Atrial Arrhythmias in Congestive Heart Failure

More patients are surviving longer with congestive heart failure, making their propensity for various atrial arrhythmias an increasingly urgent clinical issue. The authors discuss rate control, rhythm control, anticoagulation, and long-term management for atrial arrhythmias in this population.

By Deepak Talreja, MD, Paul Friedman, MD, and Naser Ammash, MD

 
The accurate, timely diagnosis and management of cardiac arrhythmias in patients with congestive heart failure (CHF) has become increasingly important in the primary care and emergency department settings. Patients with CHF have a sixfold increase in the incidence of atrial arrhythmias due to the hemodynamic and electrophysiologic environment created by these disorders. In this population, atrial fibrillation (AF) leads to heart failure decompensation, thromboembolism, and increased mortality. Atrial tachycardia-induced cardiomyopathy has also been reported in the absence of structural heart disease or known left ventricular dysfunction. Onundarson and colleagues demonstrated that up to 36% of patients with chronic AF subsequently developed CHF compared with 2% of age-matched controls during 14 years of follow-up. With new therapies improving survival rates in patients with CHF, the coexistence of AF and CHF and their potential complications are of major clinical importance.

The increased propensity for atrial arrhythmias in patients with CHF results from structural heart disease secondary to congenital, valvular, or ischemic etiologies. These patients have underlying substrate that predisposes them to develop electrically irritable foci, functional or fixed conduction block, and consequently recurrent tachyarrhythmias. For example, atrial enlargement and hypertrophy predisposes to atrial arrhythmias by decreasing conduction velocity and myocardial refractoriness, while low cardiac output increases sympathetic tone, thereby accelerating the frequency and prolonging the duration of such arrhythmias.

The treatment of atrial arrhythmias in the presence of CHF can be challenging due to the negative inotropic and chronotropic effects of most antiarrhythmic medications. Furthermore, the risk of proarrhythmia is augmented by a history of CHF.

In this article, we will review state-of-the-art management of atrial arrhythmias in patients with CHF.
 

ATRIAL FIBRILLATION AND ATRIAL FLUTTER

Atrial fibrillation is the most common atrial arrhythmia in patients with CHF. Its incidence correlates well with the New York Heart Functional Class (see bar graph, below). Patients with CHF have a three- to fourfold greater risk of developing AF or atrial flutter (AFL) than the general population. Predisposing factors are similar for both fibrillation and flutter: increased left ventricular end-diastolic pressure, increased left atrial dimension and/or pressure, and significant mitral and/or tricuspid regurgitation (see table, below). When present in heart failure, AF is associated with increased mortality. Mechanisms that may result in poor tolerance of atrial tachyarrhythmias in CHF include loss of atrial contribution to ventricular filling, shortened diastole, and reduced cardiac output associated with irregular ventricular contraction. Shortened diastole may increase susceptibility to myocardial ischemia and systolic dysfunction. This, in turn, leads to elevated end-diastolic pressure and diastolic dysfunction. In addition, patients with AF demonstrate a decrease in the amount of oxygen they can utilize during dynamic exercise compared to patients in normal sinus rhythm. Furthermore, AF and AFL both predispose to thromboembolism.

Effective management of atrial arrhythmias in patients with CHF has three objectives: prevention of stroke, preservation of ventricular function, and control of the arrhythmia. Therapeutic recommendations for management of fibrillation and flutter can be divided into acute and chronic measures. In acute treatment, efforts are targeted at rate control, rhythm control, and stroke prevention with anticoagulation. The relative benefit of rate control versus rhythm control has yet to be determined. Preliminary studies suggest that rhythm control results in enhanced exercise tolerance, while rate control is associated with fewer medical encounters (since repeated cardioversion is not required). Quality of life has been similar with both strategies.

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ACHIEVING RATE CONTROL

Pharmacologic rate control can be achieved with atrioventricular-nodal blocking agents (see table, below). Because all of these agents have negative inotropic effects, they need to be used more cautiously in patients with CHF than in those with normal cardiac function, and the approach to acute and long-term rate control differs as to which agents are used. Of course, patients who have AF and a rapid ventricular response and who are unstable—for example, those with altered mental status, hypotension, angina, or pulmonary edema—are not candidates for rate control and require prompt electrical cardioversion.

The typical, stable, emergency department patient requiring acute rate control is one who presents with symptoms caused by the onset of a rapid ventricular response, either from previous AF or new-onset AF. Such symptoms might include dyspnea, fatigue, palpitations, and lightheadedness. In this setting, bolus intravenous (IV) administration of the calcium channel blocker diltiazem is useful. Boluses may be followed by a continuous infusion, if needed. In the event of hypotension, calcium gluconate may be given IV, which tends to reverse diltiazem's negative inotropic effects more than its chronotropic effects. If a beta blocker is to be used, esmolol is an excellent choice, though it does require continuous IV infusion. However, it can be easily titrated, and its short half-life makes it possible to promptly reverse hypotension, in most cases, by stopping the infusion. After acute rate control is achieved, either beta blockers or calcium channel blockers can be used for long-term rate control.

If a CHF patient presents to a physician's office or the emergency department with mild, tolerable symptoms due to AF with a rapid ventricular response, then beta blockers should be considered as the first line of therapy for rate control, since their long-term use improves survival in patients with CHF. Negative inotropy in these situations seems to be outweighed by the beneficial neurohormonal effects of beta blockers. Calcium channel blockers with atrioventricular nodal effects have also been used successfully. However, these agents do not confer the same neurohormonal advantage as beta blockers, and their negative inotropic effect may be detrimental in patients with left ventricular dysfunction. beta blockers used alone have been shown to be more effective as long-term treatment than calcium channel blockers in these patients.

Digoxin, which slows atrioventricular node conduction by increasing vagal tone, is often ineffective as monotherapy in this population because of heightened sympathetic tone at baseline. Also, when the heart rate does appear controlled at rest, exertion may alter the sympathovagal balance, resulting in poor rate control. However, since digoxin is one of the few agents to improve functional capacity without impairing survival in heart failure, it should be used liberally (in conjunction with beta blockers). A small study demonstrated better synergy between digoxin and beta blockers than the combination of digoxin and calcium channel blockers. Rate control is considered adequate with ventricular response rates of 60 to 80 beats per minute at rest and 90 to 115 beats per minute during moderate exercise.

Regardless of the specific agent chosen, several caveats must be kept in mind. First, rate control must be distinguished from rhythm control; although up to 50% of patients treated with rate-controlling agents may spontaneously convert to normal sinus rhythm, this effect is fortuitous rather than causal. Second, in patients with underlying Wolff-Parkinson-White syndrome, atrioventricular-nodal blocking agents may induce dangerously rapid ventricular rates by preferentially favoring conduction over the accessory pathway. Thus, electrical impulses of AF may be conducted without even the minimal refractoriness seen with the atrioventricular node.

The presence of an accessory pathway should be suspected in patients with a rapid, irregularly-irregular, sustained, wide-complex tachycardia and in patients with AF and ventricular response rates greater than 200 beats per minute. In this setting, prompt restoration of normal sinus rhythm is mandatory. Traditionally, procainamide or direct current cardioversion (DCCV) has been used. Recent data suggest that ibutilide may also be used safely to convert patients with atrial fibrillation and Wolff-Parkinson-White syndrome to normal sinus rhythm.
 

RESTORING RHYTHM CONTROL

Restoration of normal sinus rhythm, using antiarrhythmic medications (see table, below) or DCCV, may improve functional capacity, increase oxygen consumption, alleviate symptoms, and possibly eliminate the need for long-term anticoagulation. The success rate of DCCV in our practice is better than 90%, which is comparable to the success rate of this procedure in general. Chemical cardioversion with antiarrhythmic medications has a lower efficacy rate. The success rate of both techniques is inversely proportional to the duration of the atrial arrhythmia.

Ibutilide is one antiarrhythmic agent commonly used for acute cardioversion in patients with AF or AFL without heart failure. This drug is a class III antiarrhythmic that lengthens the action potential by antagonizing the delayed rectifier potassium channel and increasing the inward sodium current. Up to 4% of patients with normal left ventricular function who take ibutilide may develop torsades de pointes, a complication that is more common in patients with left ventricular dysfunction. Therefore, this agent is avoided in patients with CHF or a known ejection fraction of less than 30%.

Dofetilide, another class III antiarrhythmic agent, was recently approved for the restoration and maintenance of sinus rhythm in patients with heart failure. This agent selectively inhibits the rapid component of the delayed rectifier potassium current and prolongs the refractory period. Hospitalization is mandated by federal regulation for initiation of therapy with dofetilide because careful QT monitoring is necessary. Dosage is calculated based on renal function. Also, many common medications may interact with dofetilide. However, the drug has been shown to be safe when properly used in high-risk patients with CHF or recent myocardial infarction.

In the DIAMOND study, patients with left ventricular dysfunction were successfully cardioverted with dofetilide in up to 59% of cases. Furthermore, 79% of these patients remained in sinus rhythm after one year. Amiodarone, another class III antiarrhythmic, can also be used for acute cardioversion. However, its slow onset limits its utility for acute pharmacologic cardioversion.

While class I agents are widely used in patients with normal ventricular function, these agents should generally be avoided in heart failure. Flecainide and propafenone should be avoided in patients with structural or ischemic heart disease or CHF because of the potential increased risk of proarrhythmia and death. Adenosine rarely converts AF or AFL to normal sinus rhythm, but by transiently slowing atrioventricular conduction so that flutter waves can be visualized, it can be useful in making the diagnosis.

Synchronized DCCV is very successful in restoring sinus rhythm and is the method of choice for unstable patients presenting with AF, including those with chest pain, hypotension, or pulmonary edema. Patients undergoing DCCV are typically treated with either a monophasic protocol in which sequential shocks of 100, 200, 300, and finally 360 Joules are delivered or a biphasic protocol with sequential shocks of 70, 120, 150, and finally 170 Joules. Increased efficacy of biphasic waveforms has been reported by Mittal and colleagues. Direct current cardioversion is further enhanced by pretreatment with ibutilide. However, this agent is generally avoided in heart failure.

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ANTICOAGULATION STRATEGIES

Atrial fibrillation or flutter of more than 48 hours' duration is associated with an increased risk of thrombus formation and thromboembolic events. The incidence of atrial thrombus in AFL, as demonstrated on echocardiography, is reported to be as high as 11%. Therefore, anticoagulation should be considered in all patients with AF or AFL of more then 48 hours' duration.

If the patient is hemodynamically stable and the duration of the AF or AFL is unknown or greater than 48 hours, anticoagulation can be started using warfarin, with a goal of achieving a therapeutic INR of 2 to 3, which should then be maintained for three to four weeks prior to an attempt to restore sinus rhythm. Patients in AF or AFL who are already known to have atrial thrombus, who are experiencing embolic symptoms, or who are otherwise at high risk for embolism should be considered for immediate anticoagulation with heparin during the time interval it takes for warfarin to become therapeutic.

Because of the increased risk of atrial mechanical dysfunction (also known as stunning), anticoagulation should be continued for at least four weeks after sinus rhythm has been restored. In the unstable patient, or if immediate restoration of sinus rhythm is desired or preferred, then transesophageal cardioversion guided by echocardiography is a safe alternative. The transesophageal echocardiogram excludes atrial thrombus; intravenous heparin should be started at the time of cardioversion if the patient's INR is not above 2. Then DCCV can be performed safely and anticoagulation continued for at least four weeks after restoration of sinus rhythm.

Chronic anticoagulation beyond four weeks is recommended in patients older than 65 with a history of left ventricular dysfunction or CHF. Other indications for chronic anticoagulation include a history of hypertension, rheumatic mitral valve disease, thromboembolic event, cyanotic congenital heart disease, and hypertrophic obstructive cardiomyopathy.
 

LONG-TERM MANAGEMENT

Patients with heart failure or depressed ventricular function who have AF or AFL have a higher mortality than patients with these conditions whose heart rates are in normal sinus rhythm. However, there is little evidence that restoration of sinus rhythm in patients with AF or AFL and ventricular dysfunction improves their survival. In one study, maintenance of sinus rhythm in patients who did not have heart failure or left ventricular dysfunction led to modest improvements in exercise tolerance but did not affect quality of life. The AFFIRM trial (Atrial Fibrillation Follow-up Investigation of Rhythm Management) has completed enrollment and may address this question.

Many antiarrhythmic agents (class IA, IC, and sotalol) have a failure rate of 50% by one year after successful DCCV and tend to increase mortality, especially in patients with ischemic cardiomyopathy and CHF. The only acceptable pharmacologic agents for maintaining sinus rhythm in heart failure patients are amiodarone and dofetilide. Amiodarone, a class III medication, has been used safely for long-term management of atrial arrhythmias in patients with left ventricular dysfunction. However, because of the side effects associated with this drug, the smallest effective dose should be used. Follow-up examinations must be performed, including a routine clinical history and physical examination with an electrocardiogram, basic serum chemistries, a chest x-ray every three to six months, liver function tests at baseline and every six months thereafter, an ophthalmologic examination at baseline and every six months thereafter, and thyroid function tests at baseline and every three months thereafter. Side effects might necessitate discontinuation of amiodarone in up to 20% of patients.

In patients with left ventricular dysfunction, amiodarone may actually reduce mortality and hospitalization rate and improve systolic function. Maintenance of normal sinus rhythm with amiodarone has been reported to be as high as 85% at one year. The use of dofetilide is not as widespread due to the requirement for individualized physician certification, the complexity of dosing, and interactions with commonly used medications.

Electrophysiologic radiofrequency catheter ablation techniques have been used in the treatment of atrial arrhythmias, including AFL, and they are now being used for AF as well. Typically, in AF, the flutter circuit follows the annulus of the tricuspid valve and is vulnerable to interruption with catheter ablation, in which the pathway of slow conduction located between the inferior vena cava and the tricuspid annulus is ablated. The initial success rate of this procedure is greater than 90%. However, 10% to 20% of patients will have a recurrence at one year; these patients can undergo a repeat procedure, which has a similar success rate.

For AF, the most common catheter-based technique is atrioventricular node ablation for ventricular rate control. This procedure does not modify atrial arrhythmias but rather results in complete heart block. Most patients have a slow ventricular escape rate following ablation; pacemaker implantation results in a physiologic ventricular rate. A ventricular-only-rate-responsive pacemaker is used in patients with chronic AF, whereas a dual-chamber mode-switching pacemaker is employed in patients with paroxysmal AF or sick sinus syndrome.

Nonpharmacologic options for maintaining sinus rhythm have also become available. Ablation of focal atrial tachycardias that initiate and maintain atrial fibrillation can eliminate arrhythmias in up to 70% of patients with paroxysmal (self-terminating) episodes of AF. Long-term follow-up is lacking, and most patients have had a near-normal ejection fraction, although patients with tachycardia-induced cardiomyopathy secondary to AF may be candidates for this procedure. The surgical Maze procedure entails making linear incisions in the atrial tissue to create scars that inhibit atrial reentry by forcing propagation of atrial wavefronts along the incisions. This procedure has a high success rate but requires a thoracotomy; it is best considered in patients who need concomitant heart surgery. Finally, atrial implantable defibrillators are a new therapeutic option, and for patients with an indication for defibrillator placement in addition to atrial tachyarrhythmias, atrial pacing and shock therapies result in a significant reduction in such arrhythmias.
 

MULTIFOCAL ATRIAL TACHYCARDIA

While AF and AFL are the most common atrial arrhythmias in patients with CHF, there are several other supraventricular arrhythmias that should be mentioned. Multifocal atrial tachycardia, for example, is another irregularly-irregular, narrow-complex tachycardia, especially common in patients with CHF or concurrent respiratory disease, that can easily be mistaken for AF. It can also result in an adverse hemodynamic profile. The hallmark of this arrhythmia is the presence on electrocardiography of premature atrial complexes with P waves having at least three distinct morphologies. Treatment should be focused on the predisposing condition (theophylline or digitalis overdose, hypomagnesemia, or hypokalemia). Calcium channel blockers, beta blockers, and amiodarone may also have some beneficial effects.

Paroxysmal supraventricular tachycardia is another narrow-complex tachycardia that involves the atrioventricular node or an accessory pathway as part of the arrhythmic circuit. The P wave can be seen either prior to the QRS, in which case it is often inverted, or hidden within the QRS complex or within the ST segment. Acute treatment in the presence of hemodynamic instability is best achieved by DCCV (25 to 50 Joules). Otherwise, vagal maneuvers can be effective. Adenosine can also be used to restore sinus rhythm; this treatment has a success rate as high as 90% in patients without an accessory pathway. Long-term control of this arrhythmia should be considered in patients with a history of CHF because of the risk of hemodynamic decompensation. Although beta blockers and amiodarone can be used safely in these patients, radiofrequency catheter ablation is now considered first-line therapy, with a success rate of 95%.
 

IMPORTANCE OF TREATMENT

Although more attention has been focused on the treatment of ventricular arrhythmias in CHF patients, the treatment of atrial arrhythmias is important for controlling symptoms, maintaining exercise tolerance, and possibly for enhancing long-term mortality. Atrial arrhythmias, especially AF, are more common in this patient population and are associated with increased morbidity and mortality. Management of such patients should include ACE inhibitors, beta blockers, digoxin, and diuretics; additionally, anticoagulation is required to prevent thromboembolic complications. Heart rate control is mandatory, and if a strategy of long-term maintenance of sinus rhythm is adopted, amiodarone or dofetilide is used. Nonpharmacologic options offer therapeutic alternatives for the refractory patient.

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