Cardiac Arrhythmias Part 3: Pharmacotherapy of

Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Slides 95-99 summarize arrhythmia content from Part I & II but in a different format.
Cardiac Arrhythmias Reviewed in Part I & II – 95
Background information
1. Definitions and classifications
2. EKG recognition
3. Re–entry
4. Vaughn-Williams Classification of anti-arrhythmic drugs (AAD)
Classification – individual agents and digoxin
Heart blocks – briefly discussed
Atrial fibrillation/flutter
Treatment of A-Fib
1. rate control
2. rhythm control
3. stroke prevention: warfarin, dabigatran, rivaroxaban, apixaban
Proposed Treatment Model Based on Patient Presentation: A-Fib – 96
Slides 95-99 summarize arrhythmia content from Part I & II but in a different format. It presents it in
terms of pt. presentation: 1. First episode; 2. Asymptomatic recurrence; or 3. Symptomatic recurrence
First Episode Summary: A-Fib – 97
Pt. presentation: Hemodynamic instability→ DCC immediately
Duration: < 2 days→ may cardiovert immediately
Duration: >2 Days (hemodynamically stable)
 Anticoagulate x 3 weeks
 Rate control in weeks prior to cardioversion
 Attempts cardioversion
 Anticoagulate x 4 weeks post cardioversion
If cardioversion is NOT attempted then:
1. chronic rate control therapy
2. chronic stroke prevention therapy
Avoid use of chronic antiarrhythmic agent
A-Fib Recurrence: minimally symptomatic/asymptomatic – 98
Chronic rate control (AFFIRM trial based)
Chronic stroke prevention Tx IMPERATIVE: dabigatran, rivaroxaban, Apixaban, or ASA +/- Plavix based
on age and risk factor assessment (CHADS2)
A-Fib: recurrence symptomatic – 99
Recurrence in symptoms despite optimal rate “control” or inability to achieve optimal rate control →
consider restoration and maintenance of NSR
1. rate control (@ minimum till pt. cardioverted)
2. cardioversion→ DCC or chemical
3. maintain NSR→ with antiarrhythmic agent(s)
4. stroke prevention TX → pre/post cardioversion
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5592│Cardiac│ 2015
Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Non-pharmacologic management A-Fib – 100
Growing management → successfully done with data to back up procedures
1. AV nodal ablation with pacemaker placement
a. Renders AV node dysfunctional → pt. given a pacemaker
b. Some pts. left in A-Fib and MUST be given lifelong anticoagulant
2. RF ablation for a flutter
a. Find re-entrant circuit → ablate it → cures the arrhythmia
3. Surgery
a. Types:
 Maze procedure
 pulmonary vein isolation
b. 80% occurrence of NSR (normal sinus rhythm) with surgeries
c. Pts. anti-coagulated for period of time to see if pt. goes back into A-Fib
Drawing catheter placement for ablation – 101
See WPPD slides
Catheter placement shown in this slide is for Left Accessory Pathway PSVT. Procedure is similarly done
in A-Fib.
Paroxysmal Supraventricular Tachycardia (PSVT) – 102
Rapid sinus rhythm associated with AV nodal re-entry or AV re-entrant tachycardia
Mechanism causing PTSV
 Re-entrant mechanisms – usually seen age < 40 yrs.
1. Infra-nodal = inside AV Node → prominent
2. Extra-nodal = AV nodal re-entrant tachycardia i.e. Wolf Parkinson White Syndrome
Rates range from 150 – 200/min
 Pts. can be QUITE symptomatic
Non-drug TX sometimes to increase vagal tone can sometimes manage symptoms
 carotid massage
 Valsalva
 Ice water on face
Anti-coagulation NOT generally needed in PSVT because there is viable, coordinated atrial contraction
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5592│Cardiac│ 2015
Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Treatment of acute PSVT (top): prevention of recurrences (bottom) – 103
Start by evaluating symptoms
 PSVT frequently associated with Panic Attack. Unclear if Panic Attack creates PSVT or vice versa.
 Symptoms:
1. Most mild PSVT → panic is a big part of presentation
2. Chest pain
3. Shortness of breath
4. Atrial and ventricular rates can be very high → pt. very symptomatic
5. Likelihood of clot = extremely low to non-extant. Remember, in PSVT there is viable,
coordinated atrial contraction so blood is pumping. It is not stagnant which would
enhance clot formation.
 Severe symptoms → go directly to DCC (do not pass go; do not collect $200 dollars as in
Monopoly!)
 Mild symptoms → Evaluate ECG → most of the time easy to do. This stage done in ER. Look at
the QRS complex. This is the electrical picture of ventricular depolarization. Assume ventricular
contraction follows ventricular depolarization. Remember ECG, does not tell anything about the
strength of contraction.
1. Is QRS complex wide?
2. Is QRS complexes occurring 1 after another or are they irregular in frequency i.e. rate
varies.
 Irregular frequency suggests Wolf Parkinson White type of arrhythmia
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5592│Cardiac│ 2015
Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Treatment of acute PSVT (top): prevention of recurrences (bottom) – 103
Initial evaluation - basic
ECG. Look at QRS interval
Must diagnose these in
electrophysiology lab, not ER.
Treatments
Evaluating ECG
 This stage of ECG evaluation cannot be done in ER → Must be done in electrophysiology Lab.
ECG alone cannot diagnose:
1. AVNRT = AV Node Re-entrant Tachycardia
2. Orthodromic or Antidromic AV Node Tachycardia
3. A-Fib with accessory pathway
 All you know in the ER, is the basic ECG in the first step of evaluation looking at QRS complex.
Treatment
 Evaluation of the basic ECG = not always reliable. As a result treatment determination can be
challenging. See pt. presentation and scenarios below.
1. Mild symptoms – wide QRS; irregular rhythm
 Pt. administered verapamil or diltiazem→ you could make patient worse, much
worse.
 Ventricular rate of 150 could easily go to 300 and pt. deteriorate profoundly.
2. Mild symptoms – narrow QRS, regular rate.
 Pt. administered procainamide. One of two things may happen:
1. Drug may not work;
2. Drug may make patient worse.
 Treatment approach→ assume worse arrhythmia possible i.e. accessory pathway → Wolf
Parkinson White (WPW); wide QRS, irregular rate.
1. Administer test dose of adenosine→ not part of TX listed; safe; works well.
2. Possible outcomes: 1. arrhythmia worsens; atrial rate ↑; 2. nothing happens
3. T ½ adenosine = 7 seconds; very brief →it goes away almost immediately
 If atrial rate ↑ or patient worsens → can assume it is WPW or A-Fib with
accessory pathway. TX= procainamide/amiodarone.
 If pts. rate changes → it should ↓ relatively quickly and be short-lived with T ½ =
7 secs. TX options then are: verapamil or procainamide. Pt. should do well.
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5592│Cardiac│ 2015
Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias

2015
Later, patient will need other interventions i.e. AV nodal blockade
Ventricular arrhythmias types – 104
1. Premature ventricular contractions (PVCs)
2. Ventricular tachycardia (VT)
3. Ventricular fibrillation (VF)
4. Torsades de Pointes
http://www.rnceus.com/ekg/ekgtp.html
Premature ventricular contractions (PVCs) – 105
Occurrence in healthy pt. → confers little risk. Most people have with varying frequency. Occurrence
and absence of heart disease, even with symptoms, is benign.
 no drug TX needed
 if symptomatic→ TX = β-Blocker
Often occur following AMI (acute myocardial infarction)
 ↑ risk sudden cardiac death (SCD); there is a statistical association
 antiarrhythmic drugs (AADs) – except Type II, should NOT be used to suppress PVCs
 use of β-Blocker ↓ risk of death and controls symptomatic PVCs, especially in acute phase
 indicated for prevention of recurrent MI and arrhythmias during/post infarction
 See CAST Trial next slide
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Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Cardiac Arrhythmia Suppression Trial (CAST) – 106
PVCs are associated with↑ mortality post-MI
Fundamental study question: Does PVC suppression lead to mortality reduction in pts. post-MI?
Inclusion:
1. Post-MI pts. 6 days – 2 yrs.
2. > 6 PVCs/hr. (6 /hr. = 1 PVC q 10 mins.)
3. randomized to: flecainide, encainide, moricizine, placebo (flecainide parent drug of encainide)
Findings:
1. Class IC agents suppressed PVCs post-MI
2. HOWEVER, therapy resulted in a higher mortality rate compared to placebo
3. Treatment with class IC agents increase the risk of fatal ventricular arrhythmias
4. Likelihood of survival, better with placebo with P=0.0006 → highly statistically significant
observation based on P value
5. Post-MI, occasional PVC should not receive treatment with 1C agents; probably not with class
III agents either. Study did not address class III data.
6. TX for infrequent, asymptomatic PVCs with classical AAD is an appropriate.
Study
CAST
Design
RCT
Treatments
Inclusion
Findings
Flecainide (class IC)
N=1,445
1. Class IC suppressed PVCs post-MI
Encainide (class IC)
1. > 6 PVCs/min
2. ↑ Mortality rate compared to
Moricizine (class IC) 2. Post MI 6 days Placebo
Placebo
To 2 yrs.
3. Class IC agents↑ risk of fatal
Duration: ≈1.5 yrs.
Ventricular arrhythmias
CAST trial N Engl J Med 1991; 324:721 – 107; encainide removed from market after since this study
It is okay to use β-Blocker to treat PVCs
CAST trial graph - slide 108
Demonstrates likelihood of survival better with placebo
Ventricular Tachycardia (VT) – 108
Definition:
1. Series of ≥ PVCs (nothing in between)
2. Rate > 100 BPM
Determine if PVCs are sustained or non-sustained. Definition depends on duration.
1. Non-sustained = duration < 30 seconds; self terminates
2. Sustained: > 30 seconds or requires termination
PVCs; > 3 consecutively; rate = 150
BPM
http://www.practicalclinicalskills.com/ekg-reference-guide-details.aspx?lessonID=25
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Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Acute treatment: VT – 109
VT both sustained and non-sustained are associated with evolution of V-Fib which is uniformly fatal.
Patient presentation/treatment:
1. Severe symptoms/unstable (no pulse) : DCC
2. Non-sustained
 asymptomatic:
1. called pulsatile→ a pulse is detectable so there is cardiac output
2. no TX required
 symptomatic:
1. β-Blockers
2. Amiodarone or sotalol if no response to β-Blocker
 AICD?→ Problematic in non-sustained VT
3. post-MI, TX with β-Blockers or auto reverts→ no AICD
4. heart failure with non-sustained VT→ yes AICD
3. Sustained VT may become ventricular fibrillation (VF)
 Unstable: DCC, right away. If unresponsive then amiodarone.
 Stable – treat with drug: IV amiodarone, lidocaine, procainamide, or DCC
1. stable = awake; pulsatile; conscious; has BP
 AICD? → Yes, especially post-MI. Virtual standard of care to have both drug and AICD
Ventricular fibrillation (VF) – 110
Fibrillation is electrical anarchy whether in atria or ventricle
Absence of organized ventricular rhythm; no coordinated muscular contractions; no cardiac output; BP
effectively = 0
Ventricles contracting but it is individual myofibrils causing contractions
VF is thought to be common cause of sudden cardiac death (SCD) in USA→ frequency = 500,000/yr.
Treatment: DCC, only treatment that works reliably.
 DCC energy for V-Fib >> A-Fib
1. A-Fib = 50-100 up to 200 Joules
2. V-Fib = start @ 200, goes up to 400 Joules
http://www.practicalclinicalskills.com/ekg-reference-guide-details.aspx?lessonID=26
Automatic implantable Cardioverter – defibrillator (AICD) – 111
See WPPD slide
Effects on longevity well-documented with AICD
Sophisticated devices that contain: defibrillator; pacemaker; overdrive pacemakers; detects
tachycardia→ takes over rhythm and slows it down. If can’t slow rhythm → administers small jolts. If
ineffective → administers larger jolt.
Small impulse uncomfortable; larger jolt significant discomfort. Has psychological impact.
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Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
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2015
AICD + antiarrhythmic Agent – 112
40 – 70% of patients with ICD require concurrent AAD therapy; very commonly patient receives
amiodarone
Purpose of adding an ADD:
1. ↓ number of inappropriate firings
2. ↓ number of high-voltage shocks, inappropriate shocks provoked by SVT arrhythmias
3. prolong battery life
In practice it is common to see an AICD plus AAD (antiarrhythmic drug) possibly with β-Blocker / CCB
Torsades de Pointes (TdP) – 113
Difficult to treat. Goal = prevention→ minimize agents/combo of QT prolonging drugs
QTc usually > 500 milliseconds (?); ↑ associated risk of TdP
 Textbook has 560 msec→ presenter suspects it is a typo. That is the longest QTc he has seen
Common causes of TdP
 myocardial ischemia/infarction
 heart failure
 severe bradycardia → < 50 beats/minute
 hypothermia
 electrolyte imbalance: ↓ K+, ↓ Mg++
 keep K+ > 4; Mg++ > 2
 Monitor patients on AAD, diuretics, other cardiac drugs for electrolyte imbalances
Torsades de Pointes (“twisting of the points”) – 114
Describes electrophysiology phenomenon of the electrical axis of the myocardium actually turning about
an electrical axis. It turns about this axis when you see: large depiction of QRS followed by small one.
Suggests electrical axis relative to leads on the chest moving 1st towards electrodes then away from
electrodes.
in Gartner
http://medlibes.com/uploads/Screen%20shot%202010-07-06%20at%209.39.21%20PM.png
TdP risk factors:
1. heart disease heart disease
2. drugs
3. electrolyte abnormalities: ↓ K+; ↓ Mg++
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5592│Cardiac│ 2015
Cardiac Arrhythmias Part 3: Pharmacotherapy of Cardiac
Arrhythmias
2015
Common QT prolonging drugs – 115
TdP associated with large # of drugs - not all archived cardiac drugs
Drug Class
Drug Name
Antiarrhythmic drugs
quinidine
Procainamide
Disopyramide
Amiodarone (<1%)→ quite small risk
Dofetilide
Dronedarone (<1%)→ quite small risk
Sotalol
Ibutilide
Psychotropics
Haloperidol/droperidol
Phenothiazines
Tricyclic/tetracyclic
Antidepressants
Atypical antipsychotics i.e. quetiapine, ziprasidone
Toxins
Organophosphate insecticides
Arsenic
Antibiotics
Pentamidine
(Time-limited use)
Macrolides i.e. erythromycin, clarithromycin
Fluoroquinolones
Trimethoprim – sulfamethoxazole
Fluoroquinolones i.e. levofloxacin, moxifloxacin,
gemifloxacin
Voriconazole
Pain
Methadone
Miscellaneous
Liquid – protein diets
Corticosteroids
Diuretics
Quinine
Chloroquine
Chloral hydrate
Tacrolimus
TdP treatment – 116
DCC with sedation to restore stable rhythm
 sedation preferred but not always done b/c of circumstances
DOC (drug of choice) – IV Mg++ sulfate
 good but duration = short
 Pts. receiving Mg++ get DCC b/c of short duration of drug
Pt. management: Correct/remove any precipitating causes
 remove QT prolonging drugs: get ECG→ note QTc; anything approaching 500→ too long
 use 440 msec is threshold; QTc > 440→ patient at risk for TdP
 target K+ > 4.0 mEq/L; target Mg++ greater > 2.0 mg/dL
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