CARDIO SLEEP BLOG

By Melih Alvo

Afib effects 6M lives1 in US and each year ~350.000 patients undergo ablation procedure to treat this condition. Intracardiac AFib ablation is an invasive cardiac procedure, carrying some significant risk for complications, in particular these associated with the transeptal puncture and esophageal fistulas and it is associated with significant cost to the healthcare system and the patient.  Unfortunately about 50% of AFIB patient that undergo their first ablation procedure experience reoccurrence of Afibwithin one year. There are multiple thoughts on the underlaying reasons for this big variability in outcome with much dialog and efforts focusing on the procedure itself. Recently, new data published have suggested one of the gaps may not be in the ablation lines but with another condition -sleep apnea and the implications of it on the heart tissue and physiology.

Recently accelerated number of new clinical studies shows the effect of sleep apnea on Afib recurrence.  On March 2017 the American College of Cardiology invited a review paper discussing the evidence demonstrating the causality relationships of sleep apnea driving higher AFIB burden. The below illustration is a recreation of similar diagram featured in this publication:

In light of all these information’s, Dr. Elad Anter from Boston Beth Israel Deaconess Medical Center, a Harvard Medical Institute, recentlypublished yet another clinical study which may change the EPs approach to
Afib ablation.

In this multi-center prospective randomized study 86 patients with Paroxysmal Atrial Fibrillation defined under two groups; group one of 43 patients with diagnosed OSA and group two, 43 patients without OSA. Diagnosis was done both with traditional means and with the novel WatchPAT home sleep test technology.   All patients undergo comprehensive mapping of their atrial substrate, PV trigger identification and PV Isolation and non-PV trigger mapping and ablation. In addition there were retrospective 2 control groups one without OSA and one with moderate OSA. Both of those groups underwent PVI alone without mapping and ablation of Non-PV triggers.

Findings of the study were amazing.  After PV isolation, patients with OSA had significant increased incidence of clinically relevant additional Non PV triggers (4.8% vs.  11.6%; P=0.003) and patients with OSA who only underwent PV isolation without ablating non-PV triggers had increased risk of arrhythmia recurrence (83.7% vs. 64.0%; P=0.003).  Also 1 year arrhythmia-free survival was similar between patients with and without OSA that undergo both PVI and non-PV triggers ablation (83.7% vs 81.4%; P=0.59)4

As conclusion, OSA is associated with structural and functional remodeling and increased incidence of non-PV triggers. Eliminating these triggers will improve arrhythmia free survival. In other words, patients with OSA have higher chance to have non-PV triggersand therefore require different approach to AF ablation. Knowing the patients OSA status prior to the ablation process become critical piece of information that may help to define the right ablation strategy.

In below link you may see the full article.

https://www.itamar-medical.com/wp-content/uploads/2019/12/e005407.full_.pdf

The WatchPAT Home Sleep Apnea monitor is an easy to use, effective and accurate tool for OSA diagnosis in AFib patients. Contact Us for more information about WatchPAT and our comprehensive “Total Sleep Solution” for Cardiology practices. www.cardiosleepsolutions.com

1 –  Source: Seet & Chung, Anestsiology Clin 2010
2 – Effect of Obstructive Sleep Apnea Treatment on Atrial Fibrillation Recurrence
3 – Atrial substrate and triggers of paroxysmal Atrial Fibrillation in patients with obstructive sleep apnea

By Efrat Magidov

Sudden cardiac death (SCD) is defined as an “unexpected natural death from a cardiac cause within a short time period, generally ≤1 hour from the onset of symptoms, in a person without any prior condition
that would appear fatal”1.

In most cases SCD results from a malfunction of the heart electrical system, causing a sudden loss of heart function (sudden cardiac arrest). Without organized electrical input to the heart, there is no consistent constriction of the ventricles which manifests in an irregular rhythm (arrhythmia) and an inadequate cardiac output. Loss of consciousness shortly follows due to lack of blood flow to the brain, and unless emergency treatment is given immediately death is inevitable.

Although SCD is one of the largest causes of natural death, accounting for up to 450,000 deaths annually in the US2, strategies for risk stratification and prevention are still far from ideal. This is mainly due to the fact that SCD mostly occurs in people without any diagnosed cardiac problems, and thus an adequate characterization of risk factors is highly essential.

Such risk factor, that was poorly identified until recently, is obstructive sleep apnea (OSA).
The biological plausibility for OSA as a risk factor for arrhythmogenesis stems from its interventions with all three mechanisms of arrhythmias:

  1. Increased automaticity – triggered by the hypoxemia and respiratory acidosis accompanying the apneic event.
  2. Triggered activity – the enhanced sympathetic activity following an obstructive event can alter the afterhyperpolarization timing of the heart pacemaker cells.
  3. Reentry – respiration against a partially occluded airway results in a vagal stimulation which in turn can initiate a premature cardiac action potential and negative intrathoracic pressure is believed to cause micro scaring in the heart tissue as well.

In line with such important observations on the potential relationship between these two phenomena, a growing number of studies is trying to assess risk of SCD in OSA patients. One such attempt, and perhaps the most extensive one, was led by Dr. Virend Somers, the director of the Cardiovascular Facility and the Sleep Facility within Mayo Clinic’s Center for Clinical and Translational Science in Rochester, Minnesota.

In this 15 years controlled longitudinal study, 10,701 adults with suspected sleep disordered breathing admitted to the Mayo Clinic Sleep Disorders Center for a full night evaluation, the polysomnography over-night test. The apnea-hypopnea index (AHI) was calculated as the number of apneas/hypopneas per hour of sleep, and OSA diagnosis was established for an AHI 5 in accordance with AASM criteria.

The collection of follow-up data occurred up to 15 years (mean 5.3 years) from data of polysomnography to the date of SCD, resuscitated SCD, death from other causes or last follow-up. SCD was established when the cause of death was sudden cardiac death, (fatal) cardiac dysrhythmia, (fatal) cardiac arrhythmia, cardiac arrest, cardiorespiratory arrest; or coronary heart disease or myocardial infarction when the time interval from symptoms to death was specified ≤ 1 hour. Overall, 142 patients had resuscitated or had a fatal SCD, representing an annual rate of 0.27% for the study population.

In accordance with the researchers’ hypothesis, the presence of OSA predicted incident SCD and the magnitude of risk (hazard rate, HR) was predicted by multiple parameters that characterize OSA severity, including the AHI and nocturnal hypoxemia (AHI>20: HR 1.60; mean O2sat<93%: HR 2.93; lowest O2sat<78%: HR 2.60, all p<0.0001, Figure 1).

Figure 1

These findings are in line with previous studies demonstrating a two-to-fourfold greater risk of abnormal heart rhythms in people with OSA than people without OSA3-4. This risk had been shown to disappear completely in patients with treated OSA5. Taken together these findings stretch the importance of OSA diagnosis and treatment in SCD risk reduction.

WatchPAT, Home Sleep Apnea Test device, is an easy to use, effective and accurate tool for OSA diagnosis. You may learn more about WatchPAT and our comprehensive “Total Sleep Solution” for Cardiology practices in www.cardiosleepsolutions.com

  1. Zipes, D. P., & Wellens, H. J. (1998). Sudden cardiac death. Circulation98(21), 2334-2351.
  2. Kong, M. H., Fonarow, G. C., Peterson, E. D., Curtis, A. B., Hernandez, A. F., Sanders, G. D., … & Al-Khatib, S. M. (2011). Systematic review of the incidence of sudden cardiac death in the United States. Journal of the American College of Cardiology57(7), 794-801.
  3. Mehra, R., Benjamin, E. J., Shahar, E., Gottlieb, D. J., Nawabit, R., Kirchner, H. L., … & Redline, S. (2006). Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. American journal of respiratory and critical care medicine173(8), 910-916.
  4. Gami, A. S., Howard, D. E., Olson, E. J., & Somers, V. K. (2005). Day–night pattern of sudden death in obstructive sleep apnea. New England Journal of Medicine352(12), 1206-1214.
  5. Doherty, L. S., Kiely, J. L., Swan, V., & McNicholas, W. T. (2005). Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest127(6), 2076-2084.

By Efrat Magidov

Stroke, sometimes referred to as a “brain attack”, is a medical emergency and a leading cause of death around the world, occurring when the blood supply to a part of the brain is interrupted or reduced, depriving brain tissue of oxygen and nutrients. Such deficit can happen when a blood vessel in the brain bursts (Hemorrhagic stroke) or, more commonly, when a blockage develops (Ischemic stroke). If not treated immediately, brain cells begin to die within minutes, resulting in serious disability or death.

Sleep-disordered breathing (SDB), and especially its most common form – obstructive sleep apnea (OSA), has been associated with increased risk for ischemic stroke. Recently, a large prospective cohort study followed 5422 individuals without a history of stroke for a median of 8.7 years1. Chances of ischemic stroke in men were shown to be increased with OSA severity (as measured by AHI), even after adjustment for potential confounders (adjusted hazard ratio [HR] 2.86, 95% CI 1.10-7.39). Overall OSA was found to be associated with an approximately three-fold increase risk of ischemic stroke in men, resonating findings from previous studies that demonstrated 4- to 6-fold higher prevalence of OSA in stroke patients2. Moreover, it had been shown that treatment of OSA decrease mortality and improve functional recovery after stroke3.

This strong connection between OSA and stroke is not surprising considering the fact that OSA affects all major risk factors of stroke: hypertension, hyperlipidemia, hypoxemia, diabetes and atrial fibrillation. However, the underlying mechanisms by which OSA increases the risk, independent of these traditional risk factors, have not been established. Nevertheless, some notable attempts to suggest a causal mechanism have been made. Here are examples of two such suggested mechanisms:

Decreased cerebral blood flow velocity: Ordinarily, the brain regulates its blood flow to meet its own metabolic needs, even in the face of changes in blood pressure, a process known as cerebral autoregulation. The repeated surges and drops in blood pressure, oxygen level and blood flow during numerous apnea episodes each night, reduces the brain’s ability to regulate these functions. This mechanism was demonstrated by a study conducted at Yale Center for Sleep Medicine4; 48 subjects, 22 diagnosed with OSA (AHI≥30) and 26 controls (AHI<5), free of cerebrovascular and active coronary artery disease, participated in this study. Cerebral autoregulation was examined by measuring cerebral artery blood flow velocity (CBFV) and arterial blood pressure during orthostatic hypotension and recovery as well as during 5% CO2 inhalation. The findings showed that patients with OSA have decreased CBFV at baseline compared to controls (8±3 vs. 55±2 cm/s; P<0.05, respectively) and delayed cerebrovascular compensatory response to changes in blood pressure (CBFV: 0.06±0.02 vs.
0.20±0.06 cm∙s-2∙mmHg-1; P<0.05, figure 1). These perturbations may increase the risk of cerebral ischemia during obstructive apnea.

Figure 1: Rate of change of vascular conductance in response to orthostatic hypotension as a measure of cerebral autoregulation. The OSA patients (B) had significantly lower compensatory rate (the slope of CBFV/MAP/time) (P<0.05) and longer time course than the control (A).

Hypercoagulability and inflammation: Another suggested mechanism relates to the hypercoagulability and increased platelet aggregation related to OSA, which in turn increase risk of blood vessels’ blockage. This mechanism was recently demonstrated by a group of researchers from the Israeli Soroka Clinical Research Center5. 43 patients underwent a nocturnal respiratory assessment during the first 48 hours after stroke symptoms onset. In addition, Serum samples were obtained from all the study participants at the first morning after their admission, in order to track the concentration of some proinflamatory and procoagulant factors. Almost 90% of the patients had SDB (AHI>5) with 51% diagnosed with OSA (AHI ≥15), strengthening previous findings of high prevalence of SDB in patients with stroke. As the mechanism predicted, AHI was found to be correlated with indicators of inflammation and coagulability: IL-6 (ρ=0.37, P=0.02) and PAI-1 (ρ=0.31, P=0.07). PAI-1 was negatively correlated with a saturation nadir (ρ=−0.47, P=0.005) and positively correlated with a desaturation index (ρ=0.41, P=0.02). PAI-1 (pg/mL) was significantly higher in patients with an AHI≥15; mean of 176.64±74.52 versus 98.48±52.58 pg/mL, P=0.003 (Figure 2A). IL-6 (pg/mL, 6.64±5.27 versus 3.14±2.05, P=0.006, Figure 2B) and TNF (pg/mL, 6.39±5.00 versus 3.57±1.87, P=0.022, Figure 2C) were similar.

Figure 2: A, Plasminogen activator inhibitor-1 (PAI-1) levels stratified by apnoea hyponoea index (AHI). PAI-1 concentration (pg/mL) was significantly higher in serum drawn from patients with AHI≥15 than in patients with AHI<15. B, Interleukin-6 (IL-6) levels stratified by AHI. IL-6 concentration (pg/mL) was significantly higher in serum drawn from patients with AHI≥15. C, Tumor necrosis factor (TNF)-α levels stratified by AHI. TNF concentration (pg/mL) was significantly higher in serum drawn from patients with AHI≥15. Horizontal lines represent median values; the upper and lower box limits indicate the 25th and 75th percentile; whiskers represent the 10th and 90th percentiles.

The clinical importance of the last described study goes beyond the mechanism demonstration – it was the first time the respiratory assessment in stroke patients was evaluated using WatchPAT. Since WatchPAT technology is easily used as a bed-side measure in the acute post stroke period and enables rapid diagnosis and therapeutic recommendations, it’s ideal for improvement of secondary prevention.

WatchPAT, Home Sleep Apnea Test device, is an easy to use, effective and accurate tool for OSA diagnosis. You may learn more about WatchPAT and our comprehensive “Total Sleep Solution” for Cardiology practices in www.cardiosleepsolutions.com

  1. Redline, S., Yenokyan, G., Gottlieb, D. J., Shahar, E., O’Connor, G. T., Resnick, H. E., … & Ali, T. (2010). Obstructive sleep apnea–hypopnea and incident stroke: the sleep heart health study. American journal of respiratory and critical care medicine182(2), 269-277.
  2. Bassetti, C. L., Milanova, M., & Gugger, M. (2006). Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke37(4), 967-972.
  3. Ryan, C. M., Bayley, M., Green, R., Murray, B. J., & Bradley, T. D. (2011). Influence of continuous positive airway pressure on outcomes of rehabilitation in stroke patients with obstructive sleep apnea. Stroke, STROKEAHA-110.
  4. Urbano, F., Roux, F., Schindler, J., & Mohsenin, V. (2008). Impaired cerebral autoregulation in obstructive sleep apnea. Journal of applied physiology105(6), 1852-1857.
  5. Ifergane, G., Ovanyan, A., Toledano, R., Goldbart, A., Abu-Salame, I., Tal, A., … & Novack, V. (2016). Obstructive sleep apnea in acute stroke: a role for systemic inflammation. Stroke47(5), 1207-1212.

By Efrat Magidov

Atrial Fibrillation (AFib) is the most common source for abnormal heart rhythm, affecting 33.5 million people worldwide. AFib is caused by disorganized electrical signals, which make the heart’s two upper chambers -called the atria – to quiver, instead of contracting properly. There are numerous risk factors for developing AFib. A relatively new defined risk factor is Obstructive Sleep Apnea (OSA), and the understanding of the exact relationship of it to AFib is still evolving. It is estimated that 21-74% of AFib patients have OSA (exact percentile differs in dependence of OSA definition and the applied measuring technic). Conversely, patients with sleep apnea have around four times higher risk of developing AFib than control patients or the general population. 

A recently published review summarizes the current understanding on how OSA pathophysiology is associated with development of arrhythmogenic substrates, and on the ways in which OSA treatment helps AFib risk management. We present here some of the main reviewed findings.


Mechanisms by which OSA contributes to the pathogenesis of AFib

The repetitive obstructive respiratory events characterizing OSA, cause negative intrathoracic pressure swings which mostly affect the thin-walled atria, causing it to over-stretch. Such acute atrial dilation shortens atrial refractoriness, slows conduction, and increases the occurrence of intra-atrial conduction block. Moreover, the cyclical deoxygenation and reoxygenation associated with sleep apnea increase oxidative stress, contributing to the atrial myocardial damage. In addition to the atrial remodeling factors, the pronounced sympathovagal activation that occurs toward the end of an obstructive episode induces acute electrophysiological arrhythmogenic changes and an increased frequency of premature atrial contractions with the potential to initiate AFib. The progressive atrial structural remodeling, along with transient apnea-associated electrophysiological changes, contributes to the reentry substrate for AFib and creates a complex and dynamic arrhythmogenic substrate in the atrium. Importantly, other chronic comorbidities such as obesity and hypertension further increase AFib risk in OSA patients.

Challenges in OSA diagnosis in AFib patients

As not all AFib patients show symptoms of OSA (e.g. daytime sleepiness), the general recommendation is to screen all AFib patients with a sleep study evaluation. However, it’s important to notice that the Apnea Hypopnea Index (AHI) should not be the only derived index by which OSA is determined; In a cohort study of 3542 adults, the magnitude of nocturnal oxygen desaturation, but not the AHI, was shown to be an independent predictor of new-onset AFib. Thus, evaluating the hypoxemic burden, and not only the AHI, is crucial for successful AFib evaluation. Another factor that should be taken into account in the diagnosis process is screening not only for OSA, but also for Central Sleep Apnea (CSA). For example, in a study of 2911 participants, AFib was associated with CSA more than with OSA. Similarly, rhythm control by electrical cardioversion was not associate with changes in the absolute AHI scores but did have an association with reduced nocturnal central respiratory events and unmasked OSA. Nonetheless, the causal direction between AFib and CSA is not yet clear: the high proportion of central respiratory events may reflect the underlying cardiac disease, rather than representing a causal factor for AFib.

Treatment of OSA in AFib patients

The presence of OSA substantially reduces the efficacy of catheter-based and pharmacological antiarrhythmic therapy, and thus effectively treating OSA is crucial for AFib relief. CPAP, the gold-standard OSA treatment method, had been shown to be effective in AFib treatment. CPAP can help to maintain sinus rhythm in AFib-OSA patients and to reduce AFib recurrence after catheter-based AFib therapy. A recent meta-analysis revealed that patients with OSA not treated with CPAP have 57% greater risk of AFib compared to patients without OSA. However, since all the findings on CPAP efficiency in AFib are based on nonrandomized studies, and since CPAP use was only self-reported, the reviewers point to the incompleteness of the findings and suggest that more randomized prospective observations should be made before concluding on CPAP efficiency in AFib patients. Other OSA/CSA treatment interventions, such as ganglionated plexus ablation and renal sympathetic denervation, had been shown to attenuate AFib in a series of preclinical studies. Lifetime interventions that reduce OSA severity and risk such as weight control further contribute AFib ablation.

Concluding recommendations

Although, as mentioned by the reviewers, there is a need for more studies before finalizing the conclusions on the association between OSA and AFib, the professional societies already incorporate some of the current findings in their recent recommendations. The 2016 European Society of Cardiology guidelines on AFib recommends that consideration be given to elicited clinical symptoms and signs of OSA and CPAP treatment to reduce AFib recurrence and improve AFib treatment results. Similarly, The “2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation” mentions OSA as a relevant modifiable risk factor for AFib and recommends screening for signs and symptoms of OSA when evaluating a patient for an AFib ablation procedure. It also states that treatment of OSA can be useful for patients with AFib, including those who are being evaluated to undergo an AFib ablation procedure.

WatchPAT, Home Sleep Apnea Test device, is an easy to use, effective and accurate tool for OSA diagnosis. The device uses both AHI and oxygen desaturation values to determine OSA severity, and thus is ideal for the evaluation of OSA and AFib association. You may learn more about WatchPAT and our comprehensive “Total Sleep Solutions” for Cardiology practices at www.cardiosleepsolutions.com

By Efrat Magidov

Heart failure (HF) is a chronic, progressive condition in which the heart muscle is weakened and cannot pump enough blood to meet the body’s needs for blood and oxygen. Common symptoms include shortness of breath, coughing, excessive tiredness and leg swelling. In spite of continuous improvement of pharmacological and device therapy, HF remains a major public health problem associated with high morbidity, frequent hospitalizations and readmissions and high economical cost. Therefore, a better understanding of HF’s pathogenesis and co-morbidities is essential for improvement of risk stratification and prevention.

Among multiple co-morbidities, sleep-disordered breathing (SDB) and in particular obstructive sleep apnea (OSA), is the most common; Almost 50% of patients with HF have alterations of ventilation during sleep that can disrupt the positive effects of physiological sleep on the cardiovascular system. In two studies including patients with HF undergoing polysomnography, OSA was detected in 37% and 11% of patients, and the Sleep Heart Health Study – a perspective study comprising 6,424 men and women, indicated that the presence of OSA (defined as an apnoea–hypopnoea index (AHI) ≥10 per hour) favored the appearance of HF independently of other known risk factors, with a 2.20 relative risk.

The complex interaction between HF and OSA seems to be bi-directional; Some factors of HF can favor the collapse of the upper airways and thus increase risk of OSA. For example, HF is characterized by fluid shifts from the legs to central structures (peripheral oedema), especially in supine position, which can lead to upper airways narrowing. Conversely, OSA increase the risk of HF by multiple mechanisms; Obstructive apneas during sleep induce a series of systemic hemodynamic, autonomic, and humoral changes with adverse consequences for the cardiovascular system in individuals with normal ventricular function. The repeated occurrence of apneas and hypopneas has been associated with deranged endothelial function, an increase in the plasma concentration of inflammatory markers, increased platelet agreeability, and increased variability in blood pressure and heart rate.

Schematic representation of the mutual interactions between OSA and HF . (CAD, coronary artery disease; PaCO2 , arterial partial pressure of CO2 ; Pa O2 , arterial partial pressure of O2 ; RAA, renin–angiotensin–aldosterone; VO2 , oxygen consumption rate.)

Moreover, the negative intrathoracic pressure during obstructive apnea results in increased venous return to the right ventricle and increased left ventricular (LV) transmural pressure, both are damaging the LV function. These recurrent events that accompany repeated obstructive apnea determine a further increase of the already elevated sympathetic activity in patients with HF, documented by increased plasma catecholamine. Obstructive events during sleep can also have long-term effects, for example by the induction of genes involved in ventricular remodeling caused by the repetitive increases in wall stress, and by inducing myocyte slippage and contractile dysfunction. Thus there’s a growing understanding that the OSA-HF interaction has causal aspects, and does not reflect mere co-morbidity.

Thus successful diagnosis and treatment of OSA is key for HF relief. In the first study to examine the effects of treating OSA in patients with HF, CPAP treatment was associated with a significant increase in mean LV ejection fraction and a reduction in HF related dyspnoea (shortness of breath). In a study led by the renowned cardiologist Gregory Lip, treatment of OSA by CPAP therapy significantly improved structural and functional changes in the LV. In the long run OSA treatment has also been shown to lower hospital readmission rate and mortality of patients with HF. Diagnosis is not always easy since most patients with HF and OSA do not complain of daytime sleepiness (the most pronounced OSA symptom), probably because of the high sympathetic tone in HF. Thus the occurrence of sleep-disordered breathing might not be identified unless a patient’s bed partner is also interviewed. The current recommendation for physicians is to test for OSA in patients with HF presenting with paroxysmal or recurrent atrial fibrillation, hypertension refractory to optimal HF therapy, increased body mass index and unanticipated pulmonary hypertension or right ventricular dysfunction.

Since attended polysomnography is a complex test that is expensive and not easily available, home sleep apnea test might be the best solution for these patients.

Sources:

  • Butt, M., Dwivedi, G., Shantsila, A., Khair, O. A., & Lip, G. Y. (2012). Left ventricular systolic and diastolic function in obstructive sleep apnea. Circ Heart Fail5, 226-233.
  • Kasai, T. (2012). Sleep apnea and heart failure. Journal of cardiology60(2), 78-85.
  • Parati, G., Lombardi, C., Castagna, F., Mattaliano, P., Filardi, P. P., & Agostoni, P. (2016). Heart failure and sleep disorders. Nature reviews Cardiology13(7), 389.

By Efrat Magidov

Percutaneous Coronary Intervention (PCI) is nowadays part of standard therapy in patients with symptomatic Coronary Artery Disease (CAD). However, the long-term cardiovascular outcomes after this procedure remain suboptimal1, and researchers are still investigating which patient characteristics effect the post-PCI cardiovascular risks. In the past decade, multiple observational studies have examined the association between the presence of Obstructive Sleep Apnea (OSA) and the recurrence of cardiovascular events in patients treated with PCI.  Recently, a group of researchers from Beijing Anzhen Hospital conducted a systematic review and meta-analysis of these studies2, with the aim of shedding more light on the impact of OSA on subsequent cardiovascular outcomes after PCI. Overall 9 studies with 2755 participants were evaluated. In all studies, patients who underwent a successful PCI procedure were recruited prospectively for a sleep study in order to scan for OSA (based on standardized assessment of AHI in all studies, with AHI≥15 as cut-off value in most studies). The median follow-up duration was from 227 days to 5.6 years, and the primary endpoint was major adverse cardiovascular event (MACE), including all-cause or cardiovascular death, myocardial infarction, stroke, repeat revascularization, or heart failure. All studies had no treatments for OSA during this period.

Overall, the prevalence of OSA in patients treated with PCI ranged from 35.3% to 61.8%. OSA was associated with increased risk of MACE after PCI (pooled risk ratio [RR] 1.96, 95% confidence interval [CI]: 1.36–2.81, P<.001). Moreover, the studies show that the presence of OSA significantly increased the incidence of all-cause death (4 studies), cardiovascular death (4 studies) and repeat revascularization (7 studies) in patients after PCI. For example, Zhang and colleagues3 found that the presence of OSA in post-PCI patients significantly increased the incidence of MACEs, the presence of three-vessel disease, the number  of total implanted stents and the length of the stent when compared to the non-OSA group (25.0% vs 16.0%, P=0.038; 34.9% vs 23.4%, P=0.020; 3.3±2.0 vs 2.8±1.9, P=0.007; 83.8±53.1 vs 68.7±48.4 mm, P=0.010). Similarly, Mazaki and colleagues4 found that the cumulative incidence of MACE events was significantly higher in patients with Sleep Disordered Breathing (SDB) than in those without SDB (21.4% versus 7.8%, P=0.006, Figure). Importantly, this effect of SDB on MACE was significant also after adjustment for potential confounders such as age, smoking, ejection fraction, mean SaO2, minimum SaO2, use of b-blockers, and use of statins (adjusted hazard ratio 2.28, 95% CI 1.06–4.92; P=0.035).

This strong effect of OSA presence on complications and morbidity following PCI, motivated some researchers to look into the effects of OSA treatment on the post-PCI outcomes. In one retrospective cohort study, Cassar and colleagues5 found that PCI patients treated for OSA had a statistically significant decreased number of cardiac deaths on follow-up when compared with untreated OSA patients (3% vs. 10% after 5 years, p=0.027),
as well as a trend toward decreased all-cause mortality (p=0.058). However, there was no difference in the number of MACE between the two groups, leaving the question of whether treatment of OSA prevents MACE in need for further investigation.

This review helped clarifying the importance of successful diagnosis of OSA in patients who underwent PCI treatment for better assessment of the risk for potential subsequent cardiovascular events. WatchPAT, Home Sleep Apnea Test device, is an easy to use, effective and accurate tool for OSA diagnosis. You may learn more about WatchPAT and our comprehensive “Total Sleep Solution” for Cardiology practices in www.cardiosleepsolutions.com

  1. Fokkema, M. L., James, S. K., Albertsson, P., Akerblom, A., Calais, F., Eriksson, P., … & Thorvinger, B. (2013). Population trends in percutaneous coronary intervention: 20-year results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Journal of the American College of Cardiology61(12), 1222-1230.
  2. Wang, X., Fan, J. Y., Zhang, Y., Nie, S. P., & Wei, Y. X. (2018). Association of obstructive sleep apnea with cardiovascular outcomes after percutaneous coronary intervention: A systematic review and meta-analysis. Medicine97(17).
  3. Zhang, J. J., Gao, X. F., Ge, Z., Jiang, X. M., Xiao, P. X., Tian, N. L., … & Chen, S. L. (2016). Obstructive sleep apnea affects the clinical outcomes of patients undergoing percutaneous coronary intervention. Patient preference and adherence10, 871.
  4. Mazaki, T., Kasai, T., Yokoi, H., Kuramitsu, S., Yamaji, K., Morinaga, T., … & Ando, K. (2016). Impact of sleep‐disordered breathing on long‐term outcomes in patients with acute coronary syndrome who have undergone primary percutaneous coronary intervention. Journal of the American Heart Association5(6), e003270.
  5. Cassar, A., Morgenthaler, T. I., Lennon, R. J., Rihal, C. S., & Lerman, A. (2007). Treatment of obstructive sleep apnea is associated with decreased cardiac death after percutaneous coronary intervention. Journal of the American College of Cardiology50(14), 1310-1314.

By Efrat Magidov

Patent Foramen Ovale (PFO) occurs in 20-25% of the general population.  Most people with PFO are not symptomatic, and problems ordinarily arise only when the blood-flow’s directionality between the chambers is from the right atrium to the left atrium, a condition known as right to left shunting (RLS). Such right-to-left atrial shunting across the “open door” of the septum premium leads to low arterial O2 tension, promoting the occurrence of thromboembolic events and consequently the risk of ischemic strokes.

In the last two decades numerous studies found a high prevalence of PFO in Obstructive Sleep Apnea (OSA) patients. In the first attempt to check for such correlation, Shanoudy and colleagues1 examined 48 OSA patients (mean age 57 ± 12.3 years) and 24 healthy controls (mean age 65 ± 9.5 years) and found that the prevalence of PFO (detected by means of contrast transesophageal echocardiography) was 4 times higher in patients with OSA (69% vs 17%; p < 0.0001).
To determine the potential contribution of RLS, the researchers systematically measured O2 desaturation following the performance of Valsalva maneuver. They found that the drop in SaO2 was significantly higher in patients with both OSA and PFO, supporting the hypothesis of RLS as the underlying contributor for the observed OSA-PFO interaction. Since this original study, many others have replicated the observed high occurrence of RLS in OSA patients2-5, establishing the strong association between the two pathologies.

Scientists attribute this strong association to the bidirectional pathophysiological effects between PFO and OSA; on one hand the arterial desaturation associated with RLS may play a role in the development of sleep apnea, as the short hypoxemic events following RLS aggravate the already disturbed central breathing regulation in OSA. On the other hand, OSA can make PFO more symptomatic: The rising arterial pressure of carbon dioxide (PCO2) in the context of apneas induces breathing efforts against the closed glottis, which briefly elevates right atrial pressure above left atrial pressure and leads to shunting of de-oxygenated blood to the systemic side in cases of a PFO.

In support of the hypothesis that PFO may exacerbate hypoxemia and unfavorably affect physiologic sleep parameters, significant improvements of OSA symptoms were reported after PFO closure. Rimoldi and colleagues6 looked at 40 newly diagnosed OSA patients, out of which 14 had PFO and underwent initial device closure. During follow-up, apnea–hypopnea index (AHI) decreased from 38.6±16.0 to 30.4±16.1 events per hour in the PFO closure group (p = 0.0034), while not changing in the no-PFO group. This AHI reduction was accompanied by a mitigated oxygen de-saturation index (ODI), a nocturnal systemic blood pressure reduction of 5 mm Hg, and lowered pulmonary pressure values with enhanced left ventricular diastolic function. These results support the above suggested mechanism by showing a normalization of the estimated pulmonary pressure in response to PFO closure, together with augmented diastolic function of the left ventricle and reduced nocturnal systolic blood pressure. Interestingly, some attempts to study the opposite effects of the two pathologies on each other have also been made, revealing beneficial affects of OSA treatment (by means of continuous positive airway pressure)  on RLS severeness7-8, further supporting the bidirectional pathophysiology.

Taken together, these findings stretch the importance of successful diagnosis of OSA in PFO patients (and vice versa) in managing the risks the two pathologies have on each other. WatchPAT, Home Sleep Apnea Test device, is an easy to use, effective and accurate tool for OSA diagnosis. The device also supports accurate monitoring of nocturnal SaO2 and therefor ideal for assessing RLS severeness in those patients. You may learn more about WatchPAT and our comprehensive “Total Sleep Solution” for Cardiology practices in www.cardiosleepsolutions.com

  1. Shanoudy, H., Soliman, A., Raggi, P., Liu, J. W., Russell, D. C., & Jarmukli, N. F. (1998). Prevalence of patent foramen ovale and its contribution to hypoxemia in patients with obstructive sleep apnea. Chest113(1), 91-96.
  2. Beelke, M., Angeli, S., del Sette, M., de Carli, F., Canovaro, P., Nobili, L., & Ferrillo, F. (2002). Obstructive sleep apnea can be provocative for right-to-left shunting through a patent foramen ovale. Sleep25(8), 21-27.
  3. Guchlerner, M., Kardos, P., Liss-Koch, E., Franke, J., Wunderlich, N., Bertog, S., & Sievert, H. (2012). PFO and right-to-left shunting in patients with obstructive sleep apnea. Journal of Clinical Sleep Medicine8(04), 375-380.
  4. Shaikh, Z. F., Jaye, J., Ward, N., Malhotra, A., de Villa, M., Polkey, M. I., … & Morrell, M. J. (2013). Patent foramen ovale in severe obstructive sleep apnea: clinical features and effects of closure. Chest143(1), 56-63.
  5. Mojadidi, M. K., Bokhoor, P. I., Gevorgyan, R., Noureddin, N., MacLellan, W. C., Wen, E., … & Tobis, J. M. (2015). Sleep apnea in patients with and without a right-to-left shunt. Journal of Clinical Sleep Medicine11(11), 1299-1304.
  6. Rimoldi, S. F., Ott, S. R., Rexhaj, E., Von Arx, R., de Marchi, S. F., Brenner, R., … & Seiler, C. (2015). Effect of patent foramen ovale closure on obstructive sleep apnea. Journal of the American College of Cardiology65(20), 2257-2258.
  7. Pinet, C., & Orehek, J. (2005). CPAP suppression of awake right-to-left shunting through patent foramen ovale in a patient with obstructive sleep apnoea. Thorax60(10), 880-881.
  8. Beelke, M. E. (2017). CPAP treatment promotes the closure of a patent foramen ovale in subjects with obstructive sleep apnea syndrome–Results from a pilot study. SM J Neurol Disord Stroke3(1), 1015.

By Efrat Magidov

Bradycardia is defined by the American Heart Association as a heart rate of less than 60 beats per minute (BPM) but adds that what’s “too slow” depends on various factors such as age, physical fitness and physiological condition. During sleep for example, the parasympathetic tone predominates (as NREM sleep occupies 80% of total sleep time), resulting in commonly occurring bradyarrythmias, sinus pauses greater than 2 seconds, and atrioventricular (AV) conduction delays. However, some cases of nocturnal bradyarrythmias are not normal, and reflect acute bradycardia that is prevalent also in wakefulness and can lead to various hazardous complications. Obstructive Sleep Apnea (OSA) was found to be a promoting factor for such incidences.

Numerous studies have demonstrated increased prevalence of bradyarrytmias in OSA patients; In the classic study by Guilleminault et al1 who looked at 400 patients with OSA, 48% had significant nocturnal arrhythmia with 18% bradyarrhythmia, 11% sinus arrest, and 8% AV blocks. These percentiles were surprisingly high, considering that the known prevalence of nocturnal bradyarrythmias in the general population was around 3%2. There were no important differences in age, body weight, apnea-hypopnea index (AHI), or minimum oxygen saturation between those with and without arrhythmias. In a more recent Japanese study by Abe et al3, 1350 OSA patients and 44 control subjects were screened, and significant increase in incidence of sinus bradycardias (12.5% with OSA vs. 2.3% control, p=0.036) and sinus pause (8.7% with OSA vs. 2.3% control, p<0.001) was noted. Importantly, using long-term monitoring by implanted pacemakers reveals an even higher bradyarrythmias percentages (up to 34%4), suggesting that OSA increase the risk for bradycardia even more dramatically.

Not only that OSA increases the prevalence of brayarrythmias, some studies have found that OSA severity is correlated to the extent of bradyarrytmias, with up to 3 times higher incidence of bradycardic arrhythmias in severe OSA patients (compared to milder OSA)5. Such correlation implies that there’s a causal relation between the two, in which OSA promotes bradycardia.
The mechanism by which OSA can reduce the heart rate is demonstrated in the presented figure: during OSA, structural changes occur in the airway to obstruct airflow (Resp), and the resulting apnea activates hypoxic reflexes (SaO2 %), which in turn lead to profound elevation in sympathetic nerve activity (SNA) and subsequently elevation of atrial blood pressure (ABP) and decrease of the heart rhythm  (ECG). Various studies confirmed that the elevation in vagal tone is the key contributor to the bradyarrythmias, whereas other factors such as sinus node anatomy or artioventrucular conduction are largely intact in OSA patients6. The finding that intravenous atropine administration eliminates the marked sinus arrhythmia and bradyarrhythmias observed in such patients6 supports this hypothesis. Moreover, mimicking OSA in wakefulness with the Mueller maneuver results in induced bradycardia7, further confirming that the combination between prolonged negative intrathoracic pressures and the resulting hypoxemia is the necessary underlying “mix” i n this unique pathophysiology.

The crossover between Bradyarrythmias and OSA is also apparent by the beneficial implications of OSA treatment on bradycardia severity. Specifically, Positive airway pressure (PAP) therapy has been shown to be highly effective in abolition and reduction of bradyarrhythmias. In the Abe study for example, sinus bradycardia (p<0.001) and sinus pauses (P=0.004) were dramatically reduced by CPAP therapy3. Thus, the current recommendation for physicians for patients with bradyarrhythmias who are at risk for OSA, is to perform overnight polysmonography prior to pacemaker implantation, especially in younger individuals without underlying cardiac disease. Permanent pacemakers should be considered if significant bradyarrhythmia or pauses persist after adequate treatment trial with PAP therapy.

WatchPAT, Home Sleep Apnea Test device, is an easy to use, effective and accurate tool for polysomnography and OSA diagnosis. You may learn more about WatchPAT and our comprehensive “Total Sleep Solution” for Cardiology practices in www.cardiosleepsolutions.com

  1. Guilleminault, C., Connolly, S. J., & Winkle, R. A. (1983). Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. American journal of cardiology52(5), 490-494.
  2. Fleg, J. L. & Kennedy, H. L. (1982). Cardiac arrhythmias in a healthy elderly population: detection by 24-hour ambulatory electrocardiography. Chest, 81, 302–307.
  3. Abe, H., Takahashi, M., Yaegashi, H., Eda, S., Tsunemoto, H., Kamikozawa, M., … & Ikeda, U. (2010). Efficacy of continuous positive airway pressure on arrhythmias in obstructive sleep apnea patients. Heart and vessels25(1), 63-69.
  4. Simantirakis, E. N., Schiza, S. I., Marketou, M. E., Chrysostomakis, S. I., Chlouverakis, G. I., Klapsinos, N. C., … & Vardas, P. E. (2004). Severe bradyarrhythmias in patients with sleep apnoea: the effect of continuous positive airway pressure treatment: a long-term evaluation using an insertable loop recorder. European heart journal25(12), 1070-1076.
  5. Rossi, V. A., Stradling, J. R., & Kohler, M. (2013). Effects of obstructive sleep apnoea on heart rhythm. European Respiratory Journal41(6), 1439-1451.
  6. Cutler, M. J., Hamdan, A. L., Hamdan, M. H., Ramaswamy, K., & Smith, M. L. (2002). Sleep apnea: from the nose to the heart. The Journal of the American Board of Family Practice15(2), 128-141.
  7. Huettner, M., Koehler, U., Nell, C., Kesper, K., Hildebrandt, O., & Grimm, W. (2015). Heart rate response to simulated obstructive apnea while awake predicts bradycardia during spontaneous obstructive sleep apnea. International journal of cardiology186, 216-218.

By Efrat Magidov

Abdominal aortic aneurysm (AAA) is a potentially life-threatening condition that may be exacerbated by Obstructive Sleep Apnea (OSA) which has been verified as an independent causal factor in the pathogenesis of hypertension and vascular dysfunction. More specifically, several pathomechanisms have been suggested to account for the potential adverse effect of OSA on AAA:

  1. The intrathoracic pressure changes leading to shear stress on artery walls;
  2. Intermittent hypoxia leading to oxidative stress, sympathetic stimulation, and possibly atherosclerosis;
  3. Arousal-induced sympathetic activation inducing subsequent repetitive blood pressure surges and chronic hypertension.

The attempts to link obstructive sleep apnea (OSA) to AAA are based on early studies of patients with Marfan’s syndrome. In the early 90s, it was first suspected that OSA may have deleterious effects on the aorta in Marfan’s syndrome patients. Later researchers demonstrated higher prevalence of OSA in those patients and described a correlation between OSA severity (as measured by the apnea-hypopnea index (AHI)) and aortic root diameter (r=0.5, p<0.001). In a follow-up longitudinal study of 44 Marfan’s syndrome patients, only subjects with OSA developed an aortic event (after a median follow-up time of 29 months). Although the relative risk of OSA was not successfully assessed due to the small sample size, this remains the only longitudinal study which investigated the effect of OSA on the aorta by means of events (rather than disease parameters).1

Several cross-sectional studies on the general population found a positive association between the aortic root diameter and OSA severity.
Interestingly, simulating OSA in healthy volunteers with the use of Muller’s maneuver induced considerable changes in both blood pressure and proximal aortic diameter and area, probably due to increased aortic dilatory pressures. Observational studies have consistently reported that OSA is highly prevalent among patients with AAA. In one such study by Mason and colleagues, 127 patients (11 women, mean age 67.9±6) with an abdominal aortic measurement greater than or equal to 30 mm were examined. Home sleep monitoring was used to assess OSA presence in terms of ODI (>4%) and AHI. Approximately 40% of the patients were found to have an ODI greater than 10 per hour, representing a 5-fold greater incidence than in a comparable normal population. Similarly, 29% of the patients had AHI greater than 15, almost 2 times higher than the normal prevalence values.
These results correspond to other studies demonstrating up to 60% OSA presence in AAA patients which is significantly higher than the estimated prevalence of 17% in the general population. Importantly, subjective reports did not reveal a correlative sleepiness, suggesting that daytime sleepiness is not suitable for detecting OSA in AAA patients.

The researchers went on to examine whether OSA can explain occurrences of AAA expansion. They compared the AAA diameter of two duplex scans; one from the recruitment phase and another before the sleep study (median follow-up time was 18 months). Severe OSA, represented by ODI and AHI greater than 30, was found to be significantly associated with a high AAA expansion rate (ODI- 2.9 mm per year, p=0.009; AHI- 2.2 mm per year, p=0.043 – Figure 1). These results were derived after adjustment to cardiovascular risk factors and medication use, and therefore represent OSA relative risk. The presence of correlation only at severe OSA suggests a threshold effect rather than a simple linear dose–response relationship between OSA severity and AAA expansion rate.2

Through these studies, it is becoming clear that successful diagnosis of OSA in AAA patients can be an important factor in managing the risk of lethal aortic complications. Future studies will hopefully examine the potential beneficial effects of OSA-treatment on AAA. WatchPAT, a home sleep apnea test device, is a simple, accurate and reliable tool for OSA diagnosis. You may learn more about WatchPAT and our comprehensive “Total Sleep Solutions” for Cardiology practices at www.cardiosleepsolutions.com

sources:

  1. Gaisl, T., Bratton, D. J., & Kohler, M. (2015). The impact of obstructive sleep apnoea on the aorta. European Respiratory Journal46(2), 532-544.
  2. Mason, R. H., Ruegg, G., Perkins, J., Hardinge, M., Amann-Vesti, B., Senn, O., … & Kohler, M. (2011). Obstructive sleep apnea in patients with abdominal aortic aneurysms: highly prevalent and associated with aneurysm expansion. American journal of respiratory and critical care medicine183(5), 668-674.