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(Radiology. 2000;216:464-471.)
© RSNA, 2000

Cardiac Imaging

Patients with Pulmonary Fibrosis: Cardiac Function Assessed with MR Imaging1

Lucia J. M. Kroft, MD, Philip Simons, MD, Jacob M. van Laar, MD and Albert de Roos, MD

1 From the Departments of Radiology (L.J.M.K., P.S., A.d.R.) and Rheumatology (J.M.v.L.), C2-S, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. Received May 13, 1999; revision requested July 13; revision received October 18; accepted December 30, 2000. Address correspondence to A.d.R. (e-mail: a.de_roos@radiology.azl.nl).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To detect abnormalities in cardiac function by using magnetic resonance (MR) imaging in patients with mild to moderate pulmonary fibrosis and to evaluate the relationship between pulmonary function and cardiac function.

MATERIALS AND METHODS: Sixteen patients were compared with 16 sex- and age-matched healthy control subjects. Systolic function was assessed by using multisection multiphase cine MR imaging. Diastolic function was assessed with flow-sensitive MR imaging across the mitral and tricuspid valves. MR imaging results were compared with the severity of impairment in pulmonary function.

RESULTS: Biventricular systolic function and left ventricular diastolic function were normal in patients, but right ventricular diastolic function was significantly impaired versus that of control subjects, with a ratio of peak flow during early diastolic (E) filling to peak flow during atrial contraction (A) of 0.85 ± 0.40 versus 1.28 ± 0.50 (P = .035). Biventricular E/A ratios were strongly correlated to age in patients and control subjects. The right ventricular E/A ratio in patients corresponded with values that are normally expected in people 20 years older. Diastolic left and right ventricular functions were significantly correlated with each other. There was no relationship between pulmonary function and cardiac function.

CONCLUSION: Impairment of right ventricular diastolic function was found by using MR imaging in patients with mild to moderate pulmonary fibrosis, whereas left ventricular diastolic function and biventricular systolic function were preserved.

Index terms: Heart, function • Heart, MR, 51.121412, 51.121416, 51.12144 • Heart, ventricles • Lung, fibrosis, 60.6113 • Lung, function • Magnetic resonance (MR), cine study, 51.121412, 51.12144 • Magnetic resonance (MR), functional imaging, 51.12144 • Magnetic resonance (MR), volume measurements, 51.121412, 51.12144


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients with connective tissue disease often have pulmonary and cardiac abnormalities, which is of concern because these abnormalities are associated with reduced survival rates (1–5). Cardiac involvement may be a primary process in the connective tissue disease (6), but cardiac function may also be influenced by associated pulmonary disorders such as pulmonary fibrosis and pulmonary arterial hypertension (7). The prevalence of right ventricular systolic dysfunction is high in patients with end-stage pulmonary disease (8–10), but there is little information available about the relationship between non–end-stage pulmonary fibrosis and cardiac function.

Because of the complex geometry and retrosternal position of the right ventricle, it is difficult to obtain reliable measurements of right ventricular dimensions and function with echocardiography (11), and right ventricular echocardiographic recordings are often not satisfactory (9,12). Recently, magnetic resonance (MR) imaging techniques have become available for the determination of cardiac function. These techniques have been validated in both ventricles for systolic (13–16) and diastolic (17–23) functional measurements.

The aim of the present study was to detect possible abnormalities in left and right ventricular systolic and diastolic function in patients who have connective tissue disease–associated mild to moderate pulmonary fibrosis without cardiac signs or symptoms. Furthermore, the relationship between pulmonary function and cardiac function was evaluated.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Population
Twenty-three consecutive patients with connective tissue disease–associated pulmonary fibrosis were selected from our institutional database by a rheumatologist (J.M.v.L.) according to the criterion of evidence for pulmonary fibrosis at high-resolution computed tomography (CT) and/or chest radiography. The earliest radiographic changes in fibrosing alveolitis consist of a fine reticulation with lower zone predominance. More advanced disease is characterized by a coarse reticular or reticulonodular pattern throughout the lungs (24).

Radiology medical records were checked for all patients. Patients without pulmonary fibrosis were excluded from the study. In our patients, mild pulmonary fibrosis was considered if evidence of pulmonary fibrosis was found at only high-resolution CT but not at chest radiography, which is a less sensitive method for the evaluation of interstitial disease (25). Pulmonary fibrosis was considered moderate if evidence of pulmonary fibrosis was also visible on chest radiographs. No patients had pulmonary fibrosis that was judged to be extensive or severe (Table 1). Thus, half of the patients were classified as having moderate pulmonary fibrosis, and half of the patients, mild pulmonary fibrosis.


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  		TABLE 1. Underlying Disorders and Pulmonary Fibrosis Grading
 
Patients underwent biventricular systolic and diastolic functional MR imaging. From this group, patients who had completed a cardiac MR imaging procedure, who had no history of cardiac disease or hypertension, and who had their pulmonary function documented with spirometric and carbon monoxide diffusion tests were selected. As a result, seven patients were excluded. In one patient, results of MR flow imaging were inconclusive because of tachycardia. In two patients, pulmonary function was not measured. Three patients had a history of myocardial infarction, and one patient had a history of hypertension.

The resultant study group consisted of 16 patients with connective tissue disease–associated pulmonary fibrosis; underlying disorders in these patients are presented in Table 1. The group consisted of nine women and seven men (mean age, 51 years ± 14; age range, 28–72 years). Pulmonary function tests were performed for clinical reasons within 6 months (mean, 8.5 weeks ± 7.0) of the MR imaging procedure. The results in the 16 patients were compared with those of 16 sex- and age-matched healthy control subjects (mean age, 51 years ± 15; age range, 25–71 years) who had no history of cardiac disease, pulmonary disease, or hypertension. Height and weight were measured in all patients and control subjects, and their body surface areas were calculated (26). The study was performed with institutional review board approval, and informed consent was obtained from all patients and control subjects.

MR Imaging
All patients and control subjects were imaged at 1.5 T (Gyroscan, NT15; Philips Medical Systems, Best, the Netherlands). Baseline gradient-echo images were obtained in three planes. A series of vertical long-axis–plane (two-chamber–view) gradient-echo images was obtained by defining a line extending from the apex through the middle of the mitral valve on the transverse scout images. The sequence used was a prospective electrocardiographically triggered, single-section, multiphase, flow-compensated, segmented k-space, echo-planar sequence. The following parameters were used: seven ky lines per echo-planar imaging segment; echo time, 5.8 msec; phase interval, 25–35 msec, which resulted in approximately 25 phases; section thickness, 10 mm; field of view, 400 x 240 mm; matrix 128 x 115; and flip angle, 30°. Then, a horizontal long-axis–plane (pseudo four-chamber–view) series was obtained by defining a line extending from the apex through the lower part of the mitral valve on the two-chamber view. These scout images were obtained to plan short-axis and flow imaging across the mitral and tricuspid valves.

Cine MR imaging.—Short-axis, prospective, electrocardiographically triggered, multisection, multiphase, gradient-echo MR imaging was used to obtain stroke volume, ejection fractions, left ventricular mass, and left and right ventricular volumes. The short axis was defined as that perpendicular to the interventricular septum on the pseudo four-chamber views. The following imaging parameters were used: echo-planar imaging factor, seven; field of view, 400 x 240 mm; matrix, 128 x 115; echo time, 11 msec; phase interval, 25–35 msec, which resulted in approximately 25 phases per section; flip angle, 30°; section thickness, 9–11 mm; intersection gap, 0.9–1.1 mm; 10–11 section levels to encompass both ventricles; and one breath hold per section level.

Flow velocity–encoded MR imaging.—Velocity mapping with retrospective gating was performed across the mitral and tricuspid valves by using a two-dimensional flow-sensitive gradient-echo sequence to measure diastolic left and right ventricular function. The imaging plane for the mitral valve was derived from the end-systolic and end-diastolic pseudo four-chamber views with the two-chamber long-axis view. The imaging plane for the tricuspid valve was derived from the end-systolic and end-diastolic pseudo four-chamber views with the coronal scout view. Both the mitral and tricuspid valve angulations were planned midway between the end-systolic and end-diastolic locations of the valves on the pseudo four-chamber views. Velocity encoding was perpendicular to the imaging plane. Velocity sensitivity was set at 90–100 cm · sec-1 to avoid aliasing. Other imaging parameters were as follows: field of view, 300 x 300 mm; matrix, 128 x 128; temporal resolution, 20–32 msec; echo time, 5.0–6.2 msec; flip angle, 20°; section thickness, 8 mm; and 27–40 frames per cardiac cycle depending on heart rate. Imaging duration was 2.3–4.0 minutes per 27–40-frame series.

MR Imaging Analysis
The MR images were transferred to an Ultra-1 Sparc workstation (SUN Microsystems, Mountain View, Calif). Cine MR imaging data were analyzed by using the MR Analytical Software System, or MASS, (version 3.0; Division of Imaging Processing, Department of Radiology, Leiden University Medical Center, the Netherlands) (27). Left and right ventricular endocardial and epicardial contours were drawn manually (by L.J.M.K.) on end-diastolic and end-systolic images. End diastole was defined as the first image after onset of the R wave on the electrocardiogram that corresponded to the largest ventricular cavity areas. End systole was defined as the image with the smallest ventricular cavity areas. Cardiac output, ejection fractions, left ventricular mass, and left and right ventricular end-diastolic and end-systolic volumes were calculated as described before (13). Volumetric and left ventricular mass measurements were indexed per patient or control subject by body surface area.

Flow velocity-encoded MR imaging data were analyzed by using the analytical software package Flow (Division of Imaging Processing, Department of Radiology, Leiden University Medical Center) (28). The mitral and tricuspid valve contours were drawn manually (by L.J.M.K.), and flow curves were obtained by means of automatic measurement of mean flow velocity within the contours. An MR imaging–derived recording of diastolic ventricular inflow has, similar to an echo-Doppler image, a characteristic biphasic appearance. Two distinct peaks represent early and late diastolic flow (Fig 1). Diastolic function parameters derived from the inflow curves were as follows: peak flow during early diastolic (E) filling (arrow at B in Fig 1b), peak flow during late diastolic filling (atrial contraction [A] peak, arrow at E in Fig 1b), E/A peak flow ratio, and E/A volume ratio.



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  		Figure 1a. (a) Selected flow-sensitive MR images obtained in a healthy 50-year-old male control subject show the contours that were manually drawn around the tricuspid valve orifice (TV in B) and adapted in size during the cardiac cycle. In B, MV = mitral valve orifice. (b) Graph shows the normal right ventricular inflow curve for measurements obtained across the tricuspid valve orifice. The curve is biphasic, with two distinct peaks that represent early and late diastolic inflow. Images A-F in a correspond to time points A-F in b.

 


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  		Figure 1b. (a) Selected flow-sensitive MR images obtained in a healthy 50-year-old male control subject show the contours that were manually drawn around the tricuspid valve orifice (TV in B) and adapted in size during the cardiac cycle. In B, MV = mitral valve orifice. (b) Graph shows the normal right ventricular inflow curve for measurements obtained across the tricuspid valve orifice. The curve is biphasic, with two distinct peaks that represent early and late diastolic inflow. Images A-F in a correspond to time points A-F in b.

 
Pulmonary Function
The following pulmonary function parameters were measured with spirometric and CO diffusion tests: total lung capacity, residual volume, forced expiratory volume in 1 second, vital capacity, total lung CO diffusion, and CO diffusion corrected for lung volume. These pulmonary function parameters were correlated to cardiac parameters of systolic and diastolic function.

Statistical Analysis
Results were expressed as the mean ± SD. Differences in the ejection fraction and cardiac index between patients and control subjects were tested by using the independent sample t test. End-diastolic volumes and diastolic parameter measurements were corrected for differences in cardiac frequency by means of an analysis of covariance. Within-group differences between diastolic left and right ventricular function were calculated by using a paired t test. The relationships between MR imaging data and age, MR imaging data and cardiac frequency, left and right ventricular function, and MR imaging data and pulmonary function data were assessed by means of linear regression analysis. Analyses were performed by using the SPSS-PC 7.5 statistical software package (SPSS, Chicago, Ill). A P value of less than .05 was considered to indicate a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Group characteristics of patients and control subjects are presented in Table 2. Patients and control subjects were similar with regard to age, height, weight, and body surface area.


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  		TABLE 2. Baseline Characteristics of Study Population
 
Anatomic and Systolic Function Parameters
Table 3 presents anatomic and systolic function parameters in the left and right ventricles. There was no significant difference between patients and control subjects concerning their biventricular end-diastolic volume indices, cardiac indices, and ejection fractions.


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  		TABLE 3. Biventricular Anatomic and Systolic Parameters
 
Diastolic Flow Curves and Function Parameters
The measurements of left and right ventricular diastolic function in patients versus control subjects are summarized in Table 4. Right ventricular E/A peak ratios and E/A volume ratios were significantly lower in patients than in control subjects, whereas no statistical differences were found in left ventricular diastolic function parameters.


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  		TABLE 4. Diastolic Inflow Parameters in Patients versus Control Subjects
 
Table 5 shows diastolic parameters of left versus right ventricular values for patients and control subjects. In both groups, significantly higher values were found in the E peaks of the left ventricle than for the right ventricle. The A peak was higher in the left ventricle in control subjects but not in patients.


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  		TABLE 5. Diastolic Inflow Parameters in the Left versus Right Ventricle
 
The results of the E/A ratio measurements were as follows: no differences were found between the left and right ventricular E/A peak ratios and E/A volume ratios in control subjects, whereas significant differences were found in patients. In the patient group, the E/A peak ratio was 1.18 ± 0.52 in the left ventricle versus 0.85 ± 0.40 in the right ventricle (P = .002); the E/A volume ratio was 1.92 ± 0.80 in the left ventricle versus 1.20 ± 0.70 in the right ventricle (P = .001). In the control group, the E/A peak ratio was 1.35 ± 0.54 in the left ventricle versus 1.28 ± 0.50 in the right ventricle (P = .543); the E/A volume ratio was 2.22 ± 0.85 in the left ventricle versus 2.29 ± 1.01 in the right ventricle (P = .752).

There was a significant correlation between left and right ventricular diastolic parameters. The correlation coefficients between left and right ventricular values in patients were as follows: E peaks, r = 0.77 (P = .001); A peaks, r = 0.67 (P = .005); and E/A peak ratios, r = 0.73 (P = .001). The values in control subjects were as follows: E peaks, r = 0.73 (P = .001); A peaks, r = 0.57 (P = .02); and E/A peak ratios, r = 0.61 (P = .01).

The left and right ventricular E/A peak ratios decreased significantly with increasing age as is shown in Figures 2 and 3. In the left ventricle (Fig 2), differences between E/A ratios in patients and control subjects were small and not significant. The lowest left ventricular E/A peak ratio in control subjects was 0.79 and was measured in the oldest control subject (aged 71 years). Although the left ventricular E/A peak ratio was not different between the patient and control groups, six of 16 patients had a E/A peak ratio lower than 0.79. All of these patients were 50–72 years old.



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  		Figure 2. Graph shows the relationship between age (in years) and left ventricular E/A peak ratio, as measured across the mitral valve at two-dimensional flow-sensitive MR imaging. In patients (•, dashed line), E/A peak ratios are 2.73-3.05 x10-2 multiplied by age in years (r = -0.83, P < .001). In control subjects ({square}, solid line), E/A peak ratios are 2.90-3.05 x 10-2 multiplied by age in years (r = -0.83, P < .001). Differences between patients and control subjects are not statistically significant.

 


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  		Figure 3. Graph depicts the relationship between age (in years) and right ventricular E/A peak ratio, as measured across the tricuspid valve at two-dimensional flow-sensitive MR imaging. In patients (•, dashed line), E/A peak ratios are 1.96-2.19 x 10-2 multiplied by age in years (r = -0.78, P < .001). In control subjects ({square}, solid line), E/A peak ratios are 2.31-2.03 x 10-2 multiplied by age in years (r = -0.61, P = .013). Differences between patients and control subjects are statistically significant (P = .035) and indicate that right ventricular peak ratios in patients correspond to ratios that are normally expected in people 20 years older.

 
The right ventricle had more variation in E/A peak ratios than did the left ventricle in both patients and control subjects. As a result, the correlation coefficients between age and right ventricular E/A peak ratios (patients, r = -0.78; control subjects, r = -0.61) were not as strong as they were in the left ventricle (patients and control subjects, r = -0.83). However, the regression lines (Fig 3) in patients and control subjects were more or less parallel. The regression line was lower for patients than for control subjects. Figure 3 shows that right ventricular E/A peak ratios in patients were lower than those of control subjects; the ratios found in the patients are normally expected in people 20 years older.

Figure 4 shows diastolic inflow curves in the left and right ventricles in a control subject and a typical patient. In the patient, both the left and right ventricular E/A ratios were reversed, and the E/A ratios were too low for his age. Furthermore, the influence of differences in heart rate are shown. A higher cardiac frequency resulted in a fusion of E and A velocities by compression of the flow curve after the 400-msec time point after onset of the R wave on the electrocardiogram. This compression pattern was markedly consistent in patients and control subjects, but the cardiac frequency had no influence on the E peaks, A peaks, and E/A ratios.



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  		Figure 4. Graphs show the diastolic inflow curves for measurements obtained across the mitral (left ventricle) and tricuspid (right ventricle) valves at flow-sensitive MR imaging in a 54-year-old male control subject and a 50-year-old patient with pulmonary fibrosis. There is a predominant influence of early filling (E) compared with atrial filling (A) in the left and right ventricles of the control subject, whereas the relationship is reversed in the patient. Note that the higher cardiac frequency in the patient results in compression of the diastolic flow pattern after the 400-msec time point after the R wave at 0 msec. Because of interference of A in E, it is difficult to model the deceleration time or deceleration gradient of early filling with higher frequencies, whereas the E/A ratios appear relatively preserved.

 
Pulmonary Function and Cardiac Function
The mean pulmonary function data measured in patients are presented in Table 6. The mean pulmonary function impairment was moderate. No correlations were found between any of the diastolic or systolic function parameters and any of the pulmonary function parameters.


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  		TABLE 6. Pulmonary Function in the Patient Study Population
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
In this study, biventricular systolic and diastolic function in patients with connective tissue disease–associated mild to moderate pulmonary fibrosis was investigated with MR imaging. The major observations were as follows: (a) There were no differences in systolic function between patients and control subjects. (b) Differences in diastolic function were observed between patients and control subjects, in particular, in right ventricular indices. (c) Left and right ventricular E/A ratios correlated strongly with age. (d) Right ventricular E/A ratios in patients corresponded to values that are normally expected in people 20 years older. (e) Left and right ventricular diastolic functions correlated significantly with each other. (f) Pulmonary function did not predict diastolic right or left ventricular function.

Abnormalities in diastolic function have a major role in producing signs and symptoms in patients who present with heart failure (29). None of our patients had cardiac symptoms, and all had mild to moderate pulmonary fibrosis due to concomitant connective tissue disease. Systolic left and right ventricular function was normal in the patient group, but an impairment of right ventricular diastolic function was observed, with E/A peak ratios that are normally expected in people 20 years older. Impairment of right ventricular diastolic function has been associated with high pulmonary arterial pressure (30,31), but it may also be caused by other factors, such as pressure overload in patients with heart failure (30), in patients with chronic pulmonary disease, and in chronic pulmonary thromboembolism (32). In patients with systemic sclerosis, right ventricular diastolic impairment has been associated with subendocardial fibrosis (33). We suggest that the right ventricular diastolic abnormalities might be an early manifestation of cardiac disease in our patients, as diastolic dysfunction may precede the onset of systolic dysfunction in the early stages of disease (29).

The assessment of diastolic function with ventricular filling dynamics is complex, and flow curves vary with loading conditions, age, respiration, and cardiac frequency (29). In the present study, patients were matched for age and sex. Differences in loading conditions were minimized by selecting patients and control subjects who had no history of cardiac disease or hypertension. Influence of inspiration or expiration on flow curves plays no role in the current study, as flow-encoded MR images were acquired over an interval of several minutes during which patients were allowed to breath normally. Furthermore, we anticipated a possible influence of cardiac frequency on diastolic function measurements by correcting for it during statistical analysis. Moreover, individual heart rates were similar during left and right ventricular imaging, and differences between both ventricles, therefore, could not be attributed to variations in heart rate.

Dependence of the ventricular diastolic E/A ratio on age has already be shown in echo-Doppler studies of the left (34–41) and right (37,41) ventricles. These study findings showed impairment of the early E peak velocity and an increase in late A peak velocity with increasing age. In a study of healthy persons (42), it was shown that the decrease in the left ventricular E/A ratio with age is a primary intrinsic biologic effect of aging.

The dependence of left and right ventricular E/A ratios on age is now also demonstrated with MR imaging. The relationship has been observed in both patients and healthy persons. This means that, as with echocardiography, the effects of age should be taken into account when MR imaging is used in the assessment of ventricular diastolic function.

Information concerning the right ventricular diastolic function in patients with connective tissue disease is limited. In an echocardiographic study, Henein et al (33) found a decrease in the right ventricular E/A ratio in patients who had systemic sclerosis with or without associated pulmonary fibrosis. But the decrease in the E/A ratio was more obvious when there was associated pulmonary fibrosis. In the left ventricle, however, the E/A ratios were reduced only in patients with associated pulmonary fibrosis. Henein et al suggested on a theoretic basis that this finding was due to some degree of subendocardial fibrosis of the longitudinal myocardial muscle fibers, particularly in patients with pulmonary fibrosis. As in our study, abnormalities in E/A ratios in patients were more severe in the right ventricle than in the left ventricle.

Left ventricular E and A peaks were significantly higher than those of the right ventricle in control subjects, which is in accordance with findings from earlier echocardiographic studies (33,37,38). In our patients, the left ventricular E peaks were also higher than the right ventricular E peaks. The A peaks, however, did not differ between the left and right ventricles and, thus, had a relatively higher contribution to the right ventricular inflow in patients than in control subjects.

In a healthy population, close correlations have been found between individual right and left ventricular diastolic parameters (30,37). Significant correlations between left and right ventricular diastolic parameters were also found in the present study in patients and control subjects. Measurement of the function of both ventricles may improve diagnostic accuracy in the assessment of cardiac disease, as the ventricles can be compared with each other. Biventricular measurements are easily obtained with MR imaging.

The lack of correlation between the pulmonary function data and diastolic ventricular function in the present study is in agreement with the study findings of Schena et al (43). They examined patients with chronic obstructive lung disease with secondary chronic cor pulmonale, pulmonary hypertension, and poor pulmonary function. An impairment of diastolic left ventricular function was closely correlated with pulmonary hypertension levels, although no correlations were found between cardiac function data and respiratory function parameters.

In the present study, diagnosis of mild to moderate pulmonary fibrosis was confirmed at high-resolution CT and/or chest radiography in all patients. Pulmonary function tests were also performed, and the impairment of gas exchange was moderate in our patients. An earlier study (44) showed that results of conventional pulmonary function tests do not relate to the extent or severity of pulmonary fibrosis. A relationship between pulmonary fibrosis and ventricular function is possible and is even suggested because of right ventricular involvement. Nevertheless, as the present findings confirm, pulmonary function is not a good predictor of the status of ventricular function.

Clinical Implications
In our patient group, a decrease in early ventricular filling with an increase in late ventricular filling during atrial contraction was found in the right ventricle, leading to a decrease in E/A peak flow and volume ratios. This functional change is assigned as diastolic dysfunction with abnormal relaxation, grade I, on the scale proposed by Nishimura et al (29). This system grades the natural mitral flow progression of diastolic dysfunction from the normal pattern to the abnormal relaxation pattern (grade I), pseudo normalization pattern (grade II), reversible restriction pattern (grade III), and, finally, irreversible restriction pattern (grade IV diastolic dysfunction).

Left ventricular functional disturbances with abnormal relaxation, grade I, are usually not symptomatic because filling pressures are generally normal or only mildly increased. Patients may become symptomatic during exercise, as the diastolic filling period shortens and relaxation is not completed before the onset of atrial contraction (29). It is likely that this mechanism is similar in the right ventricle. Medication that affects the underlying disorder is suggested as therapy in symptomatic patients with left ventricular diastolic dysfunction; the severity of dysfunction has to be taken into account (29). Therapy for symptomatic right ventricular diastolic dysfunction may be based on similar principles.

MR imaging has proved to be useful in the evaluation of left and right ventricular systolic and diastolic function. Impairment of right ventricular diastolic function has been found in patients with connective tissue disease–associated mild to moderate pulmonary fibrosis, whereas left ventricular diastolic function and biventricular systolic function were preserved. It is suggested that the impairment of right ventricular diastolic function might be an early manifestation of cardiac disease in these patients. The effects of age should be taken into account when MR imaging is used to assess ventricular diastolic function.


   ACKNOWLEDGMENTS
 
The authors acknowledge Berend C. Stoel, PhD, for technical assistance in modeling the diastolic flow curves; Joost G. van den Aardweg, MD, for supplying pulmonary function data; and Annette van den Berg, MSc, for statistical advice.


   FOOTNOTES
 
Abbreviations: A = atrial contraction, E = early diastolic

Author contributions: Guarantor of integrity of entire study, L.J.M.K.; study concepts, all authors; study design, P.S., A.d.R., L.J.M.K.; definition of intellectual content, A.d.R., L.J.M.K., P.S.; literature research, L.J.M.K., P.S.; clinical studies, L.J.M.K., P.S.; data acquisition, L.J.M.K., P.S.; data analysis, L.J.M.K.; statistical analysis, L.J.M.K.; manuscript preparation, L.J.M.K.; manuscript editing, L.J.M.K., A.d.R., J.M.v.L.; manuscript review, A.d.R., J.M.v.L., P.S.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

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