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J Thorac Cardiovasc Surg 2009;137:174-179
© 2009 The American Association for Thoracic Surgery
Evolving Technology |
a Dipartimento Cardiovascolare Clinico e di Ricerca, Ospedali Riuniti, Bergamo, Italy
b Dipartimento di Medicina di Laboratorio, Ospedali Riuniti, Bergamo, Italy
c IMM Recherche, Paris, France
d Department of Chemical Engineering, Imperial College London, London, United Kingdom
e Laboratorio di Meccanica delle Strutture Biologiche, Politecnico di Milano, Milano, Italy
Received for publication May 15, 2008; revisions received August 18, 2008; accepted for publication August 27, 2008. * Address for reprints: Paolo Ferrazzi, MD, FETCS, Cardiac Surgery Unit, Dipartimento Cardiovascolare Clinico e di Ricerca, Ospedali Riuniti, Largo Barozzi, 1, 24128 Bergamo, Italy. (Email: pferrazzi{at}ospedaliriuniti.bergamo.it).
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Abstract |
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Methods: Ten healthy sheep underwent surgical implantation of mitral devices, the elastic component of which is represented by a helicoid metallic spring. Preimplantation and postimplantation echocardiographic parameter measurements to evaluate annular dynamics and ventricular function comprise mitral annular motion, systolic tissue Doppler imaging peak wave, transmitral pressure gradient, peak transmitral flow velocity, and ejection fraction. Postimplantation angiographic analysis allowed measurement of the mitral annular area and perimeter variations by means of segmentation of the radiopaque mitral device contour.
Results: No significant difference in terms of ejection fraction (P = .13) and systolic tissue Doppler imaging peak wave (P = .87) was found before and after implantation. Mitral annular motion (1.16 cm) was preserved. The percentage of systolic annular reduction derived from angiographic analysis was 14.1% (range, 7.7%–19.7%) in terms of area and 7.2% (range, 4.9%–10.0%) in terms of perimeter.
Conclusions: A mitral elastic ring, implantable by using a standard technique, acutely preserves mitral annular dynamics, allowing area and perimeter changes. Further chronic study is needed to verify the biocompatibility and durability of the device.
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Introduction |
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The change in the size of the annular area has been demonstrated in animal and human models, and a cyclic reduction of annular area has been revealed, with minimal area in systole.2-5 It has also been pointed out that the shape of the MA is a hyperbolic paraboloid and is therefore reminiscent of a saddle, with a higher curvature in systole.6 Furthermore, the annulus is seen to move during the cardiac cycle; it undergoes anterior displacement toward the apex during ventricular systole and posterior displacement toward the base during ventricular diastole, as well as during atrial contraction.7,8
The MA dynamics are regulated by the elastic properties of the myocardial tissue.7 Theoretically, the ideal annuloplasty ring design for functional mitral regurgitation (FMR) should, in addition to permanently abolishing mitral insufficiency, promote an MA dynamic motion, facilitate its sphincteric contraction, and provide an active force to help in the orifice's systolic mitral area reduction. A fully elastic mitral ring prototype was developed and implanted on the MAs of 10 healthy sheep to test this hypothesis. The purpose of this study was to acutely assess the maintenance of the physiologic annular motion behavior.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Mitral Device
The device used for this study is a fully elastic and flexible ring that is able to expand and bend according to MA dynamics. By definition, this device follows the law of elasticity, which states that an elastic body deforms under external forces but then returns to its original shape and dimensions when the external forces are removed.
The device is made up of 2 basic components: (1) a flexible and expandable textile suturable component that enables the implantation of the ring according to the usual annuloplasty surgical technique and (2) an elastic component represented by a helicoid spring made of a metallic alloy.
The spring has an elastic constant of 20 N/m, corresponding to an exerted force of 160g for an elongation of 20%. The elastic constant of the device has been chosen empirically after animal tests and according to Literature values of annular dynamics in healthy sheep.3 The spring is circular at rest. For the implantation, the device is mounted on a holder that has the typical kidney-bean shape of the MA, with a linear anterior border (relative to the intertrigonal segment) and a circular posterior border (relative to the shape of the annulus between the commissures). When mounted on the holder, the device is loaded and is subjected to an elongation of 20%. The predetermined dimension of the device, relative to the intercommissural diameter at implantation, has been derived from anatomic data from previous reports.2 Because the ring is stretched when implanted, it tends to contract the MA after implantation. Figure 1
shows the dimensions of the spring at rest and in implant configuration.
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Ten female Ile de France sheep, weighing 63.5 ± 4.5 kg (range, 55–70 kg) and with a mean age of 18.17 ± 6.78 months, were anesthetized with an intravenous injection of 10 mg/kg thiopental followed by isoflurane in 100% oxygen. Mechanical ventilation was maintained with an air/oxygen mixture and a tidal volume of 20 mL/kg.
In right lateral recumbency a left fourth intercostal thoracotomy was performed, and the heart was suspended in a pericardial cradle.
After full heparinization, normothermic cardiopulmonary bypass (CPB) was instituted, cannulating the right carotid artery with a 20F cannula and the right ventricle through the pulmonary artery with a 28F cannula. The pump flow was kept at a rate of 50 mL · kg–1 · min–1 by using a roller heart-lung machine primed with 1000 mL of lactated Ringer solution and bicarbonate. Blood gases were maintained in the physiologic range with a membrane oxygenator. With the heart beating, an incision on the left atrial appendage was performed, and the device was sutured to the MA by means of 10 to 12 single U stitches. The left atrium was closed and vented, and after a period of hemodynamic stabilization, the animals were weaned from CPB. After the completion of angiographic and echocardiographic evaluation, the chest was closed, and the animals were weaned from mechanical ventilation and awakened.
Echocardiography
All epicardial Doppler echocardiographic studies were performed with a multifrequency transducer attached to a Vingmed System 5 (General Electric, Fairfield, Conn). All images were obtained in real time by an experienced echocardiographer in sleeping animals before and after CPB. Two-dimensional echocardiographic analysis was performed epicardially through the intercostal thoracotomy and through the transdiaphragmatic approach. Long-axis, short-axis, 4-chamber, and 5-chamber views were obtained.
Three sets of measurements were made in each echocardiographic view at predetermined steps. The mean value of 3 measurements was used to describe the quantitative data for each animal at each step. End-diastolic and end-systolic measurements were obtained at the time of the peak R-wave and the end of the T-wave, respectively.
Measurement of mitral annular motion (MAM), which defines the systolic movement of the MA toward the apex, was done by placing the M-mode cursor perpendicular to the lateral site of the MA (Figure 3 ).
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Angiography
After the implantation of the mitral device, an angiographic scan was taken for each sheep. Images were acquired in the hemodynamically stable open-chest animals with a Stenoscop 9000 MDA (General Electric Medical Systems, Milwaukee, Wis) able to obtain 25 images per second. Angiography scans of the left ventricle and aorta were performed to check for the presence of mitral or aortic regurgitation. A number of angiographic sequences were taken to assess the right positioning of the mitral ring and its dynamics after implantation by using lateral and left anterior views. Data from the scans were digitized for the offline calculation of the ring area and perimeter.
Because of the radiopacity of the metallic alloy of the spring, it was possible to evaluate the spring position and dimensions.
For each sheep, at least 1 angiographic sequence was taken, relative to a frontal view of the ring. The outer border of the spring is assumed to move integrally with the MA with no relative displacement according to the technique of implantation and the device design. Each frame of the angiographic sequence was extracted and scaled by using a known reference dimension.
The contour of the spring in each frame was extracted, drawing a number of points (between 20 and 30) on the outer border. Least-squares cubic splines were drawn to join the points and create closed curves relative to the spring contour (Figure 4 ).
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Because of the differences in heart rate for each sheep, the cardiac cycle length was normalized to 1 to allow comparison of the data. The curves were aligned, positioning the end-diastolic phase (middle point between the maximum and minimum opening of the ring) at 0.5, according to previously reported methods.2,9
The systolic percentage of annular area and perimeter reduction was calculated for each sheep, defined as follows:
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Statistical Analysis
All variables were tested not to violate the normality assumption by using the Kolmogorov–Smirnov test and were reported as the mean ± standard deviation. Comparisons between means were performed by using the paired-sample 2-sided t test, as appropriate. When independent-samples t tests were performed, the equality of variance between samples was assessed by using the F test. Linear correlation analysis was carried out to examine the linear relation between dependent variables. Statistical analyses were performed with the SPSS version 13.0 software package (SPSS, Inc, Chicago, Ill).
Because the offline calculation derived from the angiographic scans was performed by 2 independent operators who used 2 different methods, the measurements of systolic and diastolic area and perimeter were compared. This comparison showed a significant consistency of the measurements; for all parameters, no statistical difference was found by using the paired t test and intraclass correlation coefficients (ICCs). Excellent agreement was found in case of diastolic perimeter (paired t test, P = .877, ICC = 0.895), systolic perimeter (paired t test, P = .851, ICC = 0.855), and diastolic area (paired t test, P = .653, ICC = 0.837), whereas very good agreement was found in case of systolic area (paired t test, P = .500, ICC = 0.792). ICCs proved the very high reliability of the method, yielding a value for the coefficient of greater than 0.75 for all the comparisons.
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Results |
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Echocardiographic Assessment
No mitral or aortic regurgitation was identified in any animal before and after the mitral device implantation. The systolic function, in terms of EF and S-TDI, was similar before and after implantation (EFbasal = 64.5%, EFimplantation = 65.4%, P = .13; S-TDIbasal = 0.06, S-TDIimplantation = 0.07, P = .87). MA plane motion was maintained after implantation, although it was reduced (MAMbasal = 1.4 cm, MAMimplantation = 1.2 cm, P = .0029). Transmitral mean gradient (P = .0026) and E-wave (P = .00092) increased from baseline to after implantation (Table 1
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The percentage of systolic annular reduction was 14.1% (range, 7.7%–19.7%) in terms of area and 7.2% (range, 4.9%–10.0%) in terms of perimeter. The correlation between the changes in area and perimeter was good (r = 0.77, P < .01). The average values for perimeter and area were calculated instant by instant over the nondimensionalized cardiac cycle for the sheep population and are plotted in Figure 5
. The behavior of this curve is similar to that reported in healthy sheep by other authors.2,3,9
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In this study, echocardiography was performed before and after the implantation of the mitral ring to assess hemodynamic and functional parameters, whereas angiography was performed only after the implantation to quantify the device's geometric changes during the cardiac cycle. All animals studied were healthy adult sheep, and no evidence of hemodynamically significant mitral regurgitation, as determined by means of Doppler echocardiographic analysis, was registered at the time of data collection before and after surgical intervention. All data were obtained with the animals ventilated and in normal sinus rhythm. Hemodynamics, including heart rate, EF, blood pressure, and S-TDI wave, were similar before and after the implantation (P > .1), enabling homogeneous observations of MA dynamics without confounding interference of LV function.
Although no undersizing of the MA was performed in this study, a certain degree of annular morphologic and dimensional changes occurred. It is well known that the implantation of any type of mitral ring reduces significantly the annular size, mainly because of the suturing technique: the use of interrupted horizontal mattress sutures, as in our experiment, placed around the entire MA contour causes a certain degree of annular stiffening and reduction.2 Because of this, some statistical differences between basal and postimplantation values of echocardiographic parameters have been registered: MAM, E-peak mitral flow velocity, and mean transmitral pressure gradient. Nevertheless, none of these parameters have crucial morphologic or hemodynamic relevance.
A major component in MA dynamics is represented by annular plane motion according to the cardiac cycle phases.10-12 The magnitude of MAM correlates with systolic and diastolic ventricular function,8,11 is subject to atriogenic influence,3,13 contributes to sphincteric action as an aid to ventricular filling and emptying, accounts for a relevant portion of total filling and emptying of ventricular volume, and finally determines a large amount of stroke volume.11 This MA movement is well displayed by the M-mode echocardiographic measurement of MAM. A mean MAM value of 1.2 ± 0.3 cm has been registered in the present study, which confirms that a flexible and elastic device preserves annular motion, although at a reduced level. This result is similar to those reported in previous animal and clinical studies with different types of mitral annuloplasty.14,15
Several studies performed in animals and human subjects have demonstrated that annular area and perimeter are subjected to variation during the cardiac cycle in terms of dimension and shape. This phenomenon depends on systodiastolic differences in commissure–commissure and septal–lateral diameters together with the variation in curvature of the saddle shape of the annulus.3,16 The area change reported in the Literature for healthy subjects varies from 6.9% to 16.7% in ovine models2,3,5,16-18 and from 9.3% to 26.0% in human models.1,19-21 The physiologic changes in MA area are prevalently regulated by the normal LV geometry and function.3,19,22 As reported by several authors in animal studies,2,18,23 the implantation of a complete mitral ring, no matter the type (rigid, flexible, or selectively flexible), does not allow a physiologic change in the area and perimeter of the MA. A significant annular area variation is only reported for a C-shaped annuloplasty band, which allows free motion of the intertrigonal segment of the annulus23; however, controversial results have been reported also for this type of device.18,23 In human studies mitral area variation has been reported after implantation of a flexible C-shaped band24 or flexible ring,25 whereas no significant area change was reported in case of the implantation of a rigid ring.
In our study the observed extent of ring annular area and perimeter variations were 14.1% and 7.2%, respectively, suggesting that this new flexible and fully elastic ring modifies its dimensions according to the natural MA movements, allowing a physiologic value of area and perimeter variations. This result is due to the intrinsic properties of the spring.
The reduction in MA size that occurs after any ring implantation (which occurred also in our study) would likely require a greater force than that generated by the ventricular contraction to change the annular area. Following the length–tension relationship of the cardiac muscle, a shorter length of muscle fibers associated with a shorter length of the MA causes a reduction of the annular forces.2 Hence we hypothesize that the active elastic recoil force of our device might have replaced the lack of native muscular tension and therefore contributed to the physiologic variation of the annular area.
Clinical Implications
The clinical implications of this work principally refer to the field of FMR. FMR is characterized by geometric LV remodeling, with dilatation and dysfunction typically seen in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. During the last 2 decades, many experimental and clinical studies have been performed on the interpretation of the disease8,11,19,20,26-28 and the analysis of clinical results.5,26,29-31 Evolving concepts have stimulated research on the design of new generations of mitral annuloplasty devices. The principles of mitral valve repair (MVR) have evolved in an attempt to identify the best device able to cure the mitral lesion and simultaneously replicate the MA physiologic shape and dynamics. However, the intrinsic elastic properties of the normal MA, in terms of perimeter variation, area variation, folding, contraction of the posterior portion, and extension of the anterior portion, have not been taken into account. The principles that are accepted in the best practice at present refer to undersizing of the MA, reduction and fixation of septal–lateral dimension, and adoption of cause-specific geometrically shaped rings.29 This attitude appears to be a renunciation of a new thinking on FMR optimal repair that has been advocated by many authors.3,14,16,17,19,23,32-34
The preliminary results of our study suggest that the potential benefits of a device aimed at the correction of FMR that is flexible and fully elastic allows the physiologic dynamics of the mitral valve complex and restores elastic forces where they have been reduced because of ventricular dysfunction.35
Limitations
The presence of a metal helicoid spring constituting the device has affected the amount of information that could be extracted from echocardiographic analysis. A number of measurements of aortic and mitral diameters, as well as annular contour length, have been attempted, but the intraobserver and interobserver variability were too high to accept these measures.
Area and perimeter have been calculated by means of angiographic scans because of the radiopacity of the metal. The derived anatomic definition of the MA is more subjective than in imaging based on visually identifiable structures, such as implanted annular markers or piezoelectric crystals.2,3,16 Nevertheless, the tracing of the annular contour in the present study was performed in a consistent manner with good reproducibility, as demonstrated by the absence of significant interobserver variation. Furthermore, because no sliding between the metallic ring and the MA is present, the calculated area of the outer border of the mitral ring is proportional to the actual value of the MA area. Therefore we consider the comparison of our results with those reported by others in animal models reasonable.
Most studies on MA dynamics in animals have been performed 1 week after the implantation during mild sedation or total anesthesia.2,3,32 In our study the measurements have been performed during anesthesia and mechanical ventilation before chest closure. The homogeneity of preimplantation and postimplantation settings is demonstrated by the absence of a significant difference in hemodynamic parameters, and therefore the evaluation of the MA dynamics appears to be correct.
No undersizing of the MA had been planned before the study. However, all the prototypes implanted had the same size, according to the minimum value of size reported in the literature for sheep of the same weight.2 Thus a global reduction of MA might have occurred in some animals. The variation of some echocardiographic parameters registered after the implantation could have arisen from this, although it has not affected the postimplantation dynamics.
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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