Author + information
- Received January 6, 1998
- Revision received March 27, 1998
- Accepted April 17, 1998
- Published online August 1, 1998.
- Ali M. Kizilbash, MDa,
- DuWayne L. Willett, MD, FACCa,
- M.Elizabeth Brickner, MD, FACCa,
- Sheila K. Heinle, MD, FACCa and
- Paul A. Grayburn, MD, FACCa,* ()
- ↵*Address for correspondence: Paul A. Grayburn, MD, Division of Cardiology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9047
Objectives. We used color Doppler flow mapping to determine whether vena contracta width (VCW) is a load-independent measure of the severity of mitral regurgitation.
Background. VCW has been proposed to be a relatively load-independent measure of mitral regurgitation severity in flow models using a fixed orifice. However, in patients with mitral regurgitation, VCW may not be load independent because of a dynamic regurgitant orifice.
Methods. VCW, effective regurgitant orifice area and regurgitant volume were measured by quantitative Doppler mapping in 31 patients with chronic mitral regurgitation at baseline and during nitroprusside infusion. Patients with rheumatic heart disease, annular calcification or endocarditis were considered to have a fixed regurgitant orifice, whereas patients with mitral valve prolapse, dilated cardiomyopathy or ischemia were considered to have a dynamic regurgitant orifice.
Results. Systolic blood pressure (148 ± 27 to 115 ± 25 mm Hg) and end-systolic wall stress (121 ± 50 to 89 ± 36) decreased with nitroprusside (p < 0.05). Although nitroprusside did not significantly change mean values for VCW (0.5 ± 0.2 to 0.5 ± 0.2 cm), regurgitant volume (69 ± 47 to 69 ± 56 ml) or effective regurgitant orifice area (0.5 ± 0.4 to 0.5 ± 0.6 cm2), individual patients exhibited marked directional variability. Specifically, VCW decreased in 16 patients (improved mitral regurgitation), remained unchanged in 7 patients and increased in 8 patients (worsened mitral regurgitation) with nitroprusside. Also, the VCW response to nitroprusside was concordant with changes in effective regurgitant orifice area and regurgitant volume, and was not different between dynamic and fixed orifice groups.
Conclusions. Contrary to the results from in vitro studies, VCW is not load independent in patients with mitral regurgitation caused by dynamic changes in the regurgitant orifice. The origin of mitral regurgitation does not predict accurately whether the regurgitant orifice is fixed or dynamic. Finally, short-term vasodilation with nitroprusside may significantly worsen the severity of mitral regurgitation in some patients.
Vena contracta width (VCW) as determined by Doppler color mapping has emerged recently as a simple echocardiographic marker of the severity of mitral regurgitation (MR) (1–5). The vena contracta is the narrowest portion of the regurgitant jet that occurs just downstream from the regurgitant orifice and reflects the size of that orifice. On color flow mapping, VCW is easily visualized and is not affected by flow rate, jet eccentricity or instrument factors. On the basis of in vitro studies using a fixed orifice, it has been proposed that VCW is relatively load independent (6). However, patients with MR often have a dynamic orifice, particularly in the setting of mitral valve prolapse or dilated cardiomyopathy (7–10). Therefore, this study was done to examine the effects of short-term changes in loading conditions on VCW measurements in patients with chronic MR.
The study was conducted at Parkland Memorial Hospital and the Dallas Department of Veterans Affairs and was approved by their Institutional Review Boards. All participants gave written informed consent. The study population consisted of 31 subjects with moderate or severe MR by previous echocardiographic studies. The medical history and echocardiogram were used to define the cause of MR, which was used to classify patients as having either dynamic or fixed regurgitant orifice. The dynamic orifice group consisted of patients in whom MR was caused by mitral valve prolapse, dilated cardiomyopathy or ischemia (7). The fixed orifice group consisted of patients in whom MR was caused by mitral annular calcification, endocarditis or rheumatic heart disease (7). Patients were ineligible if they had mild MR or had concomitant aortic regurgitation, aortic stenosis or mitral stenosis. Patients were also excluded from the study if they were medically unstable, had severe renal insufficiency or had a history of allergic reaction to nitroprusside.
Heart rate (HR) and blood pressure (BP) were monitored continuously by finger plethysmography (Finapres). Arm cuff BP was also recorded every minute during the study by using an automated sphygmomanometer (Dynamap). A 20-gauge venous catheter was placed in a forearm vein and 5% dextrose water infusion was started at a slow rate. After 20 minutes of supine rest, baseline BP and HR values were recorded. All patients underwent a complete two-dimensional echocardiographic and Doppler study in the left lateral decubitus position, from multiple imaging planes. Echocardiographic studies were performed using a Sonos 2500 (Hewlett-Packard, Andover, MA) with a 2.5-MHz transducer.
VCW was measured from the parasternal or apical long-axis views by Doppler color flow mapping as described previously (4,5). The narrowest sector angle that allowed visualization of the MR vena contracta was used to maximize color flow imaging frame rate. In each patient, the transducer was angled out of the standard echocardiographic planes to optimize visualization of the area of proximal flow acceleration, the vena contracta and the downstream expansion of the jet. For each echocardiographic window, zoom mode was used to optimize the visualization and measurement of VCW. In all patients VCW was seen clearly, and its largest diameter during systole was measured for at least three cardiac cycles and averaged.
Quantitative Doppler imaging was used to calculate effective regurgitant orifice area (EROA) and regurgitant volume (RgV) using a modification of the method of Enriquez-Sarano et al. (11,12). We have previously validated the accuracy of this method in our laboratory by direct comparison with gated cine magnetic resonance imaging, an independent reference standard (13). Briefly, the pulsed Doppler sample volume was positioned to obtain modal velocity profiles for the aortic and mitral annuli. The diameter of aortic annulus was measured in the parasternal long-axis view and its area calculated as a circle. Mitral annulus diameter was measured in the parasternal long-axis and apical four-chamber views and its area calculated as an ellipse (13). Continuous-wave was used to measure the velocity-time integral of the MR jet. Aortic and mitral flow volumes were calculated as the product of velocity-time integral and cross-sectional area of the aortic and mitral annuli, respectively. The RgV was determined as the mitral flow volume minus the aortic flow volume. The EROA was calculated as the RgV divided by the velocity-time integral of the MR jet.
After baseline echocardiography, sodium nitroprusside was infused at 0.25 μg/kg per minute and titrated to decrease systolic BP at least 15% with a stable plateau. Echocardiographic assessment of VCW, EROA and RgV was then repeated. All studies were recorded on super-VHS videotape for subsequent analysis.
All studies were interpreted in random order by an experienced observer who had no knowledge of patient identity and hemodynamic state. At least three measurements were averaged for each hemodynamic state. Care was taken to avoid postectopic beats. Because of previously reported observer variability in measuring VCW, we considered a change of >0.1 cm to be clinically significant (4). A paired ttest was used to compare baseline values with those obtained after nitroprusside infusion. The magnitude of change in MR with nitroprusside in the dynamic and fixed orifice groups was compared using a two-way repeated-measures analysis of variance.
The patients were 29 to 77 years old (mean 56 ± 14 years). There were 10 women and 21 men. The dynamic orifice group consisted of 18 patients, in whom MR was associated with mitral valve prolapse in 9, dilated cardiomyopathy in 7 and ischemic MR in 2. The fixed orifice group consisted of 13 patients, in whom MR was associated with mitral annular calcification in 5, infective endocarditis in 5 and rheumatic heart disease in 3. By qualitative grading, 16 patients had moderate MR and 15 had severe MR at baseline; 20 patients had an eccentric jet and 11 had a central jet.
Hemodynamic changes with nitroprusside
Hemodynamic values before and after nitroprusside infusion are shown in Table 1. Mean baseline systolic BP dropped significantly from 148 ± 27 to 115 ± 25 mm Hg with nitroprusside (p < 0.0001). Moreover, each patient had a decrease in systolic BP of at least 15%. Similarly, diastolic BP (83 ± 16 to 65 ± 16 mm Hg) and mean arterial BP (105 ± 17 to 81 ± 17 mm Hg) decreased significantly (p < 0.0001). Although both left ventricular end-diastolic dimension (preload) and end-systolic wall stress (afterload) decreased significantly with nitroprusside (p < 0.0001), the magnitude of change in afterload was more pronounced. The magnitude of change in HR, BP, left ventricular end-diastolic dimension and end-systolic wall stress was not significantly different between the dynamic and fixed orifice groups. All patients tolerated the medication well and there were no untoward events.
Change in MR severity with nitroprusside
Measurements of MR severity before and after nitroprusside infusion are shown in Table 2. Although nitroprusside did not significantly change the mean values for VCW or quantitative Doppler measures of MR severity, individual patients demonstrated marked directional variability. Specifically, 8 patients (26%) had worsened MR by all measurements, 16 (52%) had improved MR severity, and 7 (22%) were unchanged. Also, the directional change in VCW with nitroprusside in individual patients was concordant with the respective changes in EROA and RgV in 27 (87%) of 31 patients. For a 0.1-cm change in VCW, change in RgV averaged 16.4 ml. Individual values for VCW at baseline and after nitroprusside are shown in Figure 1.
MR response to nitroprusside in dynamic versus fixed orifice groups
Baseline values for mean VCW, EROA and RgV were similar for patients in the dynamic and fixed orifice groups. Likewise, the change in these values after nitroprusside was administered did not differ significantly between groups by two-way analysis of variance (F = 0.67, p = 0.42). Individual patients from both groups demonstrated marked directional change in MR severity with nitroprusside (Fig. 2).
This study was designed to test the hypothesis that VCW is independent of loading conditions in patients with chronic MR. The group mean data support this hypothesis because the change in VCW from baseline to nitroprusside administration was not statistically significant. However, despite the absence of a group mean change, individual patients had divergent responses, with a decrease in VCW in 52%, an increase in 26% and no significant change in 22% of patients. These data were concordant with the quantitative Doppler measurements of EROA and RgV, suggesting that most patients had a true change in the regurgitant orifice during nitroprusside infusion. Although in vitro studies using rigid orifices show that VCW is flow independent (6), our data confirm that the regurgitant orifice in MR is dynamic and may change in either direction with short-term change in loading conditions (7–10). All patients in this study had a decrease in BP of at least 15%, with a stable plateau to allow measurements of VCW, RgV and ROA. There was no difference in the magnitude of the change in BP (F = 1.26, p = 0.30) or HR (F = 0.80, p = 0.46) in the patients with worsened MR compared with those with improved or unchanged MR. Figure 3shows a Doppler map of a patient from this study in whom MR severity worsened during nitroprusside infusion.
Causes of MR
These data also demonstrate that, contrary to conventional wisdom, etiologic determination of MR does not always accurately predict whether the regurgitant orifice is dynamic or fixed in individual patients. For example, of nine patients with mitral valve prolapse in our study, MR worsened in four, improved in three and remained unchanged in two after nitroprusside. Similarly, divergent responses were observed in patients with MR attributable to ischemia, rheumatic heart disease, mitral annular calcification and endocarditis. Accordingly, in some patients who were classified as having a fixed orifice on the basis of an associated condition, there were marked changes in EROA with nitroprusside, whereas EROA was unchanged in some patients who presumably had a dynamic orifice.
This study also has important clinical implications regarding the use of vasodilator therapy for MR. Long-term use of vasodilator therapy for MR is controversial. Starling (14)has proposed that long-term vasodilator therapy may have adverse effects on ventricular-arterial coupling in chronic MR. There are no large-scale randomized trials that evaluated the efficacy of vasodilator therapy, and small studies yielded conflicting results. Recently, Levine and Gaasch (10)reviewed these studies, the largest of which comprised 16 patients, and proposed that the conflicting results could be attributed to inclusion of different causes of MR. Studies that included MR primarily caused by rheumatic heart disease or mitral annular calcification might fail to show benefit of vasodilator therapy because these patients are thought to have a fixed orifice. Conversely, studies including patients with MR caused by dilated cardiomyopathy might show a benefit because these patients are thought to have a dynamic orifice that becomes smaller with reduction in afterload. However, our data indicate that the cause of MR alone does not predict accurately whether the regurgitant orifice is fixed or dynamic. Moreover, worsening of MR with short-term vasodilator therapy occurred in 26% of our patients, suggesting that some patients with chronic MR might be harmed by vasodilator therapy. It remains to be determined whether the response of MR to nitroprusside can identify patients who are likely to benefit from long-term vasodilator therapy.
Although this is the largest reported study on the effects of short-term vasodilation on MR, the number of patients was too small to allow subgroup analysis of which specific etiologic categories of MR consistently benefit from short-term vasodilator therapy. However, it is worth noting that none of the patients with dilated cardiomyopathy had worsened MR after nitroprusside. It is possible that the short-term response of MR to nitroprusside does not predict the long-term response to vasodilators or angiotensin-converting enzyme inhibitors, the latter of which may have beneficial neurohormonal or myocardial effects that are unrelated to short-term hemodynamic effects. Such beneficial effects might overcome mild worsening of MR from hemodynamic changes. In addition, the hemodynamic changes in this study were moderate, as manifested by a roughly 25% reduction in BP and wall stress. Larger changes in afterload may have produced different results. We did not attempt to reduce BP further for safety reasons.
The present study was limited to patients thought to have moderate to severe MR by subjective interpretation of a previous echocardiogram. The mean values for RgV and EROA shown in Table 2are consistent with angiographically severe MR (15). However, it is evident that some individuals had mild MR by quantitative Doppler imaging and by VCW, which further emphasizes the limitations of subjective grading of MR by color flow mapping. Patients with mild MR would not be considered candidates for vasodilator therapy unless they also had underlying cardiomyopathy.
VCW is not load independent in MR because short-term changes in loading conditions produce dynamic changes in the regurgitant orifice. Cause of MR does not always predict accurately whether the regurgitant orifice is fixed or dynamic. Short-term vasodilator therapy with sodium nitroprusside worsens MR in some patients; whether this response predicts the response to long-term vasodilator therapy requires further study.
- blood pressure
- effective regurgitant orifice area
- heart rate
- mitral regurgitation
- regurgitant volume
- regurgitant orifice area
- vena contracta width
- Received January 6, 1998.
- Revision received March 27, 1998.
- Accepted April 17, 1998.
- American College of Cardiology
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