Author + information
- Received March 5, 2003
- Revision received November 19, 2003
- Accepted December 19, 2003
- Published online July 7, 2004.
- H.Mehrdad Sadeghi, MD*,* (, )
- Bruce J Kimura, MD, FACC§,
- Ajit Raisinghani, MD, FACC*,
- Daniel G Blanchard, MD, FACC*,
- Ehtisham Mahmud, MD, FACC*,
- Peter F Fedullo, MD†,
- Stuart W Jamieson, MB‡ and
- Anthony N DeMaria, MD, MACC*
- ↵*Reprint requests and correspondence:
Dr. H. Mehrdad Sadeghi, 765 Medical Center Court, Suite 211, Chula Vista, California 91911, USA.
Objectives Because pulmonary thromboendarterectomy (PTE) can result in an immediate reduction in pulmonary artery (PA) pressure, we sought to evaluate the effect of PTE on severe tricuspid regurgitation (TR) without tricuspid annuloplasty.
Background Few data exist regarding the frequency and magnitude of functional TR improvement after reduction in PA pressure.
Methods We identified 27 patients with severe TR, defined by a regurgitant index (RI) >33%, who underwent PTE. The RI, tricuspid annular diameter (TAD), apical displacement of leaflet coaptation, and estimated PA systolic pressure were determined on pre- and post-PTE echocardiograms. Patients were stratified based on resolution (RI ≤33%) or persistence (RI >33%) of severe TR.
Results Comparing pre- and post-PTE echocardiography results, severe TR resolved in 19 of 27 (70%) patients. This group had a more effective PA systolic pressure reduction after PTE (49 ± 20 mm Hg vs. 32 ± 16 mm Hg by echocardiography, p = 0.075, and 37 ± 16 mm Hg vs. 16 ± 13 mm Hg by catheter measurement, p = 0.004). No difference was observed in TAD, apical displacement of the tricuspid valve, or other features compared with the group with persistent severe TR. There was a trend toward longer hospital stays in the group with persistent severe TR (19 ± 15 days vs. 14 ± 9 days; p = 0.55).
Conclusions After significant PA pressure reduction by PTE, severe functional TR with a dilated annulus may improve without annuloplasty despite dilated tricuspid annulus diameters.
Tricuspid regurgitation (TR) in the absence of leaflet pathology commonly occurs with pulmonary hypertension and is due to right ventricular (RV) and tricuspid annular dilation. Such “functional” TR can be significant in up to 28% of patients with advanced mitral valve disease and concomitant pulmonary hypertension (1–4). In patients referred for mitral valve surgery with severe functional TR, cardiovascular specialists often face the dilemma of whether to also recommend a tricuspid valve annuloplasty. According to the latest American College of Cardiology/American Heart Association guidelines on valvular heart disease management (5), adjunctive tricuspid valve annuloplasty is strongly recommended (class I indication) in this clinical scenario because significant TR may increase postoperative morbidity and mortality (6–10).
However, TR has been observed to diminish with reduction of pulmonary hypertension after mitral valve surgery without annuloplasty (1). The degree to which reduction in pulmonary hypertension and changes in tricuspid annular and valve morphology contribute to the reduction in functional TR is unknown. Patients with chronic thromboembolic pulmonary hypertension (CTEPH) commonly have functional TR and right heart failure and demonstrate an immediate and dramatic reduction in their pulmonary artery (PA) pressures after successful pulmonary thromboendarterectomy (PTE) (11–14). These patients can serve as a model for isolating the effect of PA pressure reduction on functional TR, without surgical alteration of left heart pathology. In this study, we evaluated the impact of PA pressure reduction by PTE without tricuspid annuloplasty on the magnitude of change in TR, tricuspid annular, and valve dimensions.
Methods and study protocol
Initially, 141 consecutive patients with CTEPH who underwent PTE at the University of California at San Diego Medical Center between 1998 and 1999 were screened for severe TR. Thirty-one patients with severe TR were identified, four of whom were excluded (two postoperative deaths and two inadequate postoperative echocardiograms). The study population was composed of 27 patients who had severe TR as defined by the regurgitant index (RI). No patient had significant left-sided valvular disease. All patients had long-standing symptoms of cardiopulmonary disease, New York Heart Association functional class III to IV, and right-sided heart disease on physical examination, including elevated jugular venous pressure, palpable RV heave, hepatomegaly, or a pronounced pulmonic sound. All patients had CTEPH as documented by standard criteria (11)including right heart catheterization and pulmonary angiography before surgery.
The PTE procedure has been described elsewhere (12,13). All PTEs were performed by two surgeons experienced in the procedure. In brief, the patient undergoes median sternotomy, is placed on cardiopulmonary bypass, and circulatory arrest is initiated. Complete endarterectomy of the right PA is undertaken with alternating periods of reperfusion and circulatory arrest, and the procedure is then repeated on the left side. Intraoperative circulatory arrest times were obtained from the anesthesiologists' operative records. Intraoperative pulmonary thromboembolic disease classification (13)was available in 26 patients. This surgical classification may be useful in predicting outcome of PTE. The four disease patterns include the presence of fresh thrombus in the main lobar pulmonary arteries (type I), intimal thickening and fibrosis with or without organized thrombus proximal to the segmental pulmonary arteries (type II), fibrosis, intimal webbing, and thickening with or without organized thrombus within distal segmental pulmonary arteries only (type III), or microscopic distal arteriolar vasculopathy without classic thromboembolic disease (type IV).
Two-dimensional and Doppler echocardiograms had been obtained in parasternal and apical views according to standard protocol (15)using commercially available imaging systems (Hewlett-Packard, Andover, Massachusetts) with 2.5- to 3.5-MHz transducers on all patients. All recordings were performed on 0.50-inch VHS videotape for analysis. System operator controls and color Doppler gain were set initially to cause minimal background speckling and then slightly adjusted downward below this point to optimize the image without artificial enlargement of regurgitant jets. The peak TR velocity was measured by continuous-wave Doppler, and PA systolic pressure was estimated by the modified Bernoulli method (16)in all patients. Tricuspid regurgitation was identified in the apical four-chamber view as a large color mosaic systolic jet, and jet area (JA) and right atrial (RA) area were then planimetered on the still-frame image of maximal JA. The RI, ratio of JA to RA area expressed as a percentage, was calculated to confirm the presence of severe TR, which was defined as an RI >33% (17–20). The diastolic tricuspid annular diameter (TAD) was measured as previously described on a still image of the apical four-chamber view as the maximal distance between the insertion hinge points of the septal and anterior tricuspid leaflets at the time of maximal leaflet excursion in diastole (17,21). Apical displacement of the tricuspid coaptation point has been described as a mechanism for functional TR (17). The position of the coaptation point of the tricuspid leaflets was located, and the distance between this point and the plane of the tricuspid valve in systole was measured. On the same still image, the apical displacement area was measured as the planimetered area between the atrial surface of the leaflets and the plane of the tricuspid annulus. Echocardiograms were repeated in the early postoperative period (average of 11 ± 8 days after surgery), and the same parameters were remeasured. Patients were stratified based on resolution(RI ≤33%) or persistence (RI >33%) of severe TR (17).
All patients underwent right heart catheterization within 48 to 72 h of preoperative echocardiography. Preoperative right heart catheterization was performed in the cardiac catheterization laboratory using standard technique with a 7.5-F balloon-tipped catheter (Baxter Healthcare Corp., Santa Ana, California) inserted into the right internal jugular vein. Resting phasic and mean pressures were recorded on paper at 50 mm/s from the right heart, PA, and pulmonary capillary wedge positions. Cardiac output was determined from the mean of three injections by the thermodilution method, and pulmonary vascular resistance (PVR) was calculated. Right heart catheterization was repeated postoperatively in the surgical intensive care unit within 72 h of the echocardiogram. According to the surgical team's protocol, post-PTE pulmonary capillary wedge pressures were not obtained in some cases.
Continuous variables are expressed as mean ± SD and categorical variables as percentages. The Mann-Whitney rank-sum test was used to compare pre- and post-PTE measurement because of non-normal distribution of most variables. Differences in categorical variables, such as gender and incidence of atrial fibrillation (AF) were examined using Fisher exact test. Data analysis was performed using SAS software (version 8.0, Cary, North Carolina). A p value <0.05 was considered significant.
Only 27 patients met the RI criteria for severe TR and comprised the study population. The average age of study patients was 53 ± 15 years (range, 24 to 77 years). Baseline demographic, echocardiographic, hemodynamic data, and outcomes are presented in Tables 1 and 2. ⇓The elapsed time between preoperative echocardiogram and right heart catheterization was 1.8 ± 1.7 days. Average preoperative PA systolic pressure was 86 ± 20 mm Hg (range, 58 to 149 mm Hg) by echocardiography, and83 ± 16 mm Hg (range, 60 to 130 mm Hg) by cardiac catheterization.
Results of PTE
After PTE, 19 of 27 patients (70%) no longer met the study criteria for severe TR and were categorized as having resolved TR (Table 1). Conversely, 8 of 27 patients (30%) had persistent severe TR. Both groups were similar in age and gender (Table 1). By echocardiography, pre-PTE PA systolic pressures were similar between the two groups, but the group with TR resolution had a lower postoperative PA systolic pressure (36 ± 8 mm Hg vs. 55 ± 26 mm Hg; p = 0.019), and a trend toward a larger absolute reduction in PA systolic pressure (49 ± 20 mm Hg vs. 32 ± 16 mm Hg; p = 0.075) (Table 1). Figure 1shows that patients with improved TR were more likely to have lower post-PTE PA systolic pressures. By catheter measurements, patients with resolved TR manifested a trend toward higher mean and systolic pre-PTE PA pressures (Table 2), and the reduction in PA systolic pressure was also greater in these patients (37 ± 16 vs. 16 ± 13; p = 0.004). No preoperative differences between the two groups were observed with respect to right atrial or pulmonary capillary wedge pressures, cardiac outputs, or PVR (Table 2). Patients with persistent severe TR had slightly higher cardiac outputs but similar PVR postoperatively.
Preoperative TAD was abnormally dilated in the majority of patients (4.6 ± 0.54 cm; range, 3.4 to 5.5 cm), and decreased to 4.1 ± 0.6 cm after PTE (p < 0.01 for the change after surgery for the entire group). However, base-line, final TAD, and the magnitude of change after PTE were similar between both groups (Table 1). Postoperatively, TAD was >3.5 cm in 16 of 19 (84%) and 5 of 8 (62%) of patients in the group with resolved and persistent severe TR, respectively (p = NS). In addition, no significant difference in measurements of apical displacement of leaflet coaptation could be detected between the groups. Figures 2 and 3⇓⇓show pre- and post-PTE echocardiographic examples of two patients with resolved and persistent severe TR, respectively.
Furthermore, both groups had similar intraoperative circulatory arrest times (38 ± 10 min vs. 36 ± 12 min; p = NS), but distal thromboembolic disease, mainly type III, was somewhat more prevalent in patients with persistent severe TR (p = 0.069) (Table 1). The group with persistent severe TR tended to have a longer hospital stay (19 ± 15 days vs. 14 ± 9 days; p = NS). Patients with persistent severe TR had a 12-fold higher incidence of AF compared with patients who had improvement of their TR (62% vs. 5%; p < 0.01). All patients were in sinus rhythm at the time of discharge.
The principal finding of this study is that after reduction in PA systolic pressures after PTE, severe TR improved significantly in 70% of patients, often despite persistent tricuspid annular dilation. However, 30% of patients manifested persistent severe TR and had a lower PA pressure reduction. Persistent severe TR and less effective PA pressure reduction were more frequently associated with distal thromboembolic disease, but such distinction could not be identified by any clinical, echocardiographic, or hemodynamic parameters preoperatively. This study suggests that the resolution of severe functional TR, without tricuspid valve annuloplasty, is related to the reduction of pulmonary hypertension. The major postoperative feature that identified resolution of severe TR was a more significant improvement of pulmonary hypertension (Fig. 1).
Whether TR will improve after surgery for a left-sided valvular defect may depend on success of surgical intervention, severity of baseline pulmonary hypertension and its improvement after surgery, degree of dilation of the right heart and tricuspid annulus, and structural integrity of the tricuspid valve. As prolonged afterload stress may lead to ventricular failure and dilation, patients with either CTEPH or progressive mitral valve disease may both develop functional TR from pulmonary hypertension. Unlike the delayed resolution of pulmonary hypertension after relief of the obstruction in mitral stenosis (22), post-PTE patients have an immediate postoperative fall in RV afterload. Our data suggest that the PA pressure reduction is responsible for TR reduction and further supports the findings of a recent study from another center (14). Menzel et al. (14)demonstrated improvement of TR severity shortly after PTE without tricuspid valve repair among 39 patients with CTEPH and varying degrees of TR. They demonstrated TR improvement associated with reduction of RV afterload and TAD, but did not find any preoperative predictors of TR improvement. Similarly, our study found no preoperative predictors of TR resolution after PTE.
Apical displacement of tricuspid valve leaflets, leading to poor coaptation, has been shown to be an important determinant of functional TR (17). We were unable to detect any significant difference in the apical displacement of tricuspid leaflets between the two patient groups with and without TR resolution. Preoperatively, 93% (25 of 27) of CTEPH patients with severe TR exhibited TAD >3.5 cm. Postoperatively, the tricuspid annulus remained dilated (>3.5 cm) in 21 of 27 (78%) of patients, although the echocardiograms were performed relatively early after PTE. If the American College of Cardiology/American Heart Association guidelines for concomitant tricuspid valve repair during mitral valve surgery in the setting of pulmonary hypertension (5)were applied to the CTEPH patients, nearly all of our patients with severe TR would have undergone tricuspid annuloplasty based on their initial annular dilation. However, TR improved immediately after PTE without annuloplasty in the majority of our patients with severe TR secondary to CTEPH.
There was a trend toward longer hospital stays in the group with unresolved severe TR. This difference did not reach statistical significance, but it may be clinically important. In addition, there was a 12-fold higher incidence of postoperative AF or atrial flutter observed in patients with persistent severe TR. Our study was not powered nor designed to investigate the effect of severe TR on postoperative mortality.
There is considerable discordance between clinical and echocardiographic markers of TR severity, which is evident from lack of a true and convenient gold standard for quantifying TR. Previous studies have assessed TR severity and its limitations by echocardiographic criteria, right ventriculography, intraoperative digital palpation of the JA, and clinical parameters (17,23–30). Because the TR JA ratio may be more dependent on driving pressure than effective regurgitant orifice or volume measures of TR, it is theoretically possible that relief of severe pulmonary hypertension could diminish the JA without a similar improvement from other TR measurements. A fully discordant scenario is unlikely because patients exhibited an anatomic reduction in the TAD. Therefore, we felt that surgical results using color Doppler flow mapping, which has evolved as the most widely used technique for assessment of TR (3,17,20), must be addressed foremost. The effective TR orifice area has also been demonstrated to be a useful and reliable measure of TR (27), but was not measured in this study.
In the current study, PA systolic pressure measurements by Doppler did not correlate highly with the direct catheter measurements for multiple reasons. Echocardiography and right heart catheterization were not simultaneous, and up to 48 to 72 h elapsed between the pre-PTE study (average of 1.8 ± 1.7 days) and especially the post-PTE study. As such, direct catheter measurements were obtained after at least a 12-h fasting period, whereas Doppler measurements did not require a fasting period for the patients. It also appears that PA pressure measurements by Doppler correlate less precisely with direct catheter measurements in patients with severe pulmonary hypertension and dilated tricuspid annulus (31,32). In addition, postoperative right heart catheterization data were obtained in the intensive care unit by various nurses, which may have introduced small measurement errors. To minimize confounding conditions, afterload variations between the time of echocardiography and right heart catheterization, and potential influences on TR JA, comparisons of PA systolic pressures were made using echocardiographic and direct catheter measurements separately.
The applicability of this study is limited by the small number of patients, yet our study represents the largest experience of patients with severe TR undergoing PTE. We did not address the long-term benefits of afterload reduction in post-PTE patients. Our data suggest that RV geometry and remodeling, as reflected by the TAD and apical displacement measures, may not have an immediate response to afterload reduction, unlike TR JA. The right heart may continue to remodel beyond the immediate postoperative period with further improvement in right heart dimensions and TR.
Following successful PA systolic pressure reduction by PTE, 70% of patients with CTEPH exhibited a marked decrease in severe TR that was associated with a lower postoperative RV afterload. There were no differences detected in the magnitude of pre- or post-PTE tricuspid annular dilation, valve coaptation, or other preoperative features among patients with resolution of TR compared with those with persistent TR. The major postoperative feature that identified resolution of severe TR was a more significant improvement of pulmonary hypertension. Our study demonstrates that resolution of severe TR in CTEPH often occurs with RV afterload reduction, even without annuloplasty of a dilated tricuspid annulus.
☆ Richard L. Popp, MD, acted as guest editor for this paper.
Presented in part at the 11th Annual Scientific Sessions of the American Society of Echocardiography, Chicago, Illinois, June 2000.
- atrial fibrillation
- chronic thromboembolic pulmonary hypertension
- jet area
- pulmonary artery
- pulmonary thromboendarterectomy
- pulmonary vascular resistance
- right atrial
- regurgitant index
- right ventricle/ventricular
- tricuspid annular diameter
- tricuspid regurgitation
- Received March 5, 2003.
- Revision received November 19, 2003.
- Accepted December 19, 2003.
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