Atrial fibrillation and Coronary Artery Disease

Dalmo Antonio Ribeiro Moreira M.D, PhD

Medical Section of Electrophysiology and Cardiac Arrhythmias
Dante Pazzanese Institute of Cardiology
São Paulo, Brazil

With the improved survival of the population through identification and proper management of
cardiovascular risk factors, there is an increased longevity of the population and, therefore,
increasingly number of elderly seeking medical clinics because the diseases of old age.
Among these, for the cardiovascular system, heart failure, coronary heart disease and atrial
fibrillation are the most common.

There seems to be a direct cause and effect relationship between coronary disease and atrial
fibrillation. Epidemiological studies indicate, however, that coronary heart disease is not an
independent risk factor for the onset of atrial fibrillation in outpatients with advanced age.
Diabetes mellitus, left ventricular hypertrophy, left atrial enlargement and heart failure are more
directly associated with the onset of this rhythm disorder in the old people. This finding has
practical implications indicating that the onset of the arrhythmia does not indicate the
immediate need for investigation of coronary disease in affected patients.

Atrial Fibrillation and Acute Myocardial Infarction

Atrial fibrillation is an uncommon rhythm disturbance in patients with acute myocardial

infarction, and is more related to the degree of ventricular dysfunction and heart failure or a
possible inflammatory process that affects the pericardium, than with arterial obstruction itself.
Unlike what is often imagined, rarely patients who come to emergency with asymptomatic atrial
fibrillation have angina or acute myocardial silent ischemia and, therefore, do not require
hospitalization for suspected acute myocardial infarction based on documentation of
arrhythmia only.

Atrial fibrillation is reported in 10% of patients with acute heart failure secondary to severe
ventricular dysfunction due to acute ischemic insult to the heart. In this situation, myocardial
failure leads to increased left atrial pressure with distension of the chamber, giving the
appearance of ectopic beats that can lead to disorganization of atrial electrical activity. Other
factors associated with the onset of atrial fibrillation are older age, high levels of CPK
(indicative of more severe muscle), increased heart rate (high expression of adrenergic tone by
hemodynamic instability), Killip class 2 or greater and greater number of compromised
coronary arteries, lesser degrees of reperfusion after natural or mechanical opening of the
coronary arteries and low ejection fraction. Other conditions that predict the onset of atrial
fibrillation, the presence of hypertension, diabetes mellitus, female sex and cerebrovascular
disease.1-4

The clinical complications related to myocardial infarction are more likely to occur in patients
who had atrial fibrillation, such as death, stroke, reinfarction, cardiogenic shock, ventricular
tachyarrhythmias (particularly in patients with high heart rate), intraventricular conduction
disorders, compared with those who remain in sinus rhythm. In other words, atrial fibrillation is
more than just a heart rhythm disorder, is a warning signal to the clinician that the condition
experienced by the patient is very serious because they may present a greater extent and
severity of coronary lesions, and severe impairment of ventricular function. By means of
multivariate analysis have demonstrated that atrial fibrillation is not an independent risk factor
for death in patients with coronary artery disease, being related to other factors such as
advanced age, heart failure or cardiogenic shock, these rather more directly related higher risk
of death.

Mechanism of Atrial Fibrillation in Myocardial Ischemia

Depending on the degree of extension of coronary lesions, also of ischemic picture and the
time the patient remains with ischemia, there may be impairment of ventricular functional
status and, the greater commitment the greater will be the degree of ventricular dysfunction
presented by patients. Compensatory mechanisms that arise in this situation of heart failure
are increasing adrenergic tone, heart rate and increased reabsorption of sodium and water by
the kidneys. The increase in blood volume and ventricular end diastolic pressure, impacting
the atria causing distension of these chambers. When the atrial dilatation is associated with
increasing its internal pressure begins the firing of ectopic beats in several areas, particularly
within the openings of the large veins and pulmonary veins, which may lead to
tachyarrhythmias including atrial fibrillation.
Myocardial ischemia in itself may be a predisposing factor to the emergence of an atrial
arrhythmogenic substrate. It has been demonstrated experimentally in laboratory animals that
underwent coronary occlusion, that when the arterial obstruction is proximal in the right
coronary artery there is high possibility of occurrence of atrial lesion of variable length that is
associated with reduced conduction velocity of electrical impulse, favoring the induction and
maintenance of variable duration of atrial fibrillation4. That is, beyond the ectopic beats that
may arise, the formation of the arrhythmogenic substrate of ischemic origin increases the
probability of formation of reentrant circuits, and thus of atrial fibrillation. According to this
study, this mechanism for atrial fibrillation could arise even in infarcts of small extent, since
ischemia is the principal trigger properly. Such findings however, are not confirmed by
information obtained in humans.

Risk Factors for Coronary Insufficiency and Atrial Fibrillation

Smoking

In patients with coronary artery disease one of the most common findings associated with the
genesis of atrial fibrillation is the presence of fractionated electrical activity of long duration and
low amplitude. These changes are typical of atrial reentrant circuits that favor the onset of atrial
ectopic beats and tachyarrhythmias that may lead to atrial fibrillation or flutter. In this line of
research, it was recently demonstrated that smoking patients with paroxysmal atrial fibrillation,
have a higher possibility of changes in atrial electrical activity, and increased right atrial
activation time, compared with those who do not smoke. These changes in atrial electrical
activity were more intense the greater the amount of cigarettes consumed throughout the day
and the time at which the person used to smoke2. This finding was documented in subjects
who were undergoing ablation of pulmonary veins. Through a sophisticated system of three-
dimensional mapping of atrial electrical activity (NavX), in smokers was clear that the
amplitude of the electrical signals emitted by myocytes, particularly in the right atrium was
smaller compared to patients in similar clinical conditions and nonsmokers5. The authors have
not documented changes in the amplitude of voltage even at the time of activation of the left
atrium. Another relevant aspect was the observation of heterogeneity of distribution of changes
in right atrial electrical activity, being much higher in the anterolateral right atrium than in
others. This dispersion increases the likelihood of atrial ectopic beats and tachyarrhythmias. It
is worth noting that nicotine, besides facilitating the formation of the arrhythmogenic substrate,
can be an important trigger for ectopic activity due to increased automation of cell and
indirectly by increasing adrenergic activity on the heart. It is possible that the documentation of
voltage changes in atrial electrical activity, when added to the changes caused by ischemia in
atrial tissue in coronary heart disease, increase the probability of occurrence of atrial fibrillation
in this population.

Diabetes Mellitus

Types I and II diabetes mellitus, are associated with increased risk of atrial fibrillation in
patients with or without coronary artery disease. Vascular obstructions, changes in local
cellular metabolism concomitant with changes in myocyte electrical activity, promotes the
formation of the arrhythmogenic substrate that generates and maintains atrial fibrillation. The
autonomic cardioneupathy is another factor that increases vulnerability to atrial rhythm
disturbances, predispose to ectopic beats, electrical remodeling of the atria, and finally atrial
fibrillation.

Hypertension

Hypertension, which evolves with ventricular hypertrophy and left atrial enlargement, is another
coronary risk factor that increases the likelihood of atrial fibrillation. The increase in left
ventricular end diastolic pressure which affects the left atrium stretches this chamber and
facilitates the emergence of ectopic atrial arrhythmias. A record of P waves of long duration
identifies patients with increased chance for this arrhythmia. The presence of tissue fibrosis is
part of the arrhythmogenic substrate that generates and maintains atrial fibrillation in
hypertension.

Metabolic Syndrome

Both in the case of diabetes and in hypertension, identified as independent risk factors for
coronary artery disease may be associated with obesity, dyslipidemia and sleep apnea, thus
forming another group of risk factors known as metabolic syndrome. Specifically the production
of cytokines that cause cardiac inflammation (interleukin 6, tumor necrosis factor, C-reactive
protein and other ultra-sensitive) is highly associated with the onset of atrial fibrillation in
clinical practice, particularly in individuals with normal hearts6. The importance of this clinical
condition may be proved by the reduction of atrial fibrillation when patients are treated with
anti-inflammatory drugs or even with statins7. In general, however, treatment of each of these
factors objectively, may reduce the risk of atrial fibrillation and improving outcomes of patients
with coronary artery disease.

The information that the risk factors may be more associated with the onset of atrial fibrillation
than the actual heart disease, warns that they should be identified early and treated aiming to
improve the clinical outcome of these patients.

Atrial Fibrillation in Postoperative Myocardial Revascularization

The incidence of atrial fibrillation is between 15 and 33% of patients undergoing coronary
artery bypass surgery. Do not yet have the profile of patients at higher risk for this complication
but advanced age, presence of heart failure, ventricular hypertrophy, aortic atherosclerosis,
cannulation of both venae cavae for extracorporeal circulation, the withdrawal of beta-blocker
and converting enzyme inhibitors are the main factors8. When atrial fibrillation comes
postoperatively there is greater risk of complications such as stroke, heart failure and other
complications such as bleeding due to the use of anticoagulants. All these findings indicate the
increased morbidity of arrhythmia and cause prolonged length of stay in hospital. Pericarditis
caused by surgical manipulation, high levels of catecholamines, neurohumoral changes,
metabolic factors (hypoxia, electrolyte disturbances), increased left atrial size are all
independent factors for the onset of atrial fibrillation in this phase. The use of beta-blockers in
the preoperative or immediate postoperative period significantly reduces the incidence of
arrhythmia, confirming the influence of the sympathetic system at its origin.

Just as in the acute phase of infarction, the patients who had atrial fibrillation in postoperative
coronary artery bypass grafting have a lower survival rate than patients in similar clinical
conditions but without atrial fibrillation. There is a greater risk of death in these patients
regardless of whether or not the arrhythmia was reverted to sinus rhythm. Thus, atrial
fibrillation postoperatively indicates greater cardiac impairment and for this reason the
correction of risk factors for cardiovascular disease should always be sought so that it
mitigates the risk of future complications.
In conclusion, atrial fibrillation is an arrhythmia that may be present on clinical outcomes in
patients with coronary artery disease, however, there seems not to be a direct relationship
between myocardial ischemia properly to trigger this arrhythmia, particularly in patients who
are treated in the emergency room. Risk factors that are present in coronary patients are much
more involved in this population and must be identified early, not only to reduce its effects on
coronary atherosclerosis but also to reduce the probability of occurrence of atrial fibrillation. In
clinical practice, therapy should be individualized in order to obtain the best results. Another
practical aspect is that the search of an acute coronary obstruction as a cause of atrial
fibrillation of recent onset should not be a major clinical concern when a patient arrives at the
emergency room. The main message is that atrial fibrillation with coronary artery disease in
this population is indicative of cardiac involvement and greater extent of vascular injury.
Studies of long-term clinical follow-up support to these assertions.

References

1 - Behar S, et al. and the SPRINT Study Group. Long-term prognosis of patients with
paroxysmal atrial fibrillation complicating acute myocardial infarction. Eur Heart J. 1992;13:45-
50.
2 - Crenshaw BS, et al. for the GUSTO I Trial Investigators. Atrial fibrillation in the setting of
acute myocardial
infarction: the GUSTO I experience. J Am Coll Cardiol. 1997;30:406-13.
3 - Goldberg RJ, et al. Impact of atrial fibrillation on the in-hospital and long-term survival of
patients with
acute myocardial infarction: a community-wide perspective. Am Heart J. 1990;119:996-1001.
4 - Bell H et al. Atrial Ischemia Promotes Atrial fibrillation in dogs. Circulation 2003, 107:1930-
1936.
5 - Tua TC et al. Imparment of atrial substrates by chronic cigarret smoking in patients with
atrial fibrillation. J Cardiovasc Electrophysiol 2008; 19:259-265.
6 - Issac TT et al. Role of inflammation in Initiation and perpetuation of atrial fibrillation: a
systematic review of the published date. J Am Coll Cardiol 2007; 50:2021-2028
7 - Fauchier L et al. Antiarrhythmic effect to statin therapy and atrial fibrillation. A meta-analysis
of randomized clinical trials. J Am Col Cardiol 2008, 51:828-835.
8 - Mathew JP et al. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA.
2004; 291:1720-1729.