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Flashcards in Cardio Genetics Deck (49):

What is the "heart's pacemaker?"

- An electrical impulse called an action potential is generated at regular intervals in the sinoauricular node in the right atrium


Electrocardiogram (ECG/EKG)

A study used to record the electrical activity of the heart using electrodes attached to the skin


Electrocardiogram Terminology - P wave - PR interval - QRS complex - QRS duration - ST-T Wave - QT interval

- 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



- A test that uses ultrasound waves to visualize that heart


Color Doppler (echocardiogram)

- Used to visualize abnormal communication 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 is 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 (pulmonary arterial pressure, myocardial biopsy)



- An electronic device implanted to provide electrical impulses to regulate the heartbeat - Used in individuals witha 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 - Used in individuals at risk for sudden cardiac death.


Pedigree Clues

- "heart attack/thing/disease" - Sudden unexplained death (SIDS, Accidents, Drowning, Age


Traditional approaches to molecular genetics are limited by many factors such as

- Locus heterogeneity - Allelic heterogeneity - Phenotypic heterogeneity - Low penetrance - Age-related penetrance - Premature death


Sudden cardiac death

- Death within 1 hour of the onset of cardiac symptoms - Unexpected, unexplained, non-traumatic - Symptoms: chest pain, palpitations, dizziness, lightheaded, syncope - Example: during exercise or emotion, rest/sleep - 70-90% of SCD have atherosclerotic CAD - 20-25% of all deaths in the U.S. are as a result of SCD


Coronary heart disease and heart attack

- Multifactorial disease (with a few rare exceptions) - Risk factors: family history, sedentary lifestyle, smoking, obesity, high-fat diet - Genetic testing is not part of routine care at this time - Active area of research


Long QT Syndrome (LQTS)

- 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/SCD)


Characteristics of Long QT Syndrome

- Romano-Ward Syndrome: usually autosomal dominant, 4% risk of SCD in the 3 most common subtypes form birth to age 40 - Jervell and Lange-Nielsen syndrome: Autosomal recessive, LQTS and sensorineural deafness



- Common trigger: exercise - Age of cardiac events:



- Common trigger: Emotion - Age of cardiac events: >10 - Incidence of cardiac events: 46% - Beta blockers prevent events: less likely



- Common trigger: Rest or sleep - Age of cardiac events: >10 - Incidence of cardiac events: 18% - Beta blockers prevent events: less likely


Diagnosis of LQTS (Romano-Ward Syndrome)

- Genetic testing: multi-gene panels, detection rate ~75% when testing KCNQ1, KCNH2, and SCN5A and ~80% when testing additional genes - Schwartz LQTS scores; 3.5 points high probability


Diagnosis of LQTS (Jervell and Lange-Nielson Syndrome)

Genetic testing: - Autosomal recessive - Mutations ahve been found in either KCNQ1 or KCNE1 in 94% of individuals with clinical JLNS - Approximately 1/3 are compound heterozygotes


Agents or 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


Brugada Syndrome

- Characterized by an abnormal EKG and increased risk of sudden cardiac death - Often presents with syncope or cardiac arrest, often at rest 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)


Brugada Syndrome Management

- 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 arrythmias


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


Diagnosis of Brugada Syndrome

1) EKG abnomality (ST-segment elevation, type 1, in more than one right precordial lead [V1 to V3]) or Type 2/3 abnormality in more than one lead that converts to type 1 with medication challenge 2) PLUS at least one of these features: - Documented ventricular fibrillation - Self terminating polymorphic ventricular tachycardia - family history of sudden cardiac death (


Genetics of Brugada Syndrome

- Autosomal Dominant (reduced penetrance, more prevalent in males, variable expression) - Genetically related disorders (SCN5A and Long QT syndrome)(CACNA1C and Timothy syndrome) - SCN5A: 15-30% of Brugada syndrome - Other genes: GPD1L, CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, HCN4


Pulmonary Arterial Hypertension

- Drastic increase in the pressure in the pulmonary artery - This increase in pressure causes the right side of the heart to work harder to pump blood - As a result, the right side of the heart becomes much more muscular - The right atrium and the right ventricle often become enlarged and the walls thicken


Two types of Pulmonary Hypertension

- Primary: no underlying cause - Secondary: underlying medical cause (i.e. heart or lung problem) - 1000 new cases per year in US - Twice as common in females (average age of dx = 35)


Symptoms of pulmonary hypertension

- Signs and symptoms of PH occur when increased pressure can't be fully overcome, and blood flow to the body is insufficient - Shortness of breath (60%) - Fatigue (19%) - Syncope (8-13%) - Chest pain (7%) - Palpitations (5%) - Leg edema (3%) - Raynaud's phenomenon (10%; 95% female)


Diagnosis of Pulmonary hypertension

- Indicators: 1) Chest X-rays may show that the pulmonary arteries are enlarged 2) Electrocardiography/ echocardiography may show thickening of the right ventricle 3) Pulmonary Function tests can determine the extent of lung damage - Measurement of blood pressure in right ventricle and the pulmonary artery for clinical diagnosis 1) confirmation of the presence of pulmonary arterial hypertension 2) Exclusion of other known causes of pulmonary hypertension


Causes of Pulmonary Hypertension

- No identifiable cause - lung disorders - loss of lung tissue - chronic liver disease - obesity - drugs/toxins - low oxygen levels - heart failure - HIV - genetics


Familial Pulmonary Hypertension

- Majority of cases are caused by mutations in the BMPR2 gene (140 mutations identified) - Autosomal dominant inheritance (20% penetrance) - Anticipation



- Regulates the amount of cells in tissue - Mutations promote cell division or prevent cell death: results in an overgrowth of cells in small arteries throughout the lungs, causing them to narrow - Modifier genes probably play a role in the development of Pulmonary hypertension


Screening and management of Pulmonary hypertension

- Screening in at-risk individual every 3 - 5 years: ECG, X-ray, Echocardiogram - Special concerns: avoid heavy and strenuous exercise, discuss ALL medication use with MD, caution when considering pregnancy


Drug therapies for pulmonary hypertension

- Vasodilators: dilate blood vessles - Endothelin receptor blockers: substance in the blood that causes constriciton of the vessels - Diuretics: assist the right ventricle in maintaining normal volume - Anticoagulants: thins the blood so that it pumps more easily


Other treatments for pulmonary hypertension

- Oxygen: may reduce blood pressure in pulmonary arteries and relieve shortness of breath - Lung transplant: established method of treatment, only used in individuals with severe disease who are healthy enough for surgery



- diseases of the heart muscle (myocardium) - Can lead to heart failure (swelling of lower extremities, dyspnea - shortness of breath), risk for arrythmia, stroke, and sudden cardiac death


Types of cardiomyopathy

- Dilated cardiomyopathy - Hypertrophic cardiomyopathy - Restrictive cardiomyopathy - Arrhythmogenic Right Ventricular Dysplasia (ARVD)


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


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 - NON-GENETIC CAUSES


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 signal and causes arrhthmias - palpitations and fainting after physical activity - SOLELY GENETIC CAUSES


Hypertrophic cardiomyopathy (HCM) genes

- 60-70% caused by mutations in sarcomere genes - Autosomal dominant - Pathological feature: myocyte hypertrophy and disarray (MYH7 and MYBPC3 = big ones, each make up to 40% of HCM)


MYH7 mutations are associated with

a younger age of diagnosis of hypertrophic cardiomyopathy, more severe hypertrophy, and nearly complete penetrance, but variable survival


Other "hypertrophic cardiomyopathy" genes

- PRKAG2 and LAMP2: result in metabolic storage disease of the myocardium - mutations in PRKAG2 may result in Wolff-Parkinson-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 - GLA: results in Fabry disease, X-linked, associated with left ventricular hypertrophy, may be limited to the heart - RAS MAPK pathway genes: ~20% of individuals with Noonan syndrome develop HCM


Molecular genetic testing for HCM

- some of the responsible genes have not yet been identified: detection rate is not 100% - Up to 5% of affected individuals have more than one mutation: compound heterozygotes, double heterzygotes, homozygotes - Significant limiations in predicting clinical course


Variants of Unknown Significance in Cardio counseling

- Do NOT test unaffected relatives - DO test affected relatives and obligate carriers