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.