A. Arrhythmia Diagnosis [3]

1. Careful history with evaluation of prior events which might suggest arrhythmia
2. Family history also important, as arrhythmias can have a genetic component
3. Echocardiography is very important to evaluate cardiac structure
   1. Stress echocardiogram or nuclear study for patients with suspected ischemia
   2. Reducing ischemia can eradicate arrhythmias
4. Heart Monitoring
   1. Electrocardiogram (ECG) may identify at risk patients (long QTc, bundle branch blocks)
   2. Holter monitoring for patients with frequent events
   3. Cardiac event monitor for patients with infrequent events
5. Assess serum electrolyte levels, especially potassium, magnesium, and calcium
6. Suggestions of arrhythmia may prompt physician to electrophysiologic testing (EPS)
7. EPS is very effective in guiding therapy, particularly with ventricular arrhythmias [30]
8. Microvolt T-wave Alternans Testing [6]
   1. ECG based T wave analysis during exercise induced stress
   2. May identify patients at high risk for VTach or VF
   3. Patients with CAD and low EF with positive T wave alternans tests had ~15% event rate versus 0% of negative T wave alternans patients at 2 years
9. Critical to distinguish between atrial and ventricular arrhythmias

B. Atrial Arrhythmias [1,2]

1. Atrial Fibrillation (AF) / Flutter [4,8,23]
   1. Treatment goals to (1) control ventricular response rate and (2) convert to normal sinus rhythm (NSR)
   2. A variety of drugs with nodal blocking activity will control ventricular response rate
   3. These include ß-blockers, calcium blockers, and adenosine
   4. Transthoracic electrical cardioversion may be used first line for conversion to NSR
   5. Alternatively, anti-arrhythmic agents prior to cardioversion increases success
   6. The anti-arrhythmic agents themselves may convert to NSR ("chemical cardioversion")
   7. Anti-arrhythmic agents prolong maintenance of sinus rhythm after cardioversion
   8. Ibutilide enhances efficacy of cardioversion, particularly in patients resistant to maintaining sinus rhythm, and in patients who fail initial cardioversion [28]
   9. Type III anti-arrhythmic agents are now the agents of choice for maintaining NSR
   10. Amiodarone 200mg qd (low dose) provides ~60-70% maintenance of NSR at 1 year [4]
   11. This low dose of amiodarone has considerably less toxicity than high dose [7]
   12. Low dose amiodarone is most effective oral agent, with least long term toxicity
   13. Amiodarone intravenously for acute conversion of AF is alternative to electrical [20]
   14. AF with CAD use amiodarone, dofetilide, or sotalol [4]
   15. Type Ia Agents have ~50% maintenance of NSR at 1 year compared with 25% for placebo
   16. Propafenone can be used in patients without structural or coronary disease
   17. Dofetilide (Type III Agent) - reduces risk of atrial arrhythmias post-MI [35]
   18. Partial or complete AV nodal ablation with pacemaker backup to control rapid rates may be preferred in refractory and drug-intolerant patients [3,14,21]
   19. In addition, patients with extremely high ventricular response rates may benefit from AV nodal ablation with pacemaker [14]
   20. RF ablation may be used to treat atypical atrial flutter [14]
2. Supraventricular Tachycardias (SVT) [14,18]
   1. Most are re-entrant tachycardias with concealed bypass tracts
   2. Adenosine 6-12mg most effective for diagnosis of SVT and usually breaks arrhythmia
   3. ß-Blockers preferred in post-MI setting or in ischemic disease
   4. Verapamil is now the preferred agent in stable SVT control
   5. EPS guided conduction system ablation may also be used [21]
   6. Catheter directed radiofrequency (RF) ablation is preferred treatment (see below) [14]
   7. RF ablation near coronary sinus ostium (slow pathway) preferred over fast pathway
   8. RF ablation preferred for junctional tachycardias and for inappropriate tachycardias
3. Non-Concealed Bypass Tracts
   1. Pre-excitation syndromes including Wolff Parkinson White and LGL
   2. Nodal blocking agents are contraindicated (may worsen arrhythmia)
   3. Type IA or III agents may be effective but side effects usually problematic
   4. Electrophysiology study (EPS) with bypass tract ablation is preferred therapy [14,18,21]
4. Multifocal Atrial Tachycardia (MAT)
   1. Irregularly irregular rhythm with 3 or more distinct P waves on ECG
   2. Majority of patients have pulmonary disease and hypoxia
   3. Use of theophylline, high dose ß2-agonists, and other stimulants increases risk of MAT
   4. Rate difficult to control, particularly if hypoxia is not treated
   5. In general, treatment of underlying condition leads to resolution
   6. Intravenous verapamil or diltiazem (± diltiazem iv drip) may be used
   7. ß-blockers may be effective but many patients will develop bronchospasm
   8. RF catheter ablation generally not indicated for curative therapy
   9. However, RF induced AV node ablation with pacemaker may palliate symptoms [14]

C. Radiofrequency Ablation [14,22]

1. EPS detect specific abnormal conduction tracts
2. Radiofrequency (RF) waves are used to induce tissue destruction
3. RF waves at tip of catheter induce tissue necrosis with thermal injury
4. Accessory tracts, part of the AV node, or other areas are selectively ablated
5. Mild scarring occurs, but these techniques tend to be very successful
6. Additional drug therapy may be needed in certain conditions
7. However, techniques are often curative for SVT, WPW and other arrhythmias (as above)
8. Complications
   1. Death ~0.08%
   2. Cardiac Tamponade 0.5%
   3. Unintended AV Block 0.5%
   4. Coronary artery spasm 0.2%
   5. Mild mitral regurgitation 0.2%
   6. Femoral artery complications (hematoma, thrombosis, fistula) ~0.5%
9. Although this is an expensive proceedure, it is cost effective [33]

D. Ventricular Arrhythmia Overview [1,2]

1. Classification
   1. Premature ventricular contractions (PVC) - asymptomatic and symptomatic
   2. Ventricular Tachycardia (VT) - monofocal and polyfocal
   3. Torsades des Pointes (TDP) - specific type of polyfocal VT
   4. Ventricular Fibrillation
   5. Accellerated Idioventricular Rhythm (AIVR) - usually associated with reperfusion
   6. Agonal Rhythm - usually after severe cardiac insult; extremely poor prognosis
2. Diagnosis of Arrhythmias
   1. Cardiac rhythm recording post-MI, CABG, syncope, is critical
   2. Holter Monitoring -may be most efficient and sensitive
   3. ECG Signal Averaging - as good as EPS in many patients
   4. Electrophysiological Study (EPS) - most specific test to date (some lack of sensitivity)
3. Signal Averaged ECG
   1. Close examination of early repolarization (early ST segment)
   2. Abnormal repolarization suggests tissue with anomalous conduction after depolarization
   3. Such tissue may initiate ventricular arrhythmias by triggered activity
   4. Signal averaged ECG is more sensitive with inferior than anterior foci of arrhythmia
   5. Abnormal signal average should promt an EPS
4. Peri- or Post-MI Arrhythmias
   1. Ventricular Tachycardias - multifocal vs. unifocal
   2. Ventricular Fibrillation - primary (within 48 hrs, no Cardiogenic shock) vs. secondary VF
5. Therapy [11,12]
   1. Most commonly used oral agents are quinidine (Ia), sotalol, amiodarone
   2. Quinidine - increased risk of death compared with other Class I drugs in Ventricular arrhythmia treatment
   3. Class III anti-arrhythmics (mainly amiodarone) are now the agents of choice [22,25]
   4. Routine use of dofetilide after MI in severe LV dysfunction provides no overall benefit [35]
   5. Class Ic (Flecainide, Encainide and Moricizine) are not used due to the CAST results
   6. Radiofrequency catheter ablation in monofocal VTs are often therapy of choice [21]
   7. In post-resuscitation cardiac arrest patients, hypothermia to 32-34°C for 12-24 hours improves mortality and neurologic recovery [39,40]
6. Ischemia Associated VT/VF (see below)
   1. Ultimately, best treated with revascularization (CABG or PTCA) whenever possible
   2. EPS guided therapy is generally indicated [30]
   3. Implantable Cardioverter Defibrillator (ICD) with pacing very effective [15,24,30]
   4. ICD strongly recommended over antiarrhythmic agents in CAD patients [30,34]
   5. ICD should be considered in post-MI patients with LV ejection fraction <30% [9]
   6. Amiodarone or sotalol may be used in patients who are not surgical candidates
   7. In patients with VTach, ICD and amiodarone had similar efficacy [32]
   8. ß-adrenergic blockers should be used in all patients without absolute contradications
   9. Strongly consider ACE inhibitors as well in patients with ischemic heart disease

E. Premature Ventricular Contractions (PVC)

1. Common finding in healthy, older population
   1. Asymptomatic - treatment is completely optional
   2. Symptomatic - consider ß-blocker first line
2. Concerning in setting of other evidence for ischemia
   1. Risk factor for malignant arrhythmias
   2. Post-MI - poor prognostic marker (generally should be evaluated with EPS)
3. Treatment of Benign (non-ischemic) PVCs
   1. Syptomatic benefit only (no mortality reduction)
   2. Acebutolol (Sectral®) - ß1-specific blocking agent with excellent PVC control
   3. Also safe in post-MI patients
   4. Initiate dose 200mg po bid; Optimal Control 600-1200mg qd (<800mg qd in elderly)
   5. Other ß-Blocking Agents (prefer ß1 selective agents)

F. Malignant Ventricular Arrhythmias

1. Stepwise Treatment following Defibrillation if indicated
2. Ischemia and Cardiac Arrest Settings [36]
   1. Amiodarone (intravenous)
   2. Lidocaine (1mg/kg iv only)
   3. Bretylium is no longer available
3. Overview [26]
   [Figure] "Ventricular Arrhythmia Treatment"
   1. Following successful resuscitation due to arrest from malignant arrhythmia
   2. Many patients will have ischemia based arrhythmia and this must be investigated
   3. Coronary angiography and/or EPS should be considered
   4. Revascularization is critical to improved long term outcomes
   5. Implantable Cardioverter-Defibrillators (ICD) are now the treatment of choice
   6. When drugs are used, they may be added to ICD or used alone
   7. However, ICD are clearly first line with demonstrated mortality benefits
4. Overview of Pharmacologic Agents [26]
   1. Type III Agents including amiodarone are now the preferred drugs in many patients [25]
   2. Type Ic agents increase mortality and should generally not be used [12]
   3. Type Ia anti-arrhythmic agents were the original agents of choice
   4. They are falling out of favor due to significant pro-arrhythmic effects
   5. Monomorphic foci should be ablated with radiofrequencies whenever possible [21,26]
   6. RF catheter is also being investigated for polymorphic VTach
   7. Type I anti-arrhythmics and combinations have also been used (but not recommended)
5. Amiodarone [4,5,7,16]
   1. Ventricular arrhythmias are rapidly suppressed with oral amiodarone within 72 hours
   2. Suppression was less dramatic after 72 hours
   3. Dose was 1200mg x 14 d then 400mg qd
   4. Suppression effective 1 year post-MI using low dose (200mg / day) in newer studies
   5. Also reduced mortality with minimal side effects
   6. The intravenous formulation is now available and effective in malignant VT [20,25]
   7. Appears to prolong life by 4-5 years in patients with malignant arrhythmias [24]
   8. ICD cost more, but prolong life by 20-30% compared with amiodarone [24,27]
   9. May be useful in patients with non-ischemic cardiomyopathy and arrhythmias [19]
   10. Does not have significant anti-inotropic effects (despite ß-blocking activity)
   11. Moderate toxicity, but low risk of proarhythmic effects, especially low for torsades
   12. Interacts with digoxin to raise digoxin levels, blocks warfarin metabolism
   13. Amiodarone (400mg / day, high dose) may be preferred with frequent events
   14. Amiodarone may be combined with ICD in very high risk patients
6. Sotalol (Sotacor®, Betapace®)
   1. Non-specific potent ß-blocker activity
   2. Prolongs action potential by inhibiting delayed rectifier fast potassium current
   3. Prolongs the QT interval in very dose-dependent fashion
   4. Improved symptoms as well as mortality in patients with ventricular arrhythmias
   5. Effective adjunctive therapy in patients with ICD (see above) [29]
   6. Begin at 80mg po bid; follow QTc
   7. May increase to 160mg po bid maximal
7. For idiopathic monofocal VT, RF-ablation is preferred therapy [14]
8. Treatment of TDP
   1. Magnesium - 2-4gm iv bolus
   2. Lidocaine - 1mg/kg iv bolus
   3. Isoproterenol - increases heart rate, acts as overdrive
   4. Phentolamine
   5. Overdrive Pacemaker - this is method of choice in magnesium refractory cases
   6. Consider calcium bolus - 1-2 amps iv (decreases QTc)

G. Implantable Cardioverter Defibrillators (ICD) [10,15,26,27,37]

1. Indications for ICD Placement [13,17,26,37]
   1. Cardiac arrest due to VF or VTach, not due to transient or reversible causes
   2. Spontaenous sustained VTach
   3. Syncope of undetermined origin with clinically relevant VTach or VF on EPS
   4. Nonsustained VTach with coronary artery disease, severe LV dysfunction
   5. Nonsustained VTach with EPS inducible VF or sustained VTach not suppressed by drug
   6. Patients with CAD and ventricular arrhythmias, guided by EPS [30]
   7. Patients with familial hypertrophic cardiomyopathy [31]
2. ICD has two components
   1. Pulse generator - delivers 25-42J
   2. Leads
3. Four Essential Functions
   1. Arrhythmia detection
   2. Arrhythmia treatment
   3. Bradycardia pacing
   4. Episode-data storage
4. ICD Placement
   1. Placed without thoracotomy using endovascular insertion
   2. Intraoperative mortality is <1%, and complication rates are <2%
5. ICD Termination of Ventricular Arrhythmias
   1. Antitachycardia (overdrive) pacing
   2. Cardioversion (synchronized shock)
   3. Defibrillation (non-synchronized shocks)
   4. VTach is typically treated first by overdrive pacing, then by cardioversion
   5. About 10J is typically needed for successful defibrillation
6. Efficacy [15]
   1. ICD has been shown to reduce mortality in patients at high risk for VTach or VF
   2. ICD is more effective (but more costly) than amiodarone [2,27]
   3. ICD is cost-effective, with annualized costs per life year saved <$37,000 [27]
   4. ICD is reduces mortality better than anti-arrhythmic drugs in inducible VTach or VF [30]
7. ICD + Amiodarone
   1. Sotalol reduces inappropriate and appropriate shocks due to ICD [29]
   2. Sotalol also reduced risk of death in patients with ICD with reduced LV fraction [29]
8. Next generation ICDs for AFib and other SVTs are now in clinical trials [37]

H. Automated External Defibrillators (AED) [10,38]

1. AEDs are increasingly being used in public places (airplanes, casinos)
2. Recognition that <5% of the 250,000 out-of-hospital cardiac arrest victims survive
3. Newer units deliver biphasic wave forms
   1. Provide equal success at lower energy levels
   2. Older monophasic shocks delivered at 200, 300, then 360 Joules
   3. Biphasic waveforms use 150 Joules
4. Units typically allow electrocardiographic monitoring and analysis
5. Modest training required for skilled use

I. Treatment of Symptomatic Bradyarrhythmias

1. Atropine 0.5-2mg iv push (denervated hearts will not respond to atropine)
2. Transcutaneous Pacing (Zoll); Transvenous pacing if possible
3. Dopamine - 5-20µg/kg/min
4. Epinephrine 2-5µg/min
5. Glucagon - give iv if related to ß-blocker or calcium channel-blocker overdose
6. Isoproterenol is no longer recommended

Resources

QT Corrected

References

1. Roden DM. 1994. NEJM. 331(12):785
2. Manolis AS, Wang PJ, Estes NAM, et al. 1994. Ann Int Med. 121(6):452
3. Williamson BD, Man C, Daoud E, et al. 1994. NEJM. 331(14):910
4. Zimetbaum P. 2007. NEJM. 356(9):935
5. Julian DG, Camm AJ, Frangin G, et al. 1997. Lancet. 349:667
6. Hohnloser SH, Ikeda T, Bloomfeld DM, et al. 2003. Lancet. 362(9378):125
7. Siddoway LA. 2003. Am Fam Phys. 68(11):2189
8. Treatment of Atrial Fibrillation. 1993. Med Let. 35(893):28
9. Moss AJ, Zareba W, Hall WJ, et al. 2002. NEJM. 346(12):877
10. Kusumoto FM and Goldschlager N. 2002. JAMA. 287(14):1848
11. Cardiac Arrhythmia Suppression Trial Investigators. 1989. NEJM. 321:406
12. Cardiac Arrhythmia Suppression Trial 1. 1992. NEJM. 327:227
13. Implantable Cardioverter Defibrillator. 2002. Med Let. 44(1144):99
14. Morady F. 1999. NEJM. 340(7):534
15. Ezekowitz JA, Armstrong PW, McAlister FA. 2003. Ann Intern Med. 138(6):445
16. Hohnloser SH, Klingenheben T, Singh BH. 1994. Ann Intern Med. 121(7):529
17. Gregoratos G, Cheitlin MD, Conill A, et al. 1998. J Am Coll Cardiol. 31:1175
18. Ganz LI and Friedman PL. 1995. NEJM. 332(3):162
19. Singh SN, Fletcher RD, Fisher SG, et al. 1995. NEJM. 333(2):77
20. Amiodarone (Intravenous). 1995. Med Let. 37(963):114
21. Radiofrequency Ablation. 1996. Med Let. 38(973):40
22. Treatment of Arrythmias. 1996. Med Let. 38(982):75
23. Gilligan DM, Ellenbogen KA, Epstein AE. 1996. Am J Med. 101(4):413
24. Owens DK, Sanders GD, Harris RA, et al. 1997. Ann Intern Med. 126(1):1
25. Desai AD, Chun S, Sung RJ. 1997. Ann Intern Med. 127(4):294
26. Cannom DS and Prystowsky EN. 1999. JAMA. 281(2):172
27. Pinski SL and Fahy GJ. 1999. Am J Med. 106(4):446
28. Oral H, Souza JJ, Michaud GF, et al. 1999. NEJM. 340(24):1849
29. Pacifico A, Hohnloser SH, Williams JH, et al. 1999. NEJM. 340(24):1855
30. Buxton AE, Lee KL, Fisher JD, et al. 1999. NEJM. 341(25):1882
31. Maron BJ, Shen WK, Link MS, et al. 2000. NEJM. 342(6):365
32. Connolly SJ, Gent M, Roberts RS, et al. 2000. Circulation. 101:1297
33. Cheg CHF, Sanders GD, Hlatky MA, et al. 2000. Ann Intern Med. 133(11):864
34. Josephson ME, Callans DJ, Buxton AE. 2000. Ann Intern Med. 133(11):901
35. Keber L, Homsen PEB, Meller M, et al. 2000. Lancet. 356(9247):2052
36. Kern KB, Halperin HR, Field J. 2001. JAMA. 285(10):1267
37. Glikson M and Freidman PA. 2001. Lancet. 357(9262):1107
38. Takata TS, Page RL, Joglar JA. 2001. Ann Intern Med. 135(11):991
39. Hypothermia After Cardiac Arrest Study Group. 2002. NEJM. 346(8):549
40. Bernard SA, Gray TW, Buist MD, et al. 2002. NEJM. 346(8):557