A. Control of Heart Rate

1. Heart rate controlled by inputs to the sinoatrial (SA) node
   1. SA node consists of specialized cells found in sulcus terminalus
   2. Sulcus terminalis is found at junction of superior vena cava and right atrium
2. Blood supply to SA node
   1. In 65% of people, SA node artery originates from proximal right coronary artery (RCA)
   2. In 25% of people, SA node artery originates from circumflex artery
   3. In the remaining 10% of people, both circumflex and RCA supply SA node
3. SA node depolarizes spontaneously (pacemaker cell)
   1. Normally, these impulses propagate from SA node through the right atrium
   2. Impulses travel through right atrium to atrioventricular (AV) node
4. AV node is found in the low septal right atrium
   1. AV node receives blood supply from AV nodal artery
   2. AV nodal artery arises from proximal portion of posterior descending artery
   3. The posterior descending artery arises from the RCA in 80% of people
   4. The posterior descending artery arises from the circumflex in 10% of people
   5. Both the RCA and circumflex supply the posterior descending artery in the remainder
5. Impulses are conducted through the AV node to the bundle of His
   1. The bundle of His (pronounced "hiss") courses through the membranous septum
   2. After traversing the membranous septum, the His bundle separates into two divisions
   3. These two divisions are called the right and left bundle branches (RBB and LBB)
6. The SA and AV nodes are heavily innervated by autonomic neurons
   1. Parasympathetic tone decreases SA node automaticity and slows AV node conduction
   2. Sympathetic tone increases automaticity and speeds conduction
7. The heart rate is determined by balance between parasympethetic and sympathetic inputs
   1. Considerable variation in heart rate exists in normal persons, particularly at rest
   2. Normal resting daytime heart rates are 45-95 beats per minute (bpm)
   3. Nocturnal heart rates are an average of 24 beats slower than daytime
   4. Low degree heart block, junctional rhythms, skipped beats are common and normal at night

B. Symptoms of Bradycardia

1. Light-headedness, particularly on standing up
2. Frank syncope
3. Hypertension (compensatory) at rest
4. Organ ischemia - angina, myocardial infarction, stroke
5. Shortness of breath, particularly on exertion
6. Fatigue

C. Classification

1. Sinus Node Dysfunction
   1. Sinus Bradycardia
   2. Sick Sinus ("Tachy-Brady") Syndrome
   3. Sinus pauses or sinus arrest (>3 second pauses without atrial activity)
2. Heart Block (AV node dysfunction)
3. Other abnormal slow rhythms: Junctional, Escape

D. Sinus Bradycardia

1. Normal P waves with all QRS complexes
2. Rate <60 beats per minute (bpm)
3. Common in young and physically fit persons
4. Induced with SA nodal blockers
   1. ß-Blockade
   2. Calcium Blockers: verapamil and diltiazem (weak SA nodal blocker activity)
5. Abnormal SA node - sick sinus syndrome

E. Sinus Node Dysfunction (Sick Sinus Syndrome) [1]

1. Failure of SA node to fire properly
2. Occurs in ~1 in 600 persons >65 years old
3. Accounts for ~50% of pacemakers placed in USA
4. Can cause bradycardia or tachycardia
5. Often as a mixed tachycardia-bradycardia (tachy-brady syndrome)
6. Pacemaker [6]
   1. Treatment of choice
   2. Both ventricular and atrioventricular (dual-chamber) pacemakers have been used
   3. No difference in risk of death or nonfatal stroke between two pacemaker types
   4. Atrial fibrillation risk is slightly higher with ventricular pacing
   5. Dual chamber pacing provides slightly improved quality of life over ventricular only

F. Heart Block (HB)

1. First Degree (primary, 1°) HB = PR prolongation (>200ms)
2. Second Degree (2°) HB - Types 1 and 2
   1. Important to distinguish because type 1 is usually benign
   2. Type 2 is often indication for pacemaker
   3. In 2:1 heart block (2 PR per 1 QRS), cannot determine if Mobitz type 1 or 2 from ECG
   4. If other conduction system disease present (such as bundle branch), suspect type 2 block
3. Mobitz Type 1 Second Degree Heart Block
   1. Also called Wenckebach
   2. Progressive prolongation of PR interval with each beat until QRS is dropped
   3. Result is what appears to be "grouped beating" on ECG rhythm strip
   4. Conduction disease is in upper AV tract, called AH area
4. Mobitz Type 2, Second Degree Heart Block
   1. PR intervals constant
   2. Dropped QRS contractions
   3. Disease is in lower part of AV bundle (HV area)
5. Third Degree (3°) HB
   1. No relationship between P and QRS waves
   2. This is complete AV dissociation
   3. Atrium fires, no conduction through AV node, and ventricular escape occurs
   4. Indication for pacemaker insertion
   5. Isoarrhythmic AV Dissociation: same rate between PR and QRS (but dissociated)
   6. Dual and single chamber pacemakers showed same efficacy in high grade AV block in elderly persons (>70 years) [10]
6. Causes [7]
   1. Conduction system disease is underlying problem
   2. Myocardial Infarction - death of conduction system cells and/or high vagal tone
   3. Small Vessel Coronary Disease - slow infarction / ischemia or conduction tissue
   4. Coronary vasospasm
   5. Medications: digoxin, calcium blockers, ß-blockers, amiodarone, procainamide, type Ic anti-arrhythmics
   6. Infiltrative Diseases: amyloidosis, hemochromatosis, sarcoidosis, tumors
   7. Infection: rheumatic fever, toxoplasmosis, Chagas' disease, endocarditis, viral myocarditis, syphilis, Lyme Disease
   8. High Vagal Tone - especially medications, sensitive carotid sinus, inferior MI
   9. Autoimmune Disease - systemic lupus, scleroderma, rheumatoid arthritis, spondyloarthropathy [5]
   10. Arrhythmogenic right ventricular dysplasia (ARVD)
   11. Congenital Heart Block
   12. Epilepsy: Peri-ictal cardiac abnormalities, particularly asystole or severe bradycardia found in 4 of 20 patients with focal epilepsy (all received pacemakers) [9]
7. Congenital Heart Block [3]
   1. Associated with anti-Ro and/or anti-La Abs in ~60% of cases
   2. Majority of mothers are healthy without symptoms of autoimmune disease (~66%)
   3. Minority of mothers had systemic lupus, scleroderma, rheumatoid arthritis, Sjogren's Syndrome or other "undifferentiated" connective tissue disease
   4. ~25% of mothers with undifferentiated CTD progressed to defined disease (SLE) over eight year followup period
   5. Myocardial specific microchimerism with maternal cells in fetal hearts could provide a target for neonatal lupus congenital heart block [8]
8. Pacemaker implantation may be required for treatment

G. Other Rhythms

1. Junctional Escape
   1. AV nodal blockade - usually due to medications
   2. Digoxin, ß-blockers, calcium blockers (verapamil and diltiazem) are most common
   3. Rate usually <60, typically ~40 bpm
2. Ventricular Escape: ventricle begins to pace itself, rate usually 40-50 bpm
3. AIVR (accelerated idioventricular rhythm)
   1. Rate >50 bpm
   2. Ectopic (not escape) rhythm: initiated by nonstandard pacing cells, rate >40 bpm
   3. Typically follows reperfusion (often after thrombolytic therapy)
4. Pacemakers are often required for sinus pauses, syncope, tachy-brady syndrome

H. Evaluation

1. History and physical examination for contributing causes
2. Episodic bradycardia should prompt questions about associated events
3. Medications, including nutriceuticals, should be evaluated
4. Focus on endocrine function, particularly thyroid
5. Heart Monitoring
   1. Routine and frequent electrocardiograms (ECG)
   2. For frequent symptoms, continuous 24-48 hour loop monitoring
   3. For less frequent symptoms, event monitors and even internal devices available
6. Invasive electrophysiologic testing is rarely indicated for bradyarrhythmias

I. Emergent Treatment of Bradyarrhythmias

1. Atropine
   1. Cholinergic blocking activity
   2. Mainly for treatment of acute symptomatic bradycardia
   3. Rapid onset of action (minutes), duration 5-30 minutes (may have lasting effects)
   4. Dose is 0.25-1mg iv q5 minutes to maximum of 5 minutes
2. Epinephrine
   1. Mixed alpha and beta adrenergic activity, mainly ß- at low doses
   2. Used for asystole and for bradyarrhythmias if atropine fails
   3. Dose is 0.5-5mg (high dose) iv q 5 minutes
3. Dopamine
   1. Use in mid-dose range, ß-agonist activity predominates, inotropic and chronotropic
   2. Second line agent for symptomatic bradycardia
4. Transcutaneous (or transvenous) Pacing
   1. Preferred modality for symptomatic bradycardia
   2. However, transcutaneous (such as Zoll) is extremely uncomfortable
5. Aminophylline [4]
   1. Blockade of adenosine A1-receptors in nodal tissue
   2. Aminophylline 250mg IV push for adenosine mediated bradycardia and asystole
   3. Antidote for adenosine induced heart block
   4. No benefit in bradysystolic cardiac arrest [4]
6. Isoproterenol
   1. Pure ß-agonist with chronotropic > inotropic activity
   2. Dose is 2-10µg/min iv
   3. Considered third line therapy; generally not recommended
7. Intravenous Calcium
   1. Indicated for all calcium channel blocker overdoses with bradycardia
   2. May also be useful in hypotensive patients with poor responses to other agents
8. Permanent pacemakers are required for prolonged symptoms
9. Neurocardiogenic syncope may be treated with drugs

References

1. Mangrum JM and DiMarco JP. 2000. NEJM. 342(10):703
2. Kusumoto FM and Goldschlager N. 1996. NEJM. 334(2):89
3. Press J, Uziel Y, Laxer RM, et al. 1996. Am J Med. 100(3):328
4. Abu-Laban RB, McIntyre CM, Christenson JM, et al. 2006. Lancet. 367(9522):1577
5. Bergfeldt L. 1997. Ann Intern Med. 127(8):621
6. Lamas GA, Lee KL, Sweeney MO, et al. 2002. NEJM. 346(24):1854
7. Hajjar RJ and Kradin RL. 2002. NEJM. 346(22):1732 (Case Record)
8. Stevens AM, Hermes HM, Rutledge JC, et al. 2003. Lancet. 362(9396):1617
9. Rugg-Gunn FJ, Simister RJ, Squirrell M, et al. 2004. Lancet. 364(9152):2212
10. Toff WD, Camm AJ, Skehan JD. 2005. NEJM. 353(2):145