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European Journal of Heart Failure 2005 7(4):671-676; doi:10.1016/j.ejheart.2004.07.018
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© 2005 European Society of Cardiology

Prognostic significance of new atrial fibrillation and its relation to heart failure following acute myocardial infarction

Milika Asanin*, Jovan Perunicic, Igor Mrdovic, Mihailo Matic, Bosiljka Vujisic-Tesic, Aleksandra Arandjelovic, Zorana Vasiljevic and Miodrag Ostojic

University Institute for Cardiovascular Disease, Clinical Center of Serbia, Emergency Center Pasterova 2, 11000 Belgrade, Serbia&Montenegro

* Corresponding author. Tel.: +38 1 11 3222288; Fax: +38 1 11 2418996. E-mail address: masanin{at}Eunet.yu


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 
Background: New-onset atrial fibrillation (AF) after acute myocardial infarction (AMI) frequently occurs in association with postinfarction complications, particularly with heart failure (HF).

Aims: To evaluate whether postinfarction HF is associated with the subsequent development of AF and whether AF independently predicts poorer prognosis.

Methods and results: We examined 650 patients with AMI and compared patients with AF (n=320) to those without (n=330). AF patients were classified as either early AF (n=208)—patients who developed AF within 24 h of symptom onset or late AF (n=112)—patients who had AF thereafter. We compared outcomes between these groups, adjusting for differences in baseline characteristics and postinfarction HF. Heart failure was the most important predictor of AF. In most patients, AF occurred secondary to HF. AF patients had poorer outcomes, including higher in-hospital and 7-year mortality. After multivariate adjustment, overall, AF was not an independent predictor of in-hospital [odds ratio (OR)=0.70) and 7-year [relative risk (RR)=1.14] mortality, but late AF remained an independent predictor of 7-year (RR=2.48, 95% confidence interval, 1.26–4.87) mortality.

Conclusions: Heart failure mostly preceded the occurrence of new-onset atrial fibrillation after acute myocardial infarction, but only late atrial fibrillation was independently related to long-term mortality.

Key Words: Atrial fibrillation • Heart failure • Myocardial infarction

Received April 24, 2004; Revised May 24, 2004; Accepted July 5, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 
New-onset atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI). Previous studies have reported that the AF following AMI is associated with increased in-hospital and long-term mortality; however, after multivariable analysis, no independent effect was found [1,4,10,11].

Atrial fibrillation occurs in association with postinfarction complications mostly with heart failure (HF). Not many studies have reported the exact correlation between the timing of AF and the development of HF and the prognostic effects of AF on the patients' outcomes independently from this complication. The importance of the time of onset of AF on the prognosis of patients with AMI is also not well defined [10,13,16,17].

The aims of the present study were to evaluate whether AF followed postinfarction HF and whether AF independently predicted in-hospital and 7-year mortality, and to determine whether timing of AF had an effect on outcome.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 
In the period from January 1996 to December 1998, 3210 patients with AMI were admitted to our Coronary Care Unit. The present study focused on 650 patients—320 patients with AF who were admitted during 1996–1998 and 330 patients without AF who were consecutively admitted between April and August 1996. The AF group was further sub-classified into patients with early-onset AF (<24 h from symptom onset) and those with late-onset AF (>24 h from symptom onset). The in-hospital complications were prospectively investigated, and the timing of AF was analyzed in relation to the development of HF. This study retrospectively analyzed data from the prospective database.

The criteria for AMI were chest pain or electrocardiographic changes suggestive of infarction or ischaemia, associated with the increased level of cardiac enzymes to at least twice the upper limit of the normal value. Patients had continuous ECG monitoring during the whole period of CCU stay. The diagnosis of AF was made according to the following criteria: absence of P waves, coarse or fine fibrillatory waves, and completely irregular RR intervals. There was no specific predefined criterion of AF duration for study enrollment. Patients with history of atrial arrhythmias, rheumatic valvular disease, congenital cardiac disease, previous coronary bypass surgery, and chronic pulmonary disease (n=33) were excluded from the study.

Echocardiography was used for the screening procedure: the left ventricle wall was divided into 11 segments; segmental wall motion was graded as follows: 1=normal, 2=hypokinetic, 3=akinetic, and 4=dyskinetic. Wall motion score index at rest was calculated as the sum of the individual segment scores divided by the number of segments interpreted.

Demographic, historical, and clinical data were recorded during hospitalization on designated forms. The patients were followed up for 7 years after being discharged from hospital. Assessments were made 1 month after discharge, after an additional 2 months, and thereafter every 3 months until the study was completed. Follow-up data were obtained for 99% of patients.


   3. Statistical analysis
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
4. Results
 5. Discussion
 6. Conclusions
 References
 
Differences between groups with respect to medical history, clinical data, and complications during hospitalization were analyzed using the Chi-square and Student's t-test for categorical and continuous variables. Categorical variables were presented as percentages and continuous variables as median values. P value<0.05 was considered as significant.

Baseline characteristics and in-hospital complications that differed significantly between the AF group and no-AF group were entered into multivariable stepwise logistic modeling to determine the predictors of AF. The prognostic effect of AF on in-hospital and long-term mortality was examined using multivariable stepwise logistic modeling, adjusted first for baseline characteristics, and then postinfarction HF.

In the second part of the study, patients with early—versus late—onset of AF were compared, and variables with some predictive value were then tested in a multiple logistic regression model to identify independent predictors of late AF. Logistic regression modeling was repeated to evaluate the prognostic significance of early AF and late AF on in-hospital and long-term mortality, adjusted for baseline characteristics and then HF.


   4. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
5. Discussion
 6. Conclusions
 References
 
In the study period (1996 to 1998) of 3210 consecutive AMI patients, a total of 320 (10%) patients had AF (AF group). Out of the remaining AMI patients without AF, 330 patients, consecutively admitted between April and August 1996, were included in the study as the control group (no-AF group). Among the AMI patients with documented AF, 208 (65%) patients had AF within 24 h of symptom onset (early AF) and 112 (35%) had AF thereafter (late AF).

4.1. Baseline characteristics
Medical history, clinical data, and complications during hospitalization of patients with and without AF, as well as early and late AF are shown in Table 1. HF was the most frequent postinfarction complication in patients with AF. When the timing of AF was analysed, it was found that AF mostly followed the development of HF (84%). A significantly higher proportion of patients with late AF developed AF secondary to HF than patients with early AF (91% vs. 72%, P=0.006). All AF patients who entered the study developed paroxismal AF. The average duration of AF episodes for the whole population was 15.31±21.18 h, and we found that AF lasted longer in patients with late- than in those with early-onset of AF (12.25±17.41 vs. 20.96±25.95 h, P=0.0004). Sinus rhythm was restored during hospitalization in 317/320 (99%) patients with paroxismal AF and the remaining 3 patients died in AF during the acute phase of MI. Out of 317 patients with successful cardioversion, DC cardioversion was applied in 13 patients. Recurrent AF was recorded in 22.5% (72/320) of patients during hospitalization and was more frequent in patients with late than early AF (29.5% vs. 18.8%, P=0.029). Upon hospital discharge, all patients were in sinus rhythm. Medical treatments administered in CCU are shown in Table 2. Amiodarone was the only antiarrhythmic agent used for maintenance of sinus rhythm following cardioversion and was used in approximately 10% (31/320) of patients.


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  		Table 1 Baseline clinical characteristics

 


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  		Table 2 Medical treatment used during hospitalization in CCU

 
4.2. Predictors of AF
In multivariate analysis, the most important predictors of AF development were HF (OR=3.03, 95% CI, 2.08–4.43, P<0.0001) followed by advanced age (OR=2.48, 95% CI, 1.74–3.54, P<0.0001) and elevated creatine kinase (CK) level (OR=1.82, 95% CI, 1.26–2.62, P=0.001). The significant predictors for development of late AF were HF (OR=3.46, 95% CI, 1.98–6.04, P<0.0001) and elevated CK level (OR=2.20, 95% CI, 1.30–3.74, P=0.003).

4.3. In-hospital mortality
The unadjusted in-hospital mortality rate was significantly higher in patients with AF (18%) compared to patients without AF(10.6%); the odds ratio (OR) for death in AF patients was 1.86 (95% CI, 1.18–2.93, P=0.006). After adjusting for age, history of hypertension, history of diabetes mellitus, history of angina pectoris, previous myocardial infarction, the OR decreased to 1.41 (95% CI, 0.87–2.27). When HF was added to the model with the same baseline adjustment, the OR of in-hospital mortality for the AF group was 0.70 (95% CI, 0.41–1.20, P=0.163). The unadjusted OR for death among patients with late AF was 2.83 (95% CI, 1.56–5.15, P=0.0005); after adjusting for the previously mentioned baseline variables, the OR was the same 2.8 (95% CI, 1.56–5.00), but when HF was added to the model, OR was reduced to 1.81 (95% CI, 0.95–3.43, P=0.068).

4.4. Long-term mortality
The unadjusted long-term mortality rate was significantly higher in patients with AF (52%) compared to patients without AF (30%) (Fig. 1); the relative risk (RR) for death among AF patients was 2.54 (95% CI, 1.79–3.60, P<0.0001). After adjusting for age, gender, history of hypertension, history of diabetes mellitus, previous myocardial infarction, history of angina pectoris, thrombolysis, peak CK level, and beta blocker therapy, the risk (RR) of dying decreased to 1.26 (95% CI, 0.82–1.95, P=0.283). When HF during hospitalization was added to the model, the adjusted RR in AF patients who survived hospitalization was 1.14 (95% CI, 0.72–1.79, P=0.568).


Figure 1
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  		Fig. 1 Survival rates after hospital discharge in AMI patients with and without AF.

 
Analysis according to the time of AF onset during hospitalization showed that the unadjusted long-term mortality rate was significantly higher in patients with late AF (70%) than in patients with early AF (44%) (Fig. 2); the risk (RR) for dying among patients with late AF was 2.98 (95% CI, 1.70–5.23, P=0.0001). After adjusting for all of the above-mentioned prognostic factors, late AF in patients surviving hospitalization was associated with an increased risk of dying (RR=2.48, 95% CI, 1.26–4.87, P=0.008).


Figure 2
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  		Fig. 2 Survival rates after hospital discharge in AMI patients with early AF and those with late AF.

 
The number of deaths during follow-up and the risk associated with different variables, in AMI survivors, with and without AF, as well as in patients with early- or late-onset AF during hospitalization with respect to long-term mortality are shown in Table 3.


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  		Table 3 Number of deaths during follow-up and long-term mortality

 

   5. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
6. Conclusions
 References
 
New-onset AF is a common complication of AMI, with an incidence of 10% in the present study. In agreement with previous studies [4,13,14,17], we found that patients with AF had worse baseline characteristics and that advanced age was a significant predictor of AF. The patients with AF had a more complicated hospital course than patients with no AF. Heart failure was more common in AF patients and was probably caused by a higher incidence of preexisting ischemic heart disease (history of MI and/or angina pectoris), larger infarctions, and a higher incidence of anterior infarction in these patients. It was found that postinfarction HF was mostly followed by AF, and that HF was the most important predictor of AF. In the GUSTO-I trial [13], patients with AF had larger infarctions, more extensive coronary artery disease, poorer reperfusion, and lower left ventricular ejection fraction than those with normal sinus rhythm. Pedersen et al. [15] reported that 50% of patients with AF had left ventricular ejection fraction≤35% compared with 30% of those without AF. Similarly, our study found more extensive left ventricular systolic dysfunction in patients with AF determined by echocardiography than in those without this arrythmia. As in prior studies [4,8,11,12,14,17], we noted that worse Killip class and lower blood pressure were associated with AF, suggesting that hemodynamic decompensation was the underlying mechanism influencing the development of AF.

The patients with later onset of AF had poorer clinical status than those with earlier onset. Heart failure and worse Killip class were more frequent in this group. HF more often preceded the late- than the early-onset arrhythmia, and HF was found to be the greatest predictor of late-onset AF. A significantly higher incidence of anterior AMI and higher CK levels in patients with late AF than in those with early AF (the groups were similar with regard to previous MI and angina pectoris) may contribute to the impaired cardiac function in these patients. Serrano et al. [10] demonstrated that poor prognosis in patients with later onset of AF was related to compromised myocardium due to more severe coronary artery disease in these patients.

5.1. Mortality
The association between AF and mortality in patients with AMI has been studied extensively. Although the presence of AF is associated with adverse outcome during hospitalization, the results of previous studies have generally shown that AF is not an independent predictor of increased in-hospital mortality [1,4,8,10–14]. Findings are different for long-term mortality. In a 5-year follow-up study, Pedersen et al. [15] reported an independent effect of AF; however, these results were not confirmed in a 10-year follow-up study by Goldberg et al. [4]. Wong et al. [16] reported that postinfarction complications were more frequent in AF patients before development of AF, but AF predicted worse prognosis, independently from the baseline characteristics and pre-AF complications.

In our study, the mortality rates were similar to those reported previously (in-hospital mortality rates in patients with and without AF were 18% and 10.6%, respectively, versus 18% and 9% in the TRACE study [15]). Our mortality rate was higher than that reported for patients in the GUSTO trial [13] (13.8% during hospitalization). However, GUSTO included patients who were eligible for thrombolytic therapy, who generally had a better prognosis.

The unadjusted in-hospital and long-term mortality rates in this study were significantly higher in patients with AF than in those with normal sinus rhythm. Atrial fibrillation mostly occurred secondary to postinfarction HF, and after adjustment for baseline characteristics and in-hospital HF, overall AF was not an independent risk factor. Patients with late AF had a significantly higher incidence of HF, and they developed AF secondary to HF more frequently than patients with early AF. These findings suggest that the time of AF onset may represent different aetiologies [2,3,5–7,9] and, accordingly, may influence the prognosis in a different way. Patients with late AF had a markedly higher risk of mortality, and, after multivariable analysis, only late AF was independently associated with increased long-term mortality. This could be related to larger infarct size and its consequences in patients with late AF. Heart failure and other factors known to adversely affect prognosis after AMI were frequently found in patients with AF. Nevertheless, the development of AF reflects the overall poor clinical status and, consequently, worse prognosis in patients with AMI.


   6. Conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
References
 
Patients with atrial fibrillation were older, they had more complicated in-hospital clinical course and were inclined to poorer outcome. The majority of episodes of new-onset atrial fibrillation after acute myocardial infarction occurred in association with heart failure. Postinfarction heart failure was mostly followed by atrial fibrillation, but, after adjusting for differences in baseline characteristics and heart failure, only later onset of atrial fibrillation during hospitalization was independent predictor of long-term mortality.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusions
 References
 

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