EP Notes

Depolarization- Na in --> rapid change in transmembrane potential

Repolarization- return to baseline TMP, cannot contract at this time (refractory pd)

Resting phase- pd bn AP's, most myocytes have no net ion mvmt, but in some cells there's a gradual increase in TMP (during phase 4) until it triggers a depolarization (automaticity).

Automaticity- Sinus node cells have fastest phase 4, thus it's the pacemaker

Vagal Nerve stim to AV nd--> incr ACh @ muscarinic R's--> incr permeability to K+ & decr Ca++ mvmt

--> decr or stop spontaneous discharge (seen w vasovagal syncope)

Sympathetic Nerve stim to AV nd--> decr TMP more quickly , as NE--> incr speed at which K+ declines bn AP's, and incr Ca++ conductance. net--> incr AP amplitude, rate of spontaneous discharge, and the strength of the cardiac contraction.

Temperature incr--> similar effect as symp stim...

Myocyte AP are much longer duration than nerve/skeletal muscle bc their Ca channels are slower. This allows for regular, independent beats, and allows modulation of the strength of contraction.

EP Drugs

(Macdonald Dick II Book)

Class I= Na channel blockers

--> prolong Phase 0--> slow conduction velocity

--> make membrane return to a more hyperpolarized state, thus --> prolong refractory pd of fast response fibers bc there's a greater difference between the resting state and the threshold for activation of the Na channels to initiate Phase 0

--> suppress Purkinje/His bundle automaticity, caused by myocardial damage--> SA node resumes its dominance.

Class IA) -->slow rate of rise of Phase 0 to Vmax & prolong refractory pd

Class IB) --> conduction block at diseased myocardium, but no effect on Phase 0 or refractory pd

Class IC) --> signif decr conduction velocity, but ~no effect on refractory pd

IA -

-Quinidine - rarely used bc of xx. like quinine it's antimalerial, antipyretic, ototoxik, skel relaxant

-effect d/o dose: low [ ] --> Anti-cholinergic, at high [ ] --> direct EP effets

-SA nd & Atria: low [ ] --> inr HR; low [ ] slows depol- slows Vmax of ph 0--> slow conduction

-AV nd: low [ ] anti-chol effect--> incr conduction at AV nd, high [ ] --> decr conduction velocity and incr effective refractory pd

-HPS/Ventricle: decr ph 4 slow of depol--> inhibit automaticity, with a greater effect at HPS than SA nd, and in ventricles it blocks the Kr delayed rectifier channels (K into cell after repol to trigger next depol)--> prolongs repol'n--> inr dur of AP and incr QT on ECG

-ECG: prolong PR, QRS, and QT, w magnitude related to [ ]

-Hemodynamics: if poor fx, it can worsen it; also inhib alpha1 R--> sm muscle vasc dilation

-Pharm: complete PO avail, onset 1-3hrs, pk 1-2hrs, t1/2 6hr, hepatic metab

-Use: not often used bc of xx, can ctrl ventric arrhythmias, and short QT synd correction

-xx: diarrhea, abd xx, ligh headed, tired, palpn, HA, angina pain, rash (dose related)

-+/- thrombocytopenia

-AV & intraventricular block, VT, decr contractility

-Quinidine Syncope = VT/VF w LOC

-Cinchonis- (w large ds)--> tinnitus, HA, nausea, vision changes, vertigo, auditory acuity cahnges, then confusion, delirium, halluc'n, psychosis if large dose; hypoglycemia

-c/i xx: complete AV block, long QT can get torsades, CHF/hypotension, Digox toxicity and hyperK+ --> incr effect to decr conduction

-Drug-Drug- incr digox [ ]

-acetazolamide, CaCarb, MgOH, cimetidine decr metab of quinidine

-Procainamide -

-Tx SVT, VT, Digox induced arrhythmia

-xx- short t1/2, & side effects when chronically used

-EP Mech: like quinidine, but weaker anti-CH effect. similar ECG effect

-HD Effect: less HD xx w than quinidine, rare if taken PO

-Pharm: very PO bioavail, pks at 1-1.5hrs p adm, t1/2 2.5-4.5hrs (unless sustained release then 6-8hrs), hepatic metab, cleared in urine.

-The metabolite NAPA is cardioactive w class III properties & is eliminated via urine

-Some pts are rapid acetylators, some have renal dysfx --> accum NAPA more than procainamide

-may need slightly higher dose in neonates

-Use: AP mediated tachy, a-fib, ventric xx, and postop JET (along w pt cooling)

-if a-flutter or IART, it might --> slow conduction in flutter circuti allowing 1:1 AV conduction w incr in ventric rate, also it can slow conduction in other macroreentrant circuits, and convert self limted tachy into a slower incessant tachy.

-might be used for Brugada Dx

-Adverse Effects: decr BP, AV block, IV bock, VT, complete HB

-stop if it --> sev prolonged QRS or QT

-lupus like synd w long term use, but sx stop w stopping the Rx

-(rare) hallucinations, mental confusion

-give slowly (max 10mg/kg/min) bc of hypotension risk

-c/i xx- be careful if pt has 2nd deg AV block, BBB

-if prolonged adm, check CBC bc of r/o agranulocytosis

-Drug-Drug Interactions: cimetidine decr its metab. EtOH increases its hep clearance.

-amio or quinidine given at same time can incr procain [ ]

IB -

-Lidocaine- aka Xylocaine- local anesthetic, blocks Na Ch

-acts preferentially in diseased tissue, causing conduction block & interrupts reentrant tachy

-EP Mech:

-SA/atrium- ~no effect at Tx doses

-AV nd- min effects on conduction velocity & ERP

-HPS/Ventricle- reduce membrane responsiveness, decr automaticity

-at low [ ] --> slow ph4 depol at Perkinjes

-at high [ ] --> suppress automaticity, eliminate ph 4 depol

-ECG: no change to PR, QRS, QT (some w short QT). not much change bc it doesnt wk at healthy mycoardium much.

-HD effects- no effect on myocard fx, even w CHF

-Pharm Mech: much first pass metab--> not good orally

-immediate onset w IV, t1/2 1-2hrs. hepatic metab. Clearance decr w CHF, liver xx, cimetidine, beta-blockers.

-Clinical Use: VT/VF. NOT SVT. though amio now 1st line...

-Adverse xx- CNS xx- paresthesias, disorientated, muscle twitch, then psychosis, resp dp, sz. myocardial depression if very high doses

-c/i xx- hyperSn to local anesthestics, sev hepatic dysfx, prev grand mal sz due to lido.

-be careful if 2nd/3rd HB bc it can worsen it and abolish idioventric pacemakers

-Drug-Drug: cimetidine (not ranitidine)--> incr [ ] lidocaine. Incr risk of myocard dp if +Dilantin

-Mexiletine-

-analog of lidocaine, but prevents 1st pass metab.

-Often combine w quinidine to incr efficacy and decr proarrhythmia risk

-EP Mech: slows conduction velocity, ~no effects onrepol

-rate dependent blocking action on Na ch w rapid onset

-HD Effects: caution if already hypOtensive or sev LV dysfx

-Pharm: 90% oral bioavail. Onset 0.5-2hrs, t1/2 10-12hrs. metab by liver via bile, 10% renal

-Use: acute/ch VT/VF; ?for congen long QT

-Adverse xx- narrow Tx window

-hand tramor, then dizzy and blurred vision. Also n/v etc, lightheadedness, cordination xx, but improve w decr dose. CV xx: less common- palpn, CP, angina

-c/i xx- cardiogenic shock, 2nd/3rd degr HB (or h/o of it) if no pacemaker, and caution if SA dysfx or IV conduction xx

-Drug-Drug: phenytoin/rifampin incr hepatic metab.

IC -

-Flecainide-

-slows conduction throughout the heart, espec HPS and ventricles.

-also weakly inhib the delayed rectifier K ch (thus slight repol'n prolong), & inhib abNl automaticity

-EP Mech:

-SA/atrium- decr HR slightly, decr conduction velocity @atria, prolongs action potential

-AV nd- prolong conduction

-HPS/ventricles- slows conduction; may also slow conduction at accessory pathways

-ECG: incr PR, QRS, and to some degr QTc (just bc of incr QRS, NOT bc of a change in repol)

-HD: negative inotropy, so some pts might get decr LV Fx

-Pharm: good PO abs (80-90%) but decr w milk/milk formulas; onset 1-2hrs, t1/2 12-30hrs, liver metab and renal excrete

-Use: atrial arrhythma- espec reentrant mech, and life threatening VT/VF

-be careful if +CHD bc can cause more proarrhythmia xx

-crosses placenta, so ok for fetal tachy (after digox)

-2nd line for SVT in kids unresponsive to betablocker

-start as inpt bc of risk of proarrhythmias

-Adverse xx: dizziness, vision change, nausea, headache, dyspnea initially (first few days)

-some-> worse CHF and prolong PR and QRS

-less pro-arrhythmia than adults (?). #1 proarrhythmia is slow incessant SVT, but also VT/VF in pts s/p CHD repair

-c/i xx: 2nd/3rd HB unless +pacemaker to maint ventric rhythm; cardiogenic shock

-Drug-Drug: cimetidine decr hepatic metab--> incr toxicity; Flec --> incr digox [ ]

-Propafenone-

-blocks Na ch, and weakly blocks K channels too (like flec)

-also, weak beta-R antag, and L type Ca ch blocker

-EP Mech:

-SA nd- slows SA nd

-Atrium- prolong AP and ERP, and decr conduction velocity--> slow a-flutter to a rate that lets more rapid conduction to the ventricle (like other class I Rx), so be careful...

-AV Nd- slows AV nd conduction if given IV

-HPS/ventricle- slows conduction, inhibit automaticity

-ECG: dose dependent incr in PR and QRS

-HD effect: no signif xx on fx, but might decr mycard performance if pt already has ventric dysfx

-Pharm Mech: ~all PO absorbed, t1/2 2-10hrs, liver metab, urine excrete

-Use: SVT, life threatening VT/VF if no structural heart dz. IF CHD, can incr VT/VF

-start as inpt to monitor for arrhythmias

-Adverse xx/Drug-Drug- if give w digox, warfarin, propranolol, metoprolol, it incr serum [ ] of the other drugs. cimetidine will sightly incr its [ ].

-lidocaine, procainamide, quinidine will be additive w it.

-can interact w other drugs to depress AV nd fx, intraventric conduction, or contractility

-common xx- dizzy, light headed, metallic taste, n/v

-sev CHF, cardio shock, AV and IV conduction xx, SSS, also sev brady, low BP, obstructive pulm dz, hep/renal fail. and bc of beta-blocker action use w caution for bronchospasm

Class II = Beta-blockers

-Propranolol-

-aka Indural

-decr sympt stim by competitive bindign to beta adr R

-EP Mech: 1) remove adrenergic influence on heart

2) Membrane stabilization effects via direct effect on heart- (more at higher doses)--> effect to ctrl arrhythmias that aren't related to beta R stim

-SA nd- slow spont rate of cells by decr slopw of phase 4 depol (longer to recover)

-Atrium- local anesthetic--> decr AP amp & excitability

-AV nd- decr AV conduction velocity, incr AV nd refractory pd

-HPS & Ventricle- --> depress catechol stimulated automaticity ; if high dose, it can decr Purkinje responsiveness and reduce AP amp

-ECG: long PR, no change in QRS; QT might be short

-HD xx: decr positive inotropic & chronotropic effect of NE/E, w decr HR & BP, and decr myocard VO2

-Pharm: ...

-Use: SVT (#1 Rx along w atenolol); ventricular ectopy/VT, w suppression of PVCs and NE/E dependent ideopathic VT, and good for congen long QT synd

-Adverse xx: brady, hypotension, bronchospasm if asthma, mood changes/dp (Crosses BBB), school difficulties; infantile hypoglycemia; crosses placenta and can blunt fetal stress response at delivery

-c/i xx- depressed myocard fx, no good if +digox toxicity bc it can --> complete AV block and ventric asystole, asthma

-don't abruptly withdraw it, it can be dangerous bc of up regulation of Beta R's after long term use...

-Atenolol-

-aka Tenormin

-selects B1 R'

-better than Propranolol bc it has longer t1/2, limited BBB crossing so less CNS xx

-ECG & EP Mech like Propranolol

-Use: SVT & ventricular ectopy

-Adverse xx: still can have worsening of bronchospasm so be careful if asthmatic

-c/i xx - asthma is a relative one...

-Nadolol-

-aka Corgard

-Long acting, nonselective Beta antag, w NO membrane stabilizing or intrinsic sympathomimetic fx

-EP Mech/HD xx: just like propranolol

-Use: SVT, long QT; long t1/2 and less CNS xx like Nadolol

-Adverse xx & c/i xx- like propranolol

-Esmolol-

-short acting, IV, b1 blocker.

-no membrane stabilizing activity or sympathomimetic activity

-EP Mech/HD xx like propranolol

-Use: acute SVT Tx, acute VT Tx, and to acutely lower BP.

-rapidly lose effects when you stop the drip bc it is hydrolysed quickly

-Adverse xx & c/i xx- hypotension, nausea, dizzy, headache, dyspnea; c/i xx is CHF/cardio shock

Class III = Prolong Membrane Action Potential Duration

-Prolong Membrane AP, by delaying repol w/o changing depolarization or resting membrane potential

-signif pro-arrythmias bc of AP duration prolongation and risk of torsades de pointes.

-Amiodarone-

-mainly, it prolongs the AP, but also blocks Na and Ca Ch and binds to B receptor (so has class I, II, and IV actions)

-good to Tx most arrhythmias

-EP Mech: complex, ?known completely,

-after long term use, it --> prolong the repol & refractoriness of all cardiac tissues (thus class III)

-SA nd- inhib SA fx, espec if SSS (to the pt they'd need a pacemaker) common xx after Fontan and atrial switches

-HPS/Ventricles- slow AV nd conduction and refractory pd; ch Tx--> prolong AP at ventricles and incr their refractory pd w a decrease in conduction velocity

-ECG: prolong PR, QTC, incr U waves, and change T wave morph

-HD xx: relax smooth muscle, improve myocardial Q; and --> decr SVR so decr LV stroke work and myocardial VO2. IV adm can --> hypotension

-Pharm: poor PO bioavail (35-65%) and slow; protein bound, mainly concentrated in myocardium, adipose tissue, liver, lungs (as oppose to serum), t1/2 serum ranges fr 26-107 days; mainly liver metab w biliary excretion

-Use: broad use, little risk of torsades compared to other class III Rx, but does have other xx

-IV amio- postop pd xx: SVT, a-flutter, a-fb, IART, JET, VT

-ch PO amio- better than IV use, good for SVT and VT in most forms, but limited by xx

-Adverse xx:

-chemical hepatitis, worsen SA dysfx, thyroid dysfx (hyper/hypo), pulm fibrosis (often fatal even if u stop the amio)

-it prolongs QT but only small risk of torsades

-if underlying sinus nd dysfx, then may need pacemaker

-corneal microdeposits common & reversible, but only rare blurred vision/halos

-Skin: photoSn, blue-gray color (incr risk if fair complexion), slow regression if at all after stop Rx

-Inhib periph and intrapituitary conversion of T4 to T3 ==> incr serum T4, decr serum T3, but most pts remain euthyroid. xx = hyper and hypothyroid sx

-hand tremor

-sleep xx- vivid dreams, nightmare, insomnia

-ataxia, staggering, impared ambulation

-periph Sn and motor neuropathy, sev prox muscle weakness uncommon (resolve in a few weeks after stopping Rx)

-C/i xx- SSS, sev brady and 2nd/3rd AV block; crossess placenta and --> fetal brady/thyroid xx

-it is secreted in breastmilk

-Drug-Drug: many drugs

-Digoxin- cut the amio dose in half bc it incr amio [ ]

-Warfarin, flecainide, propafenone, progainamide, phenytoin, quinidine

-Sotalol-

-aka Betapace

-nonselective B blocker at lower doses, and at higher doses class III action by blocking K ch (w AP prolongation)

-EP Mech:

-SA nd/atrium: decrease pacemaker activity, incr atrial refract pd

-AV nd: decr conduction velocity, prolong effective refract pd

-HPS/ventricles: inhib the delayed rectifier K ch--> prolong ERP

-ECG: decr HR, prolong PR, prolong QTc; no change in QRS dur if at Nl dose

-HD xx: some decr SBP and CO bc of beta blocker effects--> decr HR, but no change in SV

-If Nl fx, SV will increase to compensate decr HR so CO stays the same

-Pharm: 50% bioavail, onset 30min, t1/2 4hrs; hepatic metab w urine excretion

-Use: both ventricular and SVT, but limited bc of proarrhythmia ventric xx; 2nd line for fetal arrhyth

-Adverse xx: tired, dyspnea, chest pn, HA, n/v; proarrhythmia

-c/i xx: sev heart failure, poor RV fx, hypoK, long QT bc incr risk of proarrythmia

-Drug Drug: QT prolonging meds (diuretics, thiazides, etc) can incr its class III effects

-Dofetilide-

-pure class III in that it prolongs the AP and the refract pd by selectively inhib the rapid component of the delayed rectifier K ch

-EP Mech: as above, no signif effect on other repolarizing K currents

-exaggerated if pt has hypErkalemia

-less effective at higher HR

-SA nd/atrium: minor slowing of SA rate bc of hyperpolarization of the maximum diastolic potential, and reduces slope of the pacemaker potential...

-AV nd: no effect

-HPS/ventricles: incr ERP (less so than in atria)

-ECG: no change in PR or QRS, but does prolong QT (directly related to [K])

-HD xx: no change in BP, HR, CO SV, or SVR

-Pharm: delayed absorption if w food, but good avail (90%), onset 7-10hrs,

-Use: a-fib, a-flutter; maybe for SVT in CHF pt, or IART w Fontan pt

-Adverse xx: risk of torsades of QT long, 3% of adult trial pts, usually w/in 1st 3 days so start as inpt

-c/i xx: baseline long QT, other QT prolonging Rx, h/o torsades, CR clear low, or use w verapamil, cimetidine, ketoconazole, or K <4, or low Mg, or pregnant/breastfeeding

-Drug Drug- Verapamil, cimetidine, ketoconazole increase its [ ]

-Ibutilide-

-aka Covert

-similar to stoalol, w similar class III effect, but only IV bc of first pass effects

-EP Mech: prolong AP, incr atrial/ventricular - activate slow inward Na current (mainly), and blocks the delayed rectifier K current--> increase the duration of atrial and ventric AP and refractoriness by slowing the initial Na in of the depol, and slows the rectifier K at the end...

-SA nd/atrium: no change in HR, incr atrial ERP without any "reverse use dependence" (works just as well at higher HR) unlike other class III Rx

-AV Nd: may slow AV nd conduction, no change in PR interval

-HPS/Ventricles: incr ERP

-ECG: no change in PR or QRS bc it doesn't effect conduction velocity; dose related QT prolong (d/o dose and rate of infusion)

-HD xx: no signif effect on CO, MAP, PCWP, no effect on cv fx

-Pharm: variale by pt bc of first pass metab, so ng for PO, metab by liver

-Use: refractory a-fib/a-flutter in adults (a-flutter better than a-fib), limited peds use for IART

-Adverse xx: QT prolong w torsades (4%), within 40min of adm, so have ECG going w DC cardioversion ready for 4-6hrs p adm

-also incr/decr BP, brady/tachycardia, AV block

-c/i xx: baseline long QT, h/o torsades, low K, low Mg, pregnant/breastfeeding

-Drug Drug: no signif issues

Class IV = Ca++ Channel Blockers

-block the slow inward Ca++ (L type Ca Ch)

-most pronounced effects on cells dependent on Ca Ch to initiate the AP- SA nd, AV nd

--> slows conduction velocity and incr AV nd refractoriness--> decr ability of AV nd to rapidly conduct an impulse to the ventricle; thus good for SVT, and to decr a-flutter/fib conduction

-Verapamil-

-inhib voltage gated Ca Ch needed to make an AP in slow response myocytes seen in SA/AV nd

-EP Mech:

-SA nd/atrium- decr SA nd rate, but no effects on atrial muscle

-AV nd: slow AV nd conduction, prolong AV nd refract pd

-HPS/ventricles: no effect on intraatrial and intraventric conduction; effects are mainly prox to HPS

-HD xx: no major arterial BP, periph vasc resistance, HR, LVEDP, contractility effect

-Pharm: much first pass metab (90%), w much incr [ ] if hepatic dysfx; t1/2 3-7 hrs

-Use: slow ventric response to atria in a tachyarrhythmia- a-flutter, a-fib; also good w enhanced automaticity xx like ectopic atrial tachy or ideopathic LV tachy; good to stop SVT that involves AV nd

-Adverse xx: PO: not much, some GI xx- upset/constipation, other xx: vertigo, HA, nervous, pruritis

-c/i xx: beta blocker use bc --> exaggerate the HR depression, decr AV nd conduction, and decr myocard contractility.

-limited use in pt <1yo, espec if CHF, bc risk of CV collapse

-caution if ventric dysfx

-Diltiazem-

-similar to Verapamil

-?less ventric depression

-Pharm: less bioavail (45% absorption), t1/2 4-7hrs; metab in liver like verapamil but mainly GI excreted

Other Rx:

-Digitalis Glycosides

-e.g. Digoxin

-positive inotropy, so used for CHF

-also useful for SVT

--> slow AV nd conduction, so good for reentry tachy if AV nd is part of the circuit

-limit AV nd conduction durng a-fib/flutter (less used for this nowadays)

-theoretically better than CCB and BB's which also slow AV nd conduction bc it has positive and not negative inotropy,

-however has only limited AV nd effects in states of high symp tone (e.g CHF)

-risk of shortening effect on the EFP of accessory pathways, it is AVOIDED in older pts w WPW

-used in infants w WPW and SVT - long, safe history of use, but not proven effective in randomized study...

-Adenosine

-endogenous nucleoside (end product of ATP)

-for rapid termination of SVT

-EP Mech:

-Adenosine R' at SA and AV nd via G protein signaling cascade--> open the outward K current activated by ACh.... Adenosine stim--> hyperpolarize the resting membrane potential, decr phase 4 depol slope, and shortening the AP duration ==> complete conudction block that terminates tachy that uses AV nd. NO affect on ventric myocytes bc the adenosine stimulated K ch isn't in ventricles.

-ECG: 10-20sec block, both antegrade and retrograde; see mild sinus slowing initially after use, then a sinus tachy due to vasodilation and hypotension. No effect on QRS or QT

-HD xx: biphasic pressor response: initial brief incr in BP, then vasodilation and 2y tachy

-Pharm: metab by rbc in <10sec...

-Use: acute termination of SVT using AV nd; and to Dx narrow complex tachy by unmasking the a-flutter and ectopic atrial tachy.

-Adverse xx: flushing, chest pn, dyspnea, bronchospasm if +RAD hx; a-fib bc shorten atrial refract pd

-c/i xx: WPW in a-fib..., asthma

-Drug Drug: methylxanthinse (theophylline) antags their effects...

-Mag Sulfate

-can terminate VT, espec polymorphic VT

-Digitalis induced arrhythmias more likely if Mg defic

-low Mg may incr risk of postop JET

-Mg sulfate can be given PO, IM, IV (preferred) if needed rapidly

-Losing DTR = you OD'd

Drug-Device Interactions

-Increase Threshold for Defibrillation:

-Amio, Flec, Lidocaine, Propafenone, Mexiletine

-Decr Threshold for Defibrillation:

-Sotalol, Dofetilide

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1st AVB

2nd AVB (Mobitz I Wenckebach) (note how PP stays same, though PR lengthens, then drop beat)

2nd AVB (Mobitz II)

3rd AVB (Complete AV Block)

Junctional bradycardia

Asystole

Bradycardia

Accelerated Junctional Rhythm

VT

VF

a-flutter

a-fib

Isolated PVCs (Uni or Multifocal)

Bigemony

How to DDx VT fr SVT w aberrant conduction?

How to determine if it is accelerated junctional rhythm? what is the relation to P waves?