Atrial Fibrillation and Ventricular Arrhythmias

Atrial Fibrillation and Ventricular Arrhythmias

Ibrahim Sales, Pharm.D.Assistant Professor of Clinical Pharmacy

King Saud [email protected]

Supraventricular Arrhythmias

• Supraventricular arrhythmia• Sinus Bradycardia• AV Nodal Block• Atrial fibrillation• Paroxysmal Supraventricular Tachycardia (PSVT)

• Ventricular arrhythmia• Ventricular Premature depolarization• Ventricular tachycardia• Ventricular fibrillation• Torsades de Pointes 2

Atrial Fibrillation

• The most common sustained arrhythmia encountered in clinical practice

• Rapid & disorganized conduction in atria leading to loss of mechanical contraction

• "irregularly irregular" appearance on ECG

• HR of 120–180 usually observed because AV node unable to block all atrial impulses

3

Classification of AF• Paroxysmal (self-terminating) :

• episodes terminate spontaneously in less than seven days,

• usually less than 48 hours. • Persistent AF :

• fails to self-terminate within 7 days. • Episodes may eventually terminate spontaneously,

or they can be terminated by cardioversion.

4

ACC/AHA/European Society of Cardiology

Classification of AF

• Permanent AF • arrhythmia lasts for more than one year and

cardioversion either has not been attempted or has failed.

• "Lone" AF:• describes paroxysmal, persistent, or

permanent AF in individuals without structural heart disease (usually young patients, <60 yrs)

5

Classification of AF

• Nonvalvular AF: • Not caused by valvular disease, prosthetic heart

valves, or valve repair

• Recurrent atrial fibrillation: • ≥ 2 episodes of atrial fibrillation

6

Causes of AF• Hypertensive heart disease • Coronary disease • Valvular heart disease • Heart failure • Hypertrophic cardiomyopathy• Congenital heart disease • pulmonary embolism • COPD• Obstructive sleep apnea• Hyperthyroidism • Alcoholism (Holiday Heart

Syndrome)• Surgery: CABG 30-40%

• Inflammation and infection• Medications: theophylline,

bisphosphonate

7

Loss of coordinated atrial Contraction

Rapid Ventricular response

Tachycardia: Shorter diastolic fill time. Reduced coronary

circulation and possible ischemia. Tachycardia medicated

cardiomyopathy

Decreased diastolic filling

Decreased cardiac output

Blood stasis and atrial clot formation

Thromboembolism

Increased risk of stroke

Increased Morbidity & Mortality

Clinical implications of AF

Am Fam Physician. 2011 Jan 1;83(1):61-68

Goals of Therapy• Disease specific goals of therapy

• Control ventricular rate• Preventing thromboembolic events• Restore sinus rhythm• Maintain sinus rhythm

• Global goals: • Reduce mortality • Improve QOL• Decrease hospitalization and ER visits• Optimize the cost effectiveness of treatment

10

Approach to therapy of AFib

1. Evaluate the need for acute treatmentBy starting a rate control drug

2. Contemplate restoration of SR taking into consideration the risks

restoring and maintaining SR may not be a desirable goal for all patients

3. Consider thromboembolic prophylaxis with appropriate antithrombotic drug based on stroke risk 11

Rate control vs. rhythm Control• Overall Conclusion:

No significant difference in overall mortality between rate-control and rhythm-control strategies

Anticoaugulant (AC) need is similar in both groups

12

Rate control Strategy

• At least as effective as rhythm control strategy for preventing stroke and death in atrial fibrillation

• Fewer adverse events than rhythm control strategy• Rhythm control with AAD maybe considered if patient remained

symptomatic despite adequate ventricular rate control• Target HR:

• Lenient resting HR< 110 bpm vs. strict rate control, resting HR< 80 BPM, have similar cardiovascular outcomes• Therefore, target a resting heart rate of < 110 bpm

13

AAD: anti-Arrhythmic Drugs


• Drugs for long-term rate control • Beta blocker (oral)

• metoprolol 50-200 mg/day, propranolol 80-240 mg/day) • Non-dihydropyridine (oral)

• diltiazem 120-360 mg/day, verapamil 120-360 mg/day) • Digoxin (oral)

• AF with HF, LVD (LVEF < 40%) or for sedentary individuals • not recommended as monotherapy to control ventricular

rate in patients with paroxysmal atrial fibrillation

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• Amiodarone (oral) • when other medical therapy has failed to control

heart rate adequately • AF with pre-excitation

• preferred drugs for rate control are oral propafenone or amiodarone

• combination therapy with any of digoxin, beta blocker, or non-DHP-CCB may be used to control heart rate at rest and with exercise

15

Rhythm control strategy

• Recommended in patients with symptomatic AF despite rate control

• Pharmacologic rhythm control strategy associated with more hospitalizations and adverse events without apparent benefit compared to rate control strategy in AF

• Rate control should be continued throughout rhythm control approach

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Rhythm control strategy• Cardioversion with DCC

• DCC is useful to start rhythm control strategy for atrial fibrillation• Pretreatment with amiodarone, flecainide, ibutilide, propafenone

or sotalol before DC cardioversion may increase success rate and prevent recurrent atrial fibrillation

• Pharmacological cardioversion:• Success rate lower than DC• Selection of agent:

• If the AF is ≤7 days duration:• Dofetilide, flecainide, ibutilide, propafenone or, to a lesser

degree, amiodarone (preferred if structural heart dz)• If the AF is >7 days duration

• dofetilide or, to a lesser degree, amiodarone or ibutilide 17

Rhythm control strategy• Thromboembolic prophylaxis during cardioversion:

• for AF of known duration < 48 hours• immediate cardioversion indicated without delay

for anticoagulation if hemodynamic instability • starting anticoagulation (with LMWH or IV UFH at

full venous thromboembolism treatment doses) before cardioversion suggested if possible

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• for atrial fibrillation of ≥ 48 hours or of unknown duration• initial therapeutic anticoagulation recommended

with either:• Option 1: Therapeutic anticoagulation (adjusted-

dose vitamin K antagonist [VKA] therapy to target INR range 2-3, LMWH at full venous thromboembolism treatment doses, or dabigatran) for at least 3 weeks before cardioversion

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• Option 2: Transesophageal echocardiography (TEE)-guided approach with initial anticoagulation (LMWH or IV heparin) then cardioversion within 24 hours of confirmation of no thrombus

• less hemorrhagic complications, but trend toward increased mortality

• Post-cardioversion anticoagulation recommended for ≥ 4 weeks 20


• Maintenance of NSR• Intermittent antiarrhythmic drug therapy

• “Pill in the Pocket”• AAD:

• Also increase the risk of arrhythmia• torsades de pointes (TdP): a potential adverse effect with

dofetilide and sotalol• ventricular tachycardia or conversion to atrial flutter with

tachyarrhythmia is a potential adverse effect with flecainide and propafenone

• The AAD associated with increased mortality include sotalol, quinidine, and possibly disopyramide

21

Rhythm control strategy• “Pill in the Pocket”

• A transient outpatient therapy for reversion of NSR in paroxysmal AF

• single oral high dose taken only when an episode of AF is recognized by the patient

• Agents: propafenone 600 mg, or flecainide 300 mg• Very strict patient criteria

• Absence of: structural heart disease, sinus and AV node dysfunction, QT interval prolongation, Brugada syndrome

• Presence of AV nodal blockade with a BB or CCB to prevent rapid AV conduction if atrial flutter occurs.

22

Recommended Antiarrhythmic Therapy in Patients with Recurrent Paroxysmal or Persistent Atrial Fibrillation:

Clinical Scenario First-line Therapies

Second-line Therapies

No or minimal heart disease, or hypertension without left ventricular hypertrophy

Dronedarone Flecainide

Propafenone Sotalol

Amiodarone Dofetilide

Catheter ablation

Hypertension with substantial left ventricular hypertrophy Amiodarone Catheter ablation

Coronary artery diseaseDofetilide

DronedaroneSotalol

Amiodarone Catheter ablation

Heart failure Amiodarone Dofetilide Catheter ablation

23

Ablation Therapy

• ablation of AV node or accessory pathway (and pacemaker implantation) • indicated when medical therapy fails to control heart rate or

produces intolerable side effects• Catheter ablation, or surgical ablation in patients having

cardiac surgery for other reasons• recommended for patients with symptomatic paroxysmal

atrial fibrillation after failure of antiarrhythmic drugs • may improve quality of life and reduce hospital

readmission rates24

Antithrombotic Therapy

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Thromboembolic Prophylaxis• Guidelines consistently agree that most patients with

AF should receive antithrombotic therapy.

• AT is recommended to patients with permanent, persistent, or paroxysmal atrial fibrillation, atrial flutter, and patients managed with rate or rhythm control strategy

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Antithrombotic in Atrial Fibrillation

• Return of SR restores effective contraction in the atria >> dislodge poorly adherent thrombi

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Selection of the antithrombotic agent depend on the level of risk:• CHADS2 or CHA2DS2-VASc score

for risk stratification

Stroke Risk Stratification

• Have ONE of the following factors: • Prior ischemic stroke, TIA• Mitral valve stenosis• Prosthetic heart valve

• Have ONLY one of the following factors: • Age > 75 y Or HTN Or DM Or moderately or severely

impaired LV systolic function and/or HF

• Age > 75 y With none of the conditions listed above in the high- or intermediate-risk categories

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Have > 2 of the • Age > 75 y• HTN• DM• Moderately or severely

impaired LVSD and/or HF

OR

High Risk Patients:

Intermediate Risk Patients:

Low-Risk Patients:

Recommendations About Antithrombotic Therapy

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Stroke Risk Stratification• CHADS2 risk score predicts stroke risk• Helps predict stroke risk in AF patients and determine which

antithrombotic (AT) is appropriate

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ACCP 9th edition, 2012 Guidelines for the Management of Patients With AF

CHADS2 Risk Factors PointsRecent Congestive HF exacerbation 1

History of Hypertension 1Age > 75 y 1Diabetes Mellitus 1Prior history of stroke or TIA 2

Recommendation for AT in AFCHADS2

ScoreAnnual stroke rate (range)

Recommended Antithrombotic therapy

0 1.9 (1.2-3)1. No RX (preferred)2. ASA (for those electing Rx)

1 2.8 (2-3.8)1. Warfarin, Dabigatran,

rivaroxaban (AC preferred)2. ASA + Clopidogrel3. ASA

2-6 4-18 1. Warfarin, dabigatran, rivaroxaban

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AC: Anticoagulation

CHA2DS2-VAScCHA2DS2-VASc Risk Factors PointsCongestive Heart Failure 1Hypertension 1Age > 75 2Diabetes 1Previous stroke, TIA, systemic embolism 2Vascular disease (MI, CAD, aortic plaque) 1Age 65-74 1Sex (Female) 1

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Recommended Antithrombotic Therapy

Score of 0 No anticoagulation (Preferred) Or ASA 75-325 mg/d

Score of =1 Either anticoagulation (Preferred) or ASA 75-325 mg/d

Score of > 1 Anticoagulation with Warfarin, Dabigatran or rivaroxaban

Overview on Antithrombotic Therapies

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Vitamin K antagonist: Warfarin • The most commonly used AC• Target INR of 2-3 in patients without

mechanical heart valves• lower target INR of 2 (range 1.6-2.5) may

be considered for patients ≥ 75 y/o or if at risk of bleeding but without contraindications to oral anticoagulant therapy

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Vitamin K antagonist: Warfarin • Starting dose 5-10 mg adjusted based on

INR • No need to bridge patient with heparin

when initiating warfarin in AF patients• Determine INR at least weekly during

initiation and monthly when INR is stable. • suggests monitoring INR at least every 12

weeks rather than every 4 weeks when INR consistently stable 35

Vitamin K antagonist: Warfarin Limitation:

Narrow therapeutic indexRequire frequent dose adjustments and

monitoring Significant drug-drug and drug-food interactiontime required to achieve its pharmacologic effect is

dependant on the T½ of the coagulation proteins.full antithrombotic effect achieved in 5 to 7 days

afterPregnancy Category X 36

Dabigatran (Pradaxa®)

• Dabigatran etexilate is a selective, competitive, reversible direct thrombin inhibitor

• Approved by FDA in 2010 for stroke prevention in atrial fibrillation

• Approved in Canada & Europe for VTE prevention after hip and knee replacement surgery

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• Oral capsule• Rapid onset of action• Half-life 12-17 hours, dosed TWICE Daily • No routine monitoring required• No reversal antidote

• dialyzable• No dietary/food interactions• SE: Bleeding, Dyspepsia (common, likely due to

tartaric acid)• Cost: $$$ compared to warfarin


• Renal elimination • CrCl >30 ml/min:

• 150 mg orally twice daily• Outside US: 110 mg twice daily for age >75 or

propensity for GI bleeding• CrCl 15-30 ml/min:

• 75 mg orally, twice daily*• Metabolism: P-gp substrate

• use with caution when administered concomitantly with P-gp inhibitors or inducers 39


Drug Interaction CommentsDronedarone dabigatran

bioavailability (70–140%)Consider dosage reduction to 75 mg twice daily in patients with Clcr 30–50 mL/minute

Ketoconazole dabigatran concentrations and AUC

Consider dosage reduction to 75 mg twice daily in patients with Clcr 30–50 mL/minute

40


41

Drug Interaction CommentsRifampin Potentially dabigatran

concentrations and AUC Avoid concurrent use

Amiodarone dabigatran concentrations

Dosage adjustment not necessary.

Verapamil Potentially dabigatran concentrations and AUC

Dosage adjustment not necessary.

Converting to and from Dabigatran

• Warfarin to Dabiatran• D/c warfarin and start dabigatran when INR <2.0

• Dabigatran to Warfarin• CrCl >50 ml/min: start warfarin 3 days before d/c

Dabi CrCl 31-50 ml/min: start warfarin 2 days before D/c dabigatran

• CrCl 15-30 ml/min: start warfarin 1 day before stopping dabigatran

• CrCl <15 ml/min: no recommendation 42


• Product Stability: • Once bottle is opened, manufacturer

recommends that drug be used within 30 days. Keep bottle tightly closed

• Manufacturer package insert indicates potency is maintained for 120 days after first opening bottle.

43


• Contraindications: • Active pathologic bleeding• History of serious hypersensitivity

reaction to dabigatran (e.g., anaphylaxis, anaphylactic shock)

• Patients with mechanical prosthetic heart valves

• Pregnancy Category C 44

Rivaroxaban (Xarelto®)

• Direct factor Xa inhibitor • Approved by FDA in 2011 for prevention of

stroke in non-valvular AF. • Also in treatment and prophylactic in DVT/PE and

following knee- or hip-replacement surgery • No laboratory monitoring required• No dosage adjustment for gender, age, extreme

body weight• No reversal

• Half life 5-9 hours


• Dosing: • Oral tablet, once daily (cost $231.60 USA)• Primarily renal elimination

• If CrCl> 50 ml/min: give 20 mg once daily with evening meal

• If Crcl 15-50 ml/min give 15 mg once daily with evening meal

• Contraindicated for creatinine clearance < 15 mL/minute

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• Contraindications: • Active pathologic bleeding• Severe hypersensitivity reaction to rivaroxaban

• Pregnancy Category C• Lactation: Discontinue nursing or the drug• DI: Drugs Affecting and/or P-glycoprotein and

CYP3A4• Avoid using with itraconazole, ketoconazole,

Antiretrovirals, HIV protease inhibitors, Carbamezapine, rifampin, phenytoin, St. John's wort

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Apixaban (Eliquis®)

• Direct factor Xa inhibitor • Approved by FDA in 2012 for risk reduction of

stroke and systemic embolism in nonvalvular AF • No routine lab testing• No reversal

• Half life 8-15 hours• Metabolized in liver via CYP3A4 and CYP

independent mechanisms• Eliminated via multiple pathways

Apixaban (Eliquis®)

• Dose: 5 mg tablet Twice daily• To switch from warfarin, stop warfarin, then start

apixaban when INR <2• Cost: (5 mg BID): $250.37 (USA)• Pregnancy Category B• Lactation: Discontinue nursing or the drug• May prolong PTT and INR in a concentration-

dependent fashion

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Stopping Pradaxa (dabigatran), Xarelto (rivaroxaban), or Eliquis (apixaban) in AF patients

• Discontinuing new oral AC places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation in clinical trials in patients with nonvalvular atrial fibrillation.

• If anticoagulation must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.

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Limitations of Novel AC • Irreversibility• Cost• Renal function

• Not studied where CrCL<30mL/min• Lack of monitoring

• No readily available test• No therapeutic interval

• Long term safety not known• No data on use in pediatric population 51

Summary of Major Results of Phase 3 Trials of New Anticoagulants vs Warfarin in AF

Drug/Trial Efficacy: Stroke/TE

Hemorrhagic stroke

Major bleeding

Dabigatran in RE-LY

34% 74% SIMILAR

Rivaraoxaban in ROCKET

Noninferior to warfarin

40% SIMILAR

Apixaban in ARISTILE

20% 50% 30%

Ventricular Arrhythmias

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Types of Ventricular Arrhythmias• Premature Ventricular Contractions (PVCs)

• Ectopic ventricular beat• non-life-threatening and usually asymptomatic. • Sx: palpitations or uncomfortable heartbeats.

• Ventricular Tachycardia (VT)• a life-threatening situation associated with hemodynamic

collapse or may be totally asymptomatic.• >3 consecutive PVCs occurring at a rate >100 beats/min• Could be monomorphic or polymorphic

• Ventricular Fibrillation (VF)• results in hemodynamic collapse, syncope, and cardiac arrest.

Cardiac output and blood pressure are not recordable. 54

PVCs Treatment

• No drug therapy indicated for asymptomatic patients without structural heart disease

• BB is drug of choice for symptomatic patients • after myocardial infarction BB improve survival• no evidence that prolonged suppression with

drugs AAD improves survival• CAST I and II studies demonstrated higher

mortality in the AAD group

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Treat Guidel Med Lett 2007 Jun;5(58):51

Ventricular Tachycardia (VT)

• Non-sustained VT: last < 30 sec• Self terminate• May consider primary prevention in high risk

groups to prevent conversion to sustained VT• Sustained VT last > 30 sec

• Requires intervention to prevent VF or SCD

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• Causes: • Ischemia: MI (very common)• Stimulant use:

• Caffeine, cocaine abuse• Metabolic abnormalities:

• Acidosis, hypoxemia, hyperkalemia, hypokalemia, hypomagnesemia

• Drugs: • Digoxin, theophylline, antipsychotics, TCA,

AAD: flecainide, dofetilide, sotalol, quinidine57


• Treatment: • correction of the underlying precipitating factors• acute episode of VT (with a pulse)

• Severe symptoms: • DCC• Long term AAD is not needed if there was

precipitating factors• Mild symptoms:

• AAD: procainamide, amiodarone, sotalol and lidocaine

• Assess patient’s risk for recurrence 58

Ventricular Tachycardia (VT)• Treatment of chronic, recurrent, sustained VT :

• Empiric amiodarone• Catheter ablation: if idiopathic• Implantable cardioverter-defibrillator (ICD)

• +/- amiodarone or sotalol• frequency of VT/VF episodes >> frequency of

shocks• rate of VT >> can be terminated with BB• episodes of concomitant supraventricular

arrhythmias• minimize patient discomfort • prolong the battery life of the ICD 59

Ventricular Tachycardia (VT)• Primary prevention of SCD in VT/VF

• High risk: CAD, LV dysfunction, and nonsustained VT• Undergo electrophysiologic testing to guide

subsequent therapy• No inducible sustained VT/VF, chronic AAD

therapy is unnecessary• If inducible sustained VT/VF, implantation of an

ICD is warranted.

• Secondary prevention of SCD in VT/VF: • ICD is the first-line treatment 60

Torsade de Pointes (TdP)• TdP is a rapid form of polymorphic VT • ECG:

• long QT interval or prominent U waves (Delayed ventricular repolarization)

• Etiology of TdP:• Genetic, electrolyte disturbances ( K, Mg),

subarachnoid hemorrhage, myocarditis, arsenic poisoning, severe hypothyroidism, or drug therapy (most common)

61

Torsade de Pointes (TdP)• Drugs that can cause TdP:• AAD: Quinidine, Procainamide, Disopyramide, Amiodarone,

Dofetilide, Dronedarone, Sotalol and Ibutilide • Psychotropics

• Phenothiazines (e.g., thioridazine, chlorpromazine) TCA (Haloperidol, Pimozide) Atypical antipsychotics (e.g., quetiapine, ziprasidone)

• Organophosphate insecticides • Arsenic Antibiotics

• Pentamidine, Macrolides (erythromycin and clarithromycin), Trimethoprim-sulfamethoxazole, Fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin) and Voriconazole

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Torsade de Pointes (TdP)• Risk factors for drug-induced TdP:

• High dose (quinidine, TdP at low doses)• concurrent structural heart disease• Evidence of mild QT prolongation at baseline• Evidence of mild QT prolongation after initiation of drug• Female gender

• QT interval prolongation has been used as a measurement of risk of TdP• If baseline QTc interval > 450 msec AVOID drugs that can prolong

QT• If QTc interval is 560 msec after the initiation of the drug >>

discontinue or reduce dose of the drug 63

Torsade de Pointes (TdP)

• Treatment of Acute TdP• DCC • Followed by IV magnesium sulfate to

prevent recurrence• Discontinue all drugs that prolong the QT

interval • Correct exacerbating factors (e.g.,

hypokalemia or hypomagnesemia) 64

Ventricular Fibrillation (VF)• A Tachyarrhythmia• The most common underlying rhythm of cardiac arrest• If not treated: pulseless electrical activity, asystole• no cardiac output leads to rapid fatality• Causes: • frequently associated with CAD (only 20% patients rescued

from VF have evidence of evolving MI)

65

Treatment of pulseless VT or VF• ABCs• CPR until defibrillator attached• Check pulse between every intervention (except sequential

shocks with persistent VF• defibrillate up to 3 times as needed for V fib or pulseless VT

(200 joules, 300 J, 360 J)• if no pulse and persistent or recurrent VF/VT –

• CPR, intubation, establish IV access• epinephrine, defib 360, lidocaine, defib 360, bretylium, repeat

epi/defib, consider bicarbonate, defib 360, bretylium, defib 360, repeat lidocaine or bretylium, defib 360, magnesium, procainamide

66

VF Treatment

• Prevention of recurrence: • long-term therapy implantable cardioverter-

defibrillator (ICD)• Amiodarone or beta blockers often added

• if ICD shocks are frequent, consider adding sotalol, amiodarone or mexiletine; if shocks recur, radiofrequency catheter ablation

67

Sinus Bradycardia• Heart rate <60 beats/min• Not always pathologic• Symptoms:

• fatigue, dizziness, inability to concentrate, forgetfulness, syncope• Causes:

• sinus node dysfunction: aging, accompanying a conduction disease (e.g. AV block, AF), CHD

• Treatment: treat the underlying cause, atropinePacemaker if patient is hemodynamically compromised

69

AV Nodal Block

• A type of bradyarrhythmia • Types

• 1st-degree heart block—PR interval >0.1ms; AV conduction remains 1:1• 2nd-degree heart block-- progressive prolongation of PR interval AV

conduction <1:1• 3rd-degree heart block—no AV conduction, atria & ventricles contract

independently from 1 another • Causes:

• Use of AV nodal blocking agents (digoxin, -blockers, nondihydropyridine CCBs, amiodarone, dronedarone), hyperkalemia

• Treatment• treat underlying cause; • symptomatic patients: atropine 0.5mg IV Q3–5min up to total 3mg, • transcutaneous pacing; permanent pacemaker needed in patients

without underlying treatable cause70

Paroxysmal Supraventricular Tachycardia (PSVT)

• HR >100bpm, • ECG: narrow QRS complexes• Symptoms: chest pressure or discomfort, dyspnea, fatigue,

lightheadedness, dizziness, palpitations; • Treatment:

• hemodynamically stable patients: vagal maneuvers to sympathetic tone are 1st line;

• Adenosine

71

Wolff-Parkinson-White (WPW) Syndrome

• A type of SVT • Etiology:

• accessory pathway that bypasses AV node & causes tachycardia; HR >200bpm,

• life-threatening, may lead to VF• Symptoms:

• chest pain or tightness, dizziness, lightheadedness, fainting, palpitations, SOB 72

Wolff-Parkinson-White (WPW) Syndrome

• Treatment: • Avoid AV nodal blocking agents (b-blockers,

non-DHP CCBs, adenosine, lidocaine, & digoxin)

• short term electrical cardioversion:• amiodarone 150mg IV over 10min; • procainamide LD 20mg/min IV until arrhythmia

resolves, hypotension, or QRS widens by >50% or total of 17mg/kg; continuous infusion 1–4mg/min

• long term catheter ablation 73

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Atrial Fibrillation and Ventricular Arrhythmias