Arrythmias

Electrophysiology

Cardiac cell tissue is divided Physiological division:

  • Contractile -> Myocytes
  • Pacemaker/Conducting -> Sino-atrial node and Atrioventricular Node

Electrophysiologically:

  • SLow conducting tissue
  • Fast conducting tissue -> Conducting tissue

Channels: Different types L type @ -40mV T type calcium voltage K+

Depolarization: Entry through Na+ at resting stage Hyperpolarization -> Exit of K+ through K+ channel at resting stage Repolarization -> Exit of K+ through K+ channel at Depolarized state

Events of polarity in Nodal Tissue

  • @-40mV rapid depolarization
  • Phase 4 - Phase 4 is not resting, because of funny current due to leakage of Na+ and K+ into the cells until it depolarizes
  • Phase 0 - L-type Calcium channels open -> Inward current -> Leads to depolarization |
  • Phase 3 - Inactivation of Ca++ channels | K+ Channels open -> outward current -> repolarization
  • In AV Node, Phase 4 is slower
  • SA node is dominant due to it’s quicker Phase 4
  • No inward rectifying channels in pace-maker

Resting MP of myocyte - -90mV of Nodal tissue -60 mV

Events of polarity in Myocyte

  • Phase 4 - Closed Na+ and Ca++ (resting state) [There’s a constant outward leak of K+ via electropotential gradient | Countering this -> Inward rectifying ]
  • When action potential is triggered in neighboring cells, sodium rushes into the RP through the gap junctions
  • Phase 0 - Na+ opens [CLASS 1 AR]
  • Phase 1 - Na+ closes, K+ opens
  • Phase 2 - Opening of K+ and L-type Calcium channel -> Inward Ca2+ current which is the trigger for myocyte contraction
  • Phase 3 - Continuous exit of K+ channel, calcium channel closed

Na influx -> Ca influx -> K+ efflux -> Na efflux -> K+ influx -> K+ equilibrium

  • Depolarization depends on Ca2+ and Na+
  • Repolarization mainly depends on K+ (delayed rectifier type)
    • Slower
    • Denotes the refractory period of cardiac tissue
  • Resting phase - depends on K+ leakage and inward rectifying current
    • Denotes automaticity in case of SAN/AVN

[[Pasted image 20210624214408.png]]

P wave - Atrial depolarization QRS - Ventricular depolarization The flat-line between P and Q - Time taken through AV Node, HIS bundle, Bundle branches and Purkinje fibers

  • AV block - causes Bradycardia
    • prolonged PR interval
    • Can cause non-conducted P wave
    • [[Pasted image 20210620161907.png]]
    • [[Pasted image 20210620163546.png]]

Antiarrythmics - try to normalize ionic fluxes

WHat is arrythmia?

  • Ionic fluxes are changed leading to changes in the rhythm of heart

Broadly classified as:

  • Bradyarrythmia (less than 60 beats)
    • Mostly due to impaired conduction
  • Tachyarytmia (greater than 100 beats)
    • Narrow QRS complex (Supraventricular Tachyarythmia) [QRS < 0.12s]
      • Sinus tachycardia: increased impulses from SAN
      • Atrial premature beat: atrial contractions triggered by ectopic foci rather than the sinoatrial node. Here it originates from the atrial myocardium causing a skipped beat
      • Atrial tachycardia: atrial contractions triggered by ectopic foci rather than the sinoatrial node. Here it originates from the atrial myocardium causing it to beat faster
      • Atrial flutter: due to reentry phenomenon
      • Atrial fibrillation: when an entire chamber of the heart is involved in multiple micro-reentry circuits and is, therefore, quivering with chaotic electrical impulses, it is said to be in fibrillation.
    • Wide QRS complex tachycardias [QRS >0.12s]
      • Ventricular premature beat/Ventricular extrasystole: Premature ventricular contractions (PVC)
      • Ventricular tachycardia: Ventricular contractions triggered by re-entry electrical circuit. Here it originates from the atrial myocardium causing it to beat faster
      • Ventricular fibrillation: can be disrupted by re-entry → chaotic, circulating excitation of the myocardium (= ventricular fibrillation); → simultaneous contractions at multiple foci → insufficient cardiac output → hemodynamic collapse → loss of consciousness and possibly death (sudden cardiac death)
      • Torsades de pointes: Uncommon and distinctive form of polymorphic ventricular tachycardia

Mechanisms of Arrythmias

Abnormal impulse genneration

  • Ectopic impulse - due to adrenergic system, hypokalemia etc
  • Enhanced Automaticity

Abnormal Impulse Conduction

  • Anatomical reentry
  • Functional reentry

Triggered activity

  • Delayed after depolarization: A beat that is delayed for a while even after depolarization
  • Early after depolarization: A beat that is seen before completion of repolarization

[[Pasted image 20210623215437.png]]

Anatomicaly defined Reentry

What is it? A re-entrance circuit either due to anatomical reasons or physiologic

  • an anatomical barrier leads to occurrence as an accessory pathway Accessory pathway connects atrium and ventricle Pathway is different from normal one (AV/Purkinje system) But it is nearly parallel As a result, rhythm of heart is affected due to reentry of impulses even before next Action potential is generated.
  • These tissues have higher refractory periods
  • Connected proximally and distally
  • With different electrophysiological and conductive properties

Functionally defined Rentry

What is it?

  • There is no fixed pathway/accessory tissue
  • A premature impulse travels through inhomogenous medium causing a differing velocity
  • There could be multiple functional foci as ischemia progresses
  • Causes:

Re-entry phenomenon

  • Two roughly parallel conducting pathways must be present
  • Connected proximally and distally by conducting tissue, forming a potential circuit
  • One pathway must have a longer refractory period than the other
  • Pathway with shorter refractory period must conduct electrical impulses (rate and conduction) slow enough that the opposite pathway re-joins the main one when it is excitable

Intiation of rentry

[[Pasted image 20210623220957.png]]

Types of Arythmias

Supraventricular

  • Atrial Fibrillation
    • Irregularly irregular pulse
    • Baseline in EKG is wavy
    • Absence of clearly defined P-wave Rate Control (<110bpm), Usually CCBs, Digoxin, Beta blockers Chemical cardioversion is done by Ibutilide (Class 3 AR) [Less used] Rhythm Control - Class 1 and Class 3
  • Atrial Flutter
    • Flutter waves in the EKG
    • Organized depolarization compared to fibrillation -> circuit usually within the right atrium
  • Paroxysmal (comes and goes) supraventricular tachycardia [Sudden onset - Electrical activity originates above ventricular] Ventricular
  • Ventricular fibrillation and flutter
  • Ventricular tachycardiad

Treatment

  • Na+ blockers decreases slope(dv/dt) of Phase 0
  • K+ blockers increases the AP duration (QT interval increased)
  • K+ openers decrease the AP duration (QT interval)

Torsades’ de pointes - twisting of the points | Feared outcome of QT prolongation

  • Uncommon and distinctive form of polymorphic ventricular tachycardia (VT)
  • Class IA and III (K+ blockers) - QT-prolongation drugs cause thus [[Pasted image 20210620173250.png]]

Classification of Anti-arrythmics

Vaughan William Classification

  • Actions may overlap and not be a sole ion channel blocker. - multiple actions [[Pasted image 20210624215033.png]]

How do they work:

  • Change shape of Cardiac AP
  • Class 1 and 3 (Na and K) mostly exert their effect on myocytes [[Pasted image 20210620171019.png]]
  • Class 2 and 4 (Beta blockers and CCB) mostly exert their effect on Nodal tissue [[Pasted image 20210620171129.png]]

Class 1: Sodium channel blocker

These reduce the sodium current o

  • Lengthens QRS
  • [[Pasted image 20210620171623.png]]
  • [[Pasted image 20210620171750.png]]
  • Use dependance of Class I: Na-channel open/inactive state ,i.e., there is binding to open/inactive state
    • Thus in tachycardia, since the heart rate is higher, the state dependency is met more often
    • Thus more binding at fast heart rates, most frequently in 1C [[Pasted image 20210623223130.png]]

Class 1A

1A -> Blocks K+ channels along with Na+ [[Pasted image 20210620171954.png]] includes:

  • Quinidine
    • Decreased automaticity, conduction velocity
    • Prolonged repolarization
    • Prolonged phase 0 -> Increased action potential duration
    • Prolonged effective refractive period
    • Hypotensive effect due to alpha blocking mechanism
    • Skeletal muscle relaxation Uses
    • Atrial and ventricular arrythmias Adverse effects
    • Arrythmias
    • Heartblock
    • Hypotension
    • QT prolongation
    • GIT, Thrombocytopenia, hepatitis
    • Cinchonism like quinine - since it is a D-isomer of quinine obtained from Cinchona bark
  • Procainamide
    • Derivative of procaine
    • No vagolytic/alpha-blocking action unlike quinide
    • Better tolerated
  • Disopyramide

Mmeonic: QP - Queen Prince

Class IB

  • 1B -> Opens K+ channels along with Na+
  • Safer than 1A
  • Act only on inactivated state
  • Least effect on AP
  • Effective for Ischemic arrythmias - as during ischemia there are more depolarized myocytes
    • Most Na Channel blocking effect of Class 1B occurs when Na channels of heart is in depolarized state
  • Useful only ventricular arrythmias
  • Especially ischemic ventricular arrythmia Includes:
  • Lignocaine/Lidocaine - DOC for Ventricular arrythmias | Converts Unidirectional -> Bidirectional
    • Also a local anesthitic
      • Given paraenterally due to high FPM
      • Use dependance makes it act on arrythmogenic tissue more
  • Mexiletine - Oral lidocaine
  • Phenytoin
  • Tocainide

Blowjob category: Lig - lick Me - my Pheny - penis Toca - (with) tongue

Class 1C

  • 1C -> No effects K+
  • Used only in patients with structurally normal hearts
  • Susceptible for prolonged QRS -> Risk for cardiac arrest
  • Due to their ability to significantly prolong the Effective Refractory Period at the AV node and accessory bypass tracts, they are useful for treating Atrial Fibrillation (and to a lesser extent, flutter) Includes -
  • Encainide
  • Flecainide
    • Used for premature ventricular arrythmias
    • No longer used due to CAST trial indicating higher arrythmic triggers
  • Propafenone

Entry of fleeing Pro-Palestine

Class 2: Beta blockers

  • Used in tachychardias and tachyarrythmias

  • Modify slope of Phase 4 of Nodal tissue

  • Lesser slope leads to slower heart rate

  • Also prolongs repolarization

  • AV node conduction is slowed

  • [[Pasted image 20210620174619.png]]

  • [[Pasted image 20210620174742.png]]

  • Proponalol

    • Treatment & prevention of supraventricular arrytmias
  • Esmolol

    • Given in IV (rapid acting)
    • Used in surgeries, following MI etc

Class 3: Agent widening action potential

[[Pasted image 20210620173043.png]]

  • Mostly potassium channel blockers
  • Lengthens QT interval : Risk of Torsade de pointes
  • [[Pasted image 20210620171635.png]]
  • Action potential increased
  • Reverse use dependance: Binding of drugs occurs when K+ channel is at resting state
    • As K+ resting state is longer when the heart is resting, lower heart rate meets state dependency for longer periods

[[Pasted image 20210623223112.png]]

Includes:

  • Bretylium [previously used as defibrillator pharmacologically]
  • Ibutilide [Atrial fibrillation] [Chemical/Pharmacological Cardioversion]
  • Dofetlide [Atrial birallation]
  • Dronedarone []
  • Amiodarone [Longest acting AA drug w/ t-half | Omni-AA because it has mechanism all classes]
    • blocks inactivated sodium channel
      • beta blocking
      • K+ blocking
      • Blocks Ca2+
      • Reduces ectopic automaticity and conduction
      • has a slow onset [2 to several weeks]
  • Sotalol [It’s a beta blocker that has dual mechanism] BInDDAS

Adverse effects of Amiodarone: The: Thyroid - can cause both hyperthyroidism and hypothyroidism (x Dronedarone doesn’t contain iodine but is less effective) | Blocks conversion of T4 to T3 Periphery: Peripheral My: Myocardial depression Lung: Lung fibrosis Liver: Hepatotoxic (longest half-life causes amiodarone accumulates) Cornea: Corneal deposits due to secretion of amiodarone by lacrimal glands Photosensitive: Rashes on skin, sunburn | May lead to Blue-man syndrome - prominent on face

#lung Other pulmonary fibrosis causing drugs:

  • Cyclophosphamide
  • Busulfan
  • Methotrexate
  • Amiodarone
  • Bleomycin All are transport modes that can blow horn - Cycle, Bus, Metho-TRUCK-sate, D-a-RONE, BLEOing horn

Class 4: Calcium channel blocker

L type - calcium channel of nodal tissue [[Pasted image 20210620174914.png]]

  • Prolonged PR interval
  • May lead to type 1 AV block
  • Conduction in AV node is reduced
  • Used commonly to control ventricular rate for atrial fibrillation Ver - heart and blood vessels Dil - heart and blood vessels Dihydropyridines - blood vessels only

Used in tachyarythmias

  • Beta blockers and Class 4 drugs must not be combined as there’s a severe risk of bradycardia and depression
  • Verapamil: decreases renal clearance of digoxin

Class 5: Miscellaneous

  • Adenosine - Shortest half-life (<10s) | DOC in PSVT anfd AVNRT (AV node reentrant tachycardia)
    • Due to it’s half life, it is given as a rapid IV push in the central veins (jugular vein)
      • Activates ACh sensitive K+ in AV Node -> Slowing of conduction through AV node
      • Causes hyperpolarization through A1 adenosine receptor (GPCRs) on SAN
      • Adverse effects
        • Nausea
        • Dyspnoea
        • Flushing
        • Headache

(Paroxysmal supraventricular tachycardia (PSVT) is a type of abnormal heart rhythm, or arrhythmia. It occurs when a short circuit rhythm develops in the upper chamber of the heart. This results in a regular but rapid heartbeat that starts and stops abruptly.)

  • Atropine - used in sinus Bradycardia (anti-cholinergic effect) and AV block - DOC
  • Digitalis - Atrial fibrillation and flutter
  • Digoxin - used for Atrial fibrillation (decreases conduction between atria and ventricle, decreasing increase in ventricular rate)
  • MgSO4 - DOC for Torsades de Pointes/ Long QT Intervals and digitalis-induced arrythmias | Blocks calcium influx into cells
  • Ivabradine - pure bradycardic and anti-anginal
  • Adrenaline

Choice of drug varies with type of arrythmias and toxicity All arrythmias need not be treated

[[Pasted image 20210624212958.png]]

#lung