By Gilad Glick | September 6, 2017

Why has sleep breathing management not integrated into cardiology care pathway?

In my previous article, I briefly mentioned the increased awareness and the broad acceptance of the role of Sleep Apnea in Cardiac disease and the main studies and scientific statements published by the ESC, AHA and ACC which were the driver behind the American Sleep Academy  “Sleep Apnea Hurts Hearts” campaign.

The question remaining is:

If the link between Sleep Apnea and several main cardiovascular diseases such as Atrial Fibrillation and Hypertension has been broadly accepted – why DO most heart patients remain undiagnosed and majority of cardiologist are not integrating this factor into their care pathway?

There are two main barriers that we hear about from practitioners:

The first obstacle is awareness of cardiologists and their patients about how prevalent Sleep Apnea is among cardiology patients and the fact that most will not be visually detected.  Most cardiologists “eyeball” patients to assess obvious signs of sleep apnea such as a thick neck, visually high BMI, chronically blocked nose etc.

This results in significant underdiagnosis of sleep apnea as demonstrated in a recent study conducted in Montefiore medical center (New York) by Dr. Wharton and Dr. Zaremski.  Their conclusion was that systematic and broad screening is recommended in cardiology clinics, with  84% of their patients screened positive for sleep apnea, while BMI was a poor predictor of screening results.

The second obstacle lies in the dynamics of referring a patient to a sleep medicine physician: to start with, cardiology patients are pre-occupied with their heart condition, and do not understand the link between their Sleep Apnea and their heart. If not given a motivational explanation by the cardiologist or pressed hard to show up at the sleep doctor – most will not make this extra effort this requires.

Furthermore, when patients finally overcome this obstacle and wish to take a sleep study, they encounter the lack of sufficient sleep certified physicians, resulting in inconvenient waiting times, sometimes reaching months combined with geographical accessibility limitations driven by the tendency to diagnose simple OSA with full in-lab polysomnography (PSG) as first line procedure which has a host of barriers imbedded in it.

For example, more and more medical insurers will require Home Sleep Apnea Test (HSAT) before authorizing PSG. Sleep physicians, preferring PSG – require the patient to undergo 2 procedures or debate the insurance. Not an insignificant portion of the patients refuse to undergo in-lab PSG because they are worried about being hospitalized or fear the financial impact of the co-pay.  Sleeping at a sleep lab is also not an experience people look forward to.

Harnessing the simplicity of home sleep tests

As a result, the integration between cardiology and sleep needs to be done differently.  Home sleep tests, which revolutionized sleep medicine and made sleep studies available to all patients, whether they lived far, had a disability or simply liked sleeping in their own beds – has the promise to enable the cardiology patient population to easily manage their sleep. By either moving the point of dispatch to Cardiology or even to direct shipment – just like Amazon did with retail.

How do we solve these challenges?

Recently Itamar Medical launched the Total Sleep Solution program that has all the components necessary to successfully integrate Sleep medicine into Cardiology patient care. It has:

(A) Cardiology oriented screening tools – combined with patient education materials to achieve efficient accessibility for all patients while maintaining a seamless and pleasant patient experience.

(B) Unique Home Sleep Testing – Enabling Technology with the WatchPAT home sleep test which offered unparalleled simple user experience, requiring only a finger sensor and a watch instead of all the cumbersome home sleep tests available. It’s FDA cleared, listed as technically adequate in the AASM guidelines for HSATs[1] and fully reimbursed*

(C) Remote sleep expert interpretation – Cloud based technology that enables immediate transmission of the test report to a sleep specialist for interpretation and diagnosis, because we at Itamar understand cardiologists are not interested in practicing sleep or pulmonary medicine and

(D) Connection to sleep apnea management service providers of high quality that understand the standards Cardiologists are expecting and help ensure patient compliance and adherence.

To learn more about our comprehensive customizable solutions, you may always contact your local Itamar Sales Representative or leave your details here:

[1] Kapur VK, et al. 2017 “Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline.”J Clin Sleep Med. 13(3):479–504.

*Please verify with your insurance mix as local policies varies

By Gilad Glick

To some it may come as a surprise that SDB (Sleep Disordered Breathing) or Sleep Apnea is common among AFIB patients, and that it has been found an independent major risk factor, significantly affecting outcomes.

However, leading electrophysiologists and cardiologists have already been increasingly aware of the link between Atrial Fibrillation and Sleep Apnea.  Such clinicians seek to actively diagnose OSA and integrate effective screening tools to identify Sleep Apnea risk among their patients as part of their patient care pathway. In addition, the ESC and ACC have updated their AFib guidelines to include sleep apnea screening and treatment in consideration of accumulating evidence linking the two

Here’s a brief overview of the AFIB practice guidelines and evidence related to the link between sleep apnea and AFIB.

Clinical Practice Guidelines  

According to the 2016 ESC guidelines for the management of atrial fibrillation interrogation for clinical signs of obstructive sleep apnea (OSA) in all AFib patients is a Class IIa, level B recommendation. Further, once OSA is diagnosed, treatment should be optimized to improve AF treatment results in appropriate patients (Class IIa, level B).¹

These guidelines have recently been cited by the ACC.

The Heart Rhythm Society also published a patient brochure to educate AFib patients about Sleep Apnea symptoms and the importance of getting tested for sleep apnea and treating it to improve their overall health. You can find it here².

The link between Atrial Fibrillation and Sleep Apnea

Obstructive Sleep Apnea is a known risk factor associated with both onset and recurrence of AFib after therapy. Sleep Apnea is now established as an independent predictor of AFib with a HR of 2.18.⁸

How common is Sleep Apnea among AFib patients?

In the general population, OSA (Obstructive Sleep Apnea) affects approximately 24% of men and 9% of women, between 30 and 60 years of age. The prevalence of Sleep Apnea rises with age. Up to 80% remain undiagnosed.^2,3

Among AFib patients, the comorbidity of Sleep Apnea is estimated at about 49%.^4,5 A recent study in Sweden showed a prevalence of over 80 percent of sleep apnea among patients treated for atrial fibrillation.

Mehra and colleagues showed, with a large, prospective, community-based cohort, that individuals with Sleep apnea had 4 times the odds to develop AFib as those without SDB (OR 4.02, 95% CI 1.03- 15.74) after adjustment for age, sex, BMI and prevalent coronary heart disease.⁶

How does Sleep Apnea and its management affect AFib outcomes?

A major challenge for electrophysiologists nowadays is a persistently high 1-year AFib recurrence despite treatment by cardioversion, catheter ablation or drugs. Often a repeat ablation is necessary to treat AFib efficiently, and AFib may still recur despite these additional interventions. Electrophysiologists were concerned about a group of patients who seemed refractory to maintenance of sinus rhythm despite aggressive therapy.

In recent years, multiple published studies linked untreated sleep apnea with substantial increases in the rate of AFIB recurrence – practically telling us that the common 20% – 40% recurrence rate has two groups:  those with Sleep Apnea, about half the patients, with a much higher rate of AFib recurrence and the other half, without Sleep Apnea, with lower rate.

Moreover, when patients with confirmed OSA complied properly with CPAP Sleep Apnea treatment, ablation success rates improved to match those among non-apnea sufferers in all AFib types.

Sleep Apnea Treatment – what is the effect on AFib outcomes?

The first to show that treatment of Sleep Apnea correlated with a lower incidence of atrial fibrillation recurrence was the team led by Dr. Virend Somers⁴.

As far back as 2010, a group led by Dr. Andrea Natale, showed that Sleep Apnea was an independent predictor for PVAI failure, and that treatment with CPAP improved PVAI success rates. Patients not treated with CPAP in addition to having higher prevalence of non-PV triggers were 8 times more likely to fail ablation.⁷

A broader landmark study was published by Dr. Fein, Dr. Anter and colleagues. These authors found that AFib-free survival rate among patients with CPAP-treated OSA was similar to a group of patients without OSA (71.9% vs. 36.7%; p = 0.01). AFib recurrence following PVI in CPAP-nonuser patients was significantly higher (HR: 2.4, p < 0.02) and similar to that of OSA patients managed medically without ablation (HR: 2.1, p = 0.68).  Summary of the study conclusions is below.⁸

The authors concluded that CPAP is an important therapy in OSA patients undergoing RF Ablation that improves arrhythmia free survival. RF Ablation offers limited value to OSA patients not treated with CPAP.⁸

A recent study from Duke University found that patients who underwent focal impulse and rotor modulation (FIRM) ablation and also suffered from OSA, exhibited increased rotor prevalence, driven predominantly by an increase in RA rotors. CPAP therapy was associated with fewer RA rotors.¹⁰

Finally, a meta-analysis conducted by Dr. Shukla, Dr. Chinitz and colleagues from the Charney Division of Cardiology, New York University Langone Medical Center in NYC,  found that the association between CPAP and reduced AF recurrence remained the same whether treated medically or with catheter ablation.⁹

CPAP use in patients with OSA was associated with a reduced relative risk of AF recurrence in comparison to non-users – with a 42% relative risk reduction and a very highly significant statistical data. Authors noted that the effect remained consistent and similar across patient populations irrespective of whether they undergo PVI.⁹

Clinical practice: Implementing AFib guidelines related to Sleep

Cardiologists are becoming increasingly aware of the possibility of the benefits of home sleep testing and cloud technology to connect with sleep specialists and pulmonologists and conduct wide screening for undiagnosed sleep breathing disorders, refer for treatment and follow up on therapy and CVD outcomes.

Given the strength of evidence, it’s no surprise that electrophysiologists were the first to take practical steps in integrating sleep medicine in cardiology care.

Since we started offering the WatchPAT home sleep test to cardiology departments around the world, we hear from physicians that they no longer convince their patients to take the test. The patients are eager to get tested at home as the process is so simple and cardiologists explain how essential it is to improve outcomes and AFib recurrence. The WatchPAT home sleep test is as easy for patients to use as a home holter monitor and clinicians can view the report via the cloud and share with pulmonologists to obtain interpretation.

And because cardiologists were anxious to verify that patients comply with treatment and linked non-usage to recurrence of AFib, we started connecting them with leading service and CPAP providers. We now offer customized solutions to all types of institutions or clinics, depending on size, workflow and physician needs.

To learn more about sleep and arrhythmias – we recommend this video series of the scientific symposium we sponsored at HRS in 2016.

I invite you to join learn more about Cardio Sleep solutions here.

References:

1 2016 ESC Guidelines for the Management of Atrial Fibrillation Developed in Collaboration With EACTS. Eur Heart J 2016; Aug 27:[Epub ahead of print]
2 http://resources.hrsonline.org/pdf/patient/HRS_AF_SleepApnea_R3.pdf
3 Young et al. The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults. N Engl J Med 1993; 328:1230-1235
4 Gami AS, Pressman G, Caples SM, et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation 2004; 110:364–7.  [PubMed]
5 Seet & Chung, Anestsiology Clin 2010
6 Mehra R, Sleep apnea ABCs: airway, breathing, circulation, Cleve Clin J Med 2014;81:479–89 | Pubmed
7 Dimpi Patel el al “Safety and Efficacy of Pulmonary Vein Antral Isolation in Patients With Obstructive Sleep Apnea” Circulation Arrhy and Electro, 2010
8 Fein AS, Anter E., et al. Treatment of obstructive sleep apnea reduces the risk of atrial fibrillation recurrence after catheter ablation. J Am Coll Cardiol. 2013; 62:300-305. | Pubmed
9 Shukla et al. CPAP Use on Recurrence of AF in Patients with OSA JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 1, NO. 1-2, 2015
10 Friedman et al, Obstructive sleep apnea is associated with increased rotor burden in patients undergoing focal impulse and rotor modification guided atrial fibrillation ablation,  Europace, eux248,  https://doi.org/10.1093/europace/eux248

By – Gilad Glick

According to latest CDC data, 1 in 3 American adults suffers from hypertension^[1], and only about 54% have their condition under control^[2]. This is surprising, given the extensive research on Hypertension as a cardiovascular risk factor and the wide variety of hypertensive drugs available. Patients also have numerous home BP measurement devices they can use. Despite all this, cardiologists and primary care providers still struggle with drug-resistant hypertension or simply badly controlled blood pressure.

Recently the AHA launched a major initiative called TargetBP committed to reducing the number of Americans with uncontrolled blood pressure. TargetBP focuses on 3 key areas with M.A.P framework: M-Measurement – accurate measurement every time; A- Action taken rapidly to address high readings; and P – Partnering with patients, families and communities to promote self-management. The program uses latest science in blood pressure control and has already shown promising results.

Starting at home

There are simple actions you can take today to improve the way hypertension is managed and how patients self-manage their condition and they both can be done at home: (1) Get blood pressure measured at home and (2) control for Sleep Apnea

Help your patients accurately measure their Blood Pressure at home

The American Heart Association recommends home monitoring for all hypertensive patients to help healthcare providers determine whether treatments are effective. And accurate measurement is at the heart of TargetBP.

The advantages of blood pressure home monitoring are known. Self-tracking of blood pressure helps empower patients to take ownership of their treatment. Clinically, a single reading at the doctor’s office is not enough, as blood pressure fluctuates and one measurement is not enough to ascertain patient’s response to medication. “White-coat” syndrome leading to higher readings at the doctor’s office is another reason to add home monitoring, where the patient is more relaxed.

Recently, though, a study in the American Journal of Hypertension showed that some home monitors can be quite inaccurate.[3]

This is the reason why many cardiologists now encourage patients to bring their automated blood pressure devices to their clinic visits once or even twice to measure their accuracy against the clinic-standard manual measurement. While they do this, patients learn how to accurately use the device.

TargetBP prepared a set of educational materials to help clinicians communicate with their patients and teach them about proper BP measurement and management:

7 simple tips to get an accurate blood pressure reading

Other TargetBP resources for patients can be found here.

Screen your patients for Sleep Apnea

And for patients at risk – refer to a home sleep test

Sleep Apnea is a major comorbidity to hypertension. In fact, sleep apnea was found in 83% of adults with drug-resistant hypertension.[4]

A meta-analysis published in the Journal of Hypertension in 2014 suggests that untreated sleep apnea may be a major factor in why medications appear to be less effective in reducing high blood pressure in some people. Further, the study shows that CPAP therapy may be the key to helping those with difficult to treat hypertension get their blood pressure under control.[5]

Already in 2008, Prof. VK Somers and colleagues published the AHA/ACCF scientific statement, Sleep Apnea and Cardiovascular disease. This statement was published by the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing, in collaboration with NIH.[6]

In this statement, authors review the evidence related to Sleep Apnea and CVD and proposed to treat OSA as an independent risk factor for the development of essential hypertension, since it can precede and predict the onset of hypertension (as demonstrated in the Wisconsin Sleep Cohort Study, which noted a consistent OSA-BP dose-response relationship, even after controlling for age, sex, BMI, and antihypertensive medications).6

Authors also noted that the weight of evidence has led the most recent Joint National Committee on the Detection and Management of Hypertension to identify OSA as an important identifiable cause of hypertension. 6

Also in 2008, AHA’s scientific statement: Resistant Hypertension: Diagnosis, Evaluation, and Treatment, listed Obstructive sleep apnea as a common secondary cause of resistant hypertension. It also recommended to screen for obstructive sleep apnea as a first step in screening for secondary causes of resistant hypertension. “Obstructive sleep apnea should be treated if present” according to statement. Treatment by CPAP is recommended, with the largest benefit in patients with severe sleep apnea and in patients already receiving antihypertensive treatment.[7]

You can easily identify patients at risk for sleep apnea with basic STOP-BANG questionnaire and can prescribe a home sleep test or an in-lab study when necessary. It’s also very easy to use our HIPAA-compliant Cloud-PAT platform to share the report with a sleep specialist or pulmonologist and get the interpretation.

Our simple screening methods can be easily integrated into any cardiac care pathway. Watch Prof. David Vorchheimer talk about his experience in successfully implementing CardioSleepSolutions in the cardiology clinics he manages.

We have tailored our solutions to suit all cardiologists and clinics of all sizes.

Contact us to arrange a discussion with one of our users or reps.

And just as a patient easily measures blood pressure at home, our WatchPAT home sleep test is one of the easiest most convenient sleep apnea tests on the market, while providing excellent clinically-validated data.

References:

^[1] Merai R, Siegel C, Rakotz M, Basch P, Wright J, Wong B; DHSc., Thorpe P. CDC Grand Rounds: A Public Health Approach to Detect and Control Hypertension. MMWR Morb Mortal Wkly Rep. 2016 Nov18;65(45):1261-1264

^[2]  Yoon SS, Fryar CD, Carroll MD. Hypertension Prevalence and Control Among Adults: United States, 2011-2014. NCHS data brief, no 220. Hyattsville, MD: National Center for Health Statistics; 2015.

[3] Ringrose J et al; An Assessment of the Accuracy of Home Blood Pressure Monitors When Used in Device Owners, American Journal of Hypertension, Volume 30, Issue 7, 1 July 2017, Pages 683–689

[4] Logan AG et al, High prevalence of unrecognized sleep apnoea in drug-resistant .J Hypertension. 2001 Dec;19(12):2271-7.

[5] Iftikhar I et al, Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis, Journal of Hypertension: December 2014 – Volume 32 – Issue 12 – p 2341–2350

[6] Somers VK et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. Circulation. 2008;118:1080–1111.

[7] Calhoun et al, Resistant Hypertension: Diagnosis, Evaluation, and Treatment A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51:1403-1419

By Gilad Glick

• Mechanical Stretch due to negative Intra-Thoracic Pressure

Obstructive Sleep Apnea is defined as a physiological event that happens when upper airway is partially or completely blocked during sleep. Mostly, as a result of collapsed soft tissue in the throat while lying on your back. This makes your diaphragm and chest muscles work harder to open the obstructed airway and pull air into the lungs. As the obstruction persists, significant negative pressure is developed in the inner space of the thorax. Breathing usually resumes when the sympathetic nerve system is activated, regaining control over the throat muscles and reopening the airways –  ending up with a loud gasp, snort, or body jerk. You may not sleep well, but you probably won’t be aware that this is happening.

Since the heart is “sitting” on the diaphragm on the lower end and attached to the aorta and pulmonary veins in the upper part, this negative intra-thoracic pressure is causing the heart muscle to stretch mechanically, potentially causing micro scarring of the left atrial tissue which in turn promotes arrhythmogenic characteristics (in particular Atrial Fibrillation).

Given that a moderate to severe sleep apnea patients experience Sleep Apnea events between 15 and 60 times an hour, or hundreds of times a night – the accumulated damage can be significant.

• Frequent interruptions to the sympathetic nerve system

As described above, most sleep apnea events end with a surge of the sympathetic branch of the autonomic nerve system. It is also known that the heart electrical system is tightly connected and to some degree regulated by this exact same system.  Therefore, it is assumed that the load sleep apnea is imposing on the system has a profound impact on the promotion of irregular electrical activation patterns or arrhythmias.

• Drop in blood oxygen saturation leads to Oxidative Stress

There are serious negative consequences of repetitive oxygen desaturations, also known as Intermittent hypoxia, occurring during Sleep Apnea and affecting the entire cardiovascular system.

“The two most significant are the formation of reactive oxygen species (ROS) and inducing oxidative stress (OS). ROS can damage biomolecules, alter cellular functions and function as signaling molecules in physiological as well as in pathophysiological conditions. Consequently, they promote inflammation, endothelial dysfunction and cardiovascular morbidity. Oxidative stress is also a crucial component in obesity, sympathetic activation and metabolic disorders such as hypertension, dyslipidemia and type 2 diabetes/insulin resistance, which aggregate with OSAHS.”[1]

Another correlation was found between the Apnea/Hypopnea Index (AHI) severity, and Lipid peroxidation, protein oxidation [2], and impaired endothelial function which is a pivotal factor in vascular pathogenesis, which is known to be adversely affected due to the promotion of oxidative stress and inflammation, resulting in educed Nitric Oxide, (NO) availability and thus diminishing its vital vascular repair capacity [3][4].

To learn more about how EPs and cardiologists address sleep apnea in their cardiac care pathway to improve outcomes, quality of life and reduce AFib recurrence – read the article “How Electrophysiologists Reduce AFib Recurrence by Addressing Sleep Apnea”

To learn more about how our Cardio-Sleep customized solutions can help you address Sleep Apnea as part of your cardiac care workflow, while maintaining a positive patient experience and minimal workload on your staff – contact us here.

[1] Lavi et al, Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link.  Eur Respir J 2009; 33: 1467–1484

[2] .  Hopps et al, Lipid peroxidation and protein oxidation are related to the severity of OSAS. European Review for Medical and Pharmacological Sciences 2014; 18: 3773-3778

[3] Oxidative Stress, and Repair Capacity of the Vascular Endothelium in Obstructive Sleep Apnea

Jelic S, Padeletti M, Kawut SM, Christopher Higgins C, Canfield SM, Onat D, Paolo C. Colombo PC,  Basner RC, Factor P,  and LeJemtel  TH. Circulation. 2008 April 29; 117(17): 2270–2278.

[4] Scherbakov et al, Sleep-Disordered Breathing in Acute Ischemic Stroke: A Mechanistic Link to Peripheral Endothelial Dysfunction. J Am Heart Assoc. 2017 Sep 11;6(9).

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 Afib² within 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 triggers⁴ and 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. Circulation, 98(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 Cardiology, 57(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 medicine, 173(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 Medicine, 352(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. Chest, 127(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 medicine, 182(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. Stroke, 37(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 physiology, 105(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. Stroke, 47(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.

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 Fail, 5, 226-233.
• Kasai, T. (2012). Sleep apnea and heart failure. Journal of cardiology, 60(2), 78-85.
• Parati, G., Lombardi, C., Castagna, F., Mattaliano, P., Filardi, P. P., & Agostoni, P. (2016). Heart failure and sleep disorders. Nature reviews Cardiology, 13(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 Cardiology, 61(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. Medicine, 97(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 adherence, 10, 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 Association, 5(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 Cardiology, 50(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 patients^2-5, 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 severeness^7-8, 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. Chest, 113(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. Sleep, 25(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 Medicine, 8(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. Chest, 143(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 Medicine, 11(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 Cardiology, 65(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. Thorax, 60(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 Stroke, 3(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 cardiology, 52(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 vessels, 25(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 journal, 25(12), 1070-1076.
5. Rossi, V. A., Stradling, J. R., & Kohler, M. (2013). Effects of obstructive sleep apnoea on heart rhythm. European Respiratory Journal, 41(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 Practice, 15(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 cardiology, 186, 216-218.