DOI: 10.1148/radiol.2293021363
(Radiology 2003;229:743-748.)
© RSNA, 2003
Heart Failure: Evaluation of Cardiopulmonary Transit Times with Time-resolved MR Angiography1
Stephanie M. Shors, MD,
William G. Cotts, MD,
Biljana Pavlovic-Surjancev, MD, PhD,
Christopher J. François, MD,
Mihai Gheorghiade, MD and
J. Paul Finn, MD
1 From the Department of Radiology (S.M.S., C.J.F., J.P.F.) and Department of Medicine, Division of Cardiology (W.G.C., B.P.S., M.G.), Feinberg School of Medicine, Northwestern University Medical School, Chicago, Ill. Received October 21, 2002; revision requested January 7, 2003; final revision received April 14; accepted April 30. Address correspondence to J.P.F., Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Peter V. Ueberroth Building, Suite 3371, 10945 Le Conte Ave, Los Angeles, CA 90095-7206. (e-mail: pfinn@mednet.ucla.edu).
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ABSTRACT
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PURPOSE: To measure cardiopulmonary transit times in patients with heart failure by using low-dose, time-resolved magnetic resonance (MR) angiography and to determine if transit curves reflect conventional MR indexes of cardiac function.
MATERIALS AND METHODS: Twenty-six patients with heart failure and left ventricular (LV) systolic dysfunction (17 men and nine women; age range, 22–78 years) and thirteen control subjects (eight men and five women; age range, 23–59 years) were examined with MR imaging. The examination consisted of rapid cine MR imaging throughout the heart, followed by contrast material–enhanced time-resolved three-dimensional MR angiography of the cardiac chambers and pulmonary vasculature. Time-intensity curves for the pulmonary artery and ascending aorta were derived from the MR angiography images. Cardiopulmonary transit times and dispersions (full widths at half maximum [FWHM]) were determined from the curves. Transit times and FWHM values for the patients with heart failure were compared with control values by using two-tailed t tests, and transit time was correlated with standard LV functional parameters calculated from the cine MR images.
RESULTS: Cardiopulmonary transit times and FWHM values were significantly prolonged in the patients with heart failure compared with those in the control patients (P < .001). Transit time correlated directly with LV end-diastolic and end-systolic volumes and inversely with LV ejection fraction (R > 0.60). However, transit time did not correlate strongly with age, body surface area, heart rate, LV mass, stroke volume, cardiac output, or sphericity index.
CONCLUSION: Time-resolved MR angiography allows determination of cardiopulmonary transit times that are significantly prolonged in heart failure and correlate directly with LV volumes and inversely with LV ejection fraction.
© RSNA, 2003
Index terms: Heart, failure, 51.71 • Heart, flow dynamics • Heart, MR, 51.12142 • Heart, ventricles, 51.71 • Magnetic resonance (MR), vascular studies, 51.12142
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INTRODUCTION
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It has long been believed that circulation times are prolonged in heart failure. When circulation time measurements were popularized in the 1930s, their primary application was to help distinguish cardiac failure from other diseases that produced similar symptoms (1,2). In the mid-twentieth century, circulation time measurements typically were made by injecting sodium dehydrocholate into an arm vein and measuring the time it took to produce a bitter taste on the tongue (3). Multiple researchers during this period documented prolongation of "arm-to-tongue" circulation times in patients with heart failure (4–7) and found an association between increased time and increased cardiac size (4,6,7). It was believed that large volumes of blood in the pulmonary vasculature and cardiac chambers, along with reduced cardiac output, slowed the velocity of blood flow and led to increased blood transit times in heart failure. Due to its subjective nature, however, the sodium dehydrocholate test was felt to be unreliable (8) and gradually fell out of use.
More recently, other techniques have been used to measure cardiopulmonary circulation times, including radionuclide angiocardiography, computed tomography (CT), and magnetic resonance (MR) imaging (9–15). Radionuclide angiocardiography involves injecting a radioactive tracer and monitoring its first passage through the heart and lungs with an external radiation detector. With this technique, several investigators have demonstrated prolonged cardiopulmonary transit times in patients with cardiac insufficiency (9,12,15). However, radionuclide angiocardiography is limited by poor spatial resolution and anatomic ambiguity. As with radionuclide techniques, CT and MR imaging can be used to determine circulation times from the first passage of contrast material through a specific portion of the vasculature (10,11,14). Conventional CT and MR imaging, however, have limited temporal resolution, making it difficult to detect relatively small increases in circulation times. Moreover, the large hyperosmolar contrast material load inherent in CT scanning is undesirable in patients with heart failure, whose stability is critically dependent on blood volume homeostasis.
With the advent of high-performance gradient MR imaging systems, it has recently become possible to image dynamic changes in the heart and great vessels with subsecond temporal resolution and very small contrast material doses (16). MR imaging is unrivaled for accurate and reproducible measurement of left ventricular (LV) volumes, ejection fraction, and mass (17–21). However, cardiac cine techniques generally require repeated breath holding and reliable electrocardiographic gating, which, even with recent technical advances (22), may be time consuming and yield suboptimal results in patients with heart failure. The purpose of this study was to measure cardiopulmonary transit times in patients with heart failure by using low-dose, time-resolved MR angiography and to determine if transit curves reflect conventional MR indexes of cardiac function.
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MATERIALS AND METHODS
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Subjects
Twenty-six consecutive patients with heart failure (17 men and nine women; mean age, 51 years; age range, 22–78 years) and 13 control subjects with no history of cardiac disease (eight men and five women; mean age, 39 years; age range, 23–59 years) were prospectively evaluated. All patients with heart failure had previously received a diagnosis of LV systolic dysfunction, defined as an LV ejection fraction (LVEF) less than or equal to 40% at echocardiography, radionuclide ventriculography, or contrast material–enhanced ventriculography. All of the patients were clinically stable at the time of MR imaging. The study was performed in accordance with the guidelines of the institutional review board, and written informed consent was obtained from all subjects.
Imaging Protocol
Each subject underwent a single MR examination performed with a clinical 1.5-T MR imaging unit (Magnetom Sonata; Siemens Medical Solutions, Malvern, Pa). Before imaging, an 18-gauge intravenous catheter was inserted into an antecubital vein. Subjects were placed on the imaging table in a supine position, electrocardiographic electrodes were placed on the anterior portion of the chest, and a quadrature phased-array coil was secured around the thorax. Subjects were entered headfirst into the magnet bore.
The examination consisted of cine imaging from the LV base to the apex, followed by contrast-enhanced time-resolved three-dimensional MR angiography of the heart and lungs (16). Cine images were acquired in the short and long axes by using a previously described (22) electrocardiographically triggered, segmented-k-space, true fast imaging with steady-state precession (TrueFISP; Siemens Medical Solutions) sequence. Cine image acquisition required a 6–8-second breath hold for each section position. Typical imaging parameters included repetition time msec/echo time msec, 3.2/1.6; flip angle, 60°; bandwidth, 950 Hz/pixel; field of view, 360 x 280 mm2; matrix, 256 x 140; section thickness, 6 mm; and section spacing, 4 mm. For the MR angiography portion of the examination, a 6-mL bolus of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Montvale, NJ), followed by 20 mL of normal saline, was injected at a rate of 6 mL/sec by using an automated power injector (Medrad, Indianola, Pa). During contrast material infusion, three-dimensional gradient-echo fast low-angle shot imaging was performed in an oblique sagittal ("candy cane") projection through the pulmonary artery and aorta (1.8/0.7; flip angle, 14°; bandwidth, 1,200 Hz/pixel; field of view, 350 x 280 mm2; matrix, 256 x 145; slab thickness, 90 mm; number of partitions, six; partition thickness, 15 mm; and pixel size, 1.4 x 1.9 mm2). Three-dimensional data sets were acquired at 0.4–0.7-second intervals for 25–30 seconds after contrast material injection. Subjects were requested to hold their breath in inspiration during the MR angiographic examination for as long as was comfortable.
Image Analysis
All image analysis was performed by the same investigator (S.M.S., with 18 months of experience in cardiac MR image analysis), with oversight by a senior investigator (J.P.F., with more than 10 years of experience in cardiac MR imaging). Cardiopulmonary transit times were determined from the subtracted maximum intensity projection MR angiographic images, as shown in Figure 1. Circular regions of interest were placed over the main pulmonary artery and the ascending aorta, such that the regions of interest were as large as possible (typically 40–90 pixels) without extending beyond these vessels. Time-intensity curves were generated for bolus transit through the regions of interest, and the pulmonary artery–to–ascendingaorta transit time was calculated by subtracting the time of peak signal intensity on the pulmonary artery curve from the time of peak signal intensity on the ascending aorta curve. To measure the dispersion seen in the transit curves, an additional parameter, FWHM, was calculated by measuring the width of the ascending aorta curve at half its maximal signal intensity.
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Figure 1a. Generation of transit curves from time-resolved oblique sagittal projection MR angiograms (1.8/0.8) in a healthy control subject. Circular regions of interest are placed over (a) the pulmonary artery and (b) the ascending aorta, and (c) signal intensity is plotted versus time. Transit time is calculated by subtracting the time of peak signal intensity on the pulmonary artery curve (black line in c) from the time of peak signal intensity on the ascending aorta curve (gray line in c). Full width at half maximum (FWHM) is calculated by measuring the width of the ascending aorta curve at half its maximum signal intensity.
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Figure 1b. Generation of transit curves from time-resolved oblique sagittal projection MR angiograms (1.8/0.8) in a healthy control subject. Circular regions of interest are placed over (a) the pulmonary artery and (b) the ascending aorta, and (c) signal intensity is plotted versus time. Transit time is calculated by subtracting the time of peak signal intensity on the pulmonary artery curve (black line in c) from the time of peak signal intensity on the ascending aorta curve (gray line in c). Full width at half maximum (FWHM) is calculated by measuring the width of the ascending aorta curve at half its maximum signal intensity.
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Figure 1c. Generation of transit curves from time-resolved oblique sagittal projection MR angiograms (1.8/0.8) in a healthy control subject. Circular regions of interest are placed over (a) the pulmonary artery and (b) the ascending aorta, and (c) signal intensity is plotted versus time. Transit time is calculated by subtracting the time of peak signal intensity on the pulmonary artery curve (black line in c) from the time of peak signal intensity on the ascending aorta curve (gray line in c). Full width at half maximum (FWHM) is calculated by measuring the width of the ascending aorta curve at half its maximum signal intensity.
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With the short-axis cine MR images, the following parameters were evaluated by using commercially available software (Argus; Siemens Medical Solutions): LVEF, LV mass, LV end-diastolic volume, LV end-systolic volume, stroke volume, and cardiac output. End-diastolic and end-systolic sphericity indexes were calculated from the long- and short-axis cine MR images by dividing the LV length from the apex to the plane of the mitral annulus by the LV width at the basal aspect of the papillary muscles, as shown in Figure 2.
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Figure 2a. Cine MR images (3.2/1.6) in (a) long and (b) short axes demonstrate measurement of the sphericity index. Sphericity index is measured by dividing the length of the LV from the apex to the mitral annulus (10.2 cm in a) by the width of the LV (7.0 cm in b) at the basal aspect of the papillary muscles. The end-systolic sphericity index for this patient with heart failure was 1.5, while the mean end-systolic sphericity index for the control subjects was 2.2.
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Figure 2b. Cine MR images (3.2/1.6) in (a) long and (b) short axes demonstrate measurement of the sphericity index. Sphericity index is measured by dividing the length of the LV from the apex to the mitral annulus (10.2 cm in a) by the width of the LV (7.0 cm in b) at the basal aspect of the papillary muscles. The end-systolic sphericity index for this patient with heart failure was 1.5, while the mean end-systolic sphericity index for the control subjects was 2.2.
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Statistical Analysis
Transit times and FWHM values for the patients with heart failure were compared with those for the control subjects by using two-tailed t tests. A P value of less than .05 was considered to indicate a statistically significant difference. Pearson correlation coefficients were used to assess the relationship between transit time and patient age, body surface area, heart rate, LVEF, LV mass, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, and end-diastolic and end-systolic sphericity indexes. Because transit time is likely inversely related to LVEF and cardiac output, these parameters were correlated with 1/transit time. An absolute correlation coefficient (R value) of greater than 0.60 was regarded as indicating a strong correlation. The significance of each correlation was determined with a two-tailed t distribution test, and a P value of less than .05 was considered to indicate a statistically significant difference. For correlations that were not significant, power analysis was performed to determine if the power of the study was sufficient for detection of a correlation that was statistically different from zero (ie, if the power was 0.80 or greater). To determine threshold transit time and FWHM values that best enabled discrimination between patients with systolic dysfunction and control subjects, receiver operating characteristic curves were generated by plotting the true-positive rate (sensitivity) versus the false-positive rate (1 - specificity) (23). All results were expressed as means ± SDs.
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RESULTS
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Dynamic MR angiograms of the heart, aorta, and pulmonary vasculature were successfully obtained in all of the study participants and allowed clear visualization of these anatomic structures. An example of the MR angiographic images from a patient with heart failure is shown in Figure 3.
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Figure 3. Time-resolved oblique sagittal projection MR angiograms (1.8/0.8) in a patient with heart failure show the sequential appearance of contrast material in the pulmonary artery (PA), pulmonary parenchyma (PP), left atrium (LA), and aorta (A). Eight frames are shown from a 44-frame series. Frames were acquired at time intervals of 540 msec.
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The mean MR imaging–determined LVEF for the patients with heart failure was 30% ± 14, while the mean LVEF for the control subjects was 66% ± 8. Four of the patients with heart failure with LVEFs of 40% or less at previous imaging studies had LVEFs greater than 40% at MR imaging. Data from these subjects were excluded from the receiver operating characteristic analysis but were included in all of the other statistical analyses.
Typical time-intensity curves for a patient with heart failure and a control subject are shown in Figure 4. Pulmonary artery–to–ascending aorta transit times were significantly prolonged in the patients with heart failure (at 10.4 seconds ± 3.3) compared with those in the control subjects (at 7.2 seconds ± 1.2) (P < .001). Transit times tended to be longest in the patients with the lowest LVEFs. There was no difference in transit times between the four patients with heart failure who had LVEFs greater than 40% at MR imaging and the control subjects (Table 1). Similarly, FWHM values were significantly increased in the patients with heart failure as compared with those in the control subjects, with a mean FWHM of 11.6 seconds ± 3.1 in the patients with heart failure and 7.9 seconds ± 1.5 in the control subjects (P < .001) (Table 1). Normalized distribution curves suggested that the patients with heart failure and the control subjects could be clearly separated on the basis of cardiopulmonary transit time and FWHM (Fig 5).
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Figure 4. Graphs show representative time-intensity curves for bolus transit through the pulmonary artery (black lines) and the ascending aorta (gray lines) in a control subject (left) and in a patient with heart failure (right). Pulmonary artery-to-ascending aorta transit time was 6.3 seconds in the control subject and 10.3 seconds in the patient with heart failure.
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Figure 5. Graphs show normalized distribution curves for pulmonary artery-to-ascending aorta transit time (left) and ascending aorta FWHM (right) in control subjects (black lines) and patients with heart failure (gray lines). The curves suggest that control subjects and patients with heart failure form two separate populations on the basis of these parameters.
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Cardiopulmonary transit time correlated directly with LV end-diastolic and end-systolic volumes and inversely with LVEF (R > 0.60, P < .001). Transit time also demonstrated a weak inverse correlation with cardiac output (R = 0.52, P < .001). Transit time did not correlate strongly with LV mass, end-diastolic sphericity index, or end-systolic sphericity index (R < 0.50, P < .05). Transit time also did not correlate strongly with age, body surface area, heart rate, or LV stroke volume (R < 0.50), although these results were not statistically significant (P > .05) and were statistically underpowered (power, <0.80). Correlation data are given in Table 2, and scatterplots for transit time versus LVEF, cardiac output, LV end-diastolic volume, and LV end-systolic volume are shown in Figure 6.
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Figure 6. Scatterplots include data from 39 subjects, with each point representing data from one subject. A, Linear relationship between 1/transit time and LVEF is strong. B, Linear relationship between 1/transit time and cardiac output is weaker than that in A. C, D, Strong linear relationships are shown between transit time and LV end-diastolic volume (C) and transit time and LV end-systolic volume (D).
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Receiver operating characteristic curves for cardiopulmonary transit time and FWHM are shown in Figure 7. On the basis of these curves, a threshold transit time of 8.0 seconds best discriminated (with 86% sensitivity and 85% specificity) between patients with LVEFs of 40% or lower at MR imaging and control subjects with normal LVEFs, while a threshold FWHM value of 10.5 seconds best discriminated (with 73% sensitivity and 100% specificity) between patients with LVEFs of 40% or lower at MR imaging and control subjects. When these two thresholds were combined, such that a transit time greater than 8.0 seconds and/or a FWHM value greater than 10.5 seconds suggested heart failure, the sensitivity and specificity were 91% and 85%, respectively.
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Figure 7. Graph shows receiver operating characteristic curves for transit time and FWHM. The dashed line represents the curve of a test with no ability to discriminate between patients with heart failure and control subjects, while the curve of a test with perfect discriminative ability would lie along the left and upper borders of the graph.
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DISCUSSION
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The results of this study show a strong correlation between cardiopulmonary transit time and LVEF, end-diastolic volume, and end-systolic volume, well-established predictors of outcome in heart failure (24). Although it seems intuitive that cardiopulmonary transit times are prolonged in heart failure, to our knowledge this study is the first to evaluate them prospectively with a practical, high-spatial-resolution, noninvasive imaging technique, in this case, time-resolved MR angiography. Compared with an average transit time of 7.2 seconds ± 1.2 in control subjects, the average transit time in patients with heart failure was 10.4 seconds ± 3.3. It is likely that even greater prolongation would be seen in patients with clinical decompensation, in whom fluid retention and diminished cardiac output form a destructive loop. All of the patients evaluated in this study were clinically stable at the time of the MR imaging examination and were not exhibiting signs of congestive failure.
Previous transit time studies in patients with heart failure typically involved measurement of "arm-to-tongue" circulation times, the implicit subjectivity of such a measurement rendering it impossible to directly compare the results of this study with those of most previous studies. Recently, however, Francois et al (10) retrospectively reviewed the results of 77 MR angiographic test-bolus examinations and found an average pulmonary artery–to–ascending aorta transit time of 10.4 seconds in patients with LV systolic dysfunction. That value is identical to the average transit time measured in patients with heart failure in this study. In subjects without cardiac disease, Francois et al observed an average pulmonary artery–to–ascending aorta transit time of 5.8 seconds, which is slightly shorter than the transit time of 7.2 seconds observed in the control subjects in this study. The control results reported in this study more closely agree with those of Jones et al (12), who used radionuclide angiocardiography to measure cardiopulmonary transit times in 10 healthy subjects and found an average pulmonary artery–to–ascending aorta transit time of 6.9 seconds.
The results of the current study suggest that prolonged cardiopulmonary transit times are caused by systolic dysfunction. When the pulmonary artery–to–ascending aorta transit time was compared with other cardiac parameters, transit time was also found to correlate directly with LV end-diastolic and end-systolic volumes. This result is consistent with one of the fundamental principles of tracer kinetics—that is, that the transit time of an indicator is proportional to its volume of distribution (25). It is also consistent with the results of Gernandt and Nylin (4) and Nathanson and Elek (7), who estimated cardiac blood volume from the area of the cardiac silhouette on radiographs and found a direct, although understandably less well defined, relationship between estimated blood volume and circulation time. According to the principles of tracer kinetics, transit time should also be inversely proportional to blood flow, or cardiac output (25). However, only a weak correlation was seen in this study, in which transit times were compared with cardiac outputs determined at MR imaging. This finding suggests that, even in the presence of normal resting output, cardiopulmonary blood volume is increased and is measurable with MR imaging.
As MR imaging assessment of patients with cardiac failure becomes routine, time-resolved MR angiography of the heart and thoracic vasculature may prove to be a valuable addition to the standard MR imaging examination. It is already known that MR imaging can provide accurate and reproducible measurements of multiple functional parameters, such as LVEF, mass, volume, and cardiac output (17–21), as well as identify nonviable tissue after myocardial infarction (26). The dynamic MR angiographic technique described in this study produces time-resolved images of the cardiac chambers and pulmonary circulation from which physiologic information can easily be derived. In patients with heart failure, transit curves may provide insight about the functional status of the LV and become a tool for stratifying patients with heart failure. An additional advantage of this MR angiographic technique is the small contrast material dose requirement. We used a dose of only 6 mL of gadopentetate dimeglumine for transit time measurement, which is equivalent to an osmolar load of 12 mOsm. This compares favorably with CT, for example, where osmolar loads as high as 200 mOsm are standard (27). Second, the small volume of gadopentetate dimeglumine can be injected within 1 second, greatly improving the shape of the input function compared with that yielded by schemes that require input over several seconds.
This study had several limitations. First, we determined transit times by subtracting the times of peak signal intensities rather than by subtracting the first moments of the curves, or mean transit times. However, it has been shown that peak transit time provides an accurate index of mean transit time (28–30), although peak transit time may be less reproducible, because it is more likely to be influenced by alterations in bolus configuration than the mean transit time (12). Second, the MR angiographic portion of the examination works best with breath holding, the phase of which may influence bolus kinetics and prolong circulation times (31). All study participants were requested, in a standardized fashion, to hold their breath in inspiration during MR angiography; however, it is possible that not all subjects were able to hold their breath for the entire 25–30 seconds. Finally, transit time was measured only once in each study participant, so no conclusion can be drawn about the reproducibility of transit time measurements. However, the values for control subjects observed in this study correspond closely to those in the published literature.
In summary, cardiopulmonary transit times are significantly prolonged in heart failure and correlate directly with LV end-diastolic and end-systolic volumes and inversely with LVEF. Time-resolved three-dimensional MR angiography provides functional information about cardiopulmonary hemodynamics and may have potential relevance in evaluating and stratifying patients with heart failure.
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FOOTNOTES
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Abbreviations: FWHM = full width at half maximum,
LV = left ventricle,
LVEF = LV ejection fraction
Author contributions: Guarantor of integrity of entire study, J.P.F.; study concepts and design, all authors; literature research, S.M.S., C.J.F.; clinical studies, S.M.S., C.J.F., J.P.F.; data acquisition, S.M.S., W.G.C., B.P.S., J.P.F.; data analysis/interpretation, all authors; statistical analysis, S.M.S., J.P.F.; manuscript preparation, S.M.S.; manuscript definition of intellectual content, all authors; manuscript editing, S.M.S., J.P.F.; manuscript revision/review and final version approval, all authors
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Transit time dispersion in pulmonary and systemic circulation: effects of cardiac output and solute diffusivity
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TOP
ABSTRACT
INTRODUCTION
