Obstructive Sleep Apnea and Atrial Fibrillation
How obstructive sleep apnea and atrial fibrillation are related
This article was originally published in the A2Zzz Volume 25 Number 1 edition. To access the original article and references cited click here.
Atrial fibrillation is a heart arrhythmia characterized by an irregular and often rapid heartbeat (typically 110–140 beats/ min, but it can rise as high as 170 beats/min). Some research1,2 indicates an increased prevalence of obstructive sleep apnea (OSA) among people with atrial fibrillation. After treatment for atrial fibrillation, people with OSA are at a higher risk of recurrence, compared to people without OSA. Scientists are uncertain whether OSA contributes to or causes atrial fibrillation. However, the findings of a recent study suggest that OSA may cause, rather than simply be correlated with, atrial fibrillation.
During a normal heartbeat, the atria normally contract virtually in unison in a coordinated manner to push blood into the ventricles; the ventricles similarly contract to push blood to the lungs. During an atrial fibrillation episode, the atria contract in an uncoordinated fashion (i.e., different parts of the atria contract independently), and consequently several atrial contractions can occur before the ventricles contract. Most episodes of atrial fibrillation are asymptomatic but many people experience symptoms such as palpitations, dyspnea (i.e., difficulty breathing), fatigue, dizziness, angina (i.e., chest pain), and heart failure (i.e., inability of the heart to pump blood efficiently). Atrial fibrillation can be treated by medications that control the heart rate (e.g., beta blockers such as propanolol) or that can convert the heart rhythm back to normal (e.g., amiodarone, quinidine, disopyramide), by cardioverter devices (e.g., defibrillator, implantable cardioverter-defibrillator, external cardioverter-defibrillator), or by surgery through procedures such as pulmonary vein isolation that discretely destroys tissues associated with triggering atrial fibrillation.
In OSA, the upper airway muscles relax excessively during sleep, which allows tissues such as the tonsils and adenoids to be drawn into the airway and block airflow. The person makes increasingly stronger respiratory movements in an effort to restore airflow, to no avail. With airflow blocked, the blood oxygen level falls, which ultimately triggers a brief arousal. On arousing, the upper airway muscle tone is restored, which allows the upper airway to open, and the person is able to take a few deep quick breaths to restore the oxygen level to normal. Once the oxygen level is restored, the person resumes sleep, which may set the stage for another apnea event.
The interrelations between the heart and respiratory system may explain the correlation between atrial fibrillation and OSA. For example, the sympathetic nervous system is activated, resulting in a rapid heart rate, when a person arouses to take a few breaths after an episode of apnea. Some research has found that a sudden surge in sympathetic activation followed by an abrupt shift to vagal activation occurs immediately before the onset of an atrial fibrillation episode.4 It may be that the OSA-related surges in sympathetic activity could set the stage for atrial fibrillation in some people.
Other researchers have focused on nerves on or near the heart as the trigger for episodes of atrial fibrillation, which may become activated during an OSA episode. For example, Tan and colleagues5 used a canine model of paroxysmal (i.e., sudden) atrial fibrillation to examine whether blocking the stellate ganglia (which have a role in heart rate variability6 ) and the superior cardiac branch of the vagus nerve (which mediates the interplay between respiration and heart rate and blood pressure [i.e., cardiorespiratory coupling ]7 ) would prevent or reduce atrial fibrillation episodes. After blocking these nerves, Tan artificially induced atrial fibrillation intermittently in the dogs for several weeks. Episodes of atrial fibrillation would normally continue after the removal of the stimulus. However, these dogs had no episodes of atrial fibrillation once the stimulus was removed. By contrast, in another group of dogs in which these nerves remained intact, episodes of atrial fibrillation, premature atrial contractions, or atrial tachycardia continued after the stimulus had been removed.
In a canine model, Muhammad Ghias and colleagues8 focused on the role of the ganglionated plexi (i.e., a network of nerves on the atria around the pulmonary vessels) in apnea-induced atrial fibrillation. They ablated ganglionated plexi by the right pulmonary artery. Before the plexi were ablated, the dogs, whose breathing was controlled by a respirator, underwent simulated apnea while atrial fibrillation was artificially induced. In most dogs, atrial fibrillation occurred in response to the signal. The ganglionated plexi were then ablated and the dogs underwent the procedure again. This time atrial fibrillation could not be induced during the apnea. Ghias concluded that ablation of the ganglionated plexi inhibited apnea-induced atrial fibrillation.
Another factor that may contribute to atrial fibrillation is the changes in intrathoracic pressure during an OSA episode. As a person struggles to breathe through the obstructed airway, the intrathoracic pressure decreases substantially (i.e., the intrathoracic pressure becomes negative). With the resumption of breathing the intrathoracic pressure quickly rises. The sudden swings in the intrathoracic pressure result in large changes in the heart’s transmural pressure (i.e., the pressures exerted on the heart internally and externally). When the intrathoracic pressure (i.e., pressure exerted on the heart externally) is low during an apnea, the pressure exerted from blood inside the heart is greater, which can cause distension of the ventricles and atria. In addition, hypercapnia, hypoxia, and apnea-induced arousals activate the sympathetic nervous system and result in large surges in blood pressure, which also can contribute to excess intracardial (i.e., within the heart) pressure. These OSA-related factors may contribute to structural changes of the heart such as increased left ventricular mass and increased left atrial volume that have been reported in the literature.
Surgery is sometimes used to treat people with atrial fibrillation for whom drug therapy and other treatments have been unsuccessful. One procedure is pulmonary vein isolation. Four pulmonary veins arise from the left atrium (two veins take unoxygenated blood to the left lung, and two veins take unoxygenated blood to the right lung). In pulmonary vein isolation, discrete areas on the left atrium that encircle the base of each vein are ablated by radiofrequency or cryoablation (i.e., freezing). Some research has implicated these sites as a trigger for atrial fibrillation.For many people, episodes of atrial fibrillation cease after this procedure. However, people with OSA are more likely to have a recurrence of atrial fibrillation, compared to people without OSA who have undergone this treatment.
The impact of OSA treatment on atrial fibrillation recurrence after treatment has not been examined in depth. Therefore, Thomas Neilan and colleagues investigated whether therapy for OSA (e.g., continuous positive airway pressure [CPAP]) could have a beneficial effect on cardiac structural remodeling in patients with atrial fibrillation, and thereby reduce or eliminate the recurrence of atrial fibrillation episodes after pulmonary vein isolation in people with OSA. In their study, they questioned patients who were to undergo pulmonary vein isolation about whether they had OSA. The patients who reported having OSA had previously undergone a formal sleep study. After the procedure, all patients were followed up. A patient was considered to have a recurrence of atrial fibrillation if an electrocardiogram or prolonged cardiac monitoring showed episodes of atrial fibrillation occurring 3 months or later after the procedure. (The patients were followed monthly for the first 3 months and then at 3- to 6-month intervals for the first 2 years.) The sleep apnea group was divided into two groups: treated (i.e., the patients used CPAP for 4 hours or more nightly) and untreated OSA (i.e., the patients used CPAP for fewer than 4 hours nightly).
Neilan found that between the treated and untreated OSA groups, recurrence of atrial fibrillation after 3 months was higher in the untreated OSA patients (68 percent) than in the treated OSA patients (35 percent). On comparing the OSA groups collectively to the non-OSA group, Neilan found that 51 percent of patients with OSA had a recurrence of atrial fibrillation after 3 months, compared to 30 percent of patients without OSA. Neilan suggests that OSA treatment has a very strong impact on the recurrence of atrial fibrillation.
Other phenomena Neilan noted were increased left ventricular mass (i.e., thickened ventricle, which can lead to heart failure), enlarged left atrium and right ventricle, and reduced right ventricular function in people with OSA, compared to people without OSA; people whose OSA was treated had a lower left ventricular mass and a reduced left atrial size, compared to people with untreated OSA; and a large number of patients (20 percent) who had been referred for pulmonary vein isolation also had OSA. Neilan encourages more work on the impact of OSA treatment on atrial fibrillation treatment.
Daniel Gottlieb, citing the work of Neilan and other researchers, believes that such findings may implicate OSA as a cause of atrial fibrillation. However, Gottlieb cautions that the design of Neilan’s study does not allow one to determine conclusively whether CPAP therapy truly reduced the risk of recurrence of atrial fibrillation since the patients’ heart dimensions were measured only once before the pulmonary vein isolation procedure. Gottlieb suggests that had the heart structure of the patients with OSA been measured soon after they had begun CPAP therapy (the patients had been on the therapy approximately 18–31 months) but before the study, it would have been easier to distinguish the true extent of treatment-related remodeling of their heart structure, and the extent to which such remodeling reduced the risk of recurrent atrial fibrillation.
Some people with refractory (i.e., treatment-unresponsive) atrial fibrillation may have undiagnosed OSA. If scientists determine that OSA is a cause of atrial fibrillation, then physicians may need to consider assessing patients with atrial fibrillation sooner for OSA. It may be that treating OSA could improve the response to or reduce the need for medications or could improve treatment outcome in patients who undergo ablation surgery.