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Ann Thorac Surg 2006;82:1362-1368
© 2006 The Society of Thoracic Surgeons
a Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia
b University of Texas Southwestern Medical Center, Lubbock, Texas
c Texas Tech University, Lubbock, Texas
Accepted for publication May 4, 2006.
* Address correspondence to Dr Yoganathan, Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology and Emory University, Room 2119, U.A. Whitaker Bldg, 313 Ferst Dr, Atlanta, GA 30332-0535 (Email: ajit.yoganathan{at}bme.gatech.edu).
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Abstract |
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 Top Abstract IntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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METHODS: Fifteen porcine mitral valves were studied in a physiologic left heart simulator with a variable size annulus (dilated = 8.22 cm2, normal = 6.86 cm2, contracted = 5.5 cm2). Mitral valves were tested under steady and physiologic pulsatile flow conditions (cardiac outputs: 4 to 6 L/min), at peak transmitral pressures between 100 mm Hg and 140 mm Hg. A miniature force transducer was used to measure the Alfieri stitch force (FA). Mitral flow rate (MFR), transmitral pressure, effective orifice area, mitral regurgitation, and FA were monitored.
RESULTS: The edge-to-edge repair led to a decrease in effective orifice area of 16.55% ± 8.22%; further reduction in effective orifice area was attained with annular contraction. Mitral regurgitation after the edge-to-edge repair was significantly higher (p <0.05) with annular dilation. In the pulsatile experiments, two peaks in FA were observed: one during systole (FA = 0.059 ± 0.024 N) and a second during diastole (FA = 0.072 ± 0.021 N). Multivariate analysis of variance analysis showed that during systole, transmitral pressure and mitral annular area (MAA) had significant effects on FA [FA = (4.40 x 10–4) transmitral pressure (mm Hg) + (5.0 x 10–3) MAA (cm2) – 0.05 (R2= 0.80)], whereas during diastole MFR and MAA had significant effects on FA [FA = (1.03 x 10–4) MFR2 (L/min) – (1.60 x 10–3) MAA (cm2) + 0.02 (R2 = 0.90)].
CONCLUSIONS: With annular dilation, mitral regurgitation persisted even after the edge-to-edge repair. The edge-to-edge repair does not cause clinically relevant mitral valve stenosis in a normal size mitral valve. Mitral flow rate and transmitral pressure are the main determinants of FA during the cardiac cycle. Increasing annular area increases FA during systole but decreases FA during diastole. Systolic FA may become dominant with increases in MAA or peak transmitral pressure, or both.
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Introduction |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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The edge-to-edge repair has shown to be a simple and effective adjunctive procedure when dealing with MV insufficiency [5]. However, the specific etiologies in which this tool may be used and its long-term efficacy are still controversial [6].
Generally, the edge-to-edge repair is accompanied by concomitant annuloplasty, since recent studies have shown suboptimal results when performing the edge-to-edge technique without annular resizing [7]. The development of edge-to-edge techniques without concomitant annuloplasty is important because it increases the feasibility of repairing the MV using less invasive approaches [8–10]. Therefore, understanding the effects of annular size on MV function and mechanics after the edge-to-edge repair is fundamental not only to understand current repair procedures, but also for the development of future techniques.
To improve the understanding of MV mechanics after the edge-to-edge repair, several studies have recently been performed [11–15]. Variables of valve function and mechanics such as regurgitation volume [6, 7, 14], transvalvular pressure gradient [14, 15], leaflet stress [11], and Alfieri stitch force (FA) [12, 13] have been studied.
Although edge-to-edge stitch failure is uncommon, FA is an important factor that may affect repair durability. Additionally, less invasive techniques [8–10], aimed at restoring MV function associated with dilated cardiomyopathy or ischemic mitral regurgitation will require the use of mechanical devices such as clips, to hold the leaflets together. Knowledge of the loading to which these devices will be exposed is essential to their design. Innovative studies by Nielsen and colleagues [12] and Timek and associates [13] demonstrated how annular size and geometry could be correlated statistically to FA. Since these studies were conducted in vivo, they did not allow for control over independent variables. Therefore, it is not possible to determine in vivo the independent effects of mitral flow rate (MFR) and mitral annular area (MAA) on FA. In addition, in the second of these studies [13], a significant decrease in FA was observed with increased peak transmitral pressure, a result that is counterintuitive. Therefore, further understanding of the effects of annular size, MFR, and transmitral pressure on FA in a controlled mechanical environment is required.
The present in vitro study aims to expound the relation between FA and variables such as annular area, transmitral pressure, and MFR, under conditions present after annular or ventricular remodeling associated with ischemic mitral regurgitation or dilated cardiomyopathy. The in vitro approach will allow control over the variables of interest and thus provide an understanding of their individual contributions to FA. Additionally, effective orifice area and regurgitation volumes will also be determined to assess the efficacy of the edge-to-edge procedure in the studied conditions.
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Material and Methods |
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Left heart simulator
The in vitro experiments were conducted in the Georgia Tech Left Heart Simulator, which has been described in previous publications [16–18]. This system is capable of physiologic and pathophysiologic flow and pressure waveforms [16–18].
To simulate variable MAA, a variable size annular model was constructed. Details of a similar model have been reported in a previous publication [17]. The annulus in the normal position had a 3.5-cm commissural diameter and 2.5-cm septal-lateral diameter (MAA = 6.86 cm2). Under dilation conditions, the annular septal-lateral diameter increased to 3 cm (MAA = 8.22 cm2), and in the contracted position, the annular septal-lateral diameter was 2 cm (MAA = 5.50 cm2). The large annulus simulated a level of annular dilation found after acute ventricular remodeling, and the small annular area was selected by linearly extrapolating the normal and dilated conditions.
C-ring force transducers
A miniature C-shaped force transducer was used to quantify FA. Details on these C-ring force transducers have been presented in previous publications [12, 13, 16, 20].
Experimental Method
A C-ring force transducer was sutured onto the anterior and posterior leaflets 5 mm from their tips, as shown in Figure 1. This assembly was then coupled onto the left heart simulator.
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Baseline experiments were carried out at MFRs from 0 to 30 L/min in 5 L/min increments, with the MV in the different annulus configurations, but without the edge-to-edge repair. The force transducer was then sutured onto the leaflets. The experiments were then repeated for MFRs from 0 to 30 L/min in 2 L/min intervals in the different annular configurations.
Pulsatile experiments
The MV with the C-ring force transducer was mounted onto the Georgia Tech Left Heart Simulator. Both papillary muscles were then displaced 5 mm apicaly, 5 mm laterally, and 5 mm posteriorly from the defined normal papillary muscle position [19], as described in Figure 2. The simulator was operated under physiologic conditions (heart rate, 70 beats per minute; systolic duration, 300 ms). The FA data were collected at peak transmitral pressures of 100 mm Hg, 120 mm Hg, and 140 mm Hg, while maintaining a cardiac output of 5 L/min. Data were also obtained at cardiac outputs of 4 L/min and 6 L/min at a peak transmitral pressure of 120 mm Hg. All of these measurements were repeated for the three different annular sizes.
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Statistical Analysis
All data are reported as the mean ± 1 SD, unless otherwise stated. Multivariate analysis of variance (ANOVA) was conducted to observe if MFR, transmitral pressure, and MAA had a significant effect on FA. Paired t tests were used to compare the different groups. A 95% confidence interval was used to determine if the differences were statistically significant.
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Results |
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| (1) |
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The pressure drop across the valve (
P- mm Hg) demonstrated to be linearly related to FA:
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| (2) |
Using the pressure drop (mm Hg) and the respective MFR (L/min), the effective orifice area (EOA [cm2]) was calculated. As shown in Figures 5A and B, EOA increases rapidly with increasing MFR and levels out after 20 L/min. Before the edge-to-edge repair, the EOA was 4.06 ± 0.27 cm2, 5.24 ± 0.24 cm2, and 6.31 ± 0.66 cm2 with the contracted, normal, and dilated annuli, respectively, at 30 L/min. After the edge-to-edge repair, the EOA was 3.67 ± 0.21 cm2, 4.64 ± 0.24 cm2, and 5.50 ± 0.31 cm2 with the contracted, normal, and dilated annuli, respectively (30 L/min). The average EOA (over flow rates from 5 to 30 L/min) decreased significantly (p < 0.05) after the edge-to-edge repair: 13.16% ± 7.38%, 17.54% ± 11.28%, and 18.93% ± 5.11% for the contracted, normal, and dilated annuli, respectively. There were no significant differences between the different annular configurations. Therefore, the edge-to-edge repair alone induced an average level of stenosis of 16.55% ± 8.22%, which was independent of annular size. The MVs in the contracted annular configuration after the edge-to-edge repair presented a level of stenosis of 32.80% ± 8.09% compared with the normal MV. Therefore, the edge-to-edge repair in conjunction with annular contraction resulted in a moderate level of MV stenosis.
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The average diastolic pressure drops through the MV were 2.49 ± 1.49 mm Hg, 1.61 ± 2.02 mm Hg, and 1.69 ± 2.11 mm Hg; corresponding to effective orifice areas of 3.88 ± 1.75 cm2, 5.78 ± 3.15 cm2, and 6.29 ± 4.63 cm2, for the contracted, normal, and dilated annuli, respectively.
The FA curves showed two distinctive peaks during the cardiac cycle, as shown in Figure 6. The first peak coincided with the peak transmitral pressure, and the second peak occurred at maximum forward flow during diastole.
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| (3) |
The FA was also recorded at peak transmitral pressures of 100 mm Hg, 120 mm Hg, and 140 mm Hg at a constant cardiac output of 5 L/min. As peak transmitral pressure increased, peak systolic FA increased from 0.051 ± 0.018 N to 0.063 ± 0.022 N to 0.065 ± 0.025 N, respectively, in the normal annulus configuration. Peak systolic FA increased from 0.081 ± 0.027 N to 0.092 ± 0.03 N to 0.096 ± 0.034 N as peak transmitral pressure increased from 100 mm Hg, to 120 mm Hg, to 140 mm Hg, respectively, in the dilated annulus configuration. The increases in FA from 100 mm Hg to 120 mm Hg were statistically significant (p < 0.05), whereas the increases from 120 mm Hg to 140 mm Hg were not significant for both annular configurations. There was no significant difference (p > 0.05) in mean diastolic FA for cardiac outputs of 4 L/min (0.040 ± 0.021 N), 5 L/min (0.037 ± 0.019 N), and 6 L/min (0.038 ± 0.018 N), at a constant transmitral pressure of 120 mm Hg.
Multivariate ANOVA analysis showed that transmitral pressure, MFR, and MAA had a significant (p < 0.05) effect on FA during the cardiac cycle. As observed in Figure 6, FA follows the MFR curve during diastole and the transmitral pressure curve during systole. Additionally, FA increased with MAA during systole, but decreased with MAA during diastole, with the most significant variation occurring during systole. Because FA changes from diastole to systole in a complex fashion, a single statistical model for FA could not be fit (R2 < 0.6) over the entire cardiac cycle. Therefore, two different functions were derived, one for systole and one for diastole. During systole ANOVA analysis showed that both transmitral pressure (TP - mm Hg) and mitral annular area (MAA - cm2) had significant (p < 0.05) effects on FA(N):
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| (4) |
As observed in the steady flow experiments, FA correlated well with the square of MFR. Therefore, MAA (cm2) and MFR2 (L2/min2) were used to construct the ANOVA model for diastole:
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| (5) |
Similar ANOVA models may be obtained using transmitral pressure (TP) and annular septal-lateral diameter (SL-cm) as independent variables during systole:
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| (6) |
And MFR and annular septal-lateral diameter (SL-cm) as independent variables during diastole:
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| (7) |
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Comment |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Mitral Valve Function After Edge-to-Edge Repair
Several clinical studies have demonstrated that without concomitant annuloplasty, the long-term results of edge-to-edge repair are suboptimal [7]. The results of this study showed that after symmetrical displacement of the papillary muscles and with approximately 20% dilation of the mitral annulus, significant regurgitation was still present after the edge-to-edge repair. Although decreasing annular size resulted in a significant decrease in mitral regurgitation, modest regurgitation still persisted in the normal annulus configuration. Further contraction of the annulus did not significantly decrease this modest but remnant mitral regurgitation resulting from papillary muscle displacement. These results help to confirm the concept that for superior results the edge-to-edge repair should be accompanied by annuloplasty.
The current study also demonstrates that, on average, the Alfieri stitch alone decreased EOA by approximately 16%, which may be characterized as an insignificant to mild level of MV stenosis. When both annular undersizing and the Alfieri stitch were present, the EOA was reduced by approximately 33%, which represents a moderate level of MV stenosis. Therefore, although concomitant annuloplasty improves the efficiency of the edge-to-edge repair, correct annuloplasty ring sizing is essential. These results agree with previous clinical and animal studies showing that the edge-to-edge repair when correctly performed does not cause functional MV stenosis [14, 15].
Determinants of Alfieri Stitch Force
Nielsen and coworkers [12] and Timek and colleagues [13] used similar force transducers to those used in the present study in sheep to measure FA during the cardiac cycle. The FA curves in these in vivo studies and the current in vitro study, showed two peaks during the cardiac cycle: one peak during systole and a second during diastole. Peak FA values obtained in the present study are smaller than those observed in the aforementioned in vivo studies, but are of the same order of magnitude. We believe that most of the discrepancy in the magnitude and differences in the FA curves are due to the location of the force transducer. In the in vivo studies, the transducer was attached to the atrial side of the leaflets, whereas in the current in vitro study, the transducer was placed on the ventricular side. In the present study, the transducer was zeroed under zero flow and zero transmitral pressure conditions in the simulator, because in the normal valve configuration the leaflets do not need to be pulled together. In the in vivo studies [12, 13], under normal annular conditions, the leaflets are brought together, and thus there is a static force under zero flow and zero pressure. Thus, the in vivo FA curves do not demonstrate the severe reduction of force between the two peaks and maintain a FA baseline of approximately 0.1 N. The in vitro transducer location was aimed at minimizing interference with leaflet motion, which Nielsen and colleagues [12] acknowledged as a possible limitation of their in vivo experiments. In vivo annular contractility and differences in valve size may also contribute to the difference in FA magnitude between the studies.
These in vivo studies [12, 13] also showed that the diastolic peak was dominant during the cardiac cycle. This trend was also observed in the present study under normal annular conditions. Nielsen and coworkers [12] also studied sheep with ischemic mitral regurgitation and subsequent annular dilation. In sheep with ischemic mitral regurgitation, FA increased during the entire cardiac cycle, but the most significant increase was observed at end systole [12]. These results agree with the present study, as the results showed that peak FA during systole increases linearly with MAA.
Nielsen and colleagues [12] reported end-systolic mitral annular areas of 720 ± 40 mm2 and 820 ± 50 mm2 in normal and ischemic sheep, respectively, corresponding to an annular dilation of approximately 14%. In the Nielsen study, the left ventricular pressure decreased in the ischemic sheep, and the level of dilation was smaller compared with the dilation used in the current study. These two differences may explain why Nielsen did not observe that peak systolic FA becomes dominant in the presence of annular dilation, as demonstrated in the present study. Under normal annulus conditions, the Alfieri stitch only helps the tips of the MV leaflets to initially coapt. With annular dilation, coaptation length decreases [19], and therefore the leaflets are brought together with the stitch. In such conditions, a non-zero baseline in FA is present owing to the force needed to bring the leaflets together. In the present study, the non-zero baseline associated with pulling the leaflets together was not present, owing to the relatively small increase in annular septal-lateral diameter in the dilated configuration.
Nielsen and coworkers [12] and Timek and colleagues [13] also reported a positive correlation between annular septal-lateral diameter and diastolic FA [12, 13], contradicting the findings of the present study in which a negative correlation between diastolic FA and MAA was revealed. During diastole, the leaflets are pulled apart by the flow through the valve, and the force on the leaflets is directly related to the surface area of the leaflets and force imparted by the passing fluid. During diastole, the Alfieri stitch prevents the tips of the leaflets from separating completely. Thus, FA is determined to a large extent by MFR. Under normal in vivo conditions, the mitral annulus expands during diastole. Therefore, the positive correlation between septal-lateral diameter and FA found in previous studies [12, 13] was mostly due to the increase in flow through the valve. To some extent, this positive correlation was also due to annular expansion. Although the component of tension associated with annular expansion is artificially magnified by transducer placement through a non-zero baseline in the normal valve configuration. The negative correlation found between FA and MAA in the present study may be explained by physics. At a constant flow rate, decreased orifice cross-sectional area will result in increased velocity. The increase in velocity during diastole will increase the force on the leaflets and subsequently FA.
Limitations
The Georgia Tech Left Heart Simulator does not mimic ventricular wall motion and papillary muscle contraction, but has been used in several published studies of MV mechanics [16–18]. Although under the pathologic conditions of interest most annular dynamics are lost, sphincteric annular contraction may have a significant influence on FA under normal annular conditions. In the current study, annular dilation is relatively moderate, and thus the baseline FA required to pull the leaflets together under pathologic conditions was minimal. Thus, further research with larger levels of dilation is warranted. The use of a transducer to hold the leaflets together instead of a single stitch may not simulate perfectly the clinical setting. Nevertheless, we believe that the current transducer location obstructs less leaflet motion and flow when compared with the placement used in previous pioneering studies [12, 13]. The present in vitro methodology provided good control over the variables of interest, and as this is a comparative study, the shortcomings of the model should not have a significant impact on the conclusions.
In conclusion, the results of the present study demonstrate that the edge-to-edge repair alone will not eliminate mitral regurgitation in the setting of associated annular dilation. The edge-to-edge repair with concomitant annuloplasty does not cause significant functional MV stenosis if the annuloplasty reduces the annulus to its normal dimensions. Although FA during diastole decreases with increased annular area, systolic FA increases and becomes dominant with annular dilation. Therefore, correctly sized concomitant annuloplasty is required to improve the long-term results of the edge-to-edge repair both in terms of efficacy and durability. Mitral flow rate and transmitral pressure are the main determinant of changes in FA during the cardiac cycle and may be used in conjunction with MAA to approximate the magnitude of the force on the Alfieri stitch.
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Acknowledgments |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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References |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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This article has been cited by other articles:
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  H. Hasegawa, Y. Araki, A. Usui, J. Yokote, S. Saito, H. Oshima, and Y. Ueda Mitral valve motion after performing an edge-to-edge repair in an isolated swine heart J. Thorac. Cardiovasc. Surg., September 1, 2008; 136(3): 590 - 596. [Abstract] [Full Text] [PDF]
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T. A. Timek, S. L. Nielsen, D. T. Lai, D. Liang, G. T. Daughters, N. B. Ingels Jr, and D. C. Miller Effect of Chronotropy and Inotropy on Stitch Tension in the Edge-to-Edge Mitral Repair Circulation, September 11, 2007; 116(11_suppl): I-276 - I-281. [Abstract] [Full Text] [PDF]
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