Dofetilide

A 76-year-old retired, decorated police officer consulted his family physician because of palpitations 1 day in duration. He had been feeling well and physically active doing household chores and yard work: he was not taking any medications. Although uncomfortable because of the palpitations; he was not dyspneic and had no chest pains. On physical examination, his blood pressure was 130/75 mm Hg in the right arm, and the lungs were clear on auscultation. The point of maximal cardiac impulse was in the 5th intercostal space at the midclavicular line. The ventricular rate was 98 beats/rain and very irregular. An electrocardiogram (ECG) confirmed the physician's impression of a diagnosis of atrial fibrillation (AF). There were no acute repolarization changes (ST-T) and no abnormal Q waves. The jugular venous pulses were not elevated and there was no hepato-jugular reflux, thus eliminating the possibility of congestive heart failure. The patient was reassured that the arrhythmia could be managed and he would be able to return to full activity.

QUESTIONS

1. The treatment of AF has included which of the following?

a. measures to control the heart rate

b. measures to restore sinus rhythm

c. anticoagulation to prevent thromboembolism

d. the "MAZE procedure"

e. ablation of atrial foci at the insertion of the pulmonary veins

f. any of the above in addition to "c."

2. Historically the aim in managing AF was which of the following?

a. rate control

b. rhythm control

c. anticoagulation

3. Rate control therapeutic measures in AF include which of the following?

a. drugs that block atrioventricular (AV) nodal transmission

b. ablation of the AV node

c. pacemaker implantation

d. anticoagulation

e. all of the above

ANSWERS

1. f. any of the above in addition to "c."

Atrial fibrillation is a chaotic atrial rhythm with an atrial rate so fast (350-600 discharges/min) that it makes it difficult to discern P waves on an ECG (Figure 1). Many atrial impulses encounter refractory tissue at the AV node, and as a result only some of the depolarizations are conducted to the ventricle in a very irregular rhythm. Atrial fibrillation, the most common sustained arrhythmia is found in 0.5% of the general population, affects over 2 million patients in the United States, and is more prevalent in males? (1,2) The incidence of AF is approximately 1% in patients under 60 years of age and over 8% in those more than 80 years of age. (3) Seventy percent of patients with AF are 65 to 80 years of age. The increased prevalence of AF in the elderly may be the result of the longer life span currently experienced in patients with chronic diseases. AF is associated with cardiac diseases (eg, hypertensive heart disease, rheumatic mitral stenosis, coronary artery disease, congestive heart failure) and noncardiac diseases (eg, hyperthyroidism, hypoxic pulmonary lesions, surgery, alcohol intoxication, sleep apnea, and obesity). There is a 5-fold increased risk of stroke and a 2-fold increase in mortality in patients with AF, even after adjustments are made for preexisting cardiovascular diseases. (2,4) Lone AF is a diagnosis in patients less than 60 years of age who have no evidence of other cardiovascular diseases, hypertension, or diabetes. Echocardiography can confirm the lack of structural heart disease. In lone AE the risk of stroke is low and anticoagulation for stroke prevention is considered unnecessary; nevertheless, low-dose aspirin is still used because epidemiologically aspirin lessens the risk of stroke and acute myocardial infarction (MI) in patients with lone AF. The incidence of stroke in patients with lone AF is low; nevertheless, the occurrence of a cerebral vascular accident can be devastating. (5)

[FIGURE 1 OMITTED]

The treatment of AF has gone through many changes in the past 30 years. These have varied from therapy aimed at rate control to treatment controlling rhythm; however, anticoagulation was never an option. In the "MAZE procedure," multiple surgical incisions are made in the left and right atria to create barriers to stop atrial propagation of reentrant waves. (6) The result is a more directed atrial impulse. Recently catheter ablation of rapid atrial foci localized near the insertion of the pulmonary veins has been effective at suppression of AE Successful catheter ablation of the AV node causing AV block requires implantation of a permanent pacemaker to ensure an adequate ventricular rate. Recent reports in the Atrial Fibrillation Follow-up Investigation of Rhythm Management Trial (AFFIRM) revealed that stable patients with AF had similar survival rates and had no difference in quality of life whether on rhythm or rate control therapy. (7) Other trials report that hospitalization rates and costs are lower with rate control rather than with rhythm control. Important to note is that AF occurring postoperatively or following an acute MI can often be rapidly converted to sinus rhythm with [beta]-blocker therapy. Early use of [beta]-blockers at the onset of an acute MI and prior to extensive surgery in populations that have an increased potential for AF developing will often prevent the occurrence of AF (L.L., personal observation). Short-term daily use of low-molecular-weight heparin and aspirin is relatively safe in cases of postoperative AF, which is usually transient following surgery.

2. b. rhythm control

c. anticoagulation

Pharmacological conversion therapy aimed at rhythm control (reestablishing sinus rhythm) has been achieved with any of the following agents: ibutilide, flecainide, dofetilide, propafenone, or amiodarone; moderate efficacy has been observed with quinidine therapy. The chief drawbacks in antiarrhythmic drug therapy are the adverse reactions to these drugs and the potential hazards of torsades de pointes that can occur in the presence of a prolonged QT interval. Torsades de pointes translates to "twisting of the points" and is a polymorphic ventricular tachycardia presenting as varying amplitudes of the QRS as if the complexes are "twisting" about the baseline. The dangers of torsades de pointes are syncope and ventricular fibrillation (Figure 2).

[FIGURE 2 OMITTED]

Maintenance of normal sinus rhythm after electrical or pharmacological conversion from AF is difficult: recurrence rates are high, 75% in untreated and 50% in treated patients. (8) Rates of recurrence are particularly high in those 65 years of age and older, the segment of the population with the highest incidence of AE Continued pharmacotherapy is often required to prevent recurrence of AE Initiation of antiarrhythmic therapy with agents such as amiodarone, sotalol, dofetilide, disopyramide, and propafenone carries risks of proarrhythmia and sudden cardiac death and usually requires hospitalization and close follow-up. The risks are even greater in those with structural heart disease. Anticoagulation therapy is routine in AF regardless of the treatment mode.

3. e. all of the above

Treatment of persistent AF aimed at rate control is clinically simple and less hazardous than therapy for rhythm control. Atenolol, metoprolol, diltiazem, and verapamil have been used with varying degrees of effectiveness in the control of the ventricular response rate in AE Rate control can be achieved with the combined use of digoxin, and a [beta]-blocker titrated to a targeted ventricular response rate appropriate at rest and during moderate exercise, for example, walking 30 yards at a brisk pace (L.L., personal observation). Age, the physical state, and the clinical state influence the optimal resting and exercise ventricular response rate in AE Rate control is appropriate when the ventricular response with moderate exertion is not excessive. As a general rule, with normal left ventricular function, a resting heart rate of 60 to 70 beats/min and rates of 80 to 90 beats/min with moderate exertion are appropriate.

AV nodal blockade may often lead to secondary bradycardia and subsequent pacemaker implantation for rate support. Hemodynamically significant breakthrough rapid ventricular rates, or the occurrence of disabling symptoms despite adequate AV nodal blocking agents, may require AV node ablation. Following AV node ablation, implantation of a permanent pacemaker (rate responsive VVI or DDD) is required to provide physiological rate support. As with any therapeutic regimen in AF, anticoagulation is standard therapy.

Summary

AF is the most commonly sustained clinical arrhythmia, with an incidence that increases 2-fold with every decade after 55 years of age. There is an estimated prevalence of about 2 million Americans with AE AF is the most frequent principal diagnosis of cardiac arrhythmias, responsible for approximately 265 000 hospital admissions annually. (7) These statistics make managing AF a major issue. The therapeutic goal in the past was to restore and maintain sinus rhythm. Cardioversion was successful and often used; however, maintaining sinus rhythm following conversion required the use of antiarrhythmic drugs that were potentially proarrhythmic. The AFFIRM trial proved that rhythm control of AF has no mortality benefits over rate control therapy. (7) In fact, in elderly patients, rhythm control was associated with a higher mortality than rate control. (9) The quality of life substudy of the AFFIRM trial revealed no differences in the quality of life between the rate- and rhythm-controlled patients.

Current therapy recommends that patients with AF can be successfully managed and will experience an equal quality of life when treated to control the heart rate or to maintain a sinus rhythm following conversion of AF. However, rate control especially in the elderly is preferable.

ACKNOWLEDGMENT

Supported in part by a grant from the Applebaum Foundation in loving memory of Joseph Applebaum.

Request for reprints: Louis Lemberg, MD, University of Miami School of Medicine, Division of Cardiology, (D-39), P.O. Box 016960, Miami, FL 33101.

REFERENCES

(1.) Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation. Am J Coll Cardiol. 2003:41:1690-1696.

(2.) de Denus S, Sanoski CA, Carlsson J, et al. Rate vs rhythm control in patients with atrial fibrillation. Arch Intern Med. 2005;165:258-262.

(3.) Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med. 2003;139:1009-1017.

(4.) Wasmund Sl, Li JM, Page RL, et al. Effect of atrial fibrillation and an irregular ventricular response on sympathetic nerve activity in human subjects. Circulation. 2003; 107:2011-2015.

(5.) Engel TR, Topalian SK. The pathology of lone atrial fibrillation. Chest. 2005; 127:424-425.

(6.) Futterman LG, Lemberg L. An alternative to pharmacologic management of atrial fibrillation: the MAZE procedure. Am J Crit Care. 1994;3:238-242.

(7.) The AFFIRM Investigators. Quality of life in atrial fibrillation: The atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study. Am Heart J. 2005;149:112-120.

(8.) Saxonhouse SJ, Curtis AB. Risks and benefits of rate control versus maintenance of sinus rhythm. Am J Cardiol. 2003;91(6A):27D-32D.

(9.) Vidaillet HJ. Rate control vs. rhythm control in the management of atrial fibrillation in elderly patients. Am J Geriatr Cardiol. 2005; 14:73-78.

SELECTED REFERENCES

Conti CR. Stroke and atrial fibrillation: to anticoagulate or not. Clin Cardiol. 1993;16:29-30.

Gronefeld GC, Lilienthal J, Kuck KH, et al. Impact of rate versus rhythm control on quality of life in patients with persistent atrial fibrillation. Eur Heart J. 2003;24:1430-1436.

Hagens VE, Ranchor AV, Van Sonderen E, et al. Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. J Am Coll Cardiol. 2004;43:241-247.

Marshall DA, Levy AR, Vidaillet H, et al. Cost-effectiveness of rhythm versus rate control in atrial fibrillation. Ann Intern Med. 2004;141:653-66l.

Newman D. Atrial fibrillation and quality of life: Clarity or evidence-based confusion? Am Heart J. 2005; 149:4-6.

Opolski G, Torbicki A, Kosior D, et al. Rhythm control versus rate control in patients with persistent atrial fibrillation: results of the HOT CAFE Polish Study. Kardiol Pol. July 2003;59:1-16.

Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med. 2005;352:1861-1872.

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347:1825-1833.

Wyse DG. Rhythm versus rate control trials in atrial fibrillation. J Cardiovasc Electrophysiol. 2003;14:S35-S39.

VanGelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002:347:1834-1840.

By Laurie G. Futterman, ARNP, MSN, CCRN, and Louis Lemberg, MD. From the Division of Cardiology, Department of Medicine, University of Miami School of Medicine, Miami, Fla.

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