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    Cardiac Resynchronization Therapy and ObstructiveSleep-Related Breathing Disorder in Patientswith Congestive Heart FailureALAA SHALABY, M.D.,*, CHARLES W. ATWOOD, M.D.,*, FAITH SELZER, PH.D.,MATTHEW SUFFOLETTO, M.D., JOHN GORCSAN III, M.D.,

    and PATRICK STROLLO, M.D.From the*Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Divisions of Cardiology,University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Pulmonary, Allergy and Critical Care Medicine,Pittsburgh, Pennsylvania; and Epidemiology Data Center, Graduate School of Public Health, University ofPittsburgh, Pittsburgh, Pennsylvania

    Objectives: To assess the impact of cardiac resynchronization therapy (CRT) with or without atrialoverdrive pacing, on sleep-related breathing disorder (SRBD).

    Introduction:CRT may have a positive influence on SRBD in patients who qualify for the therapy. Dataare inconclusive in patients with obstructive SRBD.

    Methods:Consenting patients eligible for CRT underwent a baseline polysomnography (PSG) 2 weeksafter implantation during which pacing was withheld. Patients with an apnea hypopnea index (AHI) 15but

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    Methods

    The study was designed by the investigatorsand sponsored by Boston Scientific (Natick, MA,USA). The conduct of the study was monitored

    by the Epidemiology Data Center of the Graduate

    School of Public Health, University of Pittsburgh,who were also responsible for both the integrityand analysis of the data. All patients submitteda written informed consent and the institutionalreview boards of both Veterans Affairs PittsburghHealthcare System and the University of Pitts-

    burgh approved the study.

    Patient Enrollment

    All patients were recruited at the Veter-ans Affairs Pittsburgh Healthcare System. Allcandidates for CRT defibrillator were eligiblefor enrollment while randomization occurredonly after the screening polysomnogram (PSG)

    as detailed below. Patients were consideredCRT defibrillator candidates if they had a lifeexpectancy of at least 1 year, cardiomyopathy withan EF of less than 36%, were in CHF New YorkHeart Association (NYHA) functional class III, andhad a QRS duration >120 ms. All patients were onoptimized stable medical therapy for CHF.

    Patients were excluded by any of the fol-lowing: unstable angina or decompensated heartfailure, atrial fibrillation, prior indication forCPAP, severe renal insufficiency, medication withnarcotics or benzodiazepines that could not bediscontinued for five half lives prior to any

    PSG, current alcohol or drug abuse, or if onbaseline screening PSG the mean sleep heart rate(MSHR) was found to be greater than 80 beats perminute (bpm) or the apnea hypopnea index (AHI)exceeded 50/hour on any (baseline or subsequent)PSG during the study. Severe symptomatic sinus

    bradycardia with persistent heart rates below40 bpm was also an exclusion.

    Study Procedure

    Implant and Randomization

    Enrolled patients were implanted with atransvenous CRT defibrillator device according

    to established techniques. Subsequently, patientswere discharged for a run-in period of 2 weekswhere only backup demand ventricular pacingwas programmed (VVI 40 bpm) and pacing fromthe LV lead was disabled. Two to 4 weeksafter implant, the patients underwent a baselinescreening PSG. Patients with an AHI between14 and 50 events/hour with a mean atrial rate

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    CRT AND SRBD

    peptide (BNP), overnight urine norepinephrine,and plasma norepinephrine.

    Echocardiographic Assessment of Dyssynchrony

    Blinded study echocardiograms were ob-

    tained at the University of Pittsburgh ResearchEchocardiography Laboratory at enrollment, andafter CRT at the time of each follow-up PSG,to assess for LV function and the presenceof dyssynchrony, as previously described. Thisechocardiogram for research purposes was ob-tained only after the patient was enrolled. Insummary, for tissue Doppler longitudinal dyssyn-chrony analysis, digital tissue Doppler cine-loopsfrom three consecutive beats were obtained fromthe three standard apical views. For speckle-tracking radial strain dyssynchrony analysis, cine-loops from three consecutive beats were obtainedfrom mid-LV short-axis. Off-line analysis of

    tissue Doppler longitudinal velocity and speckle-tracking radial strain were then performed.26 LVEFand volume by biplane Simpsons rule weremeasured in each case.27 The standard deviationof 12-site time to peak systolic velocity (Yu index)was also calculated.28,29 The opposing wall delaywas determined as the maximal difference in timeto peak systolic velocity across opposing my-ocardial walls in any standard apical view, with65 ms defined as significant dyssynchrony.26,28,30

    Significant radial dyssynchrony was defined as thedifference between the anteroseptal and posteriorwall peak strain 130 ms.26 A tissue Doppler

    measure of right ventricular dyssynchrony wasincluded in this study. Regions of interest wereplaced in the basal and mid segments of the RVfree wall and interventricular septum in the four-chamber view.31

    Patient Follow-Up

    Patients underwent two follow-up PSGs at12-week intervals. At each visit, including the

    baseline visit, the patients received a brief historyand physical, a 12-lead electrocardiogram, a 6-minute walk test, and an echocardiogram. Ateach visit including baseline, patients completedthe following standard questionnaires: PittsburghSleep Quality Index, Epworth Sleepiness Scale,and the Minnesotal Living with Heart FailureQuestionnaire (MLWHFQ), in addition to a self-assessment global score whereby on a scale of 13patients reported their perception of worsening,no change, or improvement in health status.

    Endpoints

    The primary endpoint was reduction in AHIfrom baseline to subsequent visits. Secondaryendpoints included change in arterial oxygen

    saturation, sleep efficiency, sleep architecture, andcardiac and neurohormonal markers.

    Response to CRT

    Response to CRT was assessed based onchange in EF, 6-minute walk test, and self-assessment global score. Patients were consideredresponders if the last echocardiogram demon-strated an absolute improvement of 5% or 15%relative to the baseline in addition to anyimprovement in 6-minute walk test and globalscore.

    Statistical Analysis

    Baseline demographic and clinical characte-ristics, sleep assessment measures, and quality oflife scores were compared on an intention-to-treat

    basis according to the randomized study groupassignment. The 2 test or Fishers exact test wereused to assess categorical data and the Wilcoxonrank sum test or Students t-test for continuousdata. Paired t-tests were used to evaluate thetreatment effect within each arm as well as in theentire cohort from baseline to first follow-up andthen again from baseline to last follow-up. A two-sided P-value 0.05 was considered statisticallysignificant.

    Results

    Between February 2006 and March 2008,

    128 patients received a de novo CRT-defibrillatorimplant at Veterans Affairs Pittsburgh HealthcareSystem and were approached for enrollmentin this study. Of those, 50 patients declinedparticipation. Of those who agreed to initialscreening, 15 were in atrial fibrillation, 13 werealready receiving CPAP for SRBD, and 11 wereon narcotics or benzodiazepines that could not

    be withheld for the study. Of the 39 patientswho met clinical criteria for this trial, threepatients withdrew consent, while 36 underwentthe screening PSG. Of those, 17 patients wereexcluded based on AHI or nocturnal heart rate

    criteria (nine had AHI >50/hour, four had AHI80 bpm). Ofthe 19 patients who were randomized, 10 wererandomized to DDD and nine to VDD. Figure 1recaps the above. On follow-up interrogations,all patients had >90% LV pacing and those inDDD arm had >92% atrial pacing. None of therandomized patients experienced heart failurehospitalizations or received device shocks forthe duration of the study. Echocardiographicoptimization of the AVD was not performed onany of the patients during the study period as

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    Table I.

    Baseline Variables of the Cohort and According to Group Assignment

    Total DDD VDD

    Variable (n = 19) (n = 9) (n = 10) P-Value

    Demographic characteristics

    Age (mean, years) 67.2 7.5 68.6 8.4 66.0 6.8 0.66Male % 100.0 100.0 100.0 -White % 78.9 77.8 80.0 1.0BMI 28.1 3.5 27.1 4.3 29.0 2.4 0.24QRS duration 149.5 33.7 155.4 42.2 144.2 24.8 0.40

    History of hypertension % 84.2 77.8 90.0 0.58Smoking (ever) % 84.2 88.9 80.0 1.0Diabetes % 63.2 55.6 70.0 0.65Peripheral vascular disease% 26.3 44.4 10.0 0.14

    Current Medication Use %Angiotensin-converting enzyme inhibitor 68.4 77.8 60.0 0.63

    Angiotensin receptor blocker 21.0 11.1 30.0 0.58-blocker 89.5 77.8 100.0 0.21

    Antihypertensive 15.8 22.2 10.0 0.58Antiarrhythmic class III 10.5 11.1 10.0 1.0Loop diuretic 78.9 77.8 80.0 1.0Aldosterone antagonist 31.6 37.5 30 0.88

    Digoxin 63.1 62.5 60.0 0.856-minute walk (feet) 1010.4 346.7 1188.2 218.5 852.3 372.8 0.13Echocardiogram

    Left ventricular ejection fraction (%) 33.3 9.8 30.2 7.3 35.7 11.2 0.30Left ventricular end-diastolic diameter (mm) 60.9 6.2 61.2 4.7 60.6 7.5 0.60Left ventricular end-systolic diameter (mm) 51.3 8.3 51.0 8.0 51.6 8.9 0.86Left atrial dimension (mm) 43.8 6.1 43.1 6.6 44.3 5.9 0.54Peak tricuspid regurgitation velocity (m/s) 2.2 0.81 2.4 0.73 1.9 0.87 0.29

    Right ventricular (RV) fractional area change (%) 39.0 8.0 36.6 9.1 41.1 7.0 0.20Dyssynchrony

    Opposing wall delay (all sites mean ms) 85.5 30.7 86.2 32.0 85.0 31.4 0.93

    12-site standard deviation (mean ms) 32.0 13.8 32.0 14.0 32.0 14.4 1.0Radial strain opposing wall delay (mean ms) 110.9 79.1 138.2 77.6 89.1 77.2 0.19RV septalfree wall dyssynchrony (mean ms) 4.1 10.6 5.0 15.1 3.3 5.0 0.66

    Inflammatory/Neurohormonal BiomarkersC-reactive protein (mg/dL) 0.64 0.22 0.64 0.24 0.65 0.20 0.81IL-6 (pg/mL) 6.0 4.4 5.6 5.1 6.4 4.0 0.62Brain natriuretic peptide (pg/mL) 350.1 329.0 390.6 317.8 317.6 351.1 0.83Plasma norepinephrine (pg/dL) 613.0 248.8 559.5 202.0 661.2 286.5 0.69

    Urine norepinephrine (g) 32.2 20.9 23.1 12.7 41.2 24.2 0.05Sleep Quality

    Epworth sleepiness score 7.3 4.0 6.2 2.9 8.5 4.9 0.45Pittsburgh sleep quality index 7.4 3.1 7.1 2.9 7.6 3.5 1.0

    Quality of Life

    Minnesota heart failure 36.9 21.9 26.6 15.4 47.3 23.2 0.11

    poor sleep efficiency and significant desaturation.SRBD was mainly obstructive in nature with a lowcentral apnea index. Table III demonstrates thechange from baseline over the two follow-up timesin clinical parameters. While the improvementin 6-minute walk distance and mean MLWHFQ

    scores at both follow-up points was significant,improvements in EF, LV dimensions, and BNPwere not. Of the various dyssynchrony measuresobtained, only the radial strain opposing walldelay decreased, albeit not significantly. Therewas no appreciable difference in scores on

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    Table II.

    Baseline Sleep Study Results for the Cohort and both Groups

    Total DDD VDD

    Sleep Study (n = 19) (n = 10) (n = 9) P-Value

    Time in bed (minutes) 406.9 75.5 419.0 40.0 394.8 100.9 0.86

    Total sleep time (minutes) 267.3 87.9 252.1 68.7 282.4 105.8 0.34Sleep efficiency (%) 65.3 16.6 60.2 15.6 70.3 16.8 0.25NREM time (minutes) 237.8 75.7 222.6 61.8 253.1 88.6 0.30REM (minutes) 29.7 28.5 29.8 15.9 29.6 38.5 0.52

    AHI (number/hour) 21.5 15.3 20.3 17.2 22.9 13.9 0.45Obstructive apnea index (number/hour) 8.7 13.5 6.7 11.9 10.8 15.3 0.38Hypopnea index (number/hour) 10.8 10.5 10.0 5.1 11.5 14.4 0.79Central apnea index (number/hour) 3.3 6.7 1.3 2.1 5.2 9.0 0.24Baseline SpO2 (%) 93.8 2.2 93.1 1.9 94.5 2.3 0.21

    Average SpO2 (%) 92.3 3.1 91.2 2.9 93.4 3.0 0.17Lowest SpO2 (%) 83.5 5.3 82.7 4.5 84.4 6.1 0.52

    sleep quality questionnaires at any follow-uptime.

    In Table IV, sleep data from all participantsare compared between baseline and over bothfollow-up points after CRT utilization. Therewas no change at either of the follow-up points.Specifically, patients continued to exhibit at leastmoderate SRBD, predominantly obstructive innature with significant sleep time desaturation.There was no change in sleep architectureor distribution of apneic/hypopneic episodesamong sleep stages with pacing for the cohort.Analysis by randomization group also revealedno difference. Figure 2 demonstrates the primaryendpoint for the cohort as a whole and within bothgroups.

    Response to CRT

    Based on the criteria listed above, eight ofthe 19 patients were classified as responders(four VDD and four DDD), while seven additionalpatients (three DDD and four VDD) demonstratedimprovement in 6-minute walk and global score

    but not in EF. In those patients who responded to

    all three measures, EF and global score improvedsignificantly (29.75 7.05 to 40.63 9.81,P = 0.003 and 2.0 0.0 to 1.37 0.5, P =0.01, respectively), whereas there was a trendto improvement in 6-minute walk distance infeet (1019.75 346.47 to 1194.375 276.8233,P = 0.08). Similar to the cohort at large, thesepatients also did not demonstrate improvementin SRBD. AHI changed from 18.9 16.3 on the

    baseline study after implant but before CRT to31.6 24.7 (P =0.11) on the last follow-up afterCRT.

    Discussion

    Main Findings

    In this study, we demonstrate that in a cohortof optimally medically treated CHF patients whootherwise qualify for CRT based on EF, functionalclass, and QRS prolongation with or withoutechocardiographic evidence of dyssynchrony,CRT application resulted in no improvementin their SRBD of moderate or severe degree.Furthermore, the utilization of atrial overdrivepacing in addition to CRT had no appreciable

    impact on SRBD. This finding held true even whenstrict criteria for CRT response were used.

    SRBD among CRT Recipients

    Among the patients we screened, SRBD washighly prevalent, when according to our inclusioncriteria the disorder had not been previouslydiagnosed. Moreover, the severity of SRBD wasmore likely to be high when found. Thus, of the36 patients screened, 32 (89%) were found tohave AHI >15 and nine (25%) had AHI >50.Moreover, the responses to the sleep qualitysurveys we utilized underestimated the SRBD

    burden subsequently identified by PSG. Thisis not unusual, as daytime sleepiness in heartfailure patients has been found to underestimatethe amount of SRBD, perhaps reflecting thedegree of sympathetic activation.32 It may beadvantageous to advance screening tools that can

    be incorporated into cardiac rhythm managementdevices to identify SRBD in these patients.33

    It is interesting that all our patients demon-strated obstructive SRBD. This comes at odds withother reports of predominantly central SRBD inCHF patients. Temporal and geographic trends in

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    Table III.

    Mean Echocardiographic, Biomarker, and Self-Assessment Values at Baseline and Follow-Up Visits. P-Values ShownReflect Change from Baseline for the Cohort and within Each Group

    All Participants DDD VDD

    Variable Mean SD P-Value Mean SD P-Value Mean SD P-Value

    EchocardiogramEjection Fraction (%)

    Baseline 33.3 9.8 30.2 7.3 35.7 11.2

    First follow-up 34.8 10.8 0.43 31.6 8.2 0.64 37.5 12.4 0.56Last fol low-up 36.1 9.3 0.14 33.5 6.9 0.36 38.6 11.1 0.29

    LV End-Diastolic Volume

    Baseline 167.2 43.5 168.1 36.1 166.5 50.7First follow-up 157.4 35.1 0.31 156.1 21.5 0.24 158.3 44.3 0.84Last follow-up 147.2 47.9 0.13 149.0 44.8 0.37 145.5 53.8 0.23

    LV End-Systolic VolumeBaseline 114.0 42.3 118.7 38.4 110.2 46.9

    First follow-up 106.5 37.0 0.31 112.6 24.6 0.46 101.8 45.3 0.54Last fol low-up 96.9 41.8 0.13 101.9 41.6 0.40 92.0 44.2 0.20

    Radial Strain Opposing Wall DelayBaseline 110.9 79.1 138.2 77.6 89.1 77.2First follow-up 90.4 66.7 0.60 101.1 54.2 0.38 82.0 77.2 0.67

    Last fol low-up 80.4 70.6 0.22 61.9 39.2 0.06 99.0 91.4 0.52RV Fractional Area Change

    Baseline 39.0 8.0 36.6 9.1 41.1 7.0

    First follow-up 38.5 6.6 0.96 40.2 9.1 0.67 37.5 5.1 0.42Last fol low-up 37.4 7.0 0.42 37.5 5.2 0.84 37.2 8.4 0.15

    Biomarkers:C-Reactive Protein

    Baseline 0.65 0.22 0.64 0.24 0.65 0.20First follow-up 0.58 0.22 0.47 0.50 0.0 0.17 0.64 0.29 0.86

    Last fol low-up 0.55 0.13 0.12 0.52 0.07 0.23 0.58 0.16 0.28IL-6

    Baseline 6.0 4.4 5.6 5.1 6.4 4.0First follow-up 5.7 4.9 0.83 3.6 1.9 0.36 7.7 6.2 0.69Last follow-up 4.6 3.5 0.38 4.3 3.9 0.71 4.8 3.3 0.33

    Brain Natriuretic PeptideBaseline 350.1 329.0 390.6 317.8 317.6 351.1First follow-up 282.1 266.1 0.06 253.0 273.5 0.14 311.2 273.9 0.29Last follow-up 309.1 333.4 0.68 205.9 157.1 0.05 400.9 425.0 0.69

    NorepinephrineBaseline 613.0 248.8 559.6 202.0 661.2 286.5First follow-up 584.6 279.3 0.64 596.9 233.2 0.92 573.8 328.9 0.51

    Last follow-up 513.7 174.0 0.06 425.2 181.2 0.01 592.3 130.5 0.41Self-Assessments

    Minnesota Heart FailureBaseline 36.9 21.9 26.6 15.4 47.3 23.2First follow-up 29.2 22.4 0.02 26.6 18.8 0.81 31.2 25.8 0.002Last fol low-up 25.5 15.4 0.004 17.1 11.0 0.08 32.7 15.4 0.03

    Epworth Sleepiness ScoreBaseline 7.3 4.0 6.2 2.9 8.5 4.9First follow-up 6.9 4.0 0.57 6.7 2.3 0.88 7.1 5.2 0.44

    Last follow-up 6.6 2.6 0.22 6.4 1.4 0.80 6.8 3.5 0.21

    Continued.

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    Table III.

    Continued

    All Participants DDD VDD

    Variable Mean SD P-Value Mean SD P-Value Mean SD P-Value

    Pittsburgh Sleep Quality IndexBaseline 7.4 3.1 7.1 2.9 7.5 3.5First follow-up 6.1 2.5 0.04 6.5 1.7 0.45 5.8 3.1 0.03

    Last follow-up 6.7 1.8 0.39 7.2 1.5 1.0 6.2 1.9 0.326-Minute Walk

    Baseline 1010.4 346.7 1188.2 218.5 852.3 372.8

    First follow-up 1245.5 200.7 0.008 1295.7 135.7 0.33 1206.4 240.5 0.01Last follow-up 1212.9 314.0 0.04 1300.6 178.2 0.42 1144.8 386.1 0.06

    Table IV.Sleep Study Results at Baseline and Follow-Up. P-Values Shown Reflect Change from Baseline for the Cohort and within

    Each Group

    All Participants DDD VDD

    Mean SD P-Value Mean SD P-Value Mean SD P-Value

    Time in BedBaseline 406.9 75.5 394.8 100.9 419.0 40.0

    First follow-up 409.2 57.7 0.15 396.0 75.4 0.27 420.9 36.9 0.35Last follow-up 429.3 30.3 0.58 413.7 22.2 0.03 443.1 30.7 0.21

    Total Sleep Time

    Baseline 267.3 87.9 282.4 105.8 252.1 68.7First follow-up 287.4 83.0 0.99 291.6 111.1 0.64 283.7 54.3 0.52Last follow-up 291.5 72.5 0.59 301.1 65.5 0.74 283.0 81.1 0.38

    Sleep EfficiencyBaseline 65.3 16.6 70.3 16.8 60.2 15.6First follow-up 70.2 17.4 0.42 72.9 21.3 0.91 67.8 14.0 0.38Last follow-up 68.3 17.9 0.69 73.2 18.0 0.86 63.9 17.7 0.73

    NREM TimeBaseline 237.8 75.7 253.1 88.6 222.6 61.8First follow-up 251.5 67.0 0.80 250.1 91.8 0.42 252.8 40.1 0.52Last follow-up 257.4 56.9 0.77 264.2 57.2 0.55 251.3 59.4 0.46

    REM TimeBaseline 29.7 28.5 29.6 38.5 29.8 15.9

    First follow-up 36.1 24.5 0.52 41.7 28.5 0.56 31.1 20.7 0.83

    Last follow-up 34.2 28.3 0.49 37.1 22.0 0.72 31.7 34.1 0.56Overnight Urinary Norepinephrine

    Baseline 32.2 20.9 23.1 12.7 41.2 24.210 weeks 28.1 18.4 0.80 21.1 15.5 0.60 34.1 19.5 0.59Last follow-up 26.7 12.7 0.20 21.0 13.5 0.66 32.4 9.6 0.25

    AHIBaseline 21.5 15.3 22.9 13.9 20.3 17.2First follow-up 18.9 16.3 0.56 15.5 12.6 0.56 21.9 19.3 0.97Last follow-up 24.9 21.9 0.34 17.5 28.8 0.42 31.4 28.1 0.17

    Continued.

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    Table IV.

    Continued

    All Participants DDD VDD

    Mean SD P-Value Mean SD P-Value Mean SD P-Value

    Obstructive Apnea IndexBaseline 8.7 13.5 10.8 15.3 6.7 11.9First follow-up 6.1 6.2 0.35 5.4 5.8 0.48 6.7 6.9 0.54

    Last follow-up 9.8 15.6 0.77 5.5 6.7 0.40 13.7 20.3 0.27Hypopnea Index

    Baseline 10.8 10.5 11.5 14.4 10.0 5.1

    First follow-up 11.5 10.3 0.66 9.6 11.1 0.59 13.1 9.9 0.73Last follow-up 10.4 9.8 0.46 8.6 5.7 0.50 12.0 12.5 0.84

    Central Apnea Index

    Baseline 3.3 6.7 5.2 9.0 1.3 2.1First follow-up 1.4 3.7 0.03 0.62 1.2 0.07 2.1 4.9 0.29Last follow-up 4.8 9.1 0.31 3.6 5.6 0.47 5.9 11.7 0.47

    Baseline SpO2Baseline 93.8 2.2 94.6 2.3 93.1 1.9First follow-up 93.5 2.3 0.58 94.0 1.8 1.0 93.1 2.8 0.42Last follow-up 93.3 1.7 0.43 93.5 1.1 0.38 93.1 2.1 0.76

    Average SpO2Baseline 92.3 3.1 93.4 3.0 91.2 2.9First follow-up 91.5 2.4 0.43 93.0 1.8 0.87 90.2 2.2 0.24

    Last follow-up 91.5 2.4 0.33 92.4 1.5 0.47 90.7 2.9 0.57Lowest SpO2

    Baseline 83.6 5.3 84.4 6.1 82.7 4.5

    First follow-up 83.0 5.0 0.70 85.2 5.7 0.27 81.0 3.4 0.54Last follow-up 82.8 4.6 1.0 83.4 3.7 0.87 82.2 5.4 0.78

    Figure 2. Change in AHI (mean standard deviation) for the cohort and according to pacinggroup (P= NS for all).

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    demographics and pharmacological therapy mayhave impacted the nature of SRBD in our patients.We note that among the published trials of CRTfor SRBD in CHF patients the only other reportedcohort with obstructive SRBD was also from theUnited States.20

    Relation to Previous Studies

    Several groups have explored the potentialimpact of CRT in reducing SRBD burden inqualifying CHF patients.1724 The cumulativeexperience endorses a benefit in reducing centralSRBD. The reduction is tied to improvementin various parameters of LV dysfunction, neu-rohormonal balance, and CHF functional statusin response to CRT application. The impact ofCRT on central SRBD is evident both acutelyand after longer periods of follow-up and is lostupon withdrawal of CRT. The reduction in SRBD

    burden is reflected in improvement in sleep-specific symptoms as well as other general qualityof life indicators.

    Data on obstructive SRBD are conflicting,however. Contrary to our findings, Stanchina et al.,who studied a group of patients eligible for CRTwith at least mild obstructive SRBD (AHI>5/hour)on a screening PSG, reported that the meanAHI had improved significantly concomitant withimprovement in EF and significantly correlatedto lung to finger circulation time, a measure ofcardiac output.20 In a subsequent night, atrialoverdrive pacing added no further improvementto the AHI.

    On the other hand, Oldenburg et al. screened77 CHF patients eligible for CRT and foundcentral SRBD in 36 and obstructive in 26.21

    The investigators determined response to CRTas good, moderate, or not relevant. On follow-up PSG, significant improvement was noted inSDB parameters in patients with central but notin those with obstructive SRBD notwithstandingtheir equivalent response to CRT. Our findingscorroborate those of Oldenburg et al. where wefound no significant improvement in our cohortwho exhibited primarily obstructive SRBD withno significant central component.21

    The lack of improvement with atrial overdrivepacing noted in our trial echoes the findings ofStanchina et al.20 and Luthje et al.,24 keeping

    in mind the latter studied a cohort with centralSRBD. In fact, the utility of atrial pacing forSRBD of any type regardless of underlying cardiacpathology is highly doubtful.3436

    Limitations

    Our study involved a relatively small numberof patients. We attribute this to the difficultyof recruiting to studies involving nighttime PSGtests. Our cohort is representative of patientsreceiving CRT, based on NYHA, EF, QRS duration,and optimal pharmacological therapy. While therewas improvement in quality of life and 6-minute walk distance, improvements in EF andcardiac reverse remodeling parameters were notsignificant. It is possible that adverse neurohor-monal activation, heightened sympathetic tone,and increased levels of circulating inflammatorymolecules and byproducts attendant with the

    degree of obstructive SRBD had significant impacton CRT response.37 Diminished response toCRT has been observed in conditions similarlycharacterized by maladaptive neurohormonal ac-tivation.3841 Finally, the decision to implant was

    based on clinical echocardiograms with EF 35 with one outlier significantlyaffecting the cohorts mean. The results hold true

    when these cases are excluded from the analysis,as they did with those who demonstrated unequiv-ocal response to CRT. Our patients were all male,reflecting the makeup of the clinical populationat a tertiary Veterans Affairs Medical Center.Since our patients represent a self-selected cohort,extrapolations as to the prevalence of SRBD amongCRT recipients should be taken with caution.

    In conclusion, in patients with advancedCHF on optimal medical therapy and who areappropriate CRT candidates, obstructive SRBD ofmoderate to severe degree was frequently encoun-tered. Despite improvement in neurohormonal

    activation and functional capacity, CRT with orwithout atrial overdrive pacing was not effectivein improving SRBD.

    References1. Bristow MR, Saxon LA, Boehmer J,KruegerS, KassDA, DeMarco T,

    Carson P, et al. Cardiac-resynchronization therapy with or withoutan implantable defibrillator in advanced chronic heart failure. NEngl J Med 2004; 350:21402150.

    2. Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S,Daubert C; REVERSE (REsynchronization reVErses Remodeling inSystolic left vEntricular dysfunction) Study Group. Randomizedtrial of cardiac resynchronization in mildly symptomatic heart

    failure patients and in asymptomatic patients with left ventriculardysfunction and previous heart failure symptoms.J Am Coll Cardiol2008; 52:18341843.

    3. Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freeman-tleN, ErdmannE, Gras D, et al.Early and sustained effects of cardiacresynchronization therapy on N-terminal pro-B-type natriureticpeptidein patients with moderate to severe heart failure andcardiacdyssynchrony. Eur Heart J 2007; 28:15921597.

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