The Association Between Obstructive Sleep Apnea and Arrhythmias

Obstructive sleep apnea (OSA) is caused by intermittent episodes of partial or complete closure of the upper airway, leading to apneic episodes while the patient is asleep. Atrial fibrillation (AF) leads to more than 750,000 hospitalizations per year and accounts for an estimated 130,000 deaths each year. The death rate from AF as the primary or a contributing cause of death has been rising for more than two decades. The material reviewed in this paper focuses on the association between OSA and arrhythmias. It goes into the details of the epidemiology, pathophysiology, and types of arrhythmias and the therapies seen in association with OSA.


Introduction And Background
Sleep-disordered breathing (SDB) is a cumulative term for sleep-related breathing disorders and abnormalities of respiration during sleep. SDB consists of obstructive sleep apnea (OSA), central sleep apnea syndrome, sleep-related hypoventilation disorder, sleep-related hypoxemia, primary snoring, and catathrenia. OSA is caused by intermittent episodes of partial or complete closure of the upper airway, leading to apneic episodes while the patient is asleep [1]. OSA is diagnosed by a combination of positive patient history and positive findings on polysomnography. An apnea-hypopnea index (AHI) of greater than five is diagnostic of OSA.

Review Epidemiology
The incidence and prevalence of OSA vary based on age in the general population. The prevalence is higher in the middle-aged and advanced age populations [2]. Based on an AHI of more than five, the prevalence ranges from 9%-38% and is higher in men than in women [2]. At an AHI of more than 15, the prevalence in the general adult population ranged from 6%-17% and was 49% in the advanced age group [2].
Atrial fibrillation (AF) has a prevalence of 9% in the 65 years and above population as compared to the 2% prevalence in the younger than 65 years population [3]. An estimated 2.7-6.1 million people in the United States have AF [3]. AF has more than 750,000 hospitalizations per year and accounts for an estimated 130,000 deaths each year [4][5]. Medical costs for AF patients are about $8,705 higher than for people without AF [3,6]. The death rate from AF as the primary or a contributing cause of death has been rising for more than two decades [4][5].

Pathophysiology
Over the years, attempts have been made to determine how arrhythmias develop in OSA patients. In OSA, the frequent collapse of the airway causes oxyhemoglobin desaturation, which leads to persistent inspiratory efforts made against a collapsed airway, often resulting in the patient's arousal from sleep [1].
One hypothesis is that OSA has reduced blood oxygen and increased carbon dioxide levels due to problems with the baroreflex and chemoreflex activity, leading to the activation of the sympathetic nervous system, causing electrical remodeling of the heart [7][8][9][10]. This remodeling can lead to arrhythmia development [1,[7][8][9][10].
Another hypothesis is that co-existing hypertension in OSA patients may be responsible for the development of AF. Past studies have shown a strong association between OSA and hypertension, as well as hypertension and AF. Hypertension has been shown to cause atrial remodeling. Similarly, in OSA patients with hypertension, it is hypothesized that persistent inspiratory efforts made against a collapsed airway cause dramatic shifts in intracardiac pressures, leading to the activation of atrial ion channels, thus creating an acute change in cardiac chamber dimensions [11][12]. This change in size can lead to AF development [11][12].
The third hypothesis is the OSA effect of applying negative intrathoracic pressure on both atrial and ventricular free walls, which will lead to cardiac stretching thus activating cardiac ion channels, causing a change in cardiac chamber size, which can lead to arrhythmias [13].
The fourth hypothesis is related to OSA causing hypoxemia that stimulates the vagal nerve, leading to cardiac vagal reflex activation. In approximately 10% of OSA patients, the resulting hypoxemia activates the cardiac vagal reflex, leading to the development of bradyarrhythmias even in the absence of cardiac conduction disease [14].

Types of arrhythmias
Different types of arrhythmias may be found in patients of OSA. Based on past research studies (see Table 1), there are several observed associations between OSA and arrhythmias. Porthan et al. [17] 115 patients OSA was common in lone AF patients. The study could not demonstrate that OSA was more common in AF patients than in corresponding controls.
Javaheri et al. [18] 81 patients AF was seen in 32% of patients. All patients were male, ambulatory, with stable HF, and had LVEF below 45%.
Flemos et al. [19] 263 patients Patients having sleep apneas were found to have a low prevalence.
Mooe et al. [20] 121 patients AF in 32% of patients with AHI more than five. Furthermore, AF was found in 18% patients with AHI less than five.

Sick sinus syndrome
Simantirakis et al. [21] 23 patients Rhythm disturbances were seen in 48% of patients. They consisted of frequent episodes of bradycardia and long pauses, which were observed in patients who had moderate to severe OSA.
Garrigue et al. [22] 98 patients There was a high prevalence of undiagnosed OSA in the patients. It was 59% and all patients had pacemakers.

patients
The study was conducted with patients who had ventricular asystole and OSA. It was concluded that there was no significant association of sinus node and AV node abnormalities with OSA.
Steiner et al.
[ Gami et al. [28] 112 patients All patients included suffered from SCD. There is a strong association between SCD and OSA. Atrial fibrillation is a commonly seen arrhythmia in OSA patients [1]. AF occurs when disordered atrial electric activity causes an abnormal electrical rhythm that replaces the normal sinus mechanism [29]. It can be caused by hypertension, myocardial infarction, hyperthyroidism, caffeine use, abnormal heart valves and is seen in sleep apnea patients. AF often goes undiagnosed for a long time because 10%-40% of AF patients are asymptomatic [30]. Symptomatic patients will present with palpitations, shortness of breath, exercise intolerance, chest pain, or malaise [29]. AF is responsible for an estimated 130,000 deaths per year and for the worsening morbidity in other diseases like stroke and heart failure [4][5]30]. AF is found in two percent of the general population, with an increasing prevalence to 9% in the above 65 years population [3,30].
Sick sinus syndrome (SSS) refers to a collection of disorders marked by the heart's inability to perform its pacemaking function [31]. SSS mostly affects older adults and consists of bradyarrhythmias with or without accompanying tachyarrhythmias [31]. At least 50% of SSS patients develop alternating bradycardia and tachycardia, also known as Tachy-Brady syndrome [31]. SSS results from degenerative fibrosis, ion channel dysfunction, and the remodeling of the sinoatrial node [31]. Signs and symptoms are often subtle early on and become more obvious as the disease progresses [31]. They are commonly related to end-organ hypoperfusion, like syncope secondary to cerebral hypoperfusion [31].
Atrioventricular block (AV block) is an arrhythmia that is caused by a delay or disturbance in the transmission of an electrical impulse from the atria to the ventricles [32]. This can be due to an anatomical or functional impairment in the heart's conduction system [32]. In general, there are three degrees of AV nodal blocks: first-degree, second-degree (Mobitz type 1 or 2), and third-degree [32]. The causes of AV blocks are myocardial infarction, post-cardiac surgery, electrolyte imbalances, idiopathic fibrosis, and medications that slow atrioventricular conduction [32]. Patients may be asymptomatic or they may present with palpitations, syncope, and dizziness.
Sudden cardiac death is defined as natural death due to cardiac causes, which will present as an abrupt loss of consciousness within the first hour of symptoms [33]. The mechanisms can be ventricular fibrillation, ventricular tachycardia, and flutter with subsequent ventricular fibrillation, torsades de pointes, and, lastly, bradyarrhythmias and asystolic arrest [33].

Treatment
There are no conclusive epidemiologic or longitudinal intervention studies that relate specifically to the prevalence, severity, and consequences of cardiac arrhythmias and the effects of OSA treatment [1]. Despite this, there have been many observations made from previous studies regarding the effectiveness of continuous positive airway pressure (CPAP) therapy for OSA patients and their therapeutic effect on arrhythmia incidence in the same patients. Based on the studies (see Table 2), CPAP therapy had an effect on reducing the incidence and prevalence of cardiac arrhythmias in OSA patients.

Conclusions
The material reviewed in this paper focuses on the association between OSA and arrhythmias. It goes into the details regarding the epidemiology, pathophysiology, and types of arrhythmias seen in association with OSA. It also addresses observations regarding CPAP therapy in reducing arrhythmias. Despite these key points being addressed, larger and more prospective studies are needed to understand the true benefits of CPAP therapy. This is a review article for busy, practicing physicians to have a cumulative view of our current situation regarding the