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Am J Physiol Heart Circ Physiol 294: H2106-H2111, 2008. First published March 7, 2008; doi:10.1152/ajpheart.01128.2007
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Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes

Tomas G. Neilan,1 Thanh-Thao Ton-Nu,1 Yoshiaki Kawase,2 Ryuichi Yoneyama,2 Kozo Hoshino,2 Federica del Monte,3 Roger J. Hajjar,3 Michael H. Picard,1 Robert A. Levine,1 and Judy Hung1

1Cardiac Ultrasound Laboratory, 2Cardiology Laboratory of Integrative Physiology and Imaging, and 3Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Submitted 28 September 2007 ; accepted in final form 11 February 2008


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The aim of this study was to determine whether severe mitral regurgitation (MR) is progressive and whether tissue-Doppler (TD)-derived indexes can detect early left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of mitral valve chordae was performed in pigs (n = 8). Before MR (baseline), immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was assessed using conventional and TD-derived indexes. The severity of MR was quantified using regurgitant fraction and effective regurgitant orifice area (EROA). In all animals, MR was severe. On follow-up, the LV dilated progressively over time, but LV ejection fraction did not decrease. With the increase in LV dimensions, the forward stroke volume remained unchanged, but the mitral annular dimensions, EROA, and regurgitant fraction increased (EROA = 41 ± 2 and 51 ± 2 mm2 post-MR and at 3 mo, respectively, P < 0.01). Peak systolic myocardial velocities, strain, and strain rate increased acutely post-MR and remained elevated at 1 mo but declined by 3 mo (anterior strain rate = 2.9 ± 0.1 and 2.4 ± 0.2 s–1 post-MR and at 3 mo, respectively, P < 0.001). Therefore, in a chronic model of MR, serial echocardiography demonstrated that MR begets MR and that those TD-derived indexes that initially increased post-MR decreased to baseline before any changes in LV ejection fraction.

effective regurgitant orifice area; strain; strain rate

THE FACTORS THAT DETERMINE the timing of surgery in asymptomatic severe mitral regurgitation (MR) are incompletely understood. The timing of intervention should relate to a combination of MR severity, the natural history, and the effect of the regurgitation on the left ventricle (LV). The prognosis associated with MR varies directly with the severity of the regurgitation and the effect of the incompetent valve on LV systolic function (6, 9). In acute experimental MR, the regurgitant orifice varies with loading conditions, ventricular size, and annular dimensions, as well as within the cardiac cycle (5, 15, 34, 35). However, it is unclear in chronic MR whether the regurgitant orifice is dynamic and can further influence ventricular remodeling. In patients with MR, LV systolic function, as assessed by ejection fraction (EF), is apparently preserved until late in the progression of the disease (31). However, despite normal preoperative EFs, deterioration of global systolic function is reported in patients undergoing surgical repair (10, 21). This, as in other models of cardiac disease (33), implies latent global or regional preoperative dysfunction that is undetectable by conventional echocardiographic techniques. Inasmuch as LV systolic function and mortality are improved if surgery is performed before the onset of LV dysfunction (8, 9, 28), surgical repair is being considered earlier for asymptomatic severe MR (20). Therefore, it is may be important to detect subtle global or regional LV contractile dysfunction that may not be apparent by standard measures such as EF.

We therefore sought to determine in a porcine model of chronic MR whether the effective regurgitant orifice area (EROA) is itself dynamic and progressive and, hence, influences further ventricular dilation and whether tissue-Doppler (TD)-derived indexes can detect LV dysfunction earlier than changes in LVEF.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Study design. The present study was carried out according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and was approved by the Subcommittee on Research Animal Care at the Massachusetts General Hospital. Eight adult female Yorkshire swine (3 mo old, 30 kg body wt) were pretreated with atropine (0.04 mg/kg) and acepromazine (0.1 mg/kg) and subsequently anesthetized with tiletamine-zolazepam (Telazol, 4.4 mg/kg) and xylazine (2 mg/kg). The animals were then intubated and ventilated with 98% O2-2% isoflurane. Heparin was given to maintain an activated clotting time of 250–300 s. After anesthesia, MR was created by percutaneous disruption of posterior chordae as previously described (16). The severity of the initial MR was confirmed by echocardiography and contrast ventriculography. By ventriculography, moderate-to-severe MR was defined as opacification of the left atrium (LA) equal to that of the LV (30). Animals were assessed, under similar anesthetic conditions, before, immediately after (post-MR), and at 1 and 3 mo after the creation of MR.

Echocardiographic measurements. A commercially available system (Vivid 7, GE Healthcare, Milwaukee, WI) and a 5.0-MHz phased-array transducer were used for standard two-dimensional, pulse-Doppler, M-mode, and TD imaging. Measurements were performed according to the guidelines of the American Society of Echocardiography (37). The severity of the MR was quantified by several methods, including vena contracta (VC) measurement, EROA determined by proximal flow convergence, and regurgitant volume (RV) and regurgitant fraction (RF) measured by quantitative Doppler methods. The VC, the maximum systolic jet width, was measured by color Doppler in the long-axis views (23). Proximal flow convergence was assessed in the apical four-chamber view, with the depth and sector width optimized for color-Doppler resolution. Baseline shifting was performed to optimize measurement of the proximal flow convergence radius (r). EROA was then calculated as 2{tau} x r2 x (aliasing velocity)/MR velocity by continuous-wave Doppler (3, 7, 29). RF was calculated as RV divided by total forward stroke volume. The total forward stroke volume was derived from the product of mitral annulus cross-sectional area and mitral diastolic inflow time-velocity integral. RV was calculated from time-velocity integral of the mitral inflow minus the aortic outflow (4). These measurements were averaged over three cardiac cycles. The severity of the MR was graded according to American Society of Echocardiography guidelines (37).

LV dimensions were measured from the relevant parasternal M-mode traces, and LV volumes were measured from the apical views by Simpson's method. Measurements from pulsed-Doppler imaging included the peak transmitral E and A wave velocities. Septal and lateral mitral annular early (E') and late (A') diastolic velocities were measured using spectral pulsed TD.

TD-derived systolic and diastolic indexes were acquired on a parasternal short-axis view at the midventricular level at a rate of 180 frames/s and a depth of 1 cm. TD image analysis was performed offline with customized software (Echopac PC, GE Medical). For peak systolic endocardial velocity (VEndo), a 4.0 x 4.0 mm region of interest was manually positioned in the ventricular wall. For radial systolic [peak VEndo, strain, and strain rate (SR)] and diastolic indexes, an 8.0 x 8.0 mm region of interest was measured. The temporal smoothing filters were set at 30 ms for all measurements. The values obtained in five consecutive cardiac cycles were analyzed and averaged.

Hemodynamic measurements. After anesthesia, intracardiac pressures were recorded by retrograde catheterization of the left carotid artery with use of a fluid-filled catheter. LV end-systolic pressure (LVESP), LV end-diastolic pressure (LVEDP), and heart rate (HR) were measured.

Interobserver variability. Interobserver variability was calculated as the standard deviation of the differences in measurements by two independent observers for 20 traces for VEndo, strain, SR, RF, and EROA. Repeat traces were independently extracted from the data sets by each observer.

Statistics. Values are means ± SD. For comparison of multiple measurements within groups, repeated-measures ANOVA was used. Significance was set at P < 0.05.


   RESULTS
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 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Conventional echocardiographic parameters. All animals developed at least moderate-to-severe MR by echocardiography (Table 1, Fig. 1) and ventriculography (Fig. 1), with EROA = 40 ± 3 mm2, RF = 0.50 ± 0.04, and VC = 0.51 ± 0.02 cm (Table 1). RV, RF, EROA, and VC increased progressively over time [EROA = 41 ± 2 and 51 ± 2 mm2 post-MR and at 3 mo, respectively (P < 0.01) and RF = 0.49 ± 0.04 and 0.60 ± 0.04 post-MR and at 3 mo, respectively (P < 0.05); Table 1, Fig. 2 ]. LV systolic dimensions and end-systolic volumes decreased post-MR, leading to a significant increase in EF and fractional shortening (FS): EF = 59 ± 2 and 73 ± 2% at baseline and post-MR, respectively (P < 0.05; Table 2, Fig. 2). However, systolic and diastolic LV dimensions and volumes progressively increased with time (Table 2, Fig. 2; LV end-diastolic volume = 63 ± 3 and 168 ± 5 ml post-MR and at 3 mo, respectively, P < 0.001). This finding was not associated with any change in overall EF. Mitral annulus and LA dimensions and LA area (LAA) increased [mitral annulus = 18 ± 1 and 42 ± 2 mm post-MR and at 3 mo, respectively (P < 0.001); LAA = 12 ± 0.5 and 26 ± 2 cm2 post-MR and at 3 mo, respectively (P < 0.001)].


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  		Table 1. Indexes of MR severity

 

Figure 1
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  		Fig. 1. Porcine model of chronic mitral regurgitation (MR). Chordal rupture was guided to ensure creation of severe MR in all pigs (A). Severity of MR was confirmed echocardiographically (B, parasternal long axis) and by contrast ventriculography [preventriculogram (C) and postventriculogram, left anterior oblique projection (D)]. LA, left atrium; LV, left ventricle.

 

Figure 2
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  		Fig. 2. Serial echocardiographic parameters. LV end-diastolic volume (LVEDV), effective regurgitant orifice area (EROA), vena contracta (VC), ejection fraction (EF), radial strain, and strain rate (SR) in the posterior wall were measured at baseline, immediately after creation of MR (post-MR), and 1 mo and 3 mo after MR. *P < 0.05 vs. baseline; {dagger}P < 0.05 vs. post-MR.

 

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  		Table 2. Conventional echocardiographic and hemodynamic parameters in a porcine model of chronic MR

 
Transmitral E and A wave velocities and the early (E') and late annular velocities increased with the development of MR [transmitral E = 0.68 ± 0.03 and 0.83 ± 0.05 m/s at baseline and post-MR, respectively (P < 0.05); lateral E' = 8.1 ± 0.2 and 11.4 ± 0.2 cm/s at baseline and post-MR, respectively (P < 0.05); Table 3 ]. The ratio of transmitral E to A and the ratio of E to E' remained unchanged acutely. As expected, the forward cardiac output and the cardiac index fell acutely after the creation of severe MR [cardiac output = 3.6 ± 0.3 and 2.8 ± 0.2 l/min at baseline and post-MR, respectively (P < 0.05); cardiac index = 4.7 ± 0.3 and 3.7 ± 0.3 l·min–1·m–2 at baseline and post-MR, respectively (P < 0.05)].


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  		Table 3. Diastolic indexes in a porcine model of MR

 
The transmitral E wave and the septal and lateral E' remained elevated for 1 mo after the creation of MR before decreasing at 3 mo [transmitral E wave = 0.83 ± 0.05 and 0.71 ± 0.04 m/s post-MR and at 3 mo, respectively (P < 0.01); lateral E' = 11.4 ± 0.2 and 6.8 ± 0.5 post-MR and at 3 mo, respectively (P < 0.01); Table 3]. Late diastolic filling, as evidenced by the transmitral A wave and the septal and lateral annular A' velocities, increased with time (lateral A' annular velocity = 6.0 ± 0.5 and 7.2 ± 0.4 cm/s post-MR and at 3 mo, respectively, P < 0.05). These changes in diastolic filling were associated with a decrease in the E-to-A ratio and an increase in the E-to-E' ratio over time (E/E' = 7.4 ± 0.2 and 10.6 ± 0.7 post-MR and at 3 mo, respectively, P < 0.001).

TD imaging. Peak VEndo increased with the development of MR (VEndo = 2.7 ± 0.1 and 3.3 ± 0.1 cm/s at baseline and post-MR, respectively, P < 0.05; Table 4). Strain, SR, and the slope of the SR acceleration also increased (anterior strain = 21 ± 1 and 28 ± 1% at baseline and post-MR, respectively, P < 0.05; Figs. 2 and 3). There was a decrease in the time to peak strain (anterior time to peak strain = 191 ± 4 and 98 ± 11 ms at baseline and post-MR, respectively).


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  		Table 4. Color TD-derived indexes of systolic function

 

Figure 3
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  		Fig. 3. Tissue-Doppler imaging (TDI)-derived strain in chronic MR. Representative strain traces were obtained at baseline (A), post-MR (B), 1 mo after MR (C), and 3 mo after MR (D).

 
Although EF and FS were unchanged, VEndo, strain, and SR decreased from immediately post-MR to 3 mo [anterior VEndo = 3.3 ± 0.1 and 2.7 ± 0.2 cm/s post-MR and at 3 mo, respectively (P < 0.05); anterior strain = 28 ± 1 and 21 ± 1 post-MR and at 3 mo, respectively (P < 0.05); inferior SR = 2.9 ± 0.1 and 2.4 ± 0.2 s–1 post-MR and at 3 mo, respectively (P < 0.05); Table 4]. With the reduction in TD-derived indexes, there was a decrease in the slope of the acceleration and an increase in the time to peak strain [anterior SR acceleration = 54 ± 3 and 25 ± 4 s–1 post-MR and at 3 mo, respectively (P < 0.001); anterior time to peak strain = 98 ± 11 and 221 ± 12 ms post-MR and at 3 mo, respectively (P < 0.001)].

Invasive hemodynamic measurements. There was a nonsignificant increase in LVEDP after creation of MR. LVESP was also unchanged. There was a small increase in HR 3 mo after creation of MR. LVESP and LVEDP were unchanged (Table 2).

Interobserver variability. Interobserver variability for VEndo, strain, SR, RF, and EROA was 4%, 6.4%, 5%, 6.5%, 6.2%, and 6.3%, respectively.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
In the present study, we determined, in an experimental animal model of chronic MR, that MR was progressive. This was evidenced by the increase in RV, RF, EROA, and VC associated with an increase in LV dimensions, mitral annular dimensions, and LAA. We also observed that TD-derived systolic indexes returned to baseline before any changes in LVEF were detected.

The volume of MR depends on the systolic pressure gradient between the ventricle and the atrium, the duration of the regurgitation, and the effective regurgitant orifice (34). The size of the effective regurgitant orifice is dependent on annular dimensions, leaflet length, and the integrity of the papillary muscle apparatus. Acutely, augmentation of loading conditions leads to ventricular enlargement, mitral annular dilatation, and increased regurgitant flow (5, 35). Although a similar process has been suggested chronically (16), it has never been confirmed. In our study, we demonstrated that MR continues to progress over time, suggesting that MR begets more MR. Mechanistically, this is not surprising, inasmuch as the increased volume load on the LV and LA results in geometric changes that adversely affect mitral valve function and lead to a further increase in the severity of MR (19, 27). The etiology of the MR progression in the present study is not clear but likely relates to the adverse remodeling effects on mitral valve geometry from a combination of increased LV size, leaflet tethering, and a dilated mitral annulus. The progressive increase in the regurgitant orifice area and the RF would support a trend toward earlier intervention to limit adverse ventricular remodeling, especially in the setting of a reparable valve (32).

In a similar chronic canine model (22, 36), chamber dilatation is also seen without a reduction in EF. However, in this model, there is no progressive change in the severity of the MR. These differences may relate to the severity of the initial insult: in previous studies initial induction of RF was ~60–70% (25, 26), whereas in our model initial RF was 50%.

Although there was no significant change in overall EF in our model, we found that TD-derived variables progressively declined during follow-up to reach baseline values before any changes in global EF were detected. These variables have previously been shown to correlate with sonomicrometer-measured regional myocardial function and pressure-volume-estimated global systolic function (11). Also, ex vivo, SR has been shown to correlate with shortening velocity at varying loading conditions in isolated muscle strips (1), whereas in vivo, in a porcine ischemia-reperfusion model, radial SR has been shown to quantify baseline cardiac function and contractile reserve (14), suggesting that these indexes accurately reflect myocardial contractility. In MR, chamber dilatation leads to individual myocyte hypertrophy, elongation, and reduced contractility (13, 32); therefore, one plausibly could expect subtle LV systolic dysfunction to precede global dysfunction as suggested in our model, and an accurate method of detection may be useful as in other models of cardiac injury (17).

Early reduction in TD-derived variables, before a change in LV EF, could potentially guide therapeutic decisions in asymptomatic patients. The utility of TD-derived indexes as predictors of the postoperative decrease in LV function has previously been shown (2) and provides some initial clinical evidence for the use of TD-derived indexes in detecting subtle LV dysfunction in chronic MR. Preoperative stratification according to TD-derived parameters may add to current recommendations for the management of asymptomatic patients with severe MR. However, although TD-derived indexes are purported to be less sensitive to load than traditional echocardiographic indexes (24), the acute creation of MR was associated with a reduction in the time to peak systolic contraction and an increase in peak endocardial systolic velocities, strain, SR, and the slope of the acceleration, suggesting that TD-derived indexes are not completely load independent.

Our work has significant limitations that warrant discussion. The weight of the pigs increased from an average of 30 kg [body surface area (BSA) = 0.76] to an average of 60 kg (BSA = 1.25), representing a 100% increase in weight and a 40% increase in BSA. We do not have a control group to determine the independent effect of this change in size on annular and chamber size. Although natural growth may influence the use of LV volumes and dimensions, it is unlikely to lead to an independent reduction in TD-derived indexes and, moreover, would limit our use of LV dimension and volumes to provide an independent assessment of the severity of MR. Although we believe that we have shown the dynamic and progressive nature of MR, we cannot rule out the contribution of late valve scarring from the procedure or the eventual rupture of damaged chordae. Although longitudinal strain and SR were previously shown to be decreased in patients with MR and impaired contractile reserve (18), these parameters were not measured because of technical limitations. We chose to use color tissue-Doppler to measure velocity, strain, and SR, which could also have been reliably measured by two-dimensional derived-speckle tracking imaging. Although the noninvasive measurement of velocity and strain is less load dependent than the traditional measurement of LV systolic function (12), it is not load independent and would be supported by work incorporating pressure-volume loop analysis.

In summary, in a chronic model of MR, serial echocardiography demonstrated that MR is dynamic and progressive, MR begets MR, and TD-derived indexes, which initially rose with EF post-MR, returned to baseline before any changes in global EF.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by an American Heart Association postdoctoral fellowship (to T. G. Neilan) and National Institutes of Health Grants K23 HL-04504 and R21 EB-005294 (to J. Hung) and RO1 HL-38176 and K24 HL-67434 (to R. A. Levine).


   FOOTNOTES
 

Address for reprint requests and other correspondence: J. Hung, Cardiac Ultrasound Laboratory, 55 Fruit St., Blake 2, Boston, MA 02115-2696 (e-mail: jhung{at}partners.org)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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  1. Abraham TP, Laskowski C, Zhan WZ, Belohlavek M, Martin EA, Greenleaf JF, Sieck GC. Myocardial contractility by strain echocardiography: comparison with physiological measurements in an in vitro model. Am J Physiol Heart Circ Physiol 285: H2599–H2604, 2003.[Abstract/Free Full Text]
  2. Agricola E, Galderisi M, Oppizzi M, Schinkel AF, Maisano F, De Bonis M, Margonato A, Maseri A, Alfieri O. Pulsed tissue Doppler imaging detects early myocardial dysfunction in asymptomatic patients with severe mitral regurgitation. Heart 90: 406–410, 2004.[Abstract/Free Full Text]
  3. Bargiggia GS, Tronconi L, Sahn DJ, Recusani F, Raisaro A, De Servi S, Valdes-Cruz LM, Montemartini C. A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice. Circulation 84: 1481–1489, 1991.[Abstract/Free Full Text]
  4. Blumlein S, Bouchard A, Schiller NB, Dae M, Byrd BF 3rd, Ports T, Botvinick EH. Quantitation of mitral regurgitation by Doppler echocardiography. Circulation 74: 306–314, 1986.[Abstract/Free Full Text]
  5. Borgenhagen DM, Serur JR, Gorlin R, Adams D, Sonnenblick EH. The effects of left ventricular load and contractility on mitral regurgitant orifice size and flow in the dog. Circulation 56: 106–113, 1977.[Abstract/Free Full Text]
  6. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, Detaint D, Capps M, Nkomo V, Scott C, Schaff HV, Tajik AJ. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med 352: 875–883, 2005.[Abstract/Free Full Text]
  7. Enriquez-Sarano M, Miller FA Jr, Hayes SN, Bailey KR, Tajik AJ, Seward JB. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol 25: 703–709, 1995.[Abstract]
  8. Enriquez-Sarano M, Schaff HV, Orszulak TA, Bailey KR, Tajik AJ, Frye RL. Congestive heart failure after surgical correction of mitral regurgitation. A long-term study. Circulation 92: 2496–2503, 1995.[Abstract/Free Full Text]
  9. Enriquez-Sarano M, Tajik AJ, Schaff HV, Orszulak TA, Bailey KR, Frye RL. Echocardiographic prediction of survival after surgical correction of organic mitral regurgitation. Circulation 90: 830–837, 1994.[Abstract/Free Full Text]
  10. Enriquez-Sarano M, Tajik AJ, Schaff HV, Orszulak TA, McGoon MD, Bailey KR, Frye RL. Echocardiographic prediction of left ventricular function after correction of mitral regurgitation: results and clinical implications. J Am Coll Cardiol 24: 1536–1543, 1994.[Abstract]
  11. Gorcsan J 3rd, Strum DP, Mandarino WA, Gulati VK, Pinsky MR. Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography. Comparison with sonomicrometry and pressure-volume relations. Circulation 95: 2423–2433, 1997.[Abstract/Free Full Text]
  12. Greenberg NL, Firstenberg MS, Castro PL, Main M, Travaglini A, Odabashian JA, Drinko JK, Rodriguez LL, Thomas JD, Garcia MJ. Doppler-derived myocardial systolic strain rate is a strong index of left ventricular contractility. Circulation 105: 99–105, 2002.[Abstract/Free Full Text]
  13. Ishihara K, Zile MR, Kanazawa S, Tsutsui H, Urabe Y, DeFreyte G, Carabello BA. Left ventricular mechanics and myocyte function after correction of experimental chronic mitral regurgitation by combined mitral valve replacement and preservation of the native mitral valve apparatus. Circulation 86: II16–II25, 1992.[Medline]
  14. Jamal F, Strotmann J, Weidemann F, Kukulski T, D'Hooge J, Bijnens B, Van de Werf F, De Scheerder I, Sutherland GR. Noninvasive quantification of the contractile reserve of stunned myocardium by ultrasonic strain rate and strain. Circulation 104: 1059–1065, 2001.[Abstract/Free Full Text]
  15. Jose AD, Bernstein L, Taylor RR. The influence of arterial pressure on mitral incompetence in man. J Clin Invest 43: 2094–2103, 1964.[Web of Science][Medline]
  16. Kleaveland JP, Kussmaul WG, Vinciguerra T, Diters R, Carabello BA. Volume overload hypertrophy in a closed-chest model of mitral regurgitation. Am J Physiol Heart Circ Physiol 254: H1034–H1041, 1988.[Abstract/Free Full Text]
  17. Koyama J, Ray-Sequin PA, Falk RH. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 107: 2446–2452, 2003.[Abstract/Free Full Text]
  18. Lee R, Hanekom L, Marwick TH, Leano R, Wahi S. Prediction of subclinical left ventricular dysfunction with strain rate imaging in patients with asymptomatic severe mitral regurgitation. Am J Cardiol 94: 1333–1337, 2004.[CrossRef][Web of Science][Medline]
  19. Levine RA, Schwammenthal E. Ischemic mitral regurgitation on the threshold of a solution: from paradoxes to unifying concepts. Circulation 112: 745–758, 2005.[Free Full Text]
  20. Ling LH, Enriquez-Sarano M, Seward JB, Tajik AJ, Schaff HV, Bailey KR, Frye RL. Clinical outcome of mitral regurgitation due to flail leaflet. N Engl J Med 335: 1417–1423, 1996.[Abstract/Free Full Text]
  21. Matsumura T, Ohtaki E, Tanaka K, Misu K, Tobaru T, Asano R, Nagayama M, Kitahara K, Umemura J, Sumiyoshi T, Kasegawa H, Hosoda S. Echocardiographic prediction of left ventricular dysfunction after mitral valve repair for mitral regurgitation as an indicator to decide the optimal timing of repair. J Am Coll Cardiol 42: 458–463, 2003.[Abstract/Free Full Text]
  22. Matsuo T, Carabello BA, Nagatomo Y, Koide M, Hamawaki M, Zile MR, McDermott PJ. Mechanisms of cardiac hypertrophy in canine volume overload. Am J Physiol Heart Circ Physiol 275: H65–H74, 1998.[Abstract/Free Full Text]
  23. Mele D, Vandervoort P, Palacios I, Rivera JM, Dinsmore RE, Schwammenthal E, Marshall JE, Weyman AE, Levine RA. Proximal jet size by Doppler color flow mapping predicts severity of mitral regurgitation. Clinical studies. Circulation 91: 746–754, 1995.[Abstract/Free Full Text]
  24. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 30: 1527–1533, 1997.[Abstract]
  25. Nemoto S, Hamawaki M, De Freitas G, Carabello BA. Differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the β-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation. J Am Coll Cardiol 40: 149–154, 2002.[Abstract/Free Full Text]
  26. Nemoto S, Razeghi P, Ishiyama M, De Freitas G, Taegtmeyer H, Carabello BA. PPAR-{gamma} agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation. Am J Physiol Heart Circ Physiol 288: H77–H82, 2005.[Abstract/Free Full Text]
  27. Otsuji Y, Handschumacher MD, Schwammenthal E, Jiang L, Song JK, Guerrero JL, Vlahakes GJ, Levine RA. Insights from three-dimensional echocardiography into the mechanism of functional mitral regurgitation: direct in vivo demonstration of altered leaflet tethering geometry. Circulation 96: 1999–2008, 1997.[Abstract/Free Full Text]
  28. Otto CM. Clinical practice. Evaluation and management of chronic mitral regurgitation. N Engl J Med 345: 740–746, 2001.[Free Full Text]
  29. Recusani F, Bargiggia GS, Yoganathan AP, Raisaro A, Valdes-Cruz LM, Sung HW, Bertucci C, Gallati M, Moises VA, Simpson IA, et al. A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study. Circulation 83: 594–604, 1991.[Abstract/Free Full Text]
  30. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease: technic, indications and interpretations in 700 cases. Am J Cardiol 14: 437–447, 1964.[CrossRef][Web of Science][Medline]
  31. Starling MR, Kirsh MM, Montgomery DG, Gross MD. Impaired left ventricular contractile function in patients with long-term mitral regurgitation and normal ejection fraction. J Am Coll Cardiol 22: 239–250, 1993.[Abstract]
  32. Urabe Y, Mann DL, Kent RL, Nakano K, Tomanek RJ, Carabello BA, Cooper GT. Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation. Circ Res 70: 131–147, 1992.[Abstract/Free Full Text]
  33. Wong CY, O'Moore-Sullivan T, Leano R, Byrne N, Beller E, Marwick TH. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation 110: 3081–3087, 2004.[Abstract/Free Full Text]
  34. Yellin EL, Yoran C, Sonnenblick EH, Gabbay S, Frater RW. Dynamic changes in the canine mitral regurgitant orifice area during ventricular ejection. Circ Res 45: 677–683, 1979.[Abstract/Free Full Text]
  35. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RW, Sonnenblick EH. Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area. Circulation 60: 170–176, 1979.[Abstract/Free Full Text]
  36. Zile MR, Tomita M, Ishihara K, Nakano K, Lindroth J, Spinale F, Swindle M, Carabello BA. Changes in diastolic function during development and correction of chronic LV volume overload produced by mitral regurgitation. Circulation 87: 1378–1388, 1993.[Abstract/Free Full Text]
  37. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, Nihoyannopoulos P, Otto CM, Quinones MA, Rakowski H, Stewart WJ, Waggoner A, Weissman NJ. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 16: 777–802, 2003.[CrossRef][Web of Science][Medline]



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