as
it should, NCCM/LVNC is the result
Clinical presentation of NCCM
Thromboembolic events
Atrial fibrillation
Ventricular tachycardia
Heart failure
What is used to diagnose NCCM
ECG and echocardiography findings are
used to diagnose NCCM, and sometimes
cardiac MRI
Most common gene to cause NCCM
MYH7
Long QT syndrome
- Inherited or acquired
• Medication
• Metabolic abnormalities
• Bradycardia
- Prolonged QT interval
- Characteristic polymorphic ventricular tachycardia • Torsades de pointes (“twisting of points”) • May result in syncope or ventricular fibrillation and cardiac arrest / sudden cardiac death
Romano-Ward syndrome
• Usually autosomal dominant
• 4% risk of sudden cardiac death in the 3 most
common subtypes from birth to age 40 years1
Jervell and Lange-Nielsen Syndrome
- Autosomal recessive
- LQTS and sensorineural deafness
- KLQT1 (KCNQ1) and KCNE1
LQT8 type
Timothy syndrome
LQT7 type
Anderson-Tawil syndrome
Anderson-Tawil syndrome
• KCNJ2
• Skeletal abnormalities
• Periodic paralysis and LQTS exacerbated by
hypokalemia (low potassium)
Timothy syndrome
- CACNA1c
- Syndactyly
- Dysmorphic features
- Intellectual disability
- Autism
- Arrhythmias
LQT1 trigger, age, beta blockers effective?
exercise, before 10 y, likely effective
LQT2 trigger, age, beta blockers effective?
emotion, after age 10, less likely effective
LQT3 trigger, age, beta blockers effective?
Rest or sleep, after age 10, less likely effective
Genes for Jervell and Lange-Nielson syndrome
KCNQ1 or KCNE1 in 94%
Agents/circumstances to avoid for LQTS
- Drugs that cause further prolongation of
the QT interval - Competitive sports/activities associated
with intense physical activity and/or
emotional stress
Short QT syndrome
- A heritable disorder of the electrical system of the heart
- Characterized by short QT interval on EKG (<320ms) and tall, peaked T waves
- Increased risk for SCD and atrial fibrillation
- Same symptoms as long QT syndromeclinical presentation is indistinguishable from long QT
Genetics of SQTS
Rare
• May account for some cases of SIDS
Variable penetrance
Austosomal Dominant
• KCNH2
• KCNQ1
• KCNJ2
Detection rate unknown
Brugada syndrome
Characterized by abnormal EKG and
increased risk of sudden cardiac death
Sudden unexpected nocturnal death syndrome
SUNDS
(Brugada) Syndrome seen in Southeast Asia in which apparently healthy young persons (often males) die from cardiac arrest
Brugada syndrome often presents:
• Often presents with syncope or cardiac arrest, often
at rest or while sleeping
• Often presents in the 3rd or 4th decade of life
• Can present as sudden infant death syndrome
(SIDS), or
• Sudden unexpected nocturnal death syndrome
(SUNDS)
Management of Brugada syndrome
- Implantable cardioverter defibrillators
(ICDs)
• Only therapy known to be effective in affected
individuals with syncope or cardiac arrest - Avoid/treat fever, cocaine use, electrolyte
disturbances, and medications that can
induce arrhythmias
Brugada syndrome EKG
- Right bundle branch block and ST segment elevation in leads V1 through V3 with a “coved morphology”
- May be spontaneous or induced by medication
Gene with largest role in Brugada
SCN5A (15-30%)
Pulmonary Arterial Hypertension (PAH)
Widespread obstruction and obliteration
of the smallest pulmonary arteries
• Resistance to blood flow through the lungs
increases and the right ventricle attempts to
compensate by generating higher pressure.
• Heart failure develops when the heart can no
longer compensate for the increased resistance.
Symptoms of PAH
dyspnea (shortness of breath), Reynaud’s phenomenon, fatigue, syncope, chest pain, near syncope, palpitations, leg edema
Diagnosis of PAH
- Right heart catheterization
• Mean pulmonary artery pressure >25 mmHg at rest
or >30 mmHg during exercise
- Exclude other known causes of pulmonary hypertension
Other known causes of pulmonary hypertension
• Advance stage lung disease • Pulmonary embolism/disease of large pulmonary vessels • Advanced heart disease • Connective tissue diseases • Cirrhosis • HIV infection
Largest genetic contributor to PAH
BMPR2 (75%)
PAH and HHT
- HHT
• Presence of multiple arteriovenous malformations
(AVMs)
If close to the surface of the skin, bleed with slight trauma
• Recurrent nosebleeds
• GI bleeding
• Complications of AVMs in the brain, liver, or lungs
- PAH and HHT can occur together
• ACVRL1
• ENG or SMAD8 (rarely)
• BMPR2 (reported in one family)
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (AFVD/C)
Progressive fibrofatty replacement of the
myocardium, predisposing to ventricular
tachycardia and sudden death
Four phases of AFVD/C
• Concealed phase (no clinical manifestations, but
potential risk of sudden cardiac death)
• Electrical disorder with symptomatic arrhythmias
• Right ventricular failure
• Biventricular pump failure resembling dilated
cardiomyopathy
Diagnosis of ARVD
- Noninvasive
• EKG, 24-hour Holter monitoring
• Echocardiogram - Invasive
• Right ventricular angiography (RVA)
• Right ventricular endomyocardial biopsy
Fibrofatty replacement of the myocardium and/or
atrophy of the right ventricular myocardium
Genes for ARVD
DSP, PKP2, DSG2
Catecholaminergic polymorphic ventricular tachycardia (CPVT)
- Cardiac electrical instability triggered by
acute activation of the adrenergic nervous
system (Catecholamines: epinephrine
(adrenaline), norepinephrine
(noradrenaline) and dopamine)
- Rapid heart beat that originates in one of
the lower chambers (the ventricles) of the
heart
• QRS complexes with frequent and rapid changes in
morphology
Symptoms of CPVT
- Syncope occurs in 80% of affected individuals • Often during exercise or acute emotion • ventricular tachycardia (bidirectional or polymorphic). • Arrhythmias may self-terminate • Or may lead to ventricular fibrillation and cause sudden cardiac arrest/death
- Cardiac arrest occurs in 30% of affected
individuals
Genes in CPVT
RYR2 (AD - 50-55%) and CASQ2 (AR - 1-2%)
Amyloid
a protein deposit exhibiting beta
sheet structure
Amyloidosis
disease where there is a buildup
of amyloid in body tissue and organs
Cardiac Amyloidosis
deposit of abnormal
protein (amyloid) in the heart tissue
• Amyloid deposits take the place of normal heart
tissue and may affected electrical signals
Transthyretin (TTR) amyloidosis
- Group of diseases caused by the accumulation
of abnormal protein in the body
- Clinical presentation can include peripheral
and autonomic sensorimotor neuropathy,
cardiomyopathy, vitreous opacities, and CNS
amyloidosis
- Transthyretin gene (TTR)
- Autosomal dominant
- De novo rate: 2/3 (66%)
Cardio pedigree questions
Congenital Heart Disease Palpitations/arrhythmias Chest pain Heart failure • Shortness of breath, edema, fatigue Enlarged heart Hypertension High cholesterol Heart murmur Stroke/TIA Deep vein thrombosis (DVT) Heart (and/or lung) transplant or surgery Pacemaker/ ICD Congenital deafness Heart attack • Age? • Coronary artery disease? Sudden unexplained death • SIDS • Odd/unexplained accidents • Single car accident • Drowning in an experienced swimmer • Sudden death in a young, apparently healthy individual Fainting, black-out, dizziness, or near fainting • Context? • Trigger? Seizures • Symptoms of other differential diagnoses • Numbness/tingling and heat/cold intolerance – Fabry disease • Arachnodactyly and dislocated lens – Marfan syndrome • Muscular Dystrophies • Other hereditary conditions
Sarcomere
heart muscle
Causes of HCM
Genetic (60-70%); non-genetic or unknown (30-40%)
