Obstructive sleep apnea and Atrial fibrillation
Obstructive sleep apnea (OSA) is a growing concern in our population, due to its close association with obesity, which is becoming more prevalent by the year in America. There are many sequalae of this devastating disease, ranging from slight headaches, to cardiac problems which would in turn lead to death. One of these cardiac issues that could be incurred as a sequalae of OSA is paroxysmal atrial fibrillation (PAF). Currently, there are no guidelines for testing or monitoring patients who are diagnosed with OSA, and not experiencing symptoms of PAF, however, many patients with PAF can experience episodes of this debilitating disease without feeling the irregular heartbeats (silent atrial fibrillation). Patients who have silent atrial fibrillation will still experience the sequalae of PAF, however they will not experience the palpitations, and this will lead to them feeling tired, irritable and a plethora of other symptoms. The issue with this is that many of these symptoms overlap with the same symptoms of OSA, which would lead the patient to not suspect the possibility of having PAF. Guidelines must be put into place for patients who have been diagnosed with OSA to be tested in a sufficient manner for PAF.
Obstructive sleep apnea is a disease which can cause many other medical issues for the patients who have it, one of the most dangerous being PAF, which is observed in about 50% of all patients suffering from OSA1. When suffering from PAF, the patient will experience irregularly irregular heartbeats, which can lead to a clot formation in the heart (most commonly in the left atrial appendage) which can then go to the brain causing a stroke which can effect the patient in many ways, including death. Though there are many ways to test for OSA, and there are many ways to test for PAF, there are no guidelines, in or set methods place for testing patients who suffer from OSA regularly and vigilantly for PAF. While the link between OSA and PAF is still not widely known to many medical providers, it is extremely important to properly test and monitor patients suffering from OSA for development of PAF.
The difficulty in diagnosing a patient with PAF is where most of the problem lies. PAF is an intermittent form of atrial fibrillation, which, while the patient is not in the arrythmia, is completely undetectable. The best way to diagnose this possibly fatal arrythmia is to catch it in the act. The problem with this is that unless the patient knows specifically what their trigger is, they do not know when they will go into an episode of AF. The testing methods for PAF include EKG, Ambulatory electrocardiogram (AECG), event monitor, and an implantable loop recorder of which the latter is considered to be more invasive yet, has much higher success rates in catching episodes of PAF, while the first three are far less likely to capture an episode of PAF.
Following a diagnosis of OSA, 50% of patients will develop PAF. How can the initiation of aggressive testing and monitoring of this population of patients through an implantable loop recorder help lower the morbidity and mortality in the population of patients who suffer from OSA? Can episodes of PAF be more consistently caught through an implantable loop recorder, rather than the other methods of testing for it? Can earlier detection of PAF in patients who suffer from OSA, and earlier initiation of preventative measures such as anticoagulation or EP study and ablation lead to lower morbidity and mortality rates?
The hypothesis is that through initiating a protocol to implant a loop recorder in every patient who is diagnosed with OSA, at first diagnosis of OSA, it could be possible to catch a diagnosis of PAF at an earlier and more treatable stage. This would lead to an improved quality of life, as well as significantly lower morbidity and mortality rates in patients who are diagnosed with OSA.
Purpose of research
The purpose of this research is to determine if there should be new guidelines in place for patients who are diagnosed with OSA to have an implantable loop recorder placed to help diagnose the sequalae of PAF in this population of patients who suffer from this at a higher than normal rate. While the implantation of a loop recording device is considered invasive, it is still questionable as to whether the benefits outweigh the risks in this subset of patients.
Peer reviewed articles obtained from the Nova Southeastern University Alvin Sherman Library were used heavily in the research for this study. National Center for Biotechnology Information (NCBI) was the main database used to search for the peer reviewed articles used to gather information for this report.
Physiology: Atrial Fibrillation
Atrial fibrillation is a common arrhythmia which arises from the atrium. In fact, it is so common, that 6.1 million people in the United States have been diagnosed with this condition, and it is actually the most common tachyarrhythmia encountered by physicians. The arrhythmia is caused by an abnormality in the electrical pathways of the atrium of the heart which cause rapid misfiring of the ectopic cells, which lead to an irregularly irregular heart beat. With the normal conduction pathway of the heart going from the SA node, to the AV node and down to the ventricles from there, Atrial fibrillation differs in the sense that the electronic signals do not pass through the AV node into the ventricles in the normal predictable patterns, and instead cross through the AV node in an unpredictable and disorganized pattern, thus leading to the irregularly irregular heartbeat. This arrhythmia will lead to an insufficient cardiac output, which could eventually lead to a cardioembolic formation, which can then travel to the brain through the aorta, and carotid arteries, causing a potentially fatal stroke. Atrial fibrillation can be paroxysmal which means that the patient will experience episodes of paroxysmal atrial fibrillation intermittently and the episodes will likely resolve on their own with no intervention. There is also persistent atrial fibrillation, as well as silent atrial fibrillation. In persistent atrial fibrillation, the patient will not spontaneously convert back to normal sinus rhythm, and will need intervention of either antiarrhythmics, or synchronized cardioversion. Silent atrial fibrillation is when a patient will experience episodes of atrial fibrillation, however they do not feel any of the symptoms of atrial fibrillation, and most patients who have silent atrial fibrillation do not even know they suffer from this arrhythmia.
Physiology: Obstructive Sleep Apnea
Obstructive Sleep Apnea (OSA) is when the patient experiences intermittent apneic episodes through the night while they sleep. This is caused by the collapse of the pharyngeal airway during the patients sleep. The amount of times this happens throughout the night is measured by the apnea hypopnea index (AHI) which is the amount of apneic episodes the patient experiences per hour through the night. An apneic episode is defined by the patient not breathing for at least 10 seconds during their sleep. The apneic episode will lead to a drop in the patients Oxygen saturation, which can lead to a plethora of medical conditions ranging from hypertension, congestive heart failure, and atrial fibrillation.
Correlation: OSA and PAF
Positive correlations between patients who suffer from OSA and those who suffer from PAF, with the PAF being developed in the patient subsequent to the development of OSA. In fact in one study it was shown that there was a four hundred percent increase in the odds of developing atrial fibrillation in patients who experience sleep disordered breathing, opposed to those who do not have these medical issues2. This study also showed a positive correlation between patients with OSA and cardiac remodeling, which means that the longer a patient has OSA, the more likely they are to experience PAF. There are many mechanisms which are theorized as to why patients with OSA have a higher risk of PAF, which include intrathoracic pressure changes, and decreased oxygen saturation which lead to fluctuating blood pressures and cardiac remodeling.
Correlation: OSA and CVA
It has already been established that PAF is more prevalent in patients who experience OSA, however it is worth noting that the incidence of patients who suffer from CVA is also significantly higher in this patient population. In one study, it was proven that the group of patients with OSA being studied had a higher incidence rate of CVA than the control group3. The incidence of these strokes were suggested to have a higher incidence rate because they have a cardioemblic origin secondary to the PAF which had been developed in the patient. This study showed that when the patients in this study were treated in a sufficient amount of time with anticoagulation therapy, that the incidence rate for stroke was far lower than in the patients that had PAF and had not been treated in time with anticoagulation therapy. In the same study, it was shown that there was a direct correlation to the development of PAF, as well as the occurrence of strokes in the patient population which had been diagnosed with OSA.
Testing for PAF
As stated before, there are multiple ways to test a patient for PAF, including electrocardiogram (ECG), ambulatory electrocardiogram (AECG), Event monitor, loop recorder and even an electrophysiology study (EPS). The issue with ECG, event monitors and AECG however is that if the patient is not currently experiencing the episode of PAF, there will be no evidence of previous episodes left behind. While the ECG, AECG, and event monitors are all the most minimally invasive and most cost effective, the EPS is the most invasive in the fact that a catheter is threaded into the left atrium, and the arrhythmia is elicited through multiple methods. The test involving the loop recorder is somewhat more invasive than the ECG, AECG, and event monitor, however not nearly as invasive as the EPS. The procedure includes placing the loop recorder just under the skin in the chest wall, and is effective in its monitoring for up to three years. Because this device is constantly recording for the duration of its lifetime, this leads to an improved capture rate of an arrhythmia when compared to the other methods discussed.
One study done in 2019 helped to prove the correlation between the increased Apnea Hypopnea Index (AHI) seen in patients with OSA, and left atrial abnormalities. The study was done with a cohort of 261 patients with a mean age of 57 years old, and 52% males. The study would be considered a case report study, where the researchers searched through the records of patients who have received sleep studies, as well as 12 lead EKG’s, and this data was used to measure any change in the patients P wave area in V1 (PWAV1). This is significant if the fact the due to the pathophysiology of PAF, any change in the P wave area in V1 would be a significant risk factor for patients to develop PAF4 The study showed (with a P value of 0.005) that there was in fact a clear correlation between patients having OSA and changes in their PWAV1. Not only were these changes noted, but there was also evidence that patients with OSA in this study also showed a significant drop in O2 saturation due to the apneic events, showing that this lowered state of oxygenation also contributes to the PWAV1 changes over time, thus leading to the formation of electrical pathways in the atrium which are the cause of PAF.
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According to another study done in 2019, it was shown that out of the 25 patients who were fitted with an AECG to test for signs of PAF secondary to OSA, all 25 did not show any sign of PAF, however with implantable loop recorders in place in the same cohort of patients, 5 of these patients did show episodes of PAF5. This study was conducted with a cohort of 25 patients who had recently been diagnosed with severe OSA (AHI >30) with no history of atrial fibrillation and are over the age of 18. These patients underwent two 24 hour AECG tests, one month apart, followed by an implantation of a loop recorder, and follow up appointments for the next 3 years, every 6 months.
The episodes of PAF in these patients were greater than 10 seconds in length, and the average duration of the episodes lasting 4.8 hours. The average time for the loop recorder to pick up an episode of PAF was between 4-18 months, which may seem like a large range, however when it is taken into account that the patients wearing the AECG only wore them for a total of 24 hours, it becomes clear that with the range being 4-18 months, and the episodes only lasting an average of 48 hours, to catch an episode of PAF, one 24 hour monitor is insufficient. In most cases, the use of a 24 hour monitor is the only testing a patient will receive for PAF, and the initial treatment is not until the patient first suffers from a transient ischemic attack (TIA).
Showing the relationship between PAF and OSA is also quite important in coming to a conclusion on the appropriate treatment plan for patients who suffer from PAF secondary to OSA. According to a study done by Kamel Hooman, and Jeff Healy in 2018, cardioembolic embolism is responsible for a significant proportion of ischemic strokes. With further information being gathered over recent years, ischemic strokes that had previously been attributed to an idiopathic origin, are now being attributed to the presence of PAF. This study goes on to explain that many previous studies required two separate episodes of PAF on two separate occasions to be monitored on EKG to be considered for antithrombotic therapy, however with implantable devices such as pacemakers and defibrillators becoming more prevalent, the detection of episodes of silent PAF has become significantly more common through these modalities6. According to the same study, it only takes one 6 minute episode of PAF to form the possibly life threatening emboli.
Anticoagulation in patients with PAF is of the utmost importance to prevent a stroke, and the sooner the patient is started on the anticoagulation therapy, the lower the chances of developing a stroke of cardioembolic origin. The method to assess if the patient is indeed in need of anticoagulation therapy is the CHA2DS2-VASc score, where many factors are taken into account such as congestive heart failure, hypertension, age, diabetes, or previous stroke (or transient ischemic attack (TIA)), and sex. If the patient has a CHA2DS2 score of 1 then they are at low/ intermediate risk, and anticoagulation therapy should be considered, while a score of 2 is a moderate to high risk and anticoagulation is strongly recommended7.
According to the AHA guidelines, the first line therapy for patients with atrial fibrillation, wither persistent or paroxysmal, is warfarin therapy, titrated to an INR of between 2-3. For patients who are not willing to, can not use warfarin, the option of apixaban is the next choice, however there is currently no approved reversal agent for this therapy8.The sooner the patient is started on anticoagulation therapy after being diagnosed with the atrial fibrillation, the lower their risk of actually suffering from the debilitating effects of a cardioembolic event.
Implications for the PA profession
The ability to catch episodes of PAF, in a more timely manner will lead to the provider being able to start life preserving measures sooner rather than later in the course of the patients treatments. The earlier detection of episodes of PAF (even more so silent episodes of PAF) through the use of an implantable loop recorder will significantly improve the outcome of the patient, and reduce the further treatment being needed from the provider due to further sequalae of the cardioembolic effects of PAF. By creating a new guideline to implant a loop recorder in all patients at first diagnosis of OSA who do not already have a diagnosis of PAF, this would lead to a more comprehensive, and thorough examination of the patient rather than intermittent testing for PAF as seen with an EKG, AECG, or event monitor.
Strengths of research
When analyzing the articles for this report, it was noted that the articles had many strengths associated with them. The articles included many explanations of mechanisms, from mechanisms of action, or pathophysiology of the disease states, the mechanisms were all stated and explained well. Furthermore, the data was presented with complete transparency, and well organized. The methods of research in all the reports were well explained and the most recent data was used as resources for their studies, which shows that proper research protocol was followed.
Weaknesses of research
There was not much weakness which was observed through the research which was being conducted, however there was one incidence of weakness which stood out the most to me. In the study which shows the issue with using AECG opposed to an implantable loop recorder to test for PAF, the cohort only included 25 people, and while 20% of the patients showed episodes of PAF with an implantable loop recorder, and this is a significant value, it is not strong evidence in the fact that it is based on such a small cohort. Furthermore, while that study did involve intense follow up with the patients, many of the studies which were included did not show this as part of their research.
Recommendations for future research
In future research it would be quite beneficial to include intensive follow up on the patients who do have OSA, but were not observed to have an episode of PAF. Some patients will tend to develop this issue over many years (>10 years), and the longest study involved in the research only went up to three years. If further follow up with these patients showed episodes of PAF as the OSA developed, it could show more of a correlation between OSA and PAF. In future research, larger cohorts could be used to give the study a stronger power.
The correlation between OSA and the development of PAF has been well proven, as well as the correlation between PAF and CVA, thus showing the correlation between OSA and CVA. With proper management of anticoagulation therapy in a timely manner secondary to detecting the arrhythmia through implantable loop recorder, the morbidity and mortality related to PAF secondary to OSA could be reduced significantly.
- Anter E, Biase LD, Contreras-Valdes FM, et al. Atrial Substrate and Triggers of Paroxysmal Atrial Fibrillation in Patients With Obstructive Sleep Apnea. Circulation: Arrhythmia and Electrophysiology. 2017;10(11). doi:10.1161/circep.117.005407.
- Geovanini GR, Lorenzi-Filho G. Cardiac rhythm disorders in obstructive sleep apnea. Journal of Thoracic Disease. 2018;10(S34). doi:10.21037/jtd.2018.12.63.
- Jehan S, Farag M, Zizi F, et al. Obstructive sleep apnea and stroke. Sleep Med Disord. 2018;2(5):120–125.
- Corotto, PS, Kang, H, Massaro, B, et al. Obstructive sleep apnea and electrocardiographic P‐wave morphology. Ann Noninvasive Electrocardiol. 2019;e12639. https://doi.org/10.1111/anec.12639
- Yeung C, Crinion D, Hammond S, et al. Ambulatory ECG predictors of atrial fibrillation are ineffective in severe sleep apnea. Journal of Electrocardiology. 2019;55:120-122. doi:10.1016/j.jelectrocard.2019.05.002.
- Kamel H, Healey JS. Cardioembolic Stroke. Circ Res. 2017;120(3):514–526. doi:10.1161/CIRCRESAHA.116.308407
- Richard J. Kovacs, Greg C. Flaker, Sherry J. Saxonhouse, et al. Practical Management of Anticoagulation in Patients With Atrial Fibrillation. Journal of the American College of Cardiology. 2015; 65(13):1340-1360.
- Amerena J, Ridley D. An Update on Anticoagulation in Atrial Fibrillation. Heart, Lung and Circulation. 2017;26(9):911-917. doi:10.1016/j.hlc.2017.05.131.
- Feng TR, White RS, Ma X, Askin G, Pryor KO. The effect of obstructive sleep apnea on readmissions and atrial fibrillation after cardiac surgery. Journal of Clinical Anesthesia. 2019;56:17-23. doi:10.1016/j.jclinane.2019.01.011.
- Genuardi MV, Ogilvie RP, Saand AR, et al. Association of Short Sleep Duration and Atrial Fibrillation. Chest. 2019. doi:10.1016/j.chest.2019.01.033.
- Goudis CA, Ketikoglou DG. Obstructive sleep and atrial fibrillation: Pathophysiological mechanisms and therapeutic implications. International Journal of Cardiology. 2017;230:293-300. doi:10.1016/j.ijcard.2016.12.120.
- Groh CA, Faulkner M, Getabecha S, et al. Patient-reported triggers of paroxysmal atrial fibrillation. Heart Rhythm. 2019. doi:10.1016/j.hrthm.2019.01.027.
- Khan A, Patel J, Sharma D, Riaz S, Demissie S, Szerszen A. Obstructive Sleep Apnea Screening in Patients With Atrial Fibrillation: Missed Opportunities for Early Diagnosis. Journal of Clinical Medicine Research. 2019;11(1):21-25. doi:10.14740/jocmr3635.
- Kwon Y, Koene RJ, Johnson AR, Lin G-M, Ferguson JD. Sleep, sleep apnea and atrial fibrillation: Questions and answers. Sleep Medicine Reviews. 2018;39:134-142. doi:10.1016/j.smrv.2017.08.005.
- Linz D, Kadhim K, Kalman JM, Sanders P. Clinical evidence for a dynamic atrial fibrillation substrate in sleep apnea. Sleep and Breathing. 2019. doi:10.1007/s11325-019-01872-w.
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