General B2 stuff Flashcards
3 mechanisms of arrhythmias
1)Increased automaticity (inappropriately excitable cells)
2)Triggered automaticity (normal action potential is interrupted or followed by an abnormal depolarization; afterdepolarizations)
3) Reentry (abnormal impulse conduction)
increased automaticity (as seen in membrane potential of SA node)
1) slop of phase 4 is increased
2) threshold potential (TP) is more negative
3) maximum diastolic potential (MDP) is more positive
Triggered automaticity (2 types/ descriptions)
1) EAD (early afterdepolarization): Interrupt repolarization
- Exacerbated by slow rate-long QT syndrome
- Torsades de Pointes results
2) DAD (Delayed (late) afterdepolarization): Occur after repolarization
1) Exacerbated by fast rates, high intracellular Ca2+
2) Digitalis toxicity and catechol-amines (NE, EPI), Ischemia
Four Ways by Which Antiarrhythmic Drugs Reduce Spontaneous Discharge in Autonomic Tissues
1) decreased phase 4 slope
2) increase threshold
3) increase maximum diastolic potential
4) increase AP duration (issues)
4 traditional Anti-arrhythmic drugs
Class I: Sodium channel blockers
Class II: Beta-blockers
Class III: Potassium channel blockers
Class IV: Calcium channel blockers
CHA2DS2VASc
C Congestive Heart Failure 1 point H Hypertension 1 point A2 Age ≥ 75 y 2 points D Diabetes 1 point S2 Stroke 2 points V Vascular disease 1 point (prior myocardial infarct or peripheral vascular disease) A Age≥65y 1point Sc Sex category, female 1 point
Maximum total score = 9 points.
ESC 2010 Anticoagulation Recommendations: Score = 0 no therapy or aspirin (no therapy preferred). Score = 1 aspirin or oral anticoagulation. Score greater than or equal to 2 oral anticoagulation (coumadin INR 2-3, Dabigatran, Apixaban, Rivaroxaban,Edoxaban) .
Requirements for Reentry:
- Two Distinct Paths for Propagation (Called α and β here)
- Slowed Conduction in at Least One Path (Either α or β)
- Unidirectional Block: Tissue capable of conduction in one but not the opposite direction. Such block is often Functional.
Physiology of Valsalva Effect
- Valsalva: forceful expiration against closed glottis
- Increases intrathoracic pressure as thoracic organs are compressed by contracting rib cage, producing increased external pressure on heart and thoracic vessels
- Venous and right atrial compression impedes venous return and preload, initially dropping cardiac output.
- Thoracic aorta compression initially increases aortic pressures, triggering medullary feedback loop that stimulates vagal efferents and slows heart.
- Changes in heart rate are reciprocal to aortic pressures due to baroreceptor reflex.
Management of VT
• Sustained VT is potentially life-threatening and may degenerate to ventricular fibrillation or be associated with hemodynamic collapse.
• Acute therapy in unstable patient: electrical cardioversion.
• Acute therapy stable patient: antiarrhythmic drugs
(amiodarone, lidocaine) or sedate/cardiovert.
• After sinus rhythm restored look for structural heart disease and correct aggravating factors.
• Long term consider need for implantable cardioverter defibrillator (ICD) for secondary prevention and potentially need for antiarrhythmic drugs or VT ablation.
-other drugs??? beta blockers???
BNP
-brain natriuretic peptide
- BNP is synthesized and released in response to ventricular stress and is typically used when diagnosis of heart failure as prime cause of patient symptoms is
in question (e.g. heart failure vs pulmonary disease)
-BNp indicates HF
Amiodarone lung SE
- Amiodarone is an amphiphilic compound (possessing both hydrophilic and lipophilic properties) which can result in long elimination half life of approximately 30-108 days with a volume of distribution close to 5 liters.
- The active principal metabolite, desethylamiodarone, penetrates tissues and accumulates therein, thus providing a sustained source of release.
- Despite Amiodarone’s intended myocardial target, Amiodarone concentrations measured in unfractionated pulmonary parenchyma significantly exceed that of the heart
Inherited arrhythmias
- Long QT syndrome (LQTS)
- Brugada syndrome (BrS)
- Catecholaminergic polymorphic ventricular tachycardia (CPVT)
- Short QT syndrome (SQTS)
- Early Repolarization
- Sudden unexplained death syndrome
- Idiopathic ventricular fibrillation
Risk Factors for SCD in Young People
- Structural congenital heart disease
- Congenital anomalies of coronaries
- Myocarditis
- Hypertrophic and other cardiomyopathies
- Wolff-Parkinson-White syndrome
- Inherited arrhythmias
Ion Channels: alpha units
Alpha units are pore-forming and mediate currents
Ion Channels: beta units
Beta units are regulatory
Long QT syndrome (LQTS)
• Prevalence: 1:3,000 – 7,000
• Clinically identified by prolonged QT interval and T wave
abnormalities on EKG and torsade de pointes (TdP)
Presents with syncope and SCD due to ventricular tachyarrhythmias (VT), typically TdP
• TdP also may cause seizures
• Syncopal episodes usually occur during exercise or high emotions, not as
often during rest or sleep
• Syncope on exertion in young patients concerning for malignant cause
• Family history of “seizures,” SCD/SCA, syncope
- QT interval corrects for heart rate
- Bazett: QTc=QT/square root of the RR
* inverserelation - Abnormal QTc
* males >470 ms
* females > 480 ms
* Borderline 450-470 ms - Average QTc for someone with the LQTS is 490 ms
- QT interval changes regularly in an individual
- Long QT patients can have normal/borderline QTc
Causes of Long QT
Acquired
• Primary myocardial problems: myocardial infarction, myocarditis, cardiomyopathy
• Electrolyte abnormalities: hypokalemia, hypomagnesemia, hypocalcemia
• Autonomic influences
• Drug effects
• Hypothermia
Congenital
• Romano-Ward syndrome (RWS) (autosomal dominant LQTS)
• Jervell and Lange-Nielson syndrome (recessive)
LQTS: Genetics
• Primary electrophysiologic disorder due to ion channel abnormalities
• Sometimes called Romano-Ward syndrome (RWS)
• Autosomal dominant disorder
• Reduced penetrance: 50% of individuals with a
disease-causing mutation will not show symptoms
• Genetic heterogeneity: 13 genes known to be associated with RWS
Jervell and Lange-Nielson Syndrome
• Congenital, profound, bilateral sensorineural DEAFNESS and QT prolongation often >500 ms
• increased risk for SIDS
• >50% of untreated children with JLNS die prior to age 15
• Autosomal recessive inheritance
• 2 genes known to be associated with JLNS
• The most common genes include:
• KCNQ1 (LQTS Type 1) 90%
• KCNE1 (LQTS Type 5) 10%
Treatment of LQT3 SCN5A gain of function Na channel
- Class I antiarrhythmics ex. Mexilitine, Flecainide
* Can lead to Brugada type EKG
Treatment and Management for LQTS
Left cardiac sympathetic denervation (LCSD)
• Breakthroughs on beta blockers, ICD
• Left supraclavicular incision, retropleural approach
• Ablation of the left stellate ganglion
• Thoracic ganglia T2-T4
• mean number of cardiac events per patient dropped by 91% after LCSD
Surgical left stellate ganglionectomy
• may be useful in infants with the severe Jervell-Lange and Nielsen form of LQTS as complimentary therapy with beta blockers and pacemakers if there is profound bradycardia
LQTS: Who Should be Treated?
Symptomatic patients
Asymptomatic patients (controversial)
• Beta blocker therapy for asymptomatic individuals
High risk
• congenital deafness
• neonates/infants (risk SCD high first months of life)
• affected siblings of children who died suddenly
• T wave alternans
• long QTc (greater than 470 ms)
• two or more pathogenic mutations
Brugada Syndrome (BrS)
- Prevalence: 1:5,000 Western populations 1:2000 southeast asia
- Cardiac conduction abnormalities, ST-segment elevation in the right precordial leads (V1-V3)
High risk for ventricular arrhythmias that can result in SCD
• For every 10 patients with BrS presenting with syncope, 8 will only be diagnosed after a cardiac arrest
Presents as chest pain, palpitations, laboured breathing during sleep, syncope, VT, SIDS or sudden unexpected nocturnal death syndrome (SUNDS)
• average age of sudden death is 40 (reported in ages up to 84)
• Common cause of sudden death in South Asian individuals under the ageof 50
8-10 times more prevalent in males
• Higher Ito epicardial outflow tract concentration in males (testosterone)
Dx criteria:
Type 1 EKG: coved ST segment elevation >2 mm, followed by negative T wave
+
AND at least 1 of the following: • Documented VF/PMVT • family h/o premature SCD • coved type EKG in family members • inducible VT at EPS • Syncope from arrhythmia cause • nocturnal agonal respiration
Brugada-like EKG Patterns – Drug Induced
- AAD- class IC, class IA, Ca channel blockers, Beta blockers
- Antianginal drugs- Ca channel blockers, nitrates
- Psychotropic drugs- tricyclics, phenothiazines, serotonin reuptake inhibitors
- Cocaine
- Alcohol intoxication
- While these drugs may produce Brugada-like ST segment elevation, it is not clear whether genetic predisposition is involved.
Brugada-like EKG Patterns – Differential Diagnosis
- Atypical right bundle branch block (RBBB)
- Left ventricular hypertrophy
- Early repolarization (upsloping rather than downsloping ST elevation)
- Pericarditis
- Acute myocardial ischemia
- Pulmonary embolism
- Prinzmetal angina
- Dissecting aortic aneurysm
- Duchenne muscular dystrophy
- Arrhythmic right ventricular dysplasia (ARVD)
- Hyperkalemia
- Hypercalcemia
- Hypothermia
BrS: Genetics
Autosomal dominant disorder
• Reduced penetrance
• Genetic heterogeneity: 16 genes known to be associated with BrS
Current detection rate: 25-30%
• Majority: alpha subunit of the cardiac voltage-gated Na+ channel (SCN5A) gene
• Other genes (
Sodium Channelopathy
Pleiotropy: pathogenic variants in SCN5A can cause both LQTS3 and BrS, among others
• Gain of function: LQTS3
• Loss of function: BrS
- Genetic modifiers, environmental factors (fever, medication) can affect phenotypic manifestations
- Evidence from families with SCN5A mutations associated with both diseases in same family
BrS: Diagnosis
• Change lead position (Brugada leads)
Provocative drug testing to unmask EKG changes typical to Brugada syndrome
• Sodium channel blocker: flecainide, pilsicainide, ajmaline, or procainamide
• Consider 80% of individuals show the characteristic changes when challenged with a sodium channel blocker (ajmaline)
• Fevers can lead to Brugada-like EKG pattern and arrhythmias
Difficult to diagnose (Raju et al., 2011)
• 49 families with confirmed sudden arrhythmic death and diagnosis of Brugada, 50 probands
• Mean age of death probands 29.1 years
• 41 (82%) males
• 68% of probands would not have fulfilled current criteria for ICD implantation
• Current markers for sudden death in Brugada Syndrome are insensitive making risk stratification challenging
BrS: SCD Risk Factors
- Prior aborted SCD, highest risk for recurrence (69%)
- Prior aborted SCD, highest risk for recurrence (69%)
- Syncope and spontaneous type I EKG (19%)
- Asymptomatic patients with spontaneous type I EKG (8%)
- Risk associated with asymptomatic pt with type I EKG only after provocation with Na channel blocker appears low
- Inducibility of VT/VF at EPS (controversial)
- Male gender
BrS: Who should be treated?
• Implantable Cardiac Defibrillators (ICD)
Symptomatic patients with:
• aborted SCD and spontaneous or drug-induced (Na channel blocker) type I EKG
• syncopal patients with type I EKG either spontaneous or drug-induced
Asymptomatic patients with:
• type I spontaneous EKG and positive EP study for induction of VT
• drug-induced type I EKG and family h/o SCD and positive EPS
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
• Prevalence 1:10,000
• Triggered by exercise or acute emotion (adrenergic stimulation) in an
individual with structurally normal heart
• Bidirectional or polymorphic ventricular tachycardia that can spontaneously resolve or degenerate into VF and sudden death
• Mean onset of symptoms between 7-12 years
• High penetrance
Cumulative survival before 30 years of age is 50-70%
• Associated with high risk sudden death if untreated: 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal episodes
CPVT: Diagnosis
• Resting EKG is often normal
Exercise stress test
• onset of arrhythmias during exercise occurs at a heart rate threshold of 100-120 beats per minute
• increase in workload, catecholamines -more adrenergic loads….
• Increase in complexity of arrhythmias premature ventricular contractions to VT
Consider personal history of:
• Syncope occurring with physical activity, acute emotion
• VF during acute stress
• exercise or emotion-related palpitations or dizziness
• Sudden cardiac arrest triggered by acute emotional stress or exercise (personal and/or family history)
CPVT: Genetics
Mutations of genes encoding proteins involved in intracellular calcium and the release of calcium from the SR result in: • inappropriate calcium leakage • cytosolic calcium overload • delayed after-depolarizations • triggered activity • ventricular arrhythmias
Autosomal dominant disorder
• RYR2 (ryanodine receptor 2): 50-55%
• CALM1 (calmodulin):
CPVT: Acute Treatment for Ventricular Tachycardia Storm
• Most critical step in acute management of VT or VF in CPVT patient is to correct inciting factors and avoid standard epinephrine infusion in resuscitation setting (can propagate arrythmias and make it worse…)
IV Beta blocker is first choice therapy

General anesthesia and sedation should be considered if beta blocker ineffective
• Diminishes the adrenergic stimulation
