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Ann Thorac Surg 2001;72:966-974
© 2001 The Society of Thoracic Surgeons

Review

Experimental and clinical assessment of mitral annular area and dynamics: what are we actually measuring?

Tomasz A. Timek, MDa, D. Craig Miller, MDa

a Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California, USA

Address reprint requests to Dr Miller, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA 94305-5247


   Abstract
Top
 Abstract
Introduction
 Animal studies
 Human studies
 Annuloplasty rings
 Conclusion
 Acknowledgments
 References
 
The mitral annulus is an essential, dynamic, and tightly coupled component of the mitral valve/left atrial/left ventricular complex that aids in effective and efficient valve closure and unimpeded left ventricular filling. Although the dynamic nature of mitral annular motion has been studied carefully for more than 30 years, accurate measurement of mitral annular area and motion continues to be a challenge for physiologists and clinicians alike. Roentgenographic ciné imaging of radiopaque markers, sonomicrometry, magnetic resonance imaging, and two-dimensional echocardiography have all been used to evaluate mitral annular area and dynamics, yet widely disparate measurements abound. Paradoxically, newer three-dimensional transesophageal echocardiographic findings may have added to this miasma. To explore the variability of these measurements, we reviewed our experimental data as well as clinical and experimental observations reported in the literature to clarify what we are actually measuring and perhaps explain the reported disagreement. The objective was to shed some light on the possible reasons for these discordant findings.


   Introduction
Top
 Abstract
 Introduction
Animal studies
 Human studies
 Annuloplasty rings
 Conclusion
 Acknowledgments
 References
 
The mitral annulus is a vital component of the mitral valve/left atrial/left ventricular complex that contributes to timely, efficient, and competent valve closure as well as unimpeded left ventricular (LV) filling during diastole. This is true even though the normal annulus anatomically is an incomplete and almost diaphanous structure. Mitral annular expansion and motion facilitates filling in diastole, while annular size reduction aids leaflet coaptation and normal closure in early systole. This sphincteric action of the annulus can be affected by hemodynamic conditions [1], lack of atrial contraction (ventricular pacing) [2], ischemia [3], atrial fibrillation [4], and end-stage heart failure [5]. The dynamics of annular motion have been an area of active investigation for decades as the mitral annular sphincteric mechanism and size may have important effects on valve performance in health and in disease states. Defining normal annular physiology and motion is also key for developing more rational approaches to the design of better annuloplasty ring prostheses, which are now almost routinely used in mitral valve repair.

Mitral annular physiology has been studied in both experimental animals and human subjects using two-dimensional (2-D) [1] and three-dimensional (3-D) [2, 3, 6] roentgenogram marker imaging, sonomicrometry [7], magnetic resonance imaging (MRI) [8], and 2-D [9, 10] and 3-D [11–14] echocardiography. The current literature consensus firmly supports dynamic motion of the annulus throughout the cardiac cycle, yet the timing and extent of annular area change has been a point of ample controversy. This debate is further compounded by discordant results in studies investigating annular motion in the setting of mitral ring annuloplasty [6, 10, 12–15]. These apparent discrepancies may be due to varying patient characteristics, species differences, and methods of measurement. We reviewed our experimental data in dogs and sheep as well as the clinical and experimental data in the literature to synthesize a more complete understanding of these inconsistencies.


   Animal studies
Top
 Abstract
 Introduction
 Animal studies
Human studies
 Annuloplasty rings
 Conclusion
 Acknowledgments
 References
 
Davis and Kinmonth [16] were the first investigators to implant radiopaque markers around the canine annulus and study its motion throughout the cardiac cycle. They reported annular area change of 30% from diastole to systole, which suggested that annular constriction occurs as the atrium starts to contract, implying presystolic annular reduction. Subsequently, Tsakiris and colleagues [1] observed a 19% to 34% reduction in annular area between late diastole and early systole in dogs with one half to two thirds of this decrease occurring during the presystolic period. More importantly, Tsakiris showed that these mitral annular dynamic changes were affected substantially by differences in inotropic state, left atrial and LV volume, LV geometry and chamber shape, LV preload, LV afterload, and cardiac rhythm. These early results were corroborated by our Stanford canine studies employing 3-D myocardial marker ciné imaging [17], although the degree of annular size reduction in our conscious, closed-chest experiment was lower than that previously reported; moreover, we agreed that maximal area occurred in mid to late diastole. Follow-up experiments in sheep revealed a 12% ± 1% annular area reduction [2] and considerable presystolic area reduction, as observed in the studies of Tsakiris and associates [1]. In fact, as seen in Figure 1, 89% ± 3% of area reduction occurred before the onset of LV systole; hence minimal mitral annular area actually occurred near the time of end-diastole.



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  		Fig 1. Mitral annular area (solid squares) in sheep (n = 7) during the cardiac cycle. Dashed vertical line represents end-diastole (ED) (t = 0), as defined by peak of the echocardiographic (ECG) R wave. Corresponding mean left ventricular pressure (LVP) tracing (solid line) is also shown over a 650 msec time window. Error bars represent one standard error of the mean. (Figure has been created using data from Glasson and associates [2].)

 
Using multiple piezoelectric miniature crystals and 3-D sonomicrometry array localization (SAL) [7], a similar magnitude of mitral annular area and decrement in area reduction during the cardiac cycle was reported by Gorman and colleagues [18] in sheep. Although annular areas were calculated at only four time points during the cardiac cycle in these experiments (slow temporal resolution), a decrease in annular size throughout diastole (from end-isovolumic relaxation to end-diastole) supports the notion of presystolic annular area reduction. In another series of sheep experiments [19], these investigators found that ventricular contractility affects mitral annular dynamics, thereby supporting the earlier findings of Tsakiris in dogs [1] and van Rijk-Zwikker in pigs [15]. Annular area in sheep measured using 3-D echocardiography [20] was consistent with earlier marker [2] and SAL [18] data.

The discrepancy in the timing of the actual nadir—or minimal—mitral area between canine [17] and ovine [2] experiments (near end-systole versus end-diastole) may possibly be related to interspecies anatomic differences. Insertion of atrial fibers in the mitral ring is more variable in dogs than in sheep, as reported by Walmsley [21]; Gorman and coworkers [7] suggested that sheep leaflets originate from atrial muscle alone, whereas the mitral leaflets in dogs are attached to the ventricular myocardium. These anatomical findings would argue for a more pronounced "atriogenic" influence in the ovine annulus, which would be responsible for more presystolic annular area reduction coincident with atrial contraction [22]. On this basis, minimal annular area would be expected to occur near end-diastole or early in systole in sheep but perhaps not in dogs.

From these experimental findings it is clear that the mitral annulus is a dynamic structure that undergoes substantial area change throughout the cardiac cycle, which is affected by inotropic state. The timing of maximum and minimum annular area and the presystolic contribution to annular area reduction vary and may be influenced by species differences. For perspective and comparison, the spectrum of measurements of annular area and extent of dynamic size change in various animal species that is available in the English literature are summarized in Figure 2.



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  		Fig 2. Diastolic mitral annular area (cm2; top panel), systolic mitral annular area (cm2; middle panel), and mitral annular area reduction (%; bottom panel) of the native annulus reported by various investigators in various animal models. Investigator names and reference numbers (in parentheses) are plotted on the x-axis of the bar graph.

 

   Human studies
Top
 Abstract
 Introduction
 Animal studies
 Human studies
Annuloplasty rings
 Conclusion
 Acknowledgments
 References
 
In contrast to the techniques used in animal experiments, mitral annular dynamics have been evaluated mainly using 2-D and 3-D echocardiography in human subjects. Using 2-D transthoracic echocardiography (TTE), Ormiston and coworkers [9] measured average maximal mitral annular area to be 7.1 ± 1.3 cm2, with a 26% ± 3% reduction in size during the cardiac cycle. Presystolic area reduction was demonstrated, thereby supporting the ovine data [2]. For comparison, mitral annular area measured visually in fresh human autopsy specimens ranges between 6.4 cm2 and 8.2 cm2 [23, 24]. Mitral annular area measurements similar to Ormiston’s data were also reported in patients using extrapolated 3-D projections derived from 2-D transesophageal echocardiography (TEE) images [12] and in normal subjects using 3-D [25]. Pai and coworkers [11], however, using 2-D echocardiography reported a 15% reduction in annular size along with a much larger measured annular area (12.2 ± 3.8 cm2 at middiastole to 10.2 ± 3.1 cm2 at end-diastole). The big discrepancy in annular size between the Pai findings and other echocardiographic data [9, 12] could possibly be related to annular dilatation, as the patients in the series were thought clinically to have cardiac disease. It is doubtful that annular dilatation alone could account for this discrepancy, however, as such gross annular area increase would be expected to be accompanied by mitral regurgitation [26].

On the other hand, similar large mitral annular sizes measured using 3-D TEE were recently reported in normal control subjects [5]. Mean mitral area was found to be 11.8 ± 2.5 cm2 in otherwise healthy persons with normal left ventricular systolic function undergoing echocardiography in search of a source of cardiac emboli. The nonplanar shape of the mitral annulus was maintained throughout the cardiac cycle, but annular "folding" during systole was also confirmed, with the anterior annulus tilting back toward the left atrium; interestingly, this folding motion appeared to be independent of LV systolic function. For perspective, mean mitral annular area was 10.2 ± 2.4 cm2 in 5 patients with hypertrophic cardiomyopathy (HOCM) and 15.2 ± 4.2 cm2 in 3 patients with dilated cardiomyopathy (p = not significant due to small numbers). Mitral annular size was largest at end-diastole and smallest at end-systole, with a 24% ± 5% reduction between maximum and minimum area in the control subjects, 32% ± 8% in those with HOCM, and 13% ± 2.3% in the patients with dilated cardiomyopathy (p < 0.001). These TEE estimates of change in mitral annular area are relatively large, assuming that true annular motion was actually being tracked; alternatively, these large annular areas and hyperdynamic variations in annular size may possibly represent motion of the basal LV myocardium. Using 2-D echocardiography, Yiu and colleagues [27] from the Mayo Clinic recently reported mitral annular area contraction to be 36% ± 6% in normal subjects and 19% ± 7% in patients with left ventricular dysfunction and functional mitral regurgitation, or FMR (approximately one half of whom had ischemic MR). These annular area reduction measurements parallel those reported by Flachskampf and colleagues [5]; importantly, however, the systolic and diastolic mitral annular areas measured by the Mayo Clinic group in normal subjects were much smaller, being only 4.4 ± 0.7 cm2 and 6.9 ± 0.8 cm2, respectively. Indeed, these 2-D echo measurements closely approximate the areas obtained in fresh specimens [23, 24]. Why such relatively large annular area reduction was calculated by these authors is unknown.

In addition to echocardiography, MRI has been used to study 3-D annular motion in humans. Komoda and coworkers [8] in Berlin studied 7 normal human volunteers and found that mitral annular area was maximal in late diastole (9.5 ± 1.4 cm2), decreased by 19% ± 8% by early systole and to 8.6 ± 1.2 cm2, and was smallest during mid to late systole (6.9 ± 1.1 cm2), for an overall size reduction of 26% ± 5% from maximum to minimum. This degree of overall relative annular size decrease was almost identical to that detected echocardiographically by Ormiston and colleagues [9] and Flachskampf and associates [5]. This same Berlin group [28] described translational motion of the posterior annulus into and out of the annular plane, which was felt to represent contraction of the bulbospiral and sinospiral muscle fibers in the basal LV myocardium. Annular systolic tilting or folding motion and the saddle or ski jump shape of the normal human mitral annulus were also observed, which supports the 3-D echocardiographic data [5]. Figure 3 illustrates the range of human mitral annular area measurements reported in the English literature; the variability of these estimates is noteworthy.



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  		Fig 3. Diastolic mitral annular area (cm2; top panel), systolic mitral annular area (cm2; middle panel), and mitral annular area reduction (%; bottom panel) of the native annulus reported by various investigators in normal human subjects. Investigator names and reference numbers (in parentheses) are plotted on the x-axis of the bar graph. (*DCM = dilated cardiomyopathy; **FMR = functional mitral regurgitation; ***HOCM = hypertrophic obstructive cardiomyopathy.)

 
The data presented above illustrate unequivocally that dynamic motion of the annulus occurs throughout the cardiac cycle in human subjects, as in animals. Annular area appears to be maximal in diastole and contracts to a minimum size in systole, with substantial presystolic area reduction observed in most human studies (and all the animal experiments). Inconsistencies in annular size measurements (see Fig 3) are most likely due to the predominant use of echocardiography, which cannot identify and track distinct anatomic landmarks in time and therefore is more subjective than the experimental imaging methods or MRI. In general, however, human annular dynamics reflect and support the findings of the experimental studies.


   Annuloplasty rings
Top
 Abstract
 Introduction
 Animal studies
 Human studies
 Annuloplasty rings
Conclusion
 Acknowledgments
 References
 
Measurement of mitral annular dynamics in the context of ring annuloplasty in animals or humans has produced the greatest inconsistency and controversy in the literature. Our investigations of complete flexible (Duran; Medtronic Heart Valve Division, Minneapolis, MN) and rigid rings (Carpentier-Edwards [C-E] Physio; Edwards Lifesciences Corp, Irvine, CA) in sheep using 3-D marker videofluoroscopy revealed that ring annuloplasty, irrespective of type of ring, completely abolished annular dynamics [6]. Subsequent experiments after implantation of a partial (posterior annulus only), flexible annuloplasty ring (Tailor ring; St Jude Medical, St Paul, MN), which is similar to the Cosgrove-Edwards annuloplasty band (Edwards Lifesciences Corp, Irvine, CA), revealed comparable results to those observed with the Duran and Carpentier-Edwards Physio rings, ie, loss of dynamic annular motion albeit set at a slightly larger mitral annular area [29]. The mitral annular area data from these animal experiments are summarized graphically in Figure 4. Based on these conscious, in vivo, closed-chest, ovine data, it appears that annular dynamics are almost totally eliminated when annular size is decreased sufficiently, no matter whether partial, complete, flexible, or semirigid annuloplasty rings are utilized.



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  		Fig 4. Mitral annular area during a 650 msec window of the cardiac cycle in the native annulus (solid squares), Duran annuloplasty ring (solid circles), Carpentier-Edwards Physio annuloplasty ring (solid triangles), and St Jude Medical Tailor annuloplasty ring (solid diamonds). Error bars represent one standard error of the mean. (Figure has been created using data from Glasson and associates [6] and Dagum and associates [29].) (SJM = St. Jude Medical.)

 
Different results, however, have been obtained in vivo by Van Rijk-Zwikker and coworkers [15] in pigs fitted with either a rigid Carpentier-Edwards Classic or a flexible Duran annuloplasty ring. Duran ring orifice area decreased by 14% during the cardiac cycle while only a 4% area decrease was observed in the C-E ring animals. Annular area reduction with a Duran ring increased approximately twofold during inotropic stimulation with isoproterenol. In an ex vivo beating heart preparation, the Duran ring did not appear to interfere with annular mobility, whereas the C-E ring showed little deformation and abolished annular rotation. The disparity in change in orifice area of the flexible annuloplasty rings between this study and our sheep experiments may be related to the different imaging methods, differences in analytical computations and reference systems, the major differences between in vivo and ex vivo preparations, and interspecies differences.

Echocardiographic evaluation of patients with annuloplasty rings has also generated a broad spectrum of findings. Okada and colleagues [30] reported that overall mitral annular area fell during the cardiac cycle in patients with a Duran flexible ring by 26% ± 4% but no change in area was seen in the patients with a Carpentier-Edwards ring. In the Duran group, as in the normal native human [9] and ovine [2] annulus, maximal annular size corresponded to the time of the ECG P wave (or atrial systole) during diastole, followed subsequently by both presystolic and systolic area reduction. Comparison of the two types of rings indicated that this pronounced difference in annular motion made a flexible Duran ring behave like a smaller C-E ring in systole (minimum area) but like a larger C-E ring in diastole when LV filling takes place. Despite the technical limitations inherent in this echocardiographic study, the results are provocative and favor a flexible annuloplasty ring.

Yamaura and associates [12] from this same Kobe group later investigated mitral repair in patients with Duran and Carpentier-Edwards Classic rings and in control human subjects. Mitral annular area was 6.5 ± 0.1 cm2 and 5.7 ± 0.9 cm2 at end-diastole and end-systole, respectively, in the normal controls (p = 0.0001), whereas it was 4.0 ± 0.1 cm2 and 3.6 ± 0.1 cm2 in the 29 mm Duran ring group (p = 0.0001). For patients with 30 mm Carpentier-Edwards rings, these areas were 3.3 ± 0.1 cm2 and 3.3 ± 0.1 cm2 (p = NS), which is smaller than the manufacturer’s geometric specifications (3.95 cm2) for this size C-E Classic ring. Consistent with their earlier findings [30], mitral annular motion in the Duran ring group was dynamic (change in area of 10% ± 2%) and similar to that seen in the control subjects (area change = 12% ± 2%). The annulus had a characteristic saddle shape at both times and descended toward the LV apex during systole. The mitral annulus in patients with a C-E ring was adynamic and had a fixed planar configuration but still moved apically during systole.

In an updated analysis using computerized 3-D image reconstruction [31], mitral annular motion was again shown to be dynamic in patients with a Duran ring, and the substantial presystolic narrowing of the human mitral annulus was confirmed again. Overall area change was 25% ± 2% in those with a Duran ring, similar to the 26% ± 4% estimate reported by Okada and colleagues [30] earlier based on 2-D TTE images. Both of these figures, however, differ markedly from the 10% ± 2% area change using TEE reported previously by this same group [12], as discussed above. Further analysis of the echocardiographic data of the Yamaura patient cohort was once again published in 1998 [32]. Mitral annular area fractional change was reported as 15% ± 2% in patients with a Duran ring (compared with 25% ± 2% reported previously in the same patient population) but this figure in their 1998 paper was the percent area change from end-diastole to end-systole rather than from the time of maximum to minimum annular area during the cardiac cycle. The raw annular areas were significantly larger for both the patients with the Duran or C-E rings than previously reported in their smaller patient cohort in 1995 (end-diastolic size of 6.6 ± 0.1 cm2 versus 4.0 ± 0.1 cm2 and 5.5 ± 0.2 cm2 versus 3.3 ± 0.1 cm2 for Duran and C-E, respectively) [12]. The most obvious explanation for this glaring inconsistency is analytical error introduced by the two different methods of computing the actual 3-D dimensions of the mitral annulus, ie, manual projections versus computerized calculations based on multiple 2-D volume data sets. Conversely, there was no demonstrable area change in patients with a C-E ring, and the annular shape was found again to be fixed in a planar configuration.

In an elegant, scientifically rigorous, automated 3-D TEE (Echoscan; TomTec GmbH, Munich, Germany) intraoperative, open chest assessment of both the partial Cosgrove-Edwards flexible and the rigid, complete Carpentier-Edwards Classic annuloplasty ring, Dall’Agata and associates [14] reported that the Cosgrove ring internal area changed by approximately 13% from end-diastole to end-systole, with a mean end-diastolic area of 4.8 ± 1.6 cm2 and mean end-systolic internal area of 4.2 ± 1.5 cm2 (for ring sizes 32 to 38 mm). The anteroposterior (A-P) mitral diameter fell significantly (p < 0.01) from 2.1 ± 0.2 cm at end-diastole to 1.9 ± 0.3 cm at end-systole, whereas the transverse (probably equivalent to the commissure-commissure dimension) mitral diameter did not change (2.5 ± 0.6 cm at ED and 2.5 ± 0.6 cm at ES) nor did the extrapolated distance between the tips of the Cosgrove band (2.3 ± 0.5 cm versus 2.1 ± 0.4 cm, respectively). As expected, the Carpentier-Edwards Classic ring completely abolished normal annular dynamics. Correlation between Cosgrove-Edwards ring true length (as provided by the manufacturer) and measured ring length was good (r = 0.95) in 16 of the 17 patient studies suitable for analysis, but the echocardiography underestimated this measurement by 11.5 mm across all ring sizes. This error was explained as possibly being due to the fact that the echocardiography measurements were based on the echo interface at the inner border of the ring. Therefore, the authors believed that these 3-D TEE measurements underestimated true dimensions and lengths by about 10% and mitral area by approximately 20%. If one multiplies the observed area by this correction factor (1.2x), the Cosgrove ring true in vivo areas would be approximately 5.8 cm2 and 5.0 cm2 at ED and ES, respectively, and the Carpentier-Edwards internal ring areas 4.4 cm2 and 4.6 cm2.

Markedly discordant measurements of partial annuloplasty ring area, however, were obtained by Cosgrove and associates [10] using TEE in 5 selected patients immediately postoperatively and at an average of 9 months after mitral repair with the Cosgrove-Edwards band. As observed with a complete flexible ring [12], these echo images confirmed that the saddle shape nature of the mitral annulus was preserved after implantation of a Cosgrove-Edwards ring. The early postoperative percent annular area reduction was 7%, increasing to a 16% area reduction 9 months later. It is noteworthy to recognize that this increase in fractional mitral area change was due in part to a 10% increase over time in diastolic area, something that is highly unlikely to occur after successful mitral ring annuloplasty, and which probably represents some type of measurement error. Systolic area was the same at both times. After 5 years, fractional mitral annular area reduction of the Cosgrove ring was found to be 28% ± 11%, closely reflecting the 25% ± 10% reduction in annular size in normal subjects [13, 33]. More troublesome is the fact that the maximum annular area of the Cosgrove ring measured in these studies was more than twice as large as that reported by Dall’Agata and associates [14] (vide supra). Assuming the average ring size was 30 mm, when the Cosgrove-Edwards band internal diameter is normalized to the geometry of a Carpentier-Edwards Physio ring, it would be expected to have a geometric orifice area of between 4.4 cm2 and 5.0 cm2. But the areas reported by Cosgrove and associates [10] are approximately twofold larger. This raises the question of exactly what cardiac structure was actually being imaged echocardiographically. Potentially, basal LV wall motion rather than annular motion or perhaps the external border of the ring were imaged, both of which might explain greater dynamic motion and the large annular areas reported. Since both the Dall’Agata group and the Cleveland Clinic group used transesophageal 3-D echocardiographic approaches, the incongruity in their data assessing the same type of ring underlines the current difficulty inherent in standardizing and calibrating 3-D TEE data, especially the derived 2-D spatial measurements.

Roentgenogram fluoroscopic determination of annular motion in human subjects in the setting of mitral annuloplasty has been used by Scrofani and colleagues [34] at 10 days, 1 year, and 5 years after mitral repair. The computed "annular areas" were actually "hemiareas" as a pericardial annuloplasty strip was placed only on the posterior annulus from commissure to commissure and thus did not include the area of the anterior annulus. Annular hemiarea reduction during systole was determined to be 9% ± 6%, 8% ± 6%, and 15% ± 10% at 10 days, 1 year, and 5 years after the operation, respectively, mirroring the apparent increasing flexibility of a Cosgrove-Edwards ring over time as reported above [10, 33]. These results must be interpreted cautiously, however, as the anterior annulus, which normally is less dynamic than the posterior annulus [3, 17, 28], was not included in these calculations of area change. Therefore, the percent hemiarea reduction probably does not reflect total annular area reduction accurately since these calculations were based only on the motion of the most dynamic portion of the mitral annulus. For easier interpretation and perspective, data from all the above studies investigating mitral orifice area and the motions of flexible annuloplasty rings in human are depicted graphically in Figure 5.



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  		Fig 5. Diastolic mitral annular area (cm2; top panel), systolic mitral annular area (cm2; middle panel), and mitral annular area reduction (%; bottom panel) reported by various investigators in animals and human subjects with flexible ring annuloplasty. Investigator names and reference numbers (in parentheses) are plotted on the x-axis of the bar graph. (SJM = St. Jude Medical.)

 
It appears that although annular dynamics are abolished by ring annuloplasty, irrespective of type, in animal myocardial marker cinefluoroscopic studies, consistent dynamic behavior of flexible rings has been demonstrated in human subjects using 2-D and 3-D echocardiography. As in measurements of the native annulus, there is wide disparity in the reported mitral annular areas and fractional size reduction in patients fitted with flexible annuloplasty rings. Again, this spectrum of measurements may represent consequences of the limitations of the echocardiographic methods used coupled with differences in patient characteristics, time of follow-up, and methods of image reconstruction.


   Conclusion
Top
 Abstract
 Introduction
 Animal studies
 Human studies
 Annuloplasty rings
 Conclusion
Acknowledgments
 References
 
Accurate measurement of mitral annular dimensions, area, geometry, and dynamic motion seems like a simple job but actually represents a formidable challenge, both clinically and in experimental settings. As the mitral annulus in most mammalian species is not a well-defined anatomic structure, it is exceedingly difficult to image and track accurately. This review underscores the difficulties inherent in this task. Nevertheless at this time the dynamic motion of the mitral annulus during the cardiac cycle is well established, both experimentally and clinically, with presystolic annular reduction playing a considerable role in annular contraction. On the other hand, mitral annular area and the magnitude of annular reduction measurements vary widely, particularly in human studies. The origin of these discordant results probably is manifold in nature. Different imaging methods may play an important role here. Experimental methods such as radiopaque marker imaging and sonomicrometry offer the distinct advantage of "tagging" specific sites on the mitral annulus that can then be identified and tracked precisely throughout the cardiac cycle, yielding the most accurate and reliable measurements. Indeed, experimental studies utilizing these imaging techniques show only small variability in the measured mitral annular areas when adjusted for differences in animal size (Fig 2, top panel). Measurement of mitral annular size reduction has created an even wider spectrum of data (Fig 2, bottom panel), but this can in part be explained on the basis of whether annular reduction is calculated from end-diastole to end-systole versus from maximum to minimum, and perhaps also on the basis of interspecies anatomic differences.

Clinical measurements of mitral annular dynamics, mostly derived from either 2-D or 3-D echocardiography, are fraught with even greater inconsistencies (Fig 3). For instance, both Gillinov and associates [13] and Dall’Agata and associates [14] used 3-D echocardiography to assess orifice area of the Cosgrove-Edwards ring but the reported annular area size obtained by the former group was about twice as large as the expected ring areas should be according to the manufacturer’s physical specifications. Methods of image analysis can also introduce error into area calculations as evidenced by Yamaura’s measurement of Duran ring area published in 1995 [12] that was 40% smaller than that reported in 1998 [32] even though some of the same patients were used in both studies. Other factors may also impact substantially on the measurement of mitral dynamics. The anatomical definition of the annulus in echocardiographic images is only defined as the leaflet "hinge point," which may differ from the true annulus that is visually identifiable and where myocardial markers or piezoelectric miniature crystals are implanted. In addition, planar geometry of the annulus is assumed in some investigations, but the annulus is actually "saddle" or "ski jump" shaped [5, 27, 35]. Individual patient variability, the presence or absence of cardiac pathology, and—importantly—differences in LV loading conditions and inotropic state could also be responsible for some of the disagreement. Besides, "control" subjects are not necessarily "normal" individuals. In an experimental setting, this variability is eliminated to a large degree and normal hearts can be analyzed but species differences must still be considered when comparing results across different experimental models.

Definition of cardiac cycle timing markers can also contribute to differences in measured end-diastolic and end-systolic annular areas as these definitions are either not standardized (Table 1) nor explicitly mentioned in most studies. Differences in image acquisition rate can limit the number of time points at which annular area is determined; therefore annular area reduction, if calculated from maximum to minimum area, may be affected. Experimental studies have shown that factors affecting cardiac function (LV preload, LV afterload, heart rate, rhythm, and contractile state) also clearly influence annular dynamics [1, 15, 19, 22] and therefore inconsistencies may not be so surprising when different contractile state and hemodynamic conditions are taken in account. For example, Cosgrove ring annular area reduction was reported to be 7% and 16% immediately postoperatively and at 9 months, respectively [10], but this difference could reflect myocardial dysfunction in the early period after cardiopulmonary bypass rather than measurement error. Annular dynamics should thus be interpreted in the overall context of the investigation being conducted to avoid misinterpretation.


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  		Table 1. Definitions of End-Diastole and End-Systole Employed in Various Experimental and Human Studies

 
As evidenced by the studies cited above, accurate and reliable imaging of the mitral annulus is a difficult undertaking yet its importance is paramount if therapeutic and surgical decisions are to be based on these measurements. If better, more physiologic annuloplasty rings and techniques are to be developed in a rational manner, not only must normal annular dynamics first be defined but also the geometric effects and motion of these devices must be evaluated in a reliable manner in vivo.

Proper imaging of the mitral annulus in pathologic states such as patients with dilated cardiomyopathy [5, 23, 36] also adds to our understanding of cardiac pathophysiology and the pathogenesis of mitral regurgitation. In addition, echocardiographically determined mitral annular velocity has recently been used as an indicator of systolic [37] and diastolic [38] LV function, and advances in echocardiographic techniques such as Doppler proximal flow convergence [27, 39] are bound to contribute further to our knowledge of mitral annular physiology. It is clear that precise measurement of annular dynamics would yield more detailed knowledge of annular physiology, which may translate directly to medical and surgical management of patients. This review underscores the need for standardization of methods, control of hemodynamic variables and loading conditions, and adjustment for individual subject characteristics to allow for valid comparisons. Future advancements in 3-D echocardiography may provide better measurements than what is currently available but validation studies are needed. An ideal validation experiment would consist of comparing 3-D TEE or epicardial 3-D echocardiographic data with measurements determined using 3-D marker cinefluoroscopy in the same animals. Additionally, new techniques such as MRI RF tagging or MR phase contrast pulse sequence imaging, which allows for tracking of discrete cardiac sites throughout the cardiac cycle, may offer other avenues to investigate the dynamics of the human mitral annulus in a noninvasive yet accurate manner.


   Acknowledgments
Top
 Abstract
 Introduction
 Animal studies
 Human studies
 Annuloplasty rings
 Conclusion
 Acknowledgments
References
 
Supported by Grant HL-29589 from the National Heart, Lung and Blood Institute. Doctor Timek is a Carl and Leah McConnell Cardiovascular Surgical Research Fellow and was supported by NHLBI Individual Research Service Award HL10452-01 and by a Thoracic Surgery Foundation Research Fellowship Award.


   References
Top
 Abstract
 Introduction
 Animal studies
 Human studies
 Annuloplasty rings
 Conclusion
 Acknowledgments
 References
 

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