Uspješnost Liječenja Fibrilacije Atrija U Hitnoj Internstičko Ambulanti

Uspješnost Liječenja Fibrilacije Atrija U Hitnoj Internstičko Ambulanti

OUTCOME OF PHARMACOLOGICAL TREATMENT OF PATIENTS WITH ATRIAL FIBRILLATION IN THE EMERGENCY ROOM

Hrvoje Ivekovic, Vladimir Gasparovic

Division of Emergency and Intensive Care Medicine,

Clinical Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia

INTRODUCTION

Atrial fibrillation (AF) is a rhythm disorder in which there is an absence of coordinated atrial systole. Loss of coordinated atrial systole results in decreased augmentation of ventricular filling, commonly known as loss of atrial kick. On the electrocardiogram (ECG), loss of atrial synchrony is represented by absence of a P wave before each QRS complex. In place of P waves, fibrillation waves representing rapid atrial depolarisations are present. Because the atrioventricular (AV) node is unable to conduct all the impulses from the atria, a haphazard conduction results and the ventricular response is often irregular and rapid. (1,2) The combination of loss of atrial kick, rapid ventricular response, and irregular rate impairs ventricular filling and can result in a substantial reduction in cardiac output (3,4) and such symptoms as palpitations, dyspnoea, chest discomfort, light headedness, and fatigue. (5,6)

AF is the most common sustained arrhythmia, is responsible for more hospitalizations and longer lengths of stays than any other arrhythmia, (7) and, due to its recurrent nature, frequently requires repeated hospitalizations.The risk for developing AF increases with age; the disorder affects about 1% of the population as a whole, about 6% of those over age 60, and about 8% of those aged 80 and over. (8-10). Overall, AF patients have a 5-fold higher morbidity (11) and a 2-fold higher mortality rate than patients with normal sinus rhythm, and they are much more likely to require hospitalization. (12).

While the aetiology of AF cannot always be determined, it is often associated with other heart conditions and events that can cause enlargement of the atria, such as mitral valve disease, atherosclerotic ischemic heart disease, and recent heart bypass surgery.

According to the AHA/ESC Guidelines, (13) AF is classified into three major categories: paroxysmal, persistent, and permanent. Paroxysmal AF is identified as AF episodes that are self-terminating. Persistent AF occurs for varying time periods and requires an intervention to restore normal sinus rhythm (NSR). Permanent AF is refractory to efforts to restore NSR, or is the type that remains, with a decision to forego maintaining NSR. In today's environment, with multiple treatments available for AF, the pattern of AF is an important consideration in determining treatment.

Two pharmacological approaches are established in the treatment of AF: "rhythm control" - usage of antiarrhythmic agents, in order to restore and maintain normal sinus rhythm and "rate control" - usage of agents which prolong cardiac atrioventricular conduction, in order to alleviate clinical symptoms. (14)

OBJECTIVES AND METHODOLOGY

Given the unknown data on the outcome of treatment of AF in Croatia, we conducted a retrospective study aiming to establish epidemiological data of patients with AF, clinical significance of the disorder and outcome of the treatment of the patients with AF in the emergency room.

Discharge Letters of all patients admitted to the ER and subsequently diagnosed with AF over one-year period were reviewed (May 2001 - May 2002). Data on age, gender, symptoms duration, drugs administered and outcome of treatment were analysed.

In accordance with the AHA/ECS guidelines (13), patients with AF were classified in three categories: patients with paroxysmal AF (duration of episode of fibrillation less than 7 days), persistent AF (episodelonger than 7 days), and permanent AF.

In this study, the main outcome measure was set up as restoration of normal sinus rhythm or rate control achieved within 24 hours upon admintance.

RESULTS

In a one-year period, AF was registered in 242 patients (pts), which represented 4% of total medical emergency admissions (n=6142). There were a total of 44,6% male patients with AF ( n=108, mean age 64 years, range 24 -86 years) and 55,4% female patients with AF (n=132, mean age 69 years, range 39 - 94 years). The distribution of patients according to sex and age is shown in Picture 1.During the course of the study the data were unavailable for two patients with AF (0,8% of all patients with AF).

In patients with AF, 64 % (n=152) had paroxysmal AF, 12% (n=29) had persistent AF, and 24% (n=58) patients had permanent AF. The distribution of patients according to the type of AF is shown in Picture 2.

The aetiology of AF have been recognised as hypertrophic cardiomyopathy in 36% of patients (n=85), ischemic heart disease in 22% of patients (n=53), older age in 9% (n=22), dilated cardiomyopathy in 4% (n=9), hyperthyreosys in 4% (n=10), chronic obstructive lung disease in 3% (n=8), as well as valvular heart disease (n=7). Hypokalemia was found in 1% of patients (n=2). According to the available medical documentation the aetiologyhas not been established in 18% (n=43) of patients with AF. The distribution of patients according to the aetiology of AF is shown in Picture 3.

Generally, in all groups of patients, pharmacological conversion to NSR was achieved in 29% of patients (n=53), "rate control" in 22% (n= 69), and 49% (n=117) of patients with AF required prolonged hospitalization. The distribution of patients according to the outcome of the treatment of AF is shown in Picture 4.

Reason for prolonged hospitalization was acute heart failure in 37% of patients (n=42), dyspnoeain 15% (n=18), failure of pharmacological conversion in 32% (n=32), chest pain in 11% (n=13), disorders of consciousness in 7% (n=8) andcardiac rhythm in 3% (n=4). The distribution of patients according to the reason for hospitalization is shown in Picture 5.

Drugs used and the outcome of the treatment of patients with paroxysmal AF is shown inTable 1a. In a group of patients with paroxysmal AF (n=152), pharmacological conversion into NSR was attempted in 74% patients (n=113), in 20% of patients (n=31) there was no treatment, spontaneous conversion occurred in 5% patients (n=7), and in one case, electro-conversion was done. In total, conversion into NSR, independent from the treatment regime, was achieved in 42% patients (n=64), "rate control" in 10% patients (n=15), and 48% patients (n=73) required prolonged hospitalization.

The drug of choice in pharmacological treatment was propafenone(Table 2). Out of the total number of patients (n=71) that were administered propafenone (70 mg iv) conversion was achieved in 61% patients (n=43), "rate control" in 29% patients (n=7), and 29% of patients (n=21) required prolonged hospitalization. Conversion with amiodarone (600 mg iv) was attempted in 8 patients with partial results: "rhythm control" was achieved in 50% of patients(n=4), whereas the other 50% required prolonged hospitalization. Attempts to achieve "rhythm control" with verapamil(2 mg iv) were less successful. Out of the total number of patients (n=8), "rate control" was achieved in 50% patients (n=4), whereas the other half was hospitalized. Cardio selectivebeta- blocker sotalol (80 mg per os) was administered in three patients with100% success in achieving "rhythm control". Conversion into NSR with positive inotropic agents (digoxine, 2 mg iv) was attempted in three patients resulting in 66% success (n=2).

Pharmacological conversion into NSR by using combination of antiarrhythmic drugs was attempted in 20 patients resulting in 20% success (n=4). Combinations of antiarrhythmic drugs used and outcome of treatment are shown in Table 2.

The outcome of treatment of persistent atrial fibrillation is shown inTable 1b. Out of the total number of patients (n=29), "rhythm control" was achieved in 17% of patients (n=5); in four cases by using pharmacological agents and in one case restoration of NSR was done by using electro-conversion. In this group of patients, "rate control" was achieved in 38% patients (n=17), whereas 45% of patients (n=13) required prolonged hospital treatment. Also, in this group of patients, propafenon was the drug of choice in pharmacological conversion into NSR (Table 1b).

The outcome of treatment of permanent atrial fibrillation is shown inTable 1c.Out of the total number of patients (n=58), "rate control" was achieved in 34% of patients (n=20), while the other patients in this group required prolonged hospital treatment.

DISCUSSION

Atrial fibrillation represents a complex condition which adversely affects mortality, morbidity and quality of life. (15)Taking into account that the prevalence increases with age, number of patients is expected to rise sharply (16). Thus, the treatment of atrial fibrillation will continue to challenge practicing physicians.

Surgical and ablative techniques for the treatment of AF continue to evolve, but pharmacologic therapy continues to be the mainstay of therapy. One of the most common pharnacological approaches in treatment of atrial fibrillation is usage of antiarrhythmic drugs, aiming to restore NSR (so called"rhythmcontrol" approach). However, results of the AFFIRM study (Atrial Fibrillation Follow-up Investigation in Rhythm Management Study) (17) andthe RACE study (Rate Control vs. Electrical Cardioversion for Persistent Atrial Fibrillation RACE) (18), indicate that the "rate control" can be considered as at least as effective as "rhythm control": in fact, the heart rate is the responsible factor for the majority of the symptoms reported in the patients. Therefore, "rate control" should be the primary target in treatment. The above approach is much simpler and is also less expensive since agents such as beta blocker are used.

Despite the data in favour of the "rate control" approach, antiarrhythmic drugs still represent an important factor in treatment of atrial fibrillation.

In the study, antiarrhythmic drugs were the drug of choice in pharmacological conversion of patients with paroxysmal atrial fibrillation. The success of conversion with propafenone (70 mg iv) was 61% (43 pts out of 71), amiodarone (600 mg iv) was 50% (4 pts out of 8). Also, in this study, we registered three patients which were successfully converted to NSR with sotalol (80 mg per os). Combination of verapamil and digoxine had 20% success.

However, in order to evaluate sustainability of the normal sinus rhythmin our group of patients further long-term prospective studies are necessary.

In that respect, the results of the "AFFIRM antiarrhythmic drug sub-study" (19) are especially instructive. This sub-study examined the individual effects of the various antiarrhythmic drugs used to treat rhythm control patients. The primary composite end point, maintenance of sinus rhythm and drug tolerance (no cardioversions) at 1 year, was achieved in 62% of patients treated with amiodarone vs only 39% of patients receiving sotalol and only 23% of patients randomized to a class I agent.

According to the "Canadian Trial of Atrial Fibrillation" study (20) amiodarone was found significantly superior to sotalol or propafenone, in patients with new onset of atrial fibrillation

Furthermore, a recently published study (21), involving patients who were converted from persistent AF found that amiodarone, when used in combination with irbesartan (an angiotensin II receptor blocker used to treat hypertension), was more effective in reducing the recurrence of AF than amiodarone therapy alone. At 2-month follow-up, compared with stand-alone amiodarone therapy (Group 1; n = 75), patients randomized to amiodarone and irbesartan (Group 2; n = 79) had fewer recurrences of AF (63.1% vs 84.8%, P = .008). In an analysis of time to first recurrence, Group 2 patients were also more likely to remain free of atrail fibrillation than Group 1 patients (79.5% vs 55.9%, P = .007).

Pharmacological conversion into normal sinus rhythm still represents the primary target in treatment of patients with paroxysmal and persistent atrial fibrillation. In patients with permanent atrial fibrillation the primary target of treatment was the achievement of the heart rate control. In that respect, the antiarrhythmic agents were the drug of choice, whereas beta blockers were of secondary importance. In order to evaluate sustainability of the normal sinus rhythm, as well as a long-term comparison between the two pharmacological approaches in the treatment of atrial fibrillation, further prospective studies are necessary.

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