User login
Obstructive sleep apnea is a prevalent and underdiagnosed sleep-related breathing disorder. The estimated prevalence of OSA in the general population of North America ranges from 9% to 38%. This prevalence is higher in men, with a roughly 2:1 male to female ratio, and it also increases with age (Senaratna CV, et al. Sleep Med Rev. 2017;34:70-81). In large epidemiologic studies, the association between OSA and atrial fibrillation (AF) has been well established. The prevalence of OSA in patients with AF is high, with estimates ranging from 21% to 74%. In the OSA population, the Sleep Heart Health Study (Mehra R, et al. Am J Respir Crit Care Med. 2006;173[8]:910-16) and the Multi Ethnic Study of Atherosclerosis (Lin GM, et al. Am J Epidemiol. 2015;182[1]:49-57) found that patients with OSA had a twofold to fourfold increased risk of AF compared with those who did not have OSA. Therefore, the most current American Heart Association guidelines recommend assessing OSA symptoms in all patients with AF and screening for OSA in recurrent patients with AF.
The pathophysiology of OSA involves multiple physiologic stressors that may contribute to an increased propensity for atrial arrhythmias in this population. Among these factors are large changes in intrathoracic pressures that may cause atrial and ventricular wall stretching, recurrent oxidative stress, and a sympathetic surge associated with shortening atrial refractory periods and atrial extrasystoles. By occurring nightly over many years, these physiologic stressors may lead to permanent atrial dilation and structural remodeling, eventually affecting the conduction system and producing a substrate conducive to reentrant circuits. Other common comorbidities in patients with OSA–such as hypertension, obesity, and metabolic syndrome–may also contribute to arrhythmogenicity (Linz D, et al. JAMA Cardiol. 2018;3[6]:532).
Does treating OSA with CPAP prevent the development of AF?
Previous case-control and retrospective observational studies suggested that having OSA makes treating AF more difficult. Patients with OSA had lower response rates to antiarrhythmic drugs, with the lowest in those with more severe OSA. Rhythm control with cardioversion and catheter-based pulmonary vein isolation was also less successful in patients with OSA due to higher rates of AF recurrence. According to one meta-analysis, patients with OSA had a 31% higher rate of AF recurrence after pulmonary vein isolation (Li L, et al. Europace. 2014;16[9]:1309-14).
Prospective studies using CPAP to treat OSA have not demonstrated a reduced risk of adverse cardiovascular outcomes. The SAVE trial is the most well-known of these studies. The primary endpoint was death from cardiovascular causes (myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack). There was no difference in this outcome between the CPAP and usual care groups. A secondary outcome in this study was new-onset AF detected by electrocardiography, and there was no difference between the CPAP and the usual care group. The low amount of CPAP usage in the treatment group was a commonly cited shortcoming of the SAVE trial–mean usage was 4.4 hours per night during the first month of treatment and subsequently decreased to 3.3 hours per night by the 12-month time point (McEvoy RD, et al. N Engl J Med. 2016;375[10]:919-31).
Caples and colleagues screened patients undergoing direct current cardioversion or catheter ablation. They chose those who were also positive for OSA by polysomnography (apnea-hypopnea index – AHI greater than five events per hour). Twenty-five patients were included in the study and were randomly assigned to either CPAP treatment or usual care. Body mass index, blood pressure, ejection fraction, AHI, and nocturnal desaturation levels were comparable between the two groups. The rate of recurrence of AF and the time point following randomization at which the AF recurred did not differ between the two groups (Caples SM, et al. Int J Cardiol. 2019;278:133-6).
A Norwegian trial by Traaen and colleagues included a larger sample of 108 patients with moderate to severe sleep apnea and paroxysmal AF who underwent catheter ablation. Patients were followed for 5 months before and 12 months after ablation. They were randomly assigned to either CPAP therapy plus usual care or usual care alone. The primary goal was to assess AF burden using implanted loop recorders. There was no significant difference in AF burden between the two groups from baseline to the final 3 months of the study (Traaen GM, et al. Am J Respir Crit Care Med. 2021;204[5]:573-82). These two prospective trials, which had AF recurrence or burden as primary outcomes, found no interaction between AF burden and CPAP use, at least within the first year of therapy. Both trials found that their participants used CPAP for more extended periods of time than the SAVE trial, with over 6 hours in the Caples and coworkers’ trial and nearly 5 hours in the Traaen and coworkers’ study.
Is the lack of efficacy due to starting CPAP too late in the course of OSA?
It has been proposed that there may be a critical early period after the onset of OSA when intervention with CPAP (or alternative therapies) will be most effective in preventing adverse cardiovascular outcomes. An answer will almost certainly necessitate a long-term prospective study enrolling people before they develop OSA. Additionally, the AHI is used in most trials to determine the presence and severity of OSA. However, the AHI has been shown to have a poor correlation with sleep-related symptoms, and it may fail to capture key OSA pathophysiologic stressors (e.g., hyperadrenergic drive, cyclical hypoxemia, etc), which may increase the risk of AF. Other disease characteristics and polysomnographic features may better capture disease severity and the cardiovascular risk factors associated with it. The respiratory arousal threshold, arousal index, degree of loop gain, hypoxic burden, heart rate variability, and cardiopulmonary coupling are some examples of such features.
Another possible explanation is that AF is not causally related, and the demonstrated association between the two is because both conditions share risk factors such as age and BMI, among others. Or, if they are causally linked, OSA may be a minor contributor, and the magnitude of that contribution is insufficient to reduce the risk of AF significantly by treating OSA. More research is needed to define the salient intervenable aspects of OSA better and design the optimal timing and duration of intervention.
Dr. Mudrakola is with the Department of Pulmonary & Critical Care Medicine, Summa Health, Akron, Ohio. Dr. Selim is with the Department of Pulmonary & Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
Obstructive sleep apnea is a prevalent and underdiagnosed sleep-related breathing disorder. The estimated prevalence of OSA in the general population of North America ranges from 9% to 38%. This prevalence is higher in men, with a roughly 2:1 male to female ratio, and it also increases with age (Senaratna CV, et al. Sleep Med Rev. 2017;34:70-81). In large epidemiologic studies, the association between OSA and atrial fibrillation (AF) has been well established. The prevalence of OSA in patients with AF is high, with estimates ranging from 21% to 74%. In the OSA population, the Sleep Heart Health Study (Mehra R, et al. Am J Respir Crit Care Med. 2006;173[8]:910-16) and the Multi Ethnic Study of Atherosclerosis (Lin GM, et al. Am J Epidemiol. 2015;182[1]:49-57) found that patients with OSA had a twofold to fourfold increased risk of AF compared with those who did not have OSA. Therefore, the most current American Heart Association guidelines recommend assessing OSA symptoms in all patients with AF and screening for OSA in recurrent patients with AF.
The pathophysiology of OSA involves multiple physiologic stressors that may contribute to an increased propensity for atrial arrhythmias in this population. Among these factors are large changes in intrathoracic pressures that may cause atrial and ventricular wall stretching, recurrent oxidative stress, and a sympathetic surge associated with shortening atrial refractory periods and atrial extrasystoles. By occurring nightly over many years, these physiologic stressors may lead to permanent atrial dilation and structural remodeling, eventually affecting the conduction system and producing a substrate conducive to reentrant circuits. Other common comorbidities in patients with OSA–such as hypertension, obesity, and metabolic syndrome–may also contribute to arrhythmogenicity (Linz D, et al. JAMA Cardiol. 2018;3[6]:532).
Does treating OSA with CPAP prevent the development of AF?
Previous case-control and retrospective observational studies suggested that having OSA makes treating AF more difficult. Patients with OSA had lower response rates to antiarrhythmic drugs, with the lowest in those with more severe OSA. Rhythm control with cardioversion and catheter-based pulmonary vein isolation was also less successful in patients with OSA due to higher rates of AF recurrence. According to one meta-analysis, patients with OSA had a 31% higher rate of AF recurrence after pulmonary vein isolation (Li L, et al. Europace. 2014;16[9]:1309-14).
Prospective studies using CPAP to treat OSA have not demonstrated a reduced risk of adverse cardiovascular outcomes. The SAVE trial is the most well-known of these studies. The primary endpoint was death from cardiovascular causes (myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack). There was no difference in this outcome between the CPAP and usual care groups. A secondary outcome in this study was new-onset AF detected by electrocardiography, and there was no difference between the CPAP and the usual care group. The low amount of CPAP usage in the treatment group was a commonly cited shortcoming of the SAVE trial–mean usage was 4.4 hours per night during the first month of treatment and subsequently decreased to 3.3 hours per night by the 12-month time point (McEvoy RD, et al. N Engl J Med. 2016;375[10]:919-31).
Caples and colleagues screened patients undergoing direct current cardioversion or catheter ablation. They chose those who were also positive for OSA by polysomnography (apnea-hypopnea index – AHI greater than five events per hour). Twenty-five patients were included in the study and were randomly assigned to either CPAP treatment or usual care. Body mass index, blood pressure, ejection fraction, AHI, and nocturnal desaturation levels were comparable between the two groups. The rate of recurrence of AF and the time point following randomization at which the AF recurred did not differ between the two groups (Caples SM, et al. Int J Cardiol. 2019;278:133-6).
A Norwegian trial by Traaen and colleagues included a larger sample of 108 patients with moderate to severe sleep apnea and paroxysmal AF who underwent catheter ablation. Patients were followed for 5 months before and 12 months after ablation. They were randomly assigned to either CPAP therapy plus usual care or usual care alone. The primary goal was to assess AF burden using implanted loop recorders. There was no significant difference in AF burden between the two groups from baseline to the final 3 months of the study (Traaen GM, et al. Am J Respir Crit Care Med. 2021;204[5]:573-82). These two prospective trials, which had AF recurrence or burden as primary outcomes, found no interaction between AF burden and CPAP use, at least within the first year of therapy. Both trials found that their participants used CPAP for more extended periods of time than the SAVE trial, with over 6 hours in the Caples and coworkers’ trial and nearly 5 hours in the Traaen and coworkers’ study.
Is the lack of efficacy due to starting CPAP too late in the course of OSA?
It has been proposed that there may be a critical early period after the onset of OSA when intervention with CPAP (or alternative therapies) will be most effective in preventing adverse cardiovascular outcomes. An answer will almost certainly necessitate a long-term prospective study enrolling people before they develop OSA. Additionally, the AHI is used in most trials to determine the presence and severity of OSA. However, the AHI has been shown to have a poor correlation with sleep-related symptoms, and it may fail to capture key OSA pathophysiologic stressors (e.g., hyperadrenergic drive, cyclical hypoxemia, etc), which may increase the risk of AF. Other disease characteristics and polysomnographic features may better capture disease severity and the cardiovascular risk factors associated with it. The respiratory arousal threshold, arousal index, degree of loop gain, hypoxic burden, heart rate variability, and cardiopulmonary coupling are some examples of such features.
Another possible explanation is that AF is not causally related, and the demonstrated association between the two is because both conditions share risk factors such as age and BMI, among others. Or, if they are causally linked, OSA may be a minor contributor, and the magnitude of that contribution is insufficient to reduce the risk of AF significantly by treating OSA. More research is needed to define the salient intervenable aspects of OSA better and design the optimal timing and duration of intervention.
Dr. Mudrakola is with the Department of Pulmonary & Critical Care Medicine, Summa Health, Akron, Ohio. Dr. Selim is with the Department of Pulmonary & Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
Obstructive sleep apnea is a prevalent and underdiagnosed sleep-related breathing disorder. The estimated prevalence of OSA in the general population of North America ranges from 9% to 38%. This prevalence is higher in men, with a roughly 2:1 male to female ratio, and it also increases with age (Senaratna CV, et al. Sleep Med Rev. 2017;34:70-81). In large epidemiologic studies, the association between OSA and atrial fibrillation (AF) has been well established. The prevalence of OSA in patients with AF is high, with estimates ranging from 21% to 74%. In the OSA population, the Sleep Heart Health Study (Mehra R, et al. Am J Respir Crit Care Med. 2006;173[8]:910-16) and the Multi Ethnic Study of Atherosclerosis (Lin GM, et al. Am J Epidemiol. 2015;182[1]:49-57) found that patients with OSA had a twofold to fourfold increased risk of AF compared with those who did not have OSA. Therefore, the most current American Heart Association guidelines recommend assessing OSA symptoms in all patients with AF and screening for OSA in recurrent patients with AF.
The pathophysiology of OSA involves multiple physiologic stressors that may contribute to an increased propensity for atrial arrhythmias in this population. Among these factors are large changes in intrathoracic pressures that may cause atrial and ventricular wall stretching, recurrent oxidative stress, and a sympathetic surge associated with shortening atrial refractory periods and atrial extrasystoles. By occurring nightly over many years, these physiologic stressors may lead to permanent atrial dilation and structural remodeling, eventually affecting the conduction system and producing a substrate conducive to reentrant circuits. Other common comorbidities in patients with OSA–such as hypertension, obesity, and metabolic syndrome–may also contribute to arrhythmogenicity (Linz D, et al. JAMA Cardiol. 2018;3[6]:532).
Does treating OSA with CPAP prevent the development of AF?
Previous case-control and retrospective observational studies suggested that having OSA makes treating AF more difficult. Patients with OSA had lower response rates to antiarrhythmic drugs, with the lowest in those with more severe OSA. Rhythm control with cardioversion and catheter-based pulmonary vein isolation was also less successful in patients with OSA due to higher rates of AF recurrence. According to one meta-analysis, patients with OSA had a 31% higher rate of AF recurrence after pulmonary vein isolation (Li L, et al. Europace. 2014;16[9]:1309-14).
Prospective studies using CPAP to treat OSA have not demonstrated a reduced risk of adverse cardiovascular outcomes. The SAVE trial is the most well-known of these studies. The primary endpoint was death from cardiovascular causes (myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack). There was no difference in this outcome between the CPAP and usual care groups. A secondary outcome in this study was new-onset AF detected by electrocardiography, and there was no difference between the CPAP and the usual care group. The low amount of CPAP usage in the treatment group was a commonly cited shortcoming of the SAVE trial–mean usage was 4.4 hours per night during the first month of treatment and subsequently decreased to 3.3 hours per night by the 12-month time point (McEvoy RD, et al. N Engl J Med. 2016;375[10]:919-31).
Caples and colleagues screened patients undergoing direct current cardioversion or catheter ablation. They chose those who were also positive for OSA by polysomnography (apnea-hypopnea index – AHI greater than five events per hour). Twenty-five patients were included in the study and were randomly assigned to either CPAP treatment or usual care. Body mass index, blood pressure, ejection fraction, AHI, and nocturnal desaturation levels were comparable between the two groups. The rate of recurrence of AF and the time point following randomization at which the AF recurred did not differ between the two groups (Caples SM, et al. Int J Cardiol. 2019;278:133-6).
A Norwegian trial by Traaen and colleagues included a larger sample of 108 patients with moderate to severe sleep apnea and paroxysmal AF who underwent catheter ablation. Patients were followed for 5 months before and 12 months after ablation. They were randomly assigned to either CPAP therapy plus usual care or usual care alone. The primary goal was to assess AF burden using implanted loop recorders. There was no significant difference in AF burden between the two groups from baseline to the final 3 months of the study (Traaen GM, et al. Am J Respir Crit Care Med. 2021;204[5]:573-82). These two prospective trials, which had AF recurrence or burden as primary outcomes, found no interaction between AF burden and CPAP use, at least within the first year of therapy. Both trials found that their participants used CPAP for more extended periods of time than the SAVE trial, with over 6 hours in the Caples and coworkers’ trial and nearly 5 hours in the Traaen and coworkers’ study.
Is the lack of efficacy due to starting CPAP too late in the course of OSA?
It has been proposed that there may be a critical early period after the onset of OSA when intervention with CPAP (or alternative therapies) will be most effective in preventing adverse cardiovascular outcomes. An answer will almost certainly necessitate a long-term prospective study enrolling people before they develop OSA. Additionally, the AHI is used in most trials to determine the presence and severity of OSA. However, the AHI has been shown to have a poor correlation with sleep-related symptoms, and it may fail to capture key OSA pathophysiologic stressors (e.g., hyperadrenergic drive, cyclical hypoxemia, etc), which may increase the risk of AF. Other disease characteristics and polysomnographic features may better capture disease severity and the cardiovascular risk factors associated with it. The respiratory arousal threshold, arousal index, degree of loop gain, hypoxic burden, heart rate variability, and cardiopulmonary coupling are some examples of such features.
Another possible explanation is that AF is not causally related, and the demonstrated association between the two is because both conditions share risk factors such as age and BMI, among others. Or, if they are causally linked, OSA may be a minor contributor, and the magnitude of that contribution is insufficient to reduce the risk of AF significantly by treating OSA. More research is needed to define the salient intervenable aspects of OSA better and design the optimal timing and duration of intervention.
Dr. Mudrakola is with the Department of Pulmonary & Critical Care Medicine, Summa Health, Akron, Ohio. Dr. Selim is with the Department of Pulmonary & Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.