Changes in Left and Right Ventricular Mechanics During the Mueller Maneuver in Healthy Adults: A...

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DOI: 10.1161/CIRCIMAGING.109.901561 published online February 16, 2010;Circ Cardiovasc Imaging

Lopez-JimenezLeinveber, Haydar K. Saleh, Tomas Konecny, Tomas Kara, Virend K. Somers and Francisco

Yuki Koshino, Hector R. Villarraga, Marek Orban, Charles J. Bruce, Gregg S. Pressman, PavelObstructive Sleep Apnea

Healthy Adults: A Possible Mechanism for Abnormal Cardiac Function in Patients with Changes in Left and Right Ventricular Mechanics during the Mueller Maneuver in

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CIRCULATIONAHA/2009/901561

Changes in Left and Right Ventricular Mechanics during the Mueller

Maneuver in Healthy Adults: a Possible Mechanism for Abnormal Cardiac

Function in Patients with Obstructive Sleep Apnea

Short title: Koshino et al; Changes in ventricular mechanics in simulated OSA

Yuki Koshino, MD, PhD1; Hector R. Villarraga, MD1; Marek Orban, MD2; Charles J. Bruce,

MD, MBChB1; Gregg S. Pressman, MD3; Pavel Leinveber, MSc2; Haydar K. Saleh, MD1;

Tomas Konecny, MD1; Tomas Kara, MD, PhD2; Virend K. Somers, MD, PhD1; Francisco

Lopez-Jimenez, MD, MSc1

From 1the Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic,

Rochester, Minnesota, 2the Department of Internal Medicine-Cardioangiology, International

Clinical Research Center Brno, St. Anne’s University Hospital, Brno, Czech Republic and 3the

Department of Internal Medicine, Division of Cardiology, Albert Einstein Medical Center;

Philadelphia, PA

Corresponding Author: Dr. Francisco Lopez-Jimenez, M.D., MSc. Mayo Clinic 200 1st St. SW Rochester, MN. 55905Telephone: (507) 284-8087 Fax: (507) 266-7929 E-mail: [email protected]

Journal Subject Codes: [11] Other heart failure; [113] Obesity; [31] Echocardiography; [105] Contractile function

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Abstract

Background: Obstructive sleep apnea (OSA) is highly prevalent in patients with cardiovascular

disease and has detrimental effects on systolic and diastolic function of the ventricles. In this

research, the changes in strain (S) and strain rate (SR) during the performance of the Mueller

maneuver (MM) in an effort to better understand how negative intrathoracic pressures affects

ventricular mechanics.

Methods and Results: The MM was performed to maintain a target intrathoracic pressure of -40

mmHg. Echocardiography was used to measure various parameters of cardiac structure and

function. Myocardial deformation measurements were performed using tissue speckle tracking.

Twenty-four healthy subjects (9 women; mean age 30 ± 6 years) were studied. Global left

ventricular (LV) longitudinal S in systole and SR in early filling were significantly decreased

during the MM (S: baseline, -17.0 ± 1.6 %; MM, -14.5 ± 2.2 %; p< 0.0001, SR: baseline, 1.09 ±

0.20 s-1; MM, 0.92 ± 0.21 s-1; p = 0.01). Global right ventricular (RV) longitudinal S was also

significantly decreased during the MM (baseline, -22.0 ± 3.1 %; MM, -17.2 ± 2.5 %; p< 0.0001)

as was global RV longitudinal systolic SR ( baseline, -1.34 ± 0.35 s-1; MM, -1.02 ± 0.21 s-1; p =

0.0006).

Conclusion: LV and RV longitudinal deformation are significantly reduced during the MM.

These results suggest that negative intrathoracic pressure during apnea may contribute to changes

in myocardial mechanics. These results could help explain the observed changes in LV and RV

mechanics in patients with OSA.

Keywords: obstructive sleep apnea, ventricular mechanics, ventricles, echocardiography, Mueller maneuver

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gitudinal S in systole and SR in early fillin ng were significant

baseline, -17.0 ± 1.6 %; MM, -14.5 ± 2.2 %; p< 0.0001, SR: b



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Introduction

Obstructive sleep apnea (OSA) is characterized by repetitive apneic events, intermittent hypoxia

and arousals occurring during sleep. The prevalence of OSA is as high as 20% in the adult

population1-5. Apneic events are caused by collapse of the pharyngeal airway associated with

vigorous ventilatory efforts that lead to generation of high negative intrathoracic pressure6.

Chronic OSA has been associated with a variety of cardiovascular complications7. These

include sudden cardiac death8, heart failure9, hypertension10, acute myocardial infarction11, and

arrhythmias12, 13. Such findings suggest that OSA may directly affect myocardial performance

and cardiovascular outcomes. However, it is not certain that OSA is an independent risk factor

for left and right ventricular dysfunction. Potential mechanisms by which OSA might adversely

impact LV function include abrupt increases in afterload resulting from high negative

intrathoracic pressure at the onset of an obstructive apnea and the subsequent increase in

sympathetic nerve activity and blood pressure 14. The apneic events in OSA, lasting 10 seconds

or more, are also associated with hypoxia and hypercapnia which may impair cardiac

contractility directly or, in the case of the right ventricle, indirectly by increasing pulmonary-

artery pressure.

In recent years strain (S) and strain rate (SR) imaging by 2D speckle tracking have been

used to quantify myocardial deformation, and the rate of deformation, in both the left ventricle

(LV) and the right ventricle (RV)15. These new techniques might better characterize cardiac

abnormalities associated with OSA than standard Doppler echocardiography.

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Methods

Twenty-four healthy young adults with normal body mass index (BMI) and normal sinus rhythm

participated in this study. The protocol was reviewed and approved by Mayo Clinic Institutional

Review Board. Data from a subgroup of these participants was published earlier16.

Study Protocol

Baseline measurements were recorded during quiet breathing and at the end of expiration while

in the supine position prior to each Mueller maneuver (MM). Subjects wore a nose clip and a

mouthpiece with a small air leak through a 21-gauge needle to prevent closure of the glottis

during the MM. Mouth pressure was visually monitored by each subject to maintain the target

intrathoracic pressure of – 40 mmHg. All subjects performed several practice MMs before data

collection started. Subjects performed 10 MMs, each lasting 12 seconds, separated by a 3-min

rest period. Echocardiography loops, ECG and bioimpedance curves were recorded at baseline,

during the MM and 10 minutes after termination of the last MM (recovery). Blood pressure was

taken by cuff at the time of echocardiography and monitored throughout the whole study using a

continuous blood pressure monitoring system (TDP Biomedical Instrumentation, Amsterdam,

The Netherlands).

Image Acquisition

Complete 2-dimensional and Doppler echocardiographic imaging was performed according to

the standards of the American Society of Echocardiography. All echocardiographic data were

stored on the hard drive of the echocardiographic machine (Siemens Sequoia C512, Mountain

View, California) and copied to compact discs for further off-line analysis. Measurements were

performed at baseline, during the MM, and 10 minutes after the last MM (recovery). The average

frame rate for the acquired images was 36 MHz. Images were acquired from the peak of the R

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ubjects performed 10 MMs, each lasting 12 seconds, separate

diography loops, ECG and bioimpedance curves were record

10 minutes after termination of the last MM (recovery). Bloo



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wave, and at least 1 complete cardiac cycle was used for analysis. Apical 4-chamber (A4C) and

apical 3-chamber (A3C) views were analyzed in each patient. The images were downloaded

from the central archive and stored in DICOM format either on magneto-optical disks or on a

computer hard drive. The images were then imported for analysis to a velocity vector imaging

(VVI) program (Syngo VVI version 2.0 software program; Siemens Healthcare, Malvern,

Pennsylvania).

Image Analysis

Three beat cine-loop clips were selected from the A4C and A3C views at baseline, during the

MM and after recovery. For the MM, we analyzed 3 stored cine clips after 8 seconds of its

initiation. For each patient, 12 segments were analyzed for the LV and 6 segments for the RV.

Ten to 15 points were placed in the myocardium starting and ending at the mitral or tricuspid

annulus. The tracing was performed at end-systolic or mid-systolic frame, whichever had better

endocardial definition. The quality of the tracking was assessed visually and the process was

repeated, as needed, to assure satisfactory tracking of the myocardium.

Strain and Strain Rate Analysis

We used VVI for the measurement of myocardial S and SR from 2-D images. This offline

software provides angle-independent measurement of 2-D velocity, displacement, S, and SR. It is

a quantitative method that provides regional and global myocardial mechanics, through the

combination of speckle tracking, tissue-blood border detection, the periodicity of the cardiac

cycle using R-R intervals, and generation of M-mode representations of the segments with mitral

annulus motion.

Once a satisfactory trace was obtained, the images were processed by the software to

obtain longitudinal velocity, S, SR, and displacement, as well as the time to peak (TTP) for each

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was performed at end-systolic or mid-systolic frame, which

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segment, (12 segments of the LV [A4C and A3C views], and 6 segments of the RV [A4C view]).

The velocity, S, systolic SR (SRs), SR in early filling (SRe), and displacement of each segment

were calculated by the software as an average of a number of points of interest within the region.

Global LV and RV values were calculated by averaging the value of 6 segments in the A4C for

the RV and 12 segments in the A4C and A3C for the LV. Average S and SRs of the basal, mid

and apical regions were also calculated. Figure 1 and Figure 2 shows examples of S and SR

curves at baseline, during the MM, and recovery phase of the LV and RV, respectively.

Reproducibility

Interobserver variability was assessed with speckle-tracking echocardiography in 8 randomly

selected patients for 3 predetermined beats of images during baseline and the MM, these were

independently performed by 2 investigators. Intraobserver reproducibility was assessed by

repeating the speckle-tracking echocardiography examinations in 3 predetermined beats of

images during baseline in 8 randomly selected patients for masked review by the same

investigator 4-8 weeks after the initial analysis. Intraobserver and interobserver variability were

assessed for S and SR, as well as TTP for each of these variables.

Statistical Analysis

Data are presented as mean SD. One-way repeated measures ANOVA was used to determine

significant differences among the individual segments for S, SR, velocity, and displacement, and

the TTP among 3 phases. To assess difference each of these variables between baseline and the

MM and between the MM and recovery, was used paired t test. In figures, the box plots

summarize the distribution of points at each factor level and the 25th and 75th quantiles. For

intra and interobserver variability, we calculated the Bland-Altman 95% limits of agreement. We

calculated the mean absolute difference between the 2 observers and the percentage of the

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difference relative to the sample mean value for each variable. The percentage difference was

calculated as the absolute difference of the 2 sets of measurements divided by the mean of the

measurements. The limits of agreement were calculated as SDs of the absolute difference

between the two observers. A P value of less than 0.05 was considered statistically significant.

JMP Statistical Discovery version 7 software (SAS Institute, Cary, North Carolina) was used to

perform the statistical analysis.

Results

Demographics

The baseline characteristics and echocardiographic data of the 24 subjects are shown in Table 1.

The mean age was 30 ± 6 years, 63 % were men, and mean BMI was 23.7 ± 2.7 kg/m2. The

mean LV ejection fraction (LVEF) was 64 ± 4 % without any abnormal findings at baseline. As

we reported in a previous paper including a part of this study population, LVEF, stroke volume,

cardiac output, cardiac index were decreased significantly (P < 0.0001) during the MM, whereas

LV systolic dimension and septal E/E’ ratio were increased [Table 2].

Longitudinal Strain and Strain Rate in the LV

The means ( SD) of the S, SRs, and SRe for the basal, mid, and apical segments of the LV and

RV along with the TTP of each of these variables in the longitudinal view are shown in Table 3.

In terms of global myocardial function, the average LV longitudinal S at baseline was -17.0 ±

1.6 % and the average TTP was 382 ± 28 ms. During the MM, global S was reduced to -14.5 ±

2.2 % (P<0.0001); after termination of the MM, S increased to -16.3 ± 2.4 % in the recovery

phase (P<0.0001) [Figure 3]. Significant changes were also noted for the base, mid and apex of

the LV segments [Table 3]. The average global longitudinal SRs at baseline was -0.95 ± 0.13 s-1

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0 ± 6 years, 63 % were men, and mean BMI was 23.7 ± 2.7

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0 ± 6 years, 63 % were men, and mean BMI was 23.7 ± 2.7

action (LVEF) was 64 ± 4 % without any abnormal findings

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and the overall average TTP of SRs at baseline was 190 ± 32 ms. Although, there was a

significant difference between the MM (-0.87 ± 0.12 s-1) and baseline (P = 0.02), there was no

significant difference between the MM and recovery (-0.87 ± 0.12 s-1) in global SRs. The

average global longitudinal SRe and TTP at baseline were 1.09 ± 0.20 s-1 and 488 ± 38 ms.

During the MM, global SRe was reduced to 0.92 ± 0.21 s-1(P = 0.01); after termination of the

MM, SRe increased to 1.03 ± 0.27 s-1 in the recovery phase (P = 0.03) [Figure 4]. TTP did not

vary between baseline, the MM and recovery. Although S and SR did change between the

different phases, dyssynchrony was not present.

Longitudinal Strain and Strain Rate in the RV

Average global RV longitudinal strain overall was -22.0 ± 3.1 % with an average global TTP of

403 ± 36 ms. Global RV S decreased to -17.2 ± 2.5 % during the MM (P < 0.0001) and returned

to -21.3 ± 3.2 % during the recovery phase (P < 0.0001 for both) [Figure 5]. Significant changes

were also noted for the base, mid and apex of the RV segments [Table 3]. The average global

longitudinal SRs in RV at baseline was -1.34 ± 0.35 s-1 and the overall average TTP was 225 ±

34 ms. SRs decreased during the MM (-1.02 ± 0.21 s-1, P = 0.0006) and improved during

recovery (-1.23 ± 0.29 s-1, P = 0.005) [Figure 6]. Significant decreases in SRs were seen in the

basal and mid segments of the RV during the MM (basal, -1.15 ± 0.30 s-1; mid, -1.06 ± 0.31 s-1)

compared to baseline (basal, -1.58 ± 0.51 s-1, P = 0.002; mid, -1.41 ± 0.41 s-1, P = 0.004) [Table

3].

Reproducibility

Tracking accuracy of speckle-tracking echocardiography was assessed visually. The intra and

interobserver variability as measured by mean absolute differences for S and SRs in the LV were

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minimal and relatively small, compared with the actual strain scale of all the readings in both LV

and RV. Details are provided in Table 4.

Discussion

In this study we evaluated changes in longitudinal LV and RV deformation during the MM in

healthy volunteers. Global LV and RV strain were significantly reduced, returning to baseline

values during the recovery phase. Global RV strain rate in systole and global LV strain rate

during early filling were also significantly reduced during the MM.

Changes in cardiac function during the Mueller Maneuver

To the best of our knowledge, this is the first report investigating the effect of the MM on

ventricular S and SR. Our study provides new information to better understand the association

between LV and RV dysfunction in patients with OSA17, 18. Previous work confirmed that the

MM closely simulated changes in intrathoracic pressure produced during sleep in subjects with

OSA and increases sympathetic nervous activity19, 20. Acute increase in right-heart volume

should be induced by the fall in pleural pressure with the MM21, 22. Additionally, there is

simultaneous increase in transmural right ventricular filling pressure and decrease in RV ejection

fraction23. In the left heart, the abrupt negative intrathoracic pressure imposes an afterload

burden on the LV and a fall in cardiac output and stroke volume24. To the extent that LV

compliance is decreased, the LV end-diastolic pressure will tend to rise25. Our previous work

showed a significant decrease in LVEF during the MM16. In the present study, further changes in

cardiac function were evidenced with altered S and SR during the MM not only in the LV but

also in the RV. Our results suggest that abrupt negative intrathoracic pressure deteriorated right

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ventricular mechanical function due to increases in pulmonary artery transmural pressure and

right ventricular afterload during the MM.

Left and right ventricular dysfunction related to OSA

In a large cross-sectional study, Chami et al. reported greater LV mass index, larger LV diastolic

dimension and lower LVEF were associated with a higher apnea-hypopnea index (AHI) and

higher hypoxemia index26. On the other hand, Niroumand et al. reported that OSA was not

associated with increased LV mass or impaired LV diastolic function27. Little is known about

mechanisms by which OSA might lead to cardiac dysfunction. Both LV and RV systolic

impairment can occur in patients with significant OSA9, 28-31. However, patients with OSA often

have coexisting disorders which might also produce ventricular dysfunction, such as obesity32,

aging33, hypertension34, and coronary artery disease35. It is unclear if the negative intrathoracic

pressure in OSA is predictive of impaired ventricular function independent of other conditions.

In the present study, however, we were able to demonstrate adverse effects of negative

intrathoracic pressure on both right and left ventricular mechanical function in young adults

without comorbidities. These findings would shed a new light on better understanding the

mechanisms of deterioration in cardiac function due to negative intrathoracic pressure as one of

the most characteristic pathophysiologic changes in OSA.

Two dimensional speckle tracking analysis of cardiac function

Changes in S and SR as assessed by 2D speckle tracking may provide a useful tool for the

characterization and early evaluation of cardiac dysfunction36-39. S and SR measurements offer

advantages over regional myocardial velocities, which can be affected by tethering from other

myocardial segments and translational motion of the entire heart. Dokainish et al. reported

systolic S and SRs were significantly depressed in patients with preserved LVEF of 59 ± 5 % but

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n34, and coronary artery disease35. It is unclear if the negativ

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elevated LV end-diastolic pressure (> 20 mmHg) using invasive hemodynamics40. Lopez-

Candales et al. reported peak longitudinal strain in the RV was a significant predictor of RV

performance in patients with pulmonary hypertension41. In the present study our findings of

changes in S and SR indicate that right and left ventricular function were impaired during the

MM. This suggests that sudden changes in loading conditions cause transient LV and RV

dysfunction. Repetitive obstructive apneas over time, such as those that occur in OSA, might

therefore be expected to have cumulative deleterious effects on both the right and left ventricles.

Limitations

It is possible that some of the comparisons that did not show any significant change in regional

or total S or SR could be due to small sample size. Patients with poor echocardiographic

windows can pose a challenge to the accurate measurement of S and SR by 2-dimensional

echocardiography. Tracking can also be affected by patient movement during the MM as well as

movement of the heart within the chest. In the present study, we measured longitudinal S and

SR; radial S and SR are also measures of LV systolic function and would be of interest to pursue

in future studies. Additionally, the MM only partially reproduced the pathophysiologic changes

seen in OSA. Although altering intrathoracic pressure, intracardiac hemodynamics and

stimulating catecholamine release with the MM, the duration of the MM itself is short and may

not replicate entirely the repetitive obstructive apneas in patients with OSA. The measurements

were not blinded to the stage of the MM due to technical limitations that would make it nearly

impossible to mask the MM stage, as the EKG tracing needed to perform the strain analysis is

usually distorted during the MM.

Conclusions

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Tracking can also be affected by patient movement during the

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Global S and SR in the LV and the RV were significantly decreased during the MM in healthy

adults. These results indicate that the imposition of abrupt negative intrathoracic pressure can

acutely impair ventricular mechanics. Our findings may provide useful insights into mechanisms

of cardiac dysfunction in patients with OSA.

Funding Sources: Dr. Koshino was supported by Japan Heart Foundation / Bayer Yakuhin

Research Grant Abroad. Dr. Orban was supported by an American Physiological Society Perkins

Memorial Award and a Travel Grant from the Czech Society of Cardiology; Dr. Kara was

supported by Grant Agency of Ministry of Health of the Czech Republic; Dr. Pressman was

supported by Albert Einstein Society. Dr. Lopez-Jimenez was supported by Mayo Clinic CR

Program and Selected Research.

Conflict of Interest Disclosures: Dr. Somers has served as a Consultant for ResMed, Boston

Scientific, Cardiac Concepts and Sepracor, and as an investigator on research grants funded by

the Respironics Sleep and Breathing foundation, Sorin Inc and Select Research.

References:

1. Bixler EO, Vgontzas AN, Lin HM, Ten Have T, Rein J, Vela-Bueno A, Kales A.

Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit

Care Med. 2001;163:608-613.

2. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-

disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235.

3. Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea

in men: I. Prevalence and severity. Am J Respir Crit Care Med. 1998;157:144-148.

RRRRepepepepepepepububububububublililililililic;c;c;c;c;c;c; D D D DDDDr.r.r.r.r.r.. PP P PP P Prerererererere

pporrrrrrrteteteteteteed d ddddd bybybybybybyby M MMMMMMayaaaaa

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s

C a

ed Research.

Disclosures: Dr. Somers has served as a Consultant for Res

Concepts and Sepracor, and as an investigator on research gra



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4. Duran J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea-hypopnea and related

clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir

Crit Care Med. 2001;163:685-689.

5. Lopez-Jimenez F, Sert Kuniyoshi FH, Gami A, Somers VK. Obstructive sleep apnea:

implications for cardiac and vascular disease. Chest. 2008;133:793-804.

6. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway

occlusion during sleep. J Appl Physiol. 1978;44:931-938.

7. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men

with obstructive sleep apnoea-hypopnoea with or without treatment with continuous

positive airway pressure: an observational study. Lancet. 2005;365:1046-1053.

8. Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in

obstructive sleep apnea. N Engl J Med. 2005;352:1206-1214.

9. Romero-Corral A, Somers VK, Pellikka PA, Olson EJ, Bailey KR, Korinek J, Orban M,

Sierra-Johnson J, Kato M, Amin RS, Lopez-Jimenez F. Decreased right and left

ventricular myocardial performance in obstructive sleep apnea. Chest. 2007;132:1863-

1870.

10. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between

sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378-1384.

11. Kuniyoshi FH, Garcia-Touchard A, Gami AS, Romero-Corral A, van der Walt C,

Pusalavidyasagar S, Kara T, Caples SM, Pressman GS, Vasquez EC, Lopez-Jimenez F,

Somers VK. Day-night variation of acute myocardial infarction in obstructive sleep apnea.

J Am Coll Cardiol. 2008;52:343-346.

12. Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J,

Redline S. Association of nocturnal arrhythmias with sleep-disordered breathing: The

Sleep Heart Health Study. Am J Respir Crit Care Med. 2006;173:910-916.

13. Koshino Y, Satoh M, Katayose Y, Yasuda K, Tanigawa T, Takeyasu N, Watanabe S,

Yamaguchi I, Aonuma K. Association of sleep-disordered breathing and ventricular

arrhythmias in patients without heart failure. Am J Cardiol. 2008;101:882-886.

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Y c

on J, Kato M, Amin RS, Lopez-Jimenez F. Decreased right a

myocardial performance in obstructive sleep apnea. Chest. 20

Young T, Palta M, Skatrud J. Prospective study of the assoc



https://www.researchgate.net/publication/5523113_Association_of_Sleep-Disordered_Breathing_and_Ventricular_Arrhythmias_in_Patients_Without_Heart_Failure?el=1_x_8&enrichId=rgreq-30bcb211-103d-42f0-ab9b-ccf103826a26&enrichSource=Y292ZXJQYWdlOzQxNDUxOTM4O0FTOjE5MjA3OTM0MDU5NzI1N0AxNDIyODA2NjkyMDU5





https://www.researchgate.net/publication/51426375_Day-Night_Variation_of_Acute_Myocardial_Infarction_in_Obstructive_Sleep_Apnea?el=1_x_8&enrichId=rgreq-30bcb211-103d-42f0-ab9b-ccf103826a26&enrichSource=Y292ZXJQYWdlOzQxNDUxOTM4O0FTOjE5MjA3OTM0MDU5NzI1N0AxNDIyODA2NjkyMDU5



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14. Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK.

Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure

in patients with obstructive sleep apnea. Circulation. 1998;97:943-945.

15. Marwick TH. Measurement of strain and strain rate by echocardiography: ready for

prime time? J Am Coll Cardiol. 2006;47:1313-1327.

16. Orban M, Bruce CJ, Pressman GS, Leinveber P, Romero-Corral A, Korinek J, Konecny

T, Villarraga HR, Kara T, Caples SM, Somers VK. Dynamic changes of left ventricular

performance and left atrial volume induced by the mueller maneuver in healthy young

adults and implications for obstructive sleep apnea, atrial fibrillation, and heart failure.

Am J Cardiol. 2008;102:1557-1561.

17. Santamore WP, Bove AA, Heckman JL. Right and left ventricular pressure-volume

response to positive end-expiratory pressure. Am J Physiol. 1984;246:H114-119.

18. Buda AJ, Pinsky MR, Ingels NB, Jr., Daughters GT, 2nd, Stinson EB, Alderman EL.

Effect of intrathoracic pressure on left ventricular performance. N Engl J Med.

1979;301:453-459.

19. Somers VK, Dyken ME, Skinner JL. Autonomic and hemodynamic responses and

interactions during the Mueller maneuver in humans. J Auton Nerv Syst. 1993;44:253-

259.

20. Bradley TD, Tkacova R, Hall MJ, Ando S, Floras JS. Augmented sympathetic neural

response to simulated obstructive apnoea in human heart failure. Clin Sci (Lond).

2003;104:231-238.

21. Robotham JL, Mintzner W. A model of the effects of respiration on left ventricular

performance. J Appl Physiol. 1979;46:411-418.

22. Robotham JL, Rabson J, Permutt S, Bromberger-Barnea B. Left ventricular

hemodynamics during respiration. J Appl Physiol. 1979;47:1295-1303.

23. Scharf SM, Brown R, Tow DE, Parisi AF. Cardiac effects of increased lung volume and

decreased pleural pressure in man. J Appl Physiol. 1979;47:257-262.

24. Magder SA, Lichtenstein S, Adelman AG. Effect of negative pleural pressure on left

ventricular hemodynamics. Am J Cardiol. 1983;52:588-593.

ololololololol. . . . . . . 1919191919191984848484848484;2;2;2;2;2;2;246464646464646:H:H:H:H:H:H:H1111111

, Stiinsnsnsnsnsnsnsonononononono E E E E EEEB,B,B,B,B,B,B, A AAAAAAl

a

3

D o

d

athoracic pressure on left ventricular performance. N Engl J

3-459.

Dyken ME, Skinner JL. Autonomic and hemodynamic respo

during the Mueller maneuver in humans. J Auton Nerv Syst.



R15

25. Virolainen J, Ventila M, Turto H, Kupari M. Effect of negative intrathoracic pressure on

left ventricular pressure dynamics and relaxation. J Appl Physiol. 1995;79:455-460.

26. Chami HA, Devereux RB, Gottdiener JS, Mehra R, Roman MJ, Benjamin EJ, Gottlieb

DJ. Left ventricular morphology and systolic function in sleep-disordered breathing: the

Sleep Heart Health Study. Circulation. 2008;117:2599-2607.

27. Niroumand M, Kuperstein R, Sasson Z, Hanly PJ. Impact of obstructive sleep apnea on

left ventricular mass and diastolic function. Am J Respir Crit Care Med. 2001;163:1632-

1636.

28. Fung JW, Li TS, Choy DK, Yip GW, Ko FW, Sanderson JE, Hui DS. Severe obstructive

sleep apnea is associated with left ventricular diastolic dysfunction. Chest. 2002;121:422-

429.

29. Otto ME, Belohlavek M, Romero-Corral A, Gami AS, Gilman G, Svatikova A, Amin RS,

Lopez-Jimenez F, Khandheria BK, Somers VK. Comparison of cardiac structural and

functional changes in obese otherwise healthy adults with versus without obstructive

sleep apnea. Am J Cardiol. 2007;99:1298-1302.

30. Dursunoglu D, Dursunoglu N, Evrengul H, Ozkurt S, Kuru O, Kilic M, Fisekci F. Impact

of obstructive sleep apnoea on left ventricular mass and global function. Eur Respir J.

2005;26:283-288.

31. Shivalkar B, Van de Heyning C, Kerremans M, Rinkevich D, Verbraecken J, De Backer

W, Vrints C. Obstructive sleep apnea syndrome: more insights on structural and

functional cardiac alterations, and the effects of treatment with continuous positive

airway pressure. J Am Coll Cardiol. 2006;47:1433-1439.

32. Sasson Z, Rasooly Y, Gupta R, Rasooly I. Left atrial enlargement in healthy obese:

prevalence and relation to left ventricular mass and diastolic function. Can J Cardiol.

1996;12:257-263.

33. Forman DE, Cannon CP, Hernandez AF, Liang L, Yancy C, Fonarow GC. Influence of

age on the management of heart failure: findings from Get With the Guidelines-Heart

Failure (GWTG-HF). Am Heart J. 2009;157:1010-1017.

ilillllllmamamamamamaman n n nn n n G,G,G,G,G,G,G, S S S SSSSvavavavavavavatititititititikokkkokkk

son ofofofofofoff c c c c cccararararararardididididididiacacacacacacac s

h t

A

D F

e

hanges in obese otherwise healthy adults with versus without

Am J Cardiol. 2007;99:1298-1302.

D, Dursunoglu N, Evrengul H, Ozkurt S, Kuru O, Kilic M, F

e sleep apnoea on left ventricular mass and global function.



R16

34. Drager LF, Bortolotto LA, Figueiredo AC, Silva BC, Krieger EM, Lorenzi-Filho G.

Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart

remodeling. Chest. 2007;131:1379-1386.

35. Mooe T, Franklin KA, Holmstrom K, Rabben T, Wiklund U. Sleep-disordered breathing

and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med.

2001;164:1910-1913.

36. Pirat B, Khoury DS, Hartley CJ, Tiller L, Rao L, Schulz DG, Nagueh SF, Zoghbi WA. A

novel feature-tracking echocardiographic method for the quantitation of regional

myocardial function: validation in an animal model of ischemia-reperfusion. J Am Coll

Cardiol. 2008;51:651-659.

37. Kosmala W, Plaksej R, Strotmann JM, Weigel C, Herrmann S, Niemann M, Mende H,

Stork S, Angermann CE, Wagner JA, Weidemann F. Progression of left ventricular

functional abnormalities in hypertensive patients with heart failure: an ultrasonic two-

dimensional speckle tracking study. J Am Soc Echocardiogr. 2008;21:1309-1317.

38. Weidemann F, Dommke C, Bijnens B, Claus P, D'Hooge J, Mertens P, Verbeken E,

Maes A, Van de Werf F, De Scheerder I, Sutherland GR. Defining the transmurality of a

chronic myocardial infarction by ultrasonic strain-rate imaging: implications for

identifying intramural viability: an experimental study. Circulation. 2003;107:883-888.

39. Wang J, Khoury DS, Thohan V, Torre-Amione G, Nagueh SF. Global diastolic strain rate

for the assessment of left ventricular relaxation and filling pressures. Circulation.

2007;115:1376-1383.

40. Dokainish H, Sengupta R, Pillai M, Bobek J, Lakkis N. Assessment of left ventricular

systolic function using echocardiography in patients with preserved ejection fraction and

elevated diastolic pressures. Am J Cardiol. 2008;101:1766-1771.

41. Lopez-Candales A, Rajagopalan N, Dohi K, Edelman K, Gulyasy B. Normal range of

mechanical variables in pulmonary hypertension: a tissue Doppler imaging study.

Echocardiography. 2008;25:864-872.

grgrgrgrgrgrgresesesesesesessisisisisisisiononononononon o o o oooof f f f f f f leleleleleleleftftftftftftft v vv vv v v

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s

F V

n de Werf F, De Scheerder I, Sutherland GR. Defining the t a

c i

speckle tracking study. J Am Soc Echocardiogr. 2008;21:13

F, Dommke C, Bijnens B, Claus P, D'Hooge J, Mertens P, V

n de Werf F, De Scheerder I, Sutherland GR. Defining the tra

cardial infarction by ultrasonic strain-rate imaging: implicati



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Tables:

Table 1. Baseline CharacteristicsCharacteristic Value Total No. 24Male, n (%) 15 (62.5) Age, years 30 ± 6 Body mass index, kg/m2 23.7 ± 2.7 Heart rate, bpm 64 ± 10 Systolic blood pressure, mmHg 122 ± 16 Diastolic blood pressure, mmHg 69 ± 10 Frame rate, Hz 35.6 ± 2.9

Table 2. Echocardiographic Features (n = 24)

Baseline Mueller

Maneuver PLV diastolic dimension, mm 47 ± 4 47 ± 5 0.3 LV systolic dimension, mm 30 ± 3 32 ± 3 0.0004 LV ejection fraction, % 64 ± 4 56 ± 5 <0.0001 Stroke volume, mL 77 ± 15 56 ± 16 <0.0001 Cardiac output, L/min 4.8 ± 0.9 3.7 ± 1.0 <0.0001 Cardiac index, L/min/mm2 2.6 ± 0.4 1.9 ± 0.4 <0.0001 Mitral E/A ratio 1.8 ± 0.3 1.9 ± 0.4 0.1 Deceleration time of E velocity, ms 213 ± 34 205 ± 33 0.3 Septal E/E' ratio 4.8 ± 1.2 5.8 ± 1.3 0.003 LV, left ventricle; LA, left atrium

rMueller

rdiographic Features (n = 24)



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Table 3. Left and Right Ventricle Longitudinal Strain and Strain Rate (n = 24) Baseline Mueller maneuver Recovery LV Strain, % Base -17.5 ± 2.2 -14.9 ± 3.0† -16.7 ± 2.8 Mid -18.4 ± 2.2 -15.6 ± 3.1† -17.4 ± 2.9 Apex -15.0 ± 3.4 -12.9 ± 2.7† -14.8 ± 3.6 Global -17.0 ± 1.6 -14.5 ± 2.2* -16.3 ± 2.4 Time to peak, ms 382 ± 28 369 ± 52 389 ± 31 Strain Rate in LV systole (SRs), s-1 Base -0.97 ± 0.13 -0.89 ± 0.17‡ -0.89 ± 0.21 Mid -0.99 ± 0.13 -0.93 ± 0.18‡ -0.91 ± 0.16 Apex -0.89 ± 0.25 -0.80 ± 0.15 -0.82 ± 0.22 Global -0.95 ± 0.13 -0.87 ± 0.12‡ -0.87 ± 0.17 Time to peak, ms 190 ± 32 177 ± 33 189 ± 28 Strain Rate in early LV filling (SRe), s-1 Base 1.00 ± 0.26 0.94 ± 0.29 0.93 ± 0.28 Mid 1.16 ± 0.22 1.04 ± 0.27 1.12 ± 0.29 Apex 1.09 ± 0.26 0.78 ± 0.23† 1.04 ± 0.36 Global 1.09 ± 0.20 0.92 ± 0.21† 1.03 ± 0.27 Time to peak, ms 488 ± 38 464 ± 50 492 ± 38 RV Strain, % Base -25.9 ± 5.7 -20.0 ± 3.7* -25.0 ± 4.6 Mid -22.7 ± 3.2 -17.9 ± 3.5* -22.1 ± 3.9 Apex -17.4 ± 5.5 -13.6 ± 3.9† -16.8 ± 4.7 Global -22.0 ± 3.1 -17.2 ± 2.5* -21.3 ± 3.2 Time to peak, ms 403 ± 36 391 ± 80 402 ± 47 Strain Rate in RV systole (SRs), s-1 Base -1.58 ± 0.51 -1.15 ± 0.30† -1.44 ± 0.42 Mid -1.41 ± 0.41 -1.06 ± 0.31† -1.28 ± 0.32 Apex -1.05 ± 0.35 -0.86 ± 0.23 -0.95 ± 0.28 Global -1.34 ± 0.35 -1.02 ± 0.21† -1.23 ± 0.29 Time to peak, ms 225 ± 34 196 ± 50‡ 227 ± 45 Strain Rate in early RV filling (SRe), s-1 Base 1.60 ± 0.65 1.45 ± 0.49 1.43 ± 0.52 Mid 1.41 ± 0.53 1.31 ± 0.40 1.26 ± 0.45 Apex 1.26 ± 0.51 1.01 ± 0.39 1.12 ± 0.43 Global 1.43 ± 0.46 1.26 ± 0.36 1.27 ± 0.40 Time to peak, ms 509 ± 43 517 ± 65 524 ± 52 LV, left ventricle; RV, right ventricle *P<0.0001 vs baseline and recovery, †P<0.05 vs baseline and recovery, ‡P<0.05 vs baseline

.94944444 ± ±±±±±± 0 000000.2.2222229 9 9999904 ±±±±±±± 0000000 27272727272727

ak, ms 488 ± 38 464 ± 50

1.09 ± 0.26 0.78 ± 0.23† 1.09 ± 0.20 0.92 ± 0.21†

ak, ms 488 ± 38 464 ± 50

-25.9 ± 5.7 -20.0 ± 3.7*



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Table 4. Mean Absolute Differences, Corresponding Percent of Sample Mean Value and 95% Limit of Agreement for Intraobserver (n=8) and Interobserver (n=8) Comparisons. LV S LV SR RV S RV SR Absolute Difference Intraobserver 0.69 ± 0.35 0.05 ± 0.03 0.91 ± 0.74 0.13 ± 0.12 ( Mean ± SD ) Interobserver 1.06 ± 0.60 0.06 ± 0.05 1.37 ± 1.17 0.09 ± 0.07% Difference Intraobserver 4.1 ± 2.0 4.9 ± 3.1 4.7 ± 4.0 9.8 ± 7.7 ( Mean ± SD ) Interobserver 6.4 ± 3.9 6.6 ± 4.8 6.6 ± 5.5 7.5 ± 5.1 95% Limit of Agreement Intraobserver -0.01, 1.39 -0.01, 0.11 -0.57, 2.39 -0.11, 0.37 (lower, upper) Interobserver -0.14, 2.26 -0.04, 0.16 -0.97, 3.71 -0.05, 0.23 S, strain; SR, strain rate; LV, left ventricle; RV, right ventricle

Figure Legends:

Figure 1. Examples of longitudinal left ventricular (LV) 2D strain (S) and strain rate (SR) curves.

Top: 2D echocardiographic image obtained from apical 4-chamber view. Left: S and SR profile

during 1 cardiac cycle at baseline. Arrows indicate measurement point used for peak systolic S,

peak systolic SR (SRs), and peak SR in early filling (SRe). Middle: During the Mueller

maneuver (MM) longitudinal S, SRs, and SRe were reduced. Right: S and SR during the

recovery phase. After the MM was discontinued, deformation returned to baseline value.

Figure 2. Examples of longitudinal right ventricular (RV) 2D strain (S) and strain rate (SR)

curves.

Top: 2D echocardiographic image obtained from apical 4-chamber view. Left: S and SR profile

during 1 cardiac cycle at baseline. Middle: During the Mueller maneuver (MM) longitudinal S

and SR were reduced,. Right: S and SR at recovery phase. After the MM was discontinued,

deformation returned to baseline values.

Figure 3. Strain (S) in left ventricle (LV)

n

g S

l p

Rs) and peak SR in early filling (SRe) Middle: During the M

of longitudinal left ventricular (LV) 2D strain (S) and strain

graphic image obtained from apical 4-chamber view. Left: S

le at baseline. Arrows indicate measurement point used for p

Rs) and peak SR in early filling (SRe) Middle: During the M



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During the Mueller maneuver, there was a significant decrease in strain compared with baseline.

After release, strain reversed and was not different from baseline. The box plots summarize the

distribution of points at each factor level. The ends of the box are the 25th and 75th quantiles.

The whiskers extend from the ends of the box to the outermost data point that falls within the

distances computed.

Figure 4. Strain rate in early left ventricular (LV) filling (SRe)

During the Mueller maneuver, there was a significant decrease in SRe compared to baseline. SRe

at recovery was not different from baseline. The box plots summarize the distribution of points at

each factor level. The ends of the box are the 25th and 75th quantiles. The whiskers extend from

the ends of the box to the outermost data point that falls within the distances computed.

Figure 5. Strain (S) in right ventricle (RV)

During the Mueller maneuver (MM), S in RV was significantly reduced compared to baseline.

After the MM, S increased significantly. The box plots summarize the distribution of points at

each factor level. The ends of the box are the 25th and 75th quantiles. The whiskers extend from

the ends of the box to the outermost data point that falls within the distances computed.

Figure 6. Strain rate in systole (SRs) in right ventricle (RV)

During the Mueller maneuver, there was a significant decrease in SRs compared to baseline.

After release, SRs reversed and was not different from baseline. The box plots summarize the

distribution of points at each factor level. The ends of the box are the 25th and 75th quantiles.

The whiskers extend from the ends of the box to the outermost data point that falls within the

distances computed.

in right ventricle (RV)

m e

r o

h k

o the outermost data point that falls within the distances com

in right ventricle (RV)

maneuver (MM), S in RV was significantly reduced compare

reased significantly. The box plots summarize the distributio

e ends of the box are the 25th and 75th quantiles. The whiskt

o the outermost data point that falls within the distances com



0 500 1000 1500

0

-1

-1.5

1

1.5

0

-10

-20

Strain

StrainRate

Baseline Mueller Maneuver RecoveryLV

%

S-1

ms

Peak Systolic S

Peak Systolic SR

Peak SR in early filling



0 600 900 1200300

0

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0

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Baseline Mueller Maneuver Recovery

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30

25

20

15

10

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0

Baseline MM Recovery

Strain(%

)

Strain in LV

p < 0.0001 p < 0.0001

-17.0 [1.6]

-14.5 [2.2]

-16.3 [2.4]



0

0.5

1

1.5

2

StrainRa

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1 )


p = 0.01 p =0.03

Strain rate in early LV filling (SRe)

1.09 [0.20]0.92 [0.21]

1.03 [0.27]



-35

-30

-25

-20

-15

-10

-5

0

Strain in RV

Strain(%

)


P < 0.0001 P < 0.0001

-22.0 [3.1]

-17.2 [2.5]

-21.3 [3.2]



Strain rate in RV systole (SRs)

-2.5

-2

-1.5

-1

-0.5

0

StrainRa

te(S

1 )


P = 0.0006 P = 0.005

-1.34 [0.35]

-1.02 [0.21]-1.23 [0.29]



Changes in Left and Right Ventricular Mechanics During the Mueller Maneuver in Healthy Adults: A...

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