Case 13 - Arrythmias

Case 13 - Arrythmias

1. Anatomy of Heart

   • Perfusion
     • RCA - RA, RV, SAN, AVN & Posterior IV Septum
     • LCA - LA, LV, Anterior IV Septum
   • Pericardium
     • Outer fibrous & Inner Serous layer
     • Heart sits in pericardial cavity
     • Endocardium --> Myocardium --> Epicardium
     • Subendocardial Layer: Contains conducting system vessels & nerves
   • Conducting cells
     • AVN & SAN - Lack of rapid Na+ channels = slow action
     • Bundle of His - Cells end to end for rapid conduction

2. Cardiac Physiology

   • Excitation-Contraction Coupling
     • Sarcolemma depolarises due to Ca2+ influx through voltage dependant L-Type Channels
     • Release of stored Ca2+ from SR via Ca2+ release channels
       • Amplified by CICR Mechanism via Ryanodine Receptors --> More Ca2+ Release
         • FKBP (Calstabin) Inhibits Ryanodine
         • Calsequestrin Inhibits Ryanodine
           • Increased Ca2+ inhibits calsequestrin
     • Myocytes contract as long as there is Ca2+ available to bind
       • Reuptake of Ca2+ by SERCA2
         • Phospholamban + Pi = Enhances SERCA2 by lowering Km
         • Phospholamban - Pi = SERCA2 inhibited
       • Actin + Myosin + ATP = Dissociation
         • Actin + Myosin + (ADP + Pi) = Myosin heads rest
           • Actin + NEW Myosin + (ADP + Pi) = Cross Bridge forms
             • Actin + NEW Myosin + ADP (-Pi) = Myosin head moves = Power Stroke
               • Actin + NEW Myosin
           • Ca2+ binds to troponin C
             • Tropomyosin displaced from actin-myosin binding site
               • Cross Bridge formation can occur
   • Action Potentials
     • Pacemaker Potential (SAN, AVN)
       • 1. Slow depolarisation: ' Funny' Na+ channels open & K+ channels close (Phase 4)
         • 2. Depolarisation -> Threshold: T-type Ca2+ channels open
           • 3. Action Potential: L-type Ca2+ channels open (Phase 0)
             • 4. Hyperpolarisation: K+ channels open & Ca2+ channels close (Phase 3)
               • Na+/K+/ATPase pumps Na+ back into cell
                 • Hypoxia = less ATP = bradycardia as decreases slope of phase 4
     • Non-Pacemaker Potentials (Myocytes & Purkinje Fibres)
       • 1. Depolarisation: Voltage gated Na+ channels open (Phase 0)
         • 2. Notch of Rapid repolarisation: K+ & Cl+ channels begin to open (Phase 1)
           • 3. Plateau: Balance of inward Ca2+ & outward K+ (Phase 2)
             • 4. Sigmoid depolarisation: Inactivation of Ca2+ current & increase in K+ current (Phase 3)
             • Ikr - Kv11.4
             • Iks - Kv7.1
             • ICa,L - Cav1.2
           • Ito - Kv1.4
         • INa - Nav1.5
     • Resting Potential - Ik1 - KIR2.1

3. Normal Electrical Regulation

   • Innervation
     • Sympathetic: Spinal Nerves T1-T4/5
       • Cardioaccelarator centre --> (Via NA & A)
         • Positive Chronotropic Effect
           • Hypokalaema (Decreased polarisation)
     • Parasympathetic: Vagus Nerve (CN X)
       • Cardioinhibitory centre (Via ACh)
         • Negative Chronotropic Effect
           • Hyperkalaemia (Increased polarisation)
   • Inotropy
     • Adrenaline binds to
       • Gs --> PKA
         • T-Type Ca2+ channels phosphorylated
           • Cytosolic Ca2+ increased
             • Positive Inotropic Effect

4. Pathological Electrical Regulation - Arrythmias

   • Re-Entry
     • AVRT
       • AV conduction slow & accessory pathway present
         • Pre excitatory beat comes whilst fast pathway in refractory period
     • AVNRT
       • No accessory pathway
         • Premature beat allows time for slow pathway to activate fast pathway
     • Scar related
       • Blocked tissue allows for slow pathway to activate fast pathway
   • Triggered Activity
     • When depolarising oscillations of membrane potential occur during or after AP
     • One oscillation strong enough to trigger new action potential
     • Phase 2 & 3 - Early after depolarisation
       • Hypokalaemia, Long QT
     • Phase 4 - Late after depolarisation
       • Ischemia, catecholamines, digoxin toxicity
   • Automaticity
     • Enhanced normal automaticity
       • Stimulation of SNS (sepsis, pain), Inhibition of PNS (drugs, CNX damage) ATP depletion (hyperaemia, ischaemia) Digoxin toxicity, Hypokalaemia
     • Abnormal automaticity
       • Decreased AP due to abnormal activity in non-pacemaker cells
       • Acute ischaemia &/or reperfusion (e.g. following stunting) & HF

5. Clinical Features of Arrythmias

   • Palpitations
     • 'Awareness' of heart beating
     • 'Pounding', 'throbbing' or 'missed beats'
     • ?duration ?onset ?severity
     • Common
   • Pain = Myocardial demand for oxygen exceeds supply
     • Increased HR --> Increased demand
     • Decreased CO --> Reduced supply
   • Breathlessness = Due to reduced CO
     • Reduced SV or HR
       • Tachycardia --> Reduced SV due to reduced time to empty ventricles
       • Bradycardia --> Reduced HR
   • Syncope/Presyncope due to reduced blood supply to brain from reduced CO

6. Anti-Arrhythmic Drugs

   • Class I: Na+ channel blockers
     • Class Ia
       • Quinidine, procainamide & disopyramide
       • Block fast Na+ channel, depressing Phase 0 depolarisation & prolong AP = slowing conduction
     • Class Ib
       • Lidocaine & phenytoin
       • More specific Na+ block with faster half life = more effective
     • Class Ic
       • Flecainide, propafenone
       • Most potent
   • Class II: β1-adrenoreceptor antagonist
     • e.g. Bisoprolol
     • CI: Sinus BC, 1st degree AVN block
     • Limits sympathetic activity, reduces slope of phase 4 AP
   • Class III: VG K+ blockers
     • Slows depolarisation & prolongs refractory period (long QT)
     • E.g. Amiodarone
   • Class IV: VG Ca2+ blockers
     • Retard Ca2+ impulses through AVN
     • Vasodilator properties: Anti-hypertensive
     • e.g. Diltiazem
   • Adenosine
     • Inhibits adenyl cyclase --> Lowers cAMP --> Triggers K+ efflux --> Hyperpolarisation & inhibits Ca2+ entry in SAN
     • IV administration

7. Interventional Arrhythmia Treatment

   • AF Ablation
     • CHADVASC higher than 1
     • “Radio frequency lesions” introduced in pattern around pulmonary veins to prevent abnormal impulses from escaping &causing AF
   • ICDs
     • Delivers shock when heart moves into abnormal rhythm
     • Painful but not harmful
     • Battery needs to be replaced after 8 years
     • Counselling required

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