Abstract
Introduction.In grading mitral regurgitation (MR) magnetic resonance imaging is the gold standard but 2D echo is mostly used in clinical practice. However, each single echo parameter is prone to confounding influences. With regard to chronic primary and secondary MR the purpose of this study was to compare a new multi-dimensional echo-based grading system with an independent pre-operatively used invasive standard. Methods. In a retrospective study we analyzed 177 patients with different degrees of MR severity, who were examined both by echocardiography and by cardiac catheterization. For MR grading a combination of four echocardiographic parameters was used: density of the regurgitation velocity profile, peak mitral inflow velocity (Vmax E-wave), radius of the proximal flow convergence zone (PISA), and vena contracta (Vc) width. Invasive grading was based on left ventriculography (Seller's method), V wave hight, and regurgitation fraction. Both methods resulted in an integrative score on an eight point scale (<I-IV in half-steps). Echocardiographic and invasive data were correlated. Results. There was a reasonable overall correlation of r = 0.72 (p = 0.001) between both grading systems. Echo tended to slightly overestimate MR severity. In patients with secondary MR, agreement was worse (p = 0.01) than in primary MR. The most powerful single echo parameter was Vc r = 0.71 (p = 0.001). Presence or absence of sinus rhythm had no significant influence on echo grading. Conclusions. The proposed echocardiographic multidimensional MR grading system is feasable and shows good correlation with invasive grading.
The evaluation of mitral regurgitation (MR) severity is a challenge in daily clinical practice [1–3]. Invasive contrast left ventriculography for assessment of ejection fraction, degree of MR severity or mechanism of MR is now only rarely required as Doppler echo provides this information. Different echo-Doppler parameters [4] are used to grade chronic MR severity. Since every specific echo-Doppler approach may be subject to confounding influences, an extensive grading system combining various echo-Doppler techniques known as MR index has been introduced by Thomas et al. [5], [6].
By comparing with an independent pre-operatively used invasive standard we evaluated a modified grading approach using a combination of the following echocardiographic Doppler criteria:
Methods
Study population
In this retrospective comparative study we analyzed patients who had been identified from our echocardiography laboratory database (January 2000 and October 2001) as having mitral regurgitation of some degree. The study population consisted of 210 patients, who had MR evaluation and heart catheterization, with a maximum delay of 7 days under stable medication. Thirty three of these patients (16%) had to be excluded from analysis because of insufficient image quality not allowing for precise measurement of the PISA radius (5 cases) or the proximal Vc width (8 cases). Other cases were excluded due to inadequate cw Doppler tracings (15 cases), or inadequate E wave tracings (5 cases).
The final cohort, thus, consisted of 177 patients (male: n = 114, female: n = 63; age: 63±14 years, range: 20–88 years) who had both a complete echocardiographic study and right and left cardiac catheterization during the same hospital stay. Echocardiography was always done before invasive assessment. Seventy one patients (40%) were classified as having primary MR, and 106 patients (60%) secondary MR due to a variety of underlying diseases (Table I) [11]. At the time of echocardiographic data aquisition 127 patients (72%) were in sinus rhythm, 50 patients (28%) in atrial fibrillation (AF).
Table I. Underlying heart disease in 177 patients with primary and secondary MR.
Echocardiographic examination
A standardized echocardiographic examination was performed utilizing multiple parasternal and apical views with the patient in the left lateral decubitus position [2], [3]. All studies were performed with echo machines (GE-Vingmed System V or Vivid V) commercially available at the time of study examinations. Examinations were performed at a standard setting (harmonic imaging as default setting, VNyquist set at 50–60 cm/sec). All data sets were archived as video loops and freeze frames in a digital format. Vc width [10], [12], with the smallest diameter of a clearly defined Vc, and PISA [9], [13], [14] were measured in the two- and four-chamber view [10], [12–14] and analyzed in three consecutive cardiac cycles. Even more than three cycles were averaged over in cases of AF. Because of the most robust acoustic window, the apical two- and four-chamber views were used. Colour Doppler zero baseline shifting was used to produce a series of blue-red interfaces with clearly apparent aliasing velocities. The final measurement was taken at 50 cm/sec. Cw Doppler tracings were recorded in the two- and four-chamber views in order to obtain the maximum velocities of the regurgitant jet. Maximum sweep speed and filter settings were used. Once the full envelope was obtained, the signal density was graded as low, medium and high [7]. PW Doppler was used to obtain Vmax of the E-wave as a correlate of the regurgitant volume after optimization of wall filter settings [8], [15]. The cut-off values we used in our study are as suggested by the European guidelines [2]. MR grading, using the synopsis of these criteria, resulted in 1 out of 8 severity grades (<I-IV in half-steps) (Table II) based on an average of the individual measurement rounded out to 0.5 increment; each measure given equal weight.
Table II. Definition of the echocardiographic and invasive single parameters forming the correlated grading systems. *PISA or Vc ≥ 10 mm = MR III, *PISA and Vc ≥ 10 mm = MR IV.
Invasive grading of MR
Cardiac catheterization included standard biplane left ventriculography, hemodynamic assessment using a Swan-Ganz pulmonary artery catheter, and coronary angiography. Left ventriculography was performed by power injection (10–15 ml/sec) of 25–45 ml of non-ionic contrast agent via a 4 or 5 Fr pigtail catheter, imaged with 25 frames/sec in the 30° right anterior oblique, and the 60° left anterior oblique projection. MR was graded angiographically according to Sellers et al. [16]. After placing a Swan-Ganz catheter cardiac output was measured using the thermodilution method [17]. The regurgitation fraction (RF) was calculated as
SV = stroke volume, angio = LV angiogram, thermo = Thermodilation method). Additionally, the V wave was measured in the pulmonary capillary “wedge” position [1]. Invasive grading was done as a synopsis of these three parameters, also resulting in 1 out of 8 severity grades (<I-IV in half-steps) (Table II).
Analysis and statistics
During the study period, 18 experienced echocardiographers and twelve experienced invasive cardiologists graded the 177 data sets on a 4 point scale (<I-IV in half-steps) (Table II). Echocardiography-based MR grading was compared with an independent invasive grading standard. Linear correlations by Pearson were performed. With regard to overall agreement we added a Bland-Altman graph. Group comparisons were performed using Student's t-test for unpaired samples. A two-tailed p-value <0.05 was considered statistically significant.
Results
MR etiology is shown in Table I. In the group with primary MR (n = 71), mitral valve prolapse was the cause in 41 cases (58%), of which 19 (27%) had a flail leaflet. In 21 patients (30%), a combined mitral defect of degenerative origin was diagnosed. Nine patients (12%) with a leaking mitral valve after mitral valve reconstruction were counted as primary MR (Table I).
In 38 patients (36%) of the group with scondary MR (n = 106), MR was considered to be a consequence of ischemic LV dysfunction. In 16 other patients (15%) with preserved global LV function, a regional scar of the posterior LV wall or the papillary muscles seemed to cause dysfunction of the mitral valvar apparatus. In 27 patients (25%), global LV dysfunction and dilatation was the cause of MR and was attributed to hypertensive heart or dilated cardiomyopathy. Fifteen patients (14%) had aortic stenosis, 10 patients (9%) had other underlying diseases such as hypertrophic or restrictive cardiomyopathy (Table I). The distribution of MR severity grades is shown in Table III.
Table III. Distribution of MR severity grades in half-steps.
Correlations
There was a strong overall correlation between echocardiographic and invasive grading for both primary and secondary MR (r = 0.72, p <0.001). As compared to the invasive assessment, echo grading tended to slightly overestimate MR by 0.5 a severity grade (Figure 1). Vc width (r = 0.71; p <0.001; Figure 2) and PISA radius (r = 0.70; p <0.001; Figure 3) demonstrated the closest correlation with the angiographic MR grading. Vc width was evaluable in 135 of 177 patients (76.3%), PISA in 131 of 177 patients (74%). Vc width and PISA corresponded to the reference standard in 67.9% and in 68.9%, respectively.
Published online:
08 October 2009Figure 1. (A) Overall correlation between echocardiographic and invasive grading disregarding primary or secondary MR reflecting r = 0.72 (p ≤ 0.001). Lines demonstrate regression and confidence intervals. Thicker circles represent higher numbers than thinner circles. (B) Bland-Altman blot reflecting agreement of the resulting MR grades based on echo and invasive assessment.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/icdv20/2009/icdv20.v043.i05/14017430802651811/20150521/images/medium/icdv_a_365351_f0001_b.jpg"})
Figure 1. (A) Overall correlation between echocardiographic and invasive grading disregarding primary or secondary MR reflecting r = 0.72 (p ≤ 0.001). Lines demonstrate regression and confidence intervals. Thicker circles represent higher numbers than thinner circles. (B) Bland-Altman blot reflecting agreement of the resulting MR grades based on echo and invasive assessment.
Published online:
08 October 2009Figure 2. The correlation of Vena contracta with invasive grading r = 0.71 (p ≤ 0.001). Lines demonstrate regression and confidence intervals. Thicker circles represent higher numbers than thinner circles.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/icdv20/2009/icdv20.v043.i05/14017430802651811/20150521/images/medium/icdv_a_365351_f0002_b.jpg"})
Figure 2. The correlation of Vena contracta with invasive grading r = 0.71 (p ≤ 0.001). Lines demonstrate regression and confidence intervals. Thicker circles represent higher numbers than thinner circles.
Published online:
08 October 2009Figure 3. The correlation of the proximal isovelocity surface area with invasive grading r = 0.70 (p ≤ 0.001). Lines demonstrate regression and confidence intervals. Thicker circles represent higher numbers than thinner circles.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/icdv20/2009/icdv20.v043.i05/14017430802651811/20150521/images/medium/icdv_a_365351_f0003_b.jpg"})
Figure 3. The correlation of the proximal isovelocity surface area with invasive grading r = 0.70 (p ≤ 0.001). Lines demonstrate regression and confidence intervals. Thicker circles represent higher numbers than thinner circles.
Discrepant results between echo and invasive grading were evident far more often in patients with secondary MR (Figure 4). At the time of examination, 50 of 177 patients (28%) were in AF, 32 (64%) with secondary MR, and 18 (36%) with primary MR (p < 0.01). The presence or absence of AF had no significant impact on the echocardiographic MR grading (Figure 5).
Published online:
08 October 2009Figure 4. Differentiating primary and secondary MR. The echo-based multidimensional and invasive MR grading show a high agreement in cases of primary MR, whereas secondary MR often results in relevant grade deviation.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/icdv20/2009/icdv20.v043.i05/14017430802651811/20150521/images/medium/icdv_a_365351_f0004_b.jpg"})
Figure 4. Differentiating primary and secondary MR. The echo-based multidimensional and invasive MR grading show a high agreement in cases of primary MR, whereas secondary MR often results in relevant grade deviation.
Published online:
08 October 2009Figure 5. Differentiating sinus rhythm and atrial fibrillation. Also in cases of AF, there is a high agreement between the echo-based multidimensional and invasive MR grading approach.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/icdv20/2009/icdv20.v043.i05/14017430802651811/20150521/images/medium/icdv_a_365351_f0005_b.jpg"})
Figure 5. Differentiating sinus rhythm and atrial fibrillation. Also in cases of AF, there is a high agreement between the echo-based multidimensional and invasive MR grading approach.
Discussion
Grading of MR severity by whatever technique is challenging due to the multitude of factors that may influence the regurgitant volume in a low-impedance leak (e.g. total cardiac output, systemic vascular resistance, left atrial pressure, heart rate). Echocardiography, in its different modalities, has largely replaced invasive techniques in primary diagnosis and follow-up of MR, leaving the pre-operative situation in older patients for invasive assessment. Two different strategies to assess MR can be outlined:
1. to abide to a single quantitative measure that has been identified in a given laboratory to best characterize MR severity, and
2. to develop a multidimensional grading system representing different functional and/or morphological aspects of the valve lesion.
Both strategies have advantages and disadvantages: while every single measure is subject to confounding factors, multidimensional approaches are by nature less susceptible to those.
One example for the first strategy is the effective regurgitant orifice (ERO) area [18] based on the PISA concept with a 40 mm2 threshold to indicate valve surgery. The current efforts aiming at three-dimensional assessment of the regurgitant orifice [19] also fit into this category. In cases of low grade MR ERO may not be determined which would have resulted in a dropout of about 30% in our study.
With respect to a multidimensional approach, the only concept found in the literature is proposed by Thomas et al. [5], [6]. Their MR index, defined as a semiquantitative echocardiographic evaluation score, considers the following six parameters: color Doppler regurgitant jet penetration, proximal isovelocity surface area (PISA), continuous wave Doppler (cw) characteristics of the regurgitant jet, tricuspid regurgitant jet-derived pulmonary artery pressure, pulse wave Doppler (PW) pulmonary venous flow pattern, and two-dimensional estimation of the left atrial dimensions [5], [6].
Their prospective study included 62 MR patients [6]. In case of a MR index of ≥2.2 high sensitivity (82%), specificity (98%) and positive predictive value (93%) was reported for identification of severe MR. Correlation with echocardiographic based RF (r = 0.73) and the ERO (r = 0.74) judged by an expert reader serving as a reference standard were significant (p = 0.0001). However, neither primary MR was differentiated from secondary MR nor was Carpentier’ classification applied in their studies [5]. Moreover, patients in AF were excluded from analysis.
Taking into consideration that pulmonary venous flow is difficult to obtain by transthoracic echo, and that the LA may be enlarged by factors other than MR severity (e. g. diastolic heart failure, presence of AF, rheumatic etiology), we modified the approach of Thomas and coworkers, reducing it to PISA radius, Vc width, cw Doppler signal characteristics, and pw Doppler measurement of the E-wave. In accordance with Spain et al. [20], we are convinced that the evaluation system to compare with should be an independent technique. Thus, we compared our echocardiographic approach to an independent invasive grading system although well knowing that firstly each of the considered single parameters has important limitations, secondly that the chosen invasive standard, is certainly not the gold standard and thirdly that in the case of disagreement, this discrepancy might be due to either technique and not necessarily to echocardioraphy.
Looking at our entire collective (Figure 1) and comparing it with that analyzed by Thomas et al. [5], [6], both systems correlate well. Thomas et al. found a similar correlation (r = 0.76) between their MR index and their echocardiography based reference standard.
The most powerful single components of our grading system were Vc width and PISA, consistent the latest guidelines of the European Society of Cardiology [2]. Nevertheless, Vmax of the E-wave and characteristics of the cw Doppler profile, both may be considered as cross-check since a high degree MR is unlikely in the presence of a low E-wave or a faint cw signal with a round contour. Moreover, Vc width and PISA showed about the same correlation coefficient as our integrative system. However, Vc and PISA corresponded to the integrative MR grade (±0.5 severity grade) in only 67.9% and 68.9%, respectively. In about one third of our 177 patients this was not the case, also supporting a multidimensional approach.
Our analysis demonstrates a better prediction of the invasive MR grade in primary MR. Furthermore, our grading system proved to predict MR severity correctly, even in the presence of AF (Figure 5).
The reason for the weaker performance in secondary MR firstly maybe the presence of more eccentric jets and secondly MR occurring only during a part of systole whereas measurements such as Vc width and PISA are instantaneous measurements that assume MR throughout systole.
Modality specific disadvantages
Searching for a more feasible grading system based on a widely spread technique one should be aware of principle disadvantages of either modality. Using echocardiography – here to be evaluated – it should be remembered that about ten percent of patients approached lacked an appropriate accustic window [7]. The fact that patients are in the left lateral decubitus position during echocardiography and in supine position during catheter studies, may influence the regurgitation volume. Irregular leaflet coaptation and regurgitant orifices causing excentric jets, requires great examiner skills to diagnose MR properly.
In this retrospective study our echocardiographic multidimensional grading system slightly overestimated MR. Despite standardized settings this is likely due to the comparably sensitive nature of the used echocardiograhic Doppler techniques with regard to blood flow detection potentially leading to false positive findings.
In angiographic MR grading other pitfalls need to be considered: injection of the radiographic contrast medium (CM) may influence regurgitant volume into the left atrium as well as left ventricular size and function. The position of the catheter end or the injection of CM may also influence invasive MR grading. The thermodilution method is susceptible to the presence of tricuspid regurgitation. The V-wave is more dependent on the compliance of the left atrium and the pulmonary circulation.
Limitations
This study was retrospective. Involvement of different examiners is a clear source of variablity. The chosen invasive evaluation standard does not represent the gold standard for MR grading. However, pre-operative MR grading is mostly obtained invasively.
The fact that our MR patients were evaluated by echocardiography and our invasive standard sequentially within a maximum of 7 days may have influenced MR grading in different ways including varying blood pressure, hydration or changes in daily medication. However, we aimed at studying clinical “true world” rather than ideal hemodynamic laboratory conditions. Moreover, this retrospective study hides the possibility that some gradings were biassed by knowledge of prior results. Furthermore, as others [10], [12–14] we decided to rely on the apical projections due to the fact that a larger amount of patients had reasonable imaging quality from this window than from the recommended parasternal approach [2], [3].
Outlook
Every regurgitant lesion is a 3D phenomenon. 2D echocardiography and angiography are both reduced to more or less 2 planes [21]. Thus, 3D techniques such as magnet resonance imaging (MRI) and 3D echocardiography may result in more comprehensive and at the same time more simple evaluation of chronic mitral regurgitation.
Conclusion
The presented multidimensional echocardiographic MR grading system combining relatively simple parameters can readily and rapidly be applied during routine echocardiography. Despite neglecting right cardiac parameters, it demonstrates a close correlation with invasive MR grading. Not surprisingly, in cases of primary MR agreement is better than in secondary MR. The absence of sinus rhythm has no significant influence on this echo-based multidimensional grading standard.
Acknowledgements
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
| 71 patients with pimary MR (40%) | |
| • Mitral valve prolapse (incl. flail leaflet: n = 19) | n = 41 |
| • Degenerative mitral valve lesion with concomittant mitral stenosis | n = 21 |
| • Other primary mitral defects | n = 9 |
| 106 patients with secondary MR (60%) | |
| • Ischemic cardiomyopathy (including 16 patients with a scar of the posterior wall with resulting papillary dysfunction) | n = 54 |
| • Dilated cardiomyopathy | n = 17 |
| • Hypertensive heart disease with left ventricular dysfunction | n = 10 |
| • Aortic valve lesions | n = 15 |
| • Other types of secondary MR (hypertrophic cardiomyopathy, restrictive cardiomyopathy, aortic valve regurgitation) | n = 10 |
| Echocardiographic grading | Invasive grading | ||||
|---|---|---|---|---|---|
| Parameter | Gr | Range | Parameter | Gr | Range |
| CW jet and density | I | low | LV angiogram | I | Discrete contrast medium (cm) in mitral valve. |
| II | medium | II | LA contrasted after several contractions. | ||
| III | equals antegrade flow | III | Same contrast density in LA and LV. | ||
| IV | III and early systolic peak | IV | LA and pulmonary veins contrasted. | ||
| Vmax E-wave | I | <1.3 | Regurgitation fraction | I | <20% |
| II | II | 21–40% | |||
| III | 1.3–1.5 | III | 41–60% | ||
| IV | >1.5 | IV | >60% | ||
| PISA | I | absent | V wave | I | <2×PCW |
| II | <5 mm | II | |||
| III | 6–9 mm | III | >2×PCW | ||
| IV | ≥10 mm* | IV | |||
| Vc | I | absent | |||
| II | <5 mm | ||||
| III | 6–9 mm | ||||
| IV | ≥10 mm* | ||||
| Distribution of echocardiographic grading in 177 patients with chronic MR | |||||||
|---|---|---|---|---|---|---|---|
| <I | I | I–II | II | II–III | III | III–IV | IV |
| n = 26 (14.7%) | n = 51 (28%) | n = 14 (7.9%) | n = 16 (9%) | n = 20 (11.3%) | n = 43 (24.3%) | n = 6 (3.4%) | n = 1 (0.6%) |
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