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Real-Time MR Imaging of Aortic Flow: Influence of Breathing on Left Ventricular Stroke Volume in Chronic Obstructive Pulmonary Disease¹

Rik J. van den Hout, MD, Hildo J. Lamb, PhD, Joost G. van den Aardweg, MD, Robert Schot, BSc, Paul Steendijk, PhD, Ernst E. van der Wall, MD, Jeroen J. Bax, MD and Albert de Roos, MD

¹ From the Departments of Radiology (R.J.v.d.H., H.J.L., E.E.v.d.W., A.d.R.), Pulmonology (J.G.v.d.A., R.S.), and Cardiology (P.S., J.J.B.), Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. From the 2001 RSNA scientific assembly. Received May 15, 2002; revision requested July 15; final revision received February 12, 2003; accepted March 28. Address correspondence to H.J.L. (e-mail: H.J.Lamb@lumc.nl).

	ABSTRACT

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PURPOSE: To assess real-time changes of left ventricular stroke volume (SV) in relation to the breathing pattern in healthy subjects and in patients with chronic obstructive pulmonary disease (COPD).

MATERIALS AND METHODS: Real-time magnetic resonance (MR) imaging flow measurements were performed in the ascending aorta of 10 healthy volunteers and nine patients with severe COPD. Breathing maneuvers were registered with an abdominal pressure belt, which was synchronized to the electrocardiographic signal and the flow measurement. Healthy subjects performed normal breathing, deep breathing, and the Valsalva maneuver. Patients with COPD performed spontaneous breathing. Paired two-tailed Student t tests were used in healthy volunteers to assess significant SV differences between normal breathing and deep breathing or the Valsalva maneuver. The results of measurements in the patients with COPD were compared with the results during normal breathing in healthy subjects with the unpaired two-tailed Student t test.

RESULTS: In healthy subjects, SV decreased during inspiration and increased during expiration (r² = 0.78, P < .05). When compared with the SV during normal breathing, mean SV did not change during deep breathing but declined during the Valsalva maneuver (P < .05). The difference between minimal and maximal SVs (ie, SV range) increased because of deep breathing or the Valsalva maneuver (P < .05). In normal and deep breathing, velocity of SV elevation and velocity of SV decrease were equal (which resulted in a ratio of 1), whereas during the Valsalva maneuver, this value increased (P < .05). Spontaneous breathing in COPD resulted in SV changes (P < .05) similar to those observed in healthy subjects who performed the Valsalva maneuver.

CONCLUSION: Real-time MR imaging of aortic flow reveals physiologic flow alterations, which are dependent on variations in the breathing pattern.

© RSNA, 2003

Index terms: Aorta, flow dynamics, 941.129416 • Aorta, MR, 941.129416 • Emphysema, 60.751 • Heart, function, 52.619, 52.719 • Heart, MR, 52.121416, 52.12144

	INTRODUCTION

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Chronic obstructive pulmonary disease (COPD) has a high prevalence and morbidity and is often associated with severe hemodynamic consequences (1). In patients with COPD, expiratory intrathoracic pressures can be increased as a result of expiratory obstruction (2). These pressure changes have a distinct influence on cardiac function (3). In combination with other factors, such as hypoxemia and pulmonary hypertension, the heart is subject to chronic hemodynamic and metabolic stress (4).

Intrathoracic blood flow toward and away from the heart is influenced by the cyclic pressure changes that occur as a result of breathing (Fig 1). The variations in intrathoracic pressure cause changes in caval flow affect the filling of the right ventricle (5). The difference between the changing intrathoracic pressure and the constant extrathoracic pressure also has an effect on the left side of the heart by means of alteration of the afterload (3). As a result of ventricular interdependency, the changing right ventricular load influences filling of the left ventricle and vice versa (6).

View larger version (35K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Diagram illustrates the sequence of hemodynamic events during inspiration. Interaction between intrathoracic pressure (Pthor) and right (RV) and left (LV) ventricle is shown. For clarity, atria are not depicted. In the following explanation of the sequence, = leads to, = decrease, and = increase. Inspiration intrathoracic pressure gradient with extrathoracic pressure inferior vena cava (VCI) flow right ventricular filling volume and pressure (P&V) right ventricular SV aortic pulmonary flow (A. PULM) blood pooling in lungs because of increased vascular capacity ventricular pulmonary flow (V. PULM) left ventricular filling volume and pressure left ventricular SV aortic flow . Note that increased right ventricular filling also causes shifting of the interventricular septum toward the left ventricle, compromising left ventricular filling and contraction. Note that during expiration the opposite occurs and left ventricular SV .

Recently, magnetic resonance (MR) flow imaging measurements became possible in real time, and this imaging allows assessment of the interaction between cardiac hemodynamics and breathing (11).

Accordingly, the purpose of the present study was to assess real-time changes of left ventricular SV in relation to the breathing pattern in healthy subjects and in patients with COPD.

	MATERIALS AND METHODS

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Subjects and Study Design
Ten randomly selected healthy volunteers who were nonsmokers (four women, six men; age range, 21–30 years) and nine consecutive men (age range, 65–73 years) who met our criteria for severe COPD (emphysema and/or chronic bronchitis; mean forced expiratory volume in 1 second, 39.2 percentage predicted ± 10.5 [SD]; reversibility, <12%) were included in the present study (Table 1). Two patients were current smokers (>15 cigarettes per day, >25 pack-years) and seven were former heavy smokers (>15 cigarettes per day, >15 pack-years) who stopped smoking more then 9 years prior to entering this study (each patient smoked >25 pack-years). The volunteers and the patients underwent a physical examination that included auscultation, and their clinical history was explored to exclude any concomitant disease. All subjects gave informed consent to participate in the protocol that was approved by the medical ethics committee of our institution.

Study Protocol
Real-time MR imaging of flow was performed during normal breathing, deep breathing, and the Valsalva maneuver in healthy subjects. In patients with COPD, real-time MR imaging flow measurements were performed during only spontaneous breathing because they were not able to perform the maneuvers in a controlled way. Within the control group, the breathing maneuvers were compared with spontaneous breathing to investigate the influence of different breathing maneuvers on SV. To determine the influence of expiratory obstruction on SV, spontaneous breathing in patients with COPD was compared with spontaneous breathing in healthy control subjects. The breathing pattern was registered by using the standard abdominal pressure belt of the imaging unit. The electrocardiographic signal and the breathing curve were tapped from the imaging unit and were recorded simultaneously by using a data acquisition software program (Conduct-PC; CDLeycom, Zoetermeer,the Netherlands). The MR imaging flow acquisitions were synchronized with the breathing curve and the electrocardiographic signal by one author (R.J.v.d.H.). The patients with COPD underwent routine pulmonary function tests (flow-volume testing before and after salbutamol administration) and arterial blood gas analysis within 2 weeks before the MR imaging examination.

Data Analysis
MR imaging flow measurements were analyzed by using a software package (Flow; Medis, Leiden, the Netherlands). The area under every flow peak in the flow-time curve was then determined by an author (R.J.v.d.H.) and represents SV of the left ventricle. A data analysis software program (CircLab; GTX Medical Software, Zoetermeer, the Netherlands) was used to display the simultaneously recorded MR imaging flow acquisition, breathing curve, and electrocardiographic signal. The calculated SVs were plotted at the time points of the corresponding aortic flow peak to demonstrate the correlation between SVs and the phase of inspiration and expiration. For five healthy control subjects, SV was plotted versus breathing phase, and the correlation coefficient was calculated. The created sequence of changing SVs during a breathing maneuver was then analyzed (R.J.v.d.H.). The average minimal SV and the average maximal SV during inspiration and expiration were calculated. In addition, the difference between the averaged minimal and maximal SVs was calculated and yielded the SV range, and the mean value of all SVs was determined. The mean slope of the SV curve between a minimum and the consecutive maximum was calculated and was called SV acceleration. The mean slope of a decrease in SV was called SV deceleration. The SV ratio was obtained by dividing the SV acceleration by the SV deceleration that followed it.

Statistical Analysis
Paired two-tailed Student t tests were used to assess significant SV differences between normal breathing and deep breathing or the Valsalva maneuver in the group of healthy volunteers. The results of measurements in the patients with COPD were compared with measurements during normal breathing in control subjects by using an unpaired two-tailed Student t test. A difference with P < .05 was considered statistically significant. All parameters were expressed as the mean ± SD.

	RESULTS

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Figure 2 demonstrates how SV was calculated from the area under the flow curve of the ascending aorta.

View larger version (63K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Images in a healthy 25-year-old man. A, Modulus and phase images of real-time MR flow imaging in the ascending aorta are displayed and resulted in the corresponding flow peak, as illustrated. B, Simultaneous real-time recording of flow in the ascending aorta. C, Breathing curve (gray line) and SV curve (black line with data points). Calculated SVs for all flow peaks result in the SV curve. SV acceleration (SVacc) and SV deceleration (SVdec) are indicated with dotted black lines. These lines demonstrate the mean slope of the ascending and descending curve. a.u. = arbitrary units. D, Electrocardiographic signal.

View larger version (50K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Graphs of typical breathing maneuvers performed by the same subject as in Figure 2. Gray line represents the breathing curve. Black line is the SV curve, with each data point representing an SV value. Dotted horizontal line represents mean SV. This value does not differ between normal and deep breathing. a.u. = arbitrary units. A, Normal breathing. Note that SV increases with expiration and decreases with inspiration. B, Deep breathing. Note the exaggerated effect of an SV increase with expiration and an SV decrease with inspiration. C, Valsalva maneuver. Note a sudden increase in SV followed by a slow decrease in SV.

View larger version (17K): [in this window] [in a new window] [Download PPT slide]   Figure 4. Graph shows correlation between thoracic excursion (inspiration or expiration) and SV during normal breathing in the same subject as in Figure 2. Each data point represents an SV value. Note that SV decreases from end-expiration toward end-inspiration (r2 = 0.77, P < .05). For the whole group, mean r2 = 0.78 ± 0.09. a.u. = arbitrary units.

View larger version (33K): [in this window] [in a new window] [Download PPT slide]   Figure 5. Graph shows SV curves of the same subject as in Figure 2 and of a 69-year-old man with COPD obtained during spontaneous breathing. Curve obtained in patient with COPD is in all aspects at a lower level, the range between minimal and maximal SV is wider (compare gray areas), and the acceleration-deceleration ratio of SV is higher as compared with values in the healthy subject. For all healthy subjects, mean SV range is 13.1 mL ± 2.7, and for the patients with COPD, the range is 19.5 mL ± 5.6 (P < .05). The acceleration-deceleration ratio is 1.0 ± 0.5 in healthy subjects and 1.8 ± 0.6 in patients with COPD. SVacc = SV acceleration, SVdec = SV deceleration.

View larger version (16K): [in this window] [in a new window] [Download PPT slide]   Figure 6. Graph shows comparison of all SV parameters as a result of normal breathing in both healthy subjects and patients with COPD. COPD causes a decrease of minimal, maximal, and mean SV (P < .05). Note the increase in SV range and acceleration-deceleration ratio in patients with COPD as compared with values in healthy subjects (P < .05). * = P < .05, unpaired two-tailed Student t test, comparison between healthy subjects and patients with COPD.

	DISCUSSION

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Real-Time Flow Imaging
Conventional MR imaging flow acquisition measures only the average of all SVs during many respiratory cycles. This technique cannot reveal the instant SV changes that occur as a result of the continuously changing intrathoracic pressures caused by breathing. With real-time MR imaging flow acquisition, it is possible to assess the direct influence of breathing on aortic flow. During inspiration, there is an instantaneous decrease of left ventricular SV, followed by an increase during the consecutive expiration. These measured SV changes confirm results of previous echocardiographic studies and computer model studies about ventricular interdependence (6,7). These results indicated that in end-inspiration the negative intrathoracic pressure results in a lower SV than in end-expiration, when intrathoracic pressure equals atmospheric pressure.

Relationship between Cardiac Flow and Different Breathing Maneuvers
With real-time MR imaging, it was possible to demonstrate that breathing maneuvers have a distinct influence on cardiac SV. The present results indicate that minimal and maximal SV show a significant change when deep breathing or the Valsalva maneuver are performed as compared with the values measured during normal breathing. It is hypothesized that more extreme intrathoracic pressures during special maneuvers cause the changes in these SV parameters (7).

In healthy subjects, the ratio of SV acceleration divided by SV deceleration equals 1 during normal and deep breathing. When there is expiratory airway obstruction, such as during the Valsalva maneuver or during spontaneous breathing in patients with COPD, this ratio increases because of the prolongation of the period in which SV decreases. The Valsalva maneuver implies an extremely obstructed expiratory phase and might therefore be a model for spontaneous breathing in COPD (13). SV increases rapidly at the beginning of the Valsalva maneuver and decreases slowly while there is still a higher (expiratory) intrathoracic pressure. This is in agreement with the findings in the study of Eichenberger et al (11), who used real-time MR imaging to assess the aortic blood flow during a few seconds of normal breathing and during the Valsalva maneuver in healthy subjects. They found a SV decrease of 25% at the end of the maneuver, as compared with the average SV during normal breathing. The present results show an SV decrease of almost 50%.

Patients with COPD
The results show that the patients with COPD have a decreased minimal, maximal, and mean left ventricular SV as compared with subjects who have normal unobstructed breathing. Heart rate did not differ between both groups. The diminished SV in patients with COPD indicates impaired cardiac function caused by the pathologically altered pressure relationships between the intra- and extrathoracic compartments as a result of the obstructed breathing pattern (5). Hypoxemia induced by both parenchymal and vascular pulmonary damage can also add to the impaired cardiac function (4). The SV range, that is, the difference between minimal and maximal SV, is wider when compared with that during normal breathing in healthy subjects. This is probably because of the increased gap between the higher end-expiratory intrathoracic pressure and the normal unobstructed inspiratory thoracic pressure. The acceleration-deceleration ratio of the SV curve is significantly higher in patients with COPD who are breathing spontaneously than it is in healthy subjects. This suggests that after the normal increase at the start of expiration, SV slowly starts to decrease during the last phase of expiration, and the decrease in SV continues during inspiration. All these differences in SV parameters in patients with COPD are comparable with the differences that occur during the Valsalva maneuver when compared with nonobstructed breathing, and these findings support the hypothesis that the Valsalva maneuver can be used as a model for breathing in patients with COPD (13).

Clinical Implications
We believe that in the future this technique can be useful in the monitoring of cardiac SV noninvasively to evaluate the effect of pulmonary medication (ie, bronchodilators) and oxygen therapy. It might also be useful in the evaluation of the hemodynamic effect of breathing retraining that is part of a pulmonary rehabilitation program (14,15).

Moderate pulmonary hypertension is frequently encountered in patients with severe COPD and results in elevated right ventricular pressures. This, in turn, may contribute to the paradoxical movement of the intraventricular septum, with an adverse effect on left ventricular SV, cardiac output, and cardiac index. The effect of medical therapy aimed at the reduction of pulmonary hypertension and right ventricular pressures may be evaluated by the proposed MR imaging protocol as well. The MR imaging protocol in this study may be useful to provide highly accurate and reproducible measurements noninvasively to monitor cardiopulmonary hemodynamics.

Limitations
Intrathoracic pressures were measured indirectly with a respiratory belt balloon. Body surface area and heart rate were equal between both groups (ie, healthy subjects and patients with COPD), although mean age was different. However, findings of some studies (16,17) indicate that SV remains constant over time or even increases with age in healthy individuals.

In conclusion, in contrast to conventional velocity-encoded MR imaging, real-time MR flow imaging can demonstrate a decrease in left ventricular SV during inspiration and an increase in SV during expiration.

In addition, instantaneous effects of changes in breathing on SV can be measured by using real-time MR flow imaging. In healthy volunteers, deep breathing caused an increase in the range of SV, whereas the mean SV and the slopes of the SV curve remained unchanged, as compared with these parameters during normal breathing. The Valsalva maneuver exaggerated the observed difference in SV range caused by deep breathing in normal subjects. The SV curve of the Valsalva maneuver became strongly asymmetrical because of a prolongation of the SV decrease, as compared with those observed during normal and deep breathing.

In patients with COPD—that is, in patients with an expiratory obstruction—the observed increase in SV range was similar to that during deep breathing and the Valsalva maneuver, as observed in healthy subjects. Moreover, the SV minimum, SV maximum, and mean SV were at a lower level, as compared with those in healthy subjects. An interesting observation was that the SV curve in COPD patients became asymmetrical with a fast SV increase and a slow decrease that reflected expiratory obstruction, as observed during the Valsalva maneuver in healthy subjects. MR imaging evaluation of hemodynamics may become useful for monitoring of the effect of therapy in patients with COPD or pulmonary hypertension. The technique also will be useful to study the pathophysiology of COPD and other diseases with heart-lung interaction.

	ACKNOWLEDGMENTS

 
We acknowledge the important contributions of Erik van den Berg, BS, and Zafiria Metafratzi, MD, in the analysis of the data and in the assistance they provided during the imaging procedures. Rik van den Hout passed away after a long illness on April 23, 2003. His coauthors dedicate this article to his memory.

	FOOTNOTES

 
Deceased.

Abbreviations: COPD = chronic obstructive pulmonary disease, SV = stroke volume

Author contributions: Guarantors of integrity of entire study, R.J.v.d.H., H.J.L., J.G.v.d.A., A.d.R.; study concepts and design, R.J.v.d.H., H.J.L., J.G.v.d.A., R.S., A.d.R.; literature research, R.J.v.d.H., H.J.L., J.G.v.d.A., J.J.B., A.d.R.; clinical studies, R.J.v.d.H., H.J.L., J.G.v.d.A., R.S., J.J.B., A.d.R., P.S.; data acquisition, R.J.v.d.H., H.J.L., J.G.v.d.A., R.S.; data analysis/interpretation, all authors; statistical analysis, R.J.v.d.H., H.J.L., J.G.v.d.A., A.d.R.; manuscript preparation and definition of intellectual content, all authors; manuscript editing, R.J.v.d.H., H.J.L., J.G.v.d.A., P.S., J.J.B., A.d.R.; manuscript revision/review, and final version approval, all authors

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

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