The cystic fibrosis transmembrane conductance regulator (CFTR): three-dimensional structure and localization of a channel gate.

Cystic fibrosis affects about 1 in 2500 live births and involves loss of transmembrane chloride flux due to a lack of a membrane protein channel termed the cystic fibrosis transmembrane conductance regulator (CFTR). We have studied CFTR structure by electron crystallography. The data were compared with existing structures of other ATP-binding cassette transporters. The protein was crystallized in the outward facing state and resembled the well characterized Sav1866 transporter. We identified regions in the CFTR map, not accounted for by Sav1866, which were potential locations for the regulatory region as well as the channel gate. In this analysis, we were aided by the fact that the unit cell was composed of two molecules not related by crystallographic symmetry. We also identified regions in the fitted Sav1866 model that were missing from the map, hence regions that were either disordered in CFTR or differently organized compared with Sav1866. Apart from the N and C termini, this indicated that in CFTR, the cytoplasmic end of transmembrane helix 5/11 and its associated loop could be partly disordered (or alternatively located).

Targeted regional injection of biocomposite microspheres alters post-myocardial infarction remodeling and matrix proteolytic pathways.

BACKGROUND: Although localized delivery of biocomposite materials, such as calcium hydroxyapatite (CHAM), have been demonstrated to potentially attenuate adverse left ventricular (LV) remodeling after myocardial infarction (MI), the underlying biological mechanisms for this effect remain unclear. This study tested the hypothesis that targeted CHAM injections would alter proteolytic pathways (matrix metalloproteinases [MMPs] and tissue inhibitors of MMPs [TIMPs]) and would be associated with parameters of post-MI LV remodeling. METHODS AND RESULTS: MI was induced in adult sheep followed by 20 targeted injections of a total volume of 1.3 mL (n=6) or 2.6 mL of CHAM (n=5) or saline (n=13) and LV end-diastolic volume (EDV) and MMP/TIMP profiles in the MI region were measured at 8 weeks after MI. LV EDV decreased with 2.6 mL CHAM versus MI only (105.4 ± 7.5 versus 80.6 ± 4.2 respectively, P<0.05) but not with 1.3 mL CHAM (94.5 ± 5.0, P=0.32). However, MI thickness increased by 2-fold in both CHAM groups compared with MI only (P<0.05). MMP-13 increased 40-fold in the MI only group (P<0.05) but fell by >6-fold in both CHAM groups (P<0.05). MMP-7 increased approximately 1.5-fold in the MI only group (P<0.05) but decreased to referent control values in both CHAM groups in the MI region (P<0.05). Collagen content was reduced by approximately 30% in the CHAM groups compared with MI only (P<0.05). CONCLUSIONS: Differential effects on LV remodeling and MMP/TIMP profiles occurred with CHAM. Thus, targeted injection of a biocomposite material can favorably affect the post-MI remodeling process and therefore holds promise as a treatment strategy in and of itself, or as a matrix with potentially synergistic effects with localized pharmacological or cellular therapies.

Preclosure technique versus arterial cutdown after percutaneous cannulation for venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Arteriotomy repair through the preclosure technique during elective arterial access procedures is well documented. Outcomes associated with application of this technique to the removal of arterial access cannulas in patients undergoing urgent venoarterial extracorporeal membrane oxygenation (VA-ECMO) have not previously been reported. METHODS: We reviewed the records of consecutive patients who required VA-ECMO for cardiogenic shock. Patients were compared by use of the preclosure device (Perclose ProGlide Suture-Mediated Closure System; Abbott Vascular, Abbott Park, Ill) at time of VA-ECMO cannulation. The rate of limb complications (composite of limb ischemia, infection, and site necrosis) and secondary end points of bleeding events, pseudoaneurysm, distal part embolization, and intensive care unit length of stay after decannulation were compared between the groups. RESULTS: Ninety-nine consecutive patients managed with VA-ECMO were identified and the preclosure device was utilized in 51 of these patients. Preclosure device failure occurred in 5 instances (9.8%) and was successfully managed with surgical repair in 4 cases and endovascular intervention in another. Use of the preclosure device was associated with both fewer limb complications (odds ratio, 0.19; 95% confidence interval, 0.03-0.78) and bleeding events (odds ratio, 0.21; 95% confidence interval, 0.04-0.89). Pseudoaneurysm (n = 0) and distal part embolization (n = 1) were infrequently encountered in the cohort and no difference in intensive care unit length of stay after decannulation was noted between the groups. CONCLUSIONS: In this cohort, use of the preclosure technique in weaning from VA-ECMO was technically feasible, safe, and associated with an approximate 80% lower likelihood of limb complications and bleeding events compared with surgical removal.

The emerging role of three-dimensional echocardiography in mitral valve repair.

Although three-dimensional (3D) echocardiography is still in its evolution, cutting edge advances that allow quantifiable images of cardiac structures to be created in real-time will begin to increase its use drastically. One of the most promising uses of the technology is in the planning, optimization, and postoperative surveillance of mitral valve repair techniques and devices. This article reviews the development of 3D echocardiography and presents illustrations of how it may be applied to improving mitral valve repair techniques. It is conceivable in the near future that mitral repair procedures will be designed and customized for each patient preoperatively using data obtained from 3D echo images and computerized virtual surgery techniques. Such tools will allow the surgeon to design operations that thoroughly analyze valve geometry and stress distribution before ever entering the operating room.

Geometric orientation of the aortic neoroot in patients with raphed bicuspid aortic valve disease undergoing primary cusp repair and a root reimplantation procedure.

OBJECTIVES: Primary cusp repair + aortic root reimplantation in bicuspid aortic valve (BAV) disease presenting with root aneurysm with aortic insufficiency (AI) is an effective surgical treatment. We assessed whether the geometric orientation of the repaired BAV into its reimplanted neoroot affects outcomes-180°/180° orientation was compared with the 150°/210° orientation. METHODS: From 2005 to 2012, 66 BAV repairs were performed. This is a retrospective review of all types of Ib/II BAV AI patients undergoing root reimplantation (n = 26) at two different geometric orientations: 180°/180° (n = 11) vs 150°/210° (n = 15). In the 180°/180° group, reimplantation into the neoroot was such that both conjoint and non-conjoint cusps occupied 180° of the annular circumference. In the 150°/210° group, the repaired valve was configured to the more typical native orientation of a type I BAV: the non-conjoint cusp occupied 150°, and the conjoint cusp occupied 210° of the annular circumference. RESULTS: Preoperative characteristics were similar in both groups. In-hospital mortality, stroke, reoperation, renal failure and pacemaker rates were zero in both groups. No patient left the operating room with >1+ AI and one had a peak gradient >20 mmHg. Transvalvular gradients were higher in the 180°/180° group, but not significant (P > 0.05). M.ean follow-ups for the 180°/180° and 150°/210° group were 48 and 33 months, respectively. Actuarial freedom from AI >2+ at 5 years was 100% in both groups. Freedom from AI >1+ at 5 years was 90 ± 10% in the 150°/210° group and 86 ± 13% in the 180°/180° group (P = 0.71). Freedom from peak gradient >20 mmHg was 80% (n = 8) in the 180°/180° group and 100% in the 150°/210° group at 1-year follow-up. Transvalvular gradients were higher in the 180°/180° group (16 ± 8 vs 10 ± 4 mmHg, P = 0.02; 9 ± 3 vs 5 ± 3 mmHg, P = 0.01). Five-year actuarial survival and freedom from aortic reoperation have remained at 100% in the entire cohort. CONCLUSION: Cusp repair + root reimplantation for BAV type Ib/II AI can be safely performed at either geometric orientation. Conceptually, 150°/210° orientation respects the natural type I BAV anatomy with regard to cusp surface area and leaflet insertion perimeter. The 180°/180° group may have higher transvalvular gradients and smaller coaptation zones than the 150°/210° group. Further follow-up may reveal the superiority of one geometric orientation over the other.

Rapid aortic arch debranching using the Gore hybrid vascular graft.

A significant fraction of patients who survive repair of a DeBakey type I aortic dissection will require a secondary intervention to address ongoing aortic remodeling. Strategic treatment of this population mandates that the technical feasibility of secondary operations be considered at the index procedure. We evaluated a hybrid-based modification of a widely accepted surgical approach that obviates the need for advanced perfusion management techniques and facilitates secondary endografting. Hybrid technology allows for the physiologic equivalent of a total arch replacement without the operative complexity associated with a traditional approach while allowing for strategic planning if a secondary operation is warranted.

Modification of infarct material properties limits adverse ventricular remodeling.

BACKGROUND: Infarct expansion after myocardial infarction (MI) is an important phenomenon that initiates and sustains adverse left ventricular (LV) remodeling. We tested the hypothesis that infarct modification by material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling. METHODS: Anteroapical infarction was induced in 21 sheep. Sheep were randomized to injection of saline (2.6 mL) or tissue filler material (2.6 mL) into the infarct within 3 hours of MI. Animals were monitored for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Morphometric measurements were performed of excised hearts to quantify infarct thickness. Regional blood flow was assessed with colored microspheres. Infarct material properties were measured using biaxial tensile testing. RESULTS: Compared with controls at 8 weeks, treatment animals had less infarct expansion, reduced LV dilatation (LV systolic volumes: 60.8±4.3 vs 80.3±6.9 mL; p<0.05), greater ejection fraction (0.310±0.026 vs 0.276±0.013; p<0.05), thicker infarcts (5.5±0.2 vs 2.2±0.3 mm; p<0.05), and greater infarct blood flow (0.22±0.04 vs 0.11±0.03 mL/min/g; p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts. CONCLUSIONS: Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection, resulting in the amelioration of infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm.

Ischemic mitral regurgitation: a quantitative three-dimensional echocardiographic analysis.

BACKGROUND: A comprehensive three-dimensional echocardiography based approach is applied to preoperative mitral valve (MV) analysis in patients with ischemic mitral regurgitation (IMR). This method is used to characterize the heterogeneous nature of the pathologic anatomy associated with IMR. METHODS: Intraoperative real-time three-dimensional transesophageal echocardiograms of 18 patients with IMR (10 with anterior, 8 with inferior infarcts) and 17 patients with normal MV were analyzed. A customized image analysis protocol was used to assess global and regional determinants of annular size and shape, leaflet tethering and curvature, relative papillary muscle anatomy, and anatomic regurgitant orifice area. RESULTS: Both mitral annular area and MV tenting volume were increased in the IMR group as compared with patients with normal MV (mitral annular area=1,065±59 mm2 versus 779±44 mm2, p=0.001; and MV tenting volume=3,413±403 mm3 versus 1,696±200 mm3, p=0.001, respectively). Within the IMR group, patients with anterior infarct had larger annuli (1,168±99 mm2) and greater tenting volumes (4,260±779 mm3 versus 2,735±245 mm3, p=0.06) than the inferior infarct subgroup. Papillary-annular distance was increased in the IMR group relative to normal; these distances were largest in patients with anterior infarcts. Whereas patients with normal MV had very consistent anatomic determinants, annular shape and leaflet tenting distribution in the IMR group were exceedingly variable. Mean anatomic regurgitant orifice area was 25.8±3.0 mm2, and the number of discrete regurgitant orifices varied from 1 to 4. CONCLUSIONS: Application of custom analysis techniques to three-dimensional echocardiography images allows a quantitative and systematic analysis of the MV, and demonstrates the extreme variability in pathologic anatomy that occurs in patients with severe IMR.

Successful support and separation from veno-venous extracorporeal membrane oxygenation support in a three-month-old patient following bidirectional Glenn procedure.

While extracorporeal membrane oxygenation (ECMO) is a useful mechanism of providing support in pediatric patients with cardiopulmonary dysfunction following surgery for congenital heart disease, outcomes have varied dramatically between distinct cardiac diagnoses. Reported outcomes of ECMO support following a bidirectional Glenn procedure in patients with single ventricle physiology are uniformly poor due in part to physiological and anatomical challenges inherent to cannulation in this population. We describe a unique veno-venous cannulation that can be applied to this patient population and has allowed for successful decannulation in our practice.

Dermal filler injection: a novel approach for limiting infarct expansion.

BACKGROUND: Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. METHODS: Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite-based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. RESULTS: All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 +/- 3.6 mL versus 44.5 +/- 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 +/- 0.016 versus 0.373 +/- 0.017; p < 0.05) at 4 weeks after infarction. CONCLUSIONS: Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling.

Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage.

BACKGROUND: This experiment assessed the dose-dependent effect of a unique allogeneic STRO-3-positive mesenchymal precursor cell (MPC) on postinfarction left ventricular (LV) remodeling. The MPCs were administered in a manner that would simulate an off-the-self, early postinfarction, preventative approach to cardiac cell therapy in a sheep transmural myocardial infarct (MI) model. METHODS: Allogeneic MPCs were isolated from male crossbred sheep. Forty-six female sheep underwent coronary ligation to produce a transmural LV anteroapical infarction. One hour after infarction, the borderzone myocardium received an injection of 25, 75, 225, or 450 x 10(6) MPCs, or cell medium. Echocardiography was performed at 4 and 8 weeks after MI to quantify LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF), and infarct expansion. CD31 and smooth muscle actin (SMA) immunohistochemical staining was performed on infarct and borderzone specimens to quantify vascular density. RESULTS: Compared with controls, low-dose (25 and 75 x 10(6) cells) MPC treatment significantly attenuated infarct expansion and increases in LVEDV and LVESV. EF was improved at all cell doses. CD31 and SMA immunohistochemical staining demonstrated increased vascular density in the borderzone only at the lower cell doses. There was no evidence of myocardial regeneration within the infarct. CONCLUSION: Allogeneic STRO-3 positive MPCs attenuate the remodeling response to transmural MI in a clinically relevant large-animal model. This effect is associated with vasculogenesis and arteriogenesis within the borderzone and infarct and is most pronounced at lower cell doses.

A methodology for assessing human mitral leaflet curvature using real-time 3-dimensional echocardiography.

OBJECTIVES: Using 3-dimensional echocardiography in conjunction with novel geometric modeling and rendering techniques, we have developed a high-resolution, quantitative, 3-dimensional methodology for imaging the human mitral valve. Leaflet and annular geometry are important determinants of mitral valve stress. Repair techniques that optimize valvular geometry will reduce stress and potentially increase repair durability. The development of such procedures will require image-processing methodologies that provide a quantitative description of 3-dimensional valvular geometry. METHODS: Ten healthy adult subjects underwent mitral valve imaging with real-time 3-dimensional echocardiography. By using specially designed image analysis software, multiple valvular geometric parameters, including 2- and 3-dimensional leaflet curvature, leaflet surface area, annular height, intercommissural width, septolateral annular diameter, and annular area were determined for each subject. Image-rendering techniques that allow for the clear and concise presentation of this detailed information are also presented. RESULTS: Although 3-dimensional annular and leaflet geometry were found to be highly conserved between healthy human subjects in general, substantial intrasubject and intersubject regional geometric heterogeneity was observed in the midposterior leaflet, the region most commonly involved in leaflet flail in subjects with myxomatous disease. CONCLUSIONS: The image-processing and graphic-rendering techniques that we have developed can be used to provide a complete description of 3-dimensional mitral valve geometry in human subjects. Widespread application of these techniques to healthy subjects and patients with mitral valve disease will provide insight into the geometric basis of both valvular pathology and repair durability.

The influence of annuloplasty ring geometry on mitral leaflet curvature.

BACKGROUND: The effect of mitral leaflet curvature on stress reduction is an important mechanism in optimizing valve function. We hypothesize that annuloplasty ring shape could directly influence leaflet curvature and, potentially, repair durability. We describe an echocardiographically based methodology for quantifying mitral valve geometry and its application to the characterization of ovine mitral valve geometry before and after implantation of an annuloplasty ring. METHODS: Multiple mitral annular and leaflet geometric variables were calculated for 8 naïve adult male sheep using real-time three-dimensional echocardiographic images. These indexes were recalculated after annuloplasty using a 30-mm Carpentier-Edward Physio ring (n = 4; Edwards Lifesciences, Irvine, CA) or a 30-mm saddle ring (n = 4). RESULTS: After implantation of the Physio ring, the annular height to commissural width ratio (AHCWR) decreased from 19.4% +/- 2.3% to 11.1% +/- 2.5% (p = 0.06). After implantation of the saddle ring, AHCWR increased from 19.6% +/- 1.3% to 24.3% +/- 1.3% (p < 0.05). Statistically significant increases in three-dimensional Gaussian curvature occurred after implantation within six defined leaflet regions (A1 to A3, P1 to P3) of the saddle ring but only within the P1 and P3 leaflet regions with the Physio ring. CONCLUSIONS: Annuloplasty ring shape affects leaflet curvature. Implantation of a saddle ring reflecting normal human annular geometry augmented ovine annular nonplanarity and increased three-dimensional leaflet curvature across the entire mitral valve surface. The Physio ring decreased annular nonplanarity and increased leaflet curvature only across limited regions of the posterior leaflet. These findings confirm the hypothesis that ring design influences leaflet curvature.

Ventricular restraint prevents infarct expansion and improves borderzone function after myocardial infarction: a study using magnetic resonance imaging, three-dimensional surface modeling, and myocardial tagging.

BACKGROUND: Infarct expansion is associated with impaired borderzone function, adverse remodeling, and poor long-term prognosis. We hypothesized that left ventricular restraint early after myocardial infarction limits infarct expansion, preserves borderzone function, and reduces remodeling. METHODS: We used an ovine model as well as high spatial and temporal resolution cardiac magnetic resonance imaging to quantify total and infarcted left ventricular epicardial surface area at baseline and 1 week and 12 weeks after anterior wall infarction in 10 animals. Five animals were randomly assigned to treatment with left ventricular restraint (Acorn cardiac support device) 1 week after infarction. Five animals were untreated controls. Total left ventricular surface area was measured by importing the end-diastolic magnetic resonance imaging-derived epicardial contours into custom software, which creates a three-dimensional surface from the two-dimensional magnetic resonance imaging contours. Infarct area was calculated from magnetic resonance imaging-detectable titanium markers placed at the infarct border. Borderzone radial and circumferential strains during systole were also assessed using myocardial tagging techniques as a measure of contractile function. RESULTS: The infarct area 1 week after infarction was 1,177 +/- 386 mm(2) in the control group and 1,124 +/- 427 mm(2) in the cardiac support device group. After 12 weeks, infarct area was 3,666 +/- 1,013 mm(2) in the control group and 1,227 +/- 301 mm(2) in the cardiac support device group. Borderzone systolic radial strain decreased from 12.6% +/- 0.77% to 3.6% +/- 0.3% after infarction in the control group and 13.7% +/- 0.87% to 4.7% +/- 0.3% in the cardiac support device group. At 12 weeks after infarction, radial strain was 3.4% +/- 0.5% in the control group and 6.7% +/- 0.4% in the cardiac support device group. CONCLUSIONS: Early postinfarction left ventricular restraint limits infarct expansion and improves borderzone contractile function.

Quantitative description of mitral valve geometry using real-time three-dimensional echocardiography.

OBJECTIVES: : Leaflet and annular geometry are important determinants of mitral valve (MV) stress. Repair techniques which optimize valvular geometry will reduce stress and potentially increase repair durability. The development of such procedures will require image processing methodologies that provide a quantitative description of three-dimensional valvular geometry. Using three-dimensional echocardiography in conjunction with novel geometric modeling and rendering techniques, we have developed a high-resolution, quantitative, three-dimensional methodology for imaging the human MV. METHODS: : Five normal adults underwent MV imaging using real-time three-dimensional echocardiography. Using specially designed image analysis software, multiple valvular geometric parameters, including the magnitude and orientation of leaflet curvature, leaflet surface area, annular height, intercommissural width, septolateral annular diameter, and annular area were determined for each subject. Image rendering techniques that allow for the clear and concise presentation of this detailed information are also presented. RESULTS: : Although three-dimensional annular and leaflet geometry were found to be highly conserved among normal human subjects, substantial regional variation in leaflet geometry was observed. Interestingly, leaflet geometric heterogeneity was most pronounced in the midposterior leaflet, the region most commonly involved in leaflet flail in subjects with myxomatous disease. CONCLUSIONS: : The image processing and graphical rendering techniques that we have developed can be used to provide a complete description of three-dimensional MV geometry in human subjects. Widespread application of these techniques to normal subjects and patients with MV disease will provide insight into the geometric basis of both valvular pathology and repair durability.

Regional and global patterns of annular remodeling in ischemic mitral regurgitation.

BACKGROUND: The mammalian mitral annulus is saddle shaped. Experimental studies have shown that loss of saddle shape occurs in ischemic mitral regurgitation. However, neither the temporal pattern of global annular remodeling nor the geometric pattern of regional annular remodeling has been described. We sought to characterize these changes using real-time three-dimensional echocardiography in an ovine model. METHODS: Ten sheep underwent real-time three-dimensional echocardiography at baseline and 1 hour and 8 weeks after posterobasal myocardial infarction. Multiple mitral annular geometric indexes were measured at each time point to assess regional and global annular remodeling. RESULTS: One hour after infarction, global annular height decreased from 5.8 +/- 0.5 mm to 4.0 +/- 0.4 mm (p < 0.001) while intercommissural width increased from 29.0 +/- 1.3 mm to 35.7 +/- 1.7 mm (p = 0.023), resulting in a decrease in the global annular height to commissural width ratio from 20.0% +/- 1.6% to 11.2% +/- 0.9% (p < 0.001). Eight weeks after infarction, global annular height decreased to 3.9 +/- 0.2 mm (p < 0.05) while intercommissural width increased to 40.7 +/- 1.5 mm (p < 0.001), resulting in an additional decrease in the global annular height to commissural width ratio to 9.4% +/- 0.4% (p < 0.001). Although annular remodeling involved the entire mitral annulus, there was regional heterogeneity in its extent. CONCLUSIONS: Significant global annular flattening and dilatation occur during the development of ischemic mitral regurgitation in an ovine model. Regional annular remodeling is heterogeneous and is not limited the posterior commissure or the posterior annulus.

Mitral valve tenting index for assessment of subvalvular remodeling.

BACKGROUND: Ischemic mitral regurgitation results from a variable combination of annular dilatation and remodeling of the subvalvular apparatus. Current surgical techniques effectively treat annular dilatation, but methods for addressing subvalvular remodeling have not been standardized. An effective technique for determining the extent of subvalvular remodeling could improve surgical results by identifying patients who are unlikely to benefit from annuloplasty alone. METHODS: A well-characterized ovine model of ischemic mitral regurgitation was used. Real-time three-dimensional echocardiography was performed on each animal at baseline and at 1 hour and 8 weeks after infarction. Multiple valvular geometric measurements were calculated at each time point. RESULTS: Immediate and long-term changes in mitral valvular geometry were observed. Annular height-to-commissural width ratio decreased from 20.0% +/- 1.6% to 11.2% +/- 0.9% 1 hour after infarction (p < 0.001) and to 9.4% +/- 0.4% 8 weeks after infarction (p < 0.001), whereas mitral annular area increased from 8.1 +/- 0.3 cm2 to 9.2 +/- 0.4 cm2 (p < 0.05) and then to 10.5 +/- 0.6 cm2 (p < 0.05). Maximum mitral valve tenting area increased from 49.7 +/- 5.1 mm2 to 58.6 +/- 4.2 mm2 (p < 0.05) and then to 106.4 +/- 3.9 mm2 (p < 0.001), whereas mitral valve tenting volume increased from 679.0 +/- 75.5 mm3 to 828.6 +/- 102.4 mm3 (p = 0.050) and then to 1530.5 +/- 97.8 mm3 (p < 0.001). The mitral valve tenting index increased from 0.83 +/- 0.08 mm to 0.88 +/- 0.08 mm (p > 0.05) and then to 1.46 +/- 0.08 mm (p < 0.001). CONCLUSIONS: We have described a technique that uses real-time three-dimensional echocardiography to perform a comprehensive assessment of leaflet tethering on the entire mitral valve. Our methodology is not influenced by viewing plane selection, regional tenting asymmetry, or annular dilatation and therefore represents a potentially useful, clinically relevant, and consistent measure of subvalvular remodeling.

Description of regional mitral annular nonplanarity in healthy human subjects: a novel methodology.

OBJECTIVE: Finite-element analysis demonstrates that the nonplanar shape of the mitral annulus diminishes mitral leaflet stress. It has therefore been postulated that repair with annuloplasty rings that maintain the nonplanar shape of the annulus could increase repair durability. Although the global nonplanarity of the mitral annulus has been adequately characterized, design of such a ring requires a quantitative description of regional annular geometry. By using real-time 3-dimensional echocardiography in conjunction with available image processing software, we developed a methodology for describing regional annular geometry and applied it to the characterization of the normal human mitral annulus. METHODS: Five healthy volunteers underwent mitral valve imaging with real-time 3-dimensional echocardiography. Regional annular height was calculated at 36 evenly spaced intervals. RESULTS: Maximal annular height/commissural width ratio was found to occur at the midpoint of the anterior annulus in all cases. These values averaged 26% +/- 3.1%, whereas those for the midposterior annulus averaged 18% +/- 3.0%. The average commissural width was 35.2 +/- 6.0 mm. Although substantial spatial heterogeneity was observed, regional annular height at a given rotational position was highly conserved among subjects when normalized to commissural width. CONCLUSIONS: These quantitative imaging and analytic techniques demonstrate that the normal human mitral annulus is regionally heterogeneous in its nonplanarity, and they establish a means of describing annular geometry at a regional level. With wider application, these techniques may be used both to characterize pathologic annular geometry and to optimize the design of mitral valve annuloplasty devices.

Effect of reperfusion on left ventricular regional remodeling strains after myocardial infarction.

BACKGROUND: Reperfusion therapy for myocardial infarction is currently the most effective means for limiting early and late mortality. We sought to elucidate how reperfusion influences remodeling strains in the infarct, borderzone, and remote myocardial regions. Understanding the effects of reperfusion on regional remodeling will help to evaluate and optimize emerging treatments for patients who do not achieve effective reperfusion after myocardial infarction. METHODS: An ovine infarct model (n = 13) was used to assess the effect of 1 hour of ischemia followed by reperfusion on regional and global myocardial geometry, function, and perfusion using sonomicrometry, echocardiography, and microspheres. Thirteen additional animals were assessed chronically (8 weeks) with echocardiography and postmortem analysis after either reperfusion (n = 5) or untreated infarction (n = 8). RESULTS: During ischemia the area at risk thinned, stretched, and became dyskinetic. The normally perfused borderzone also stretched, and contraction decreased by 40% during ischemia. Reperfusion increased area at risk wall thickness and reduced area at risk stretching but did not restore contractile function. Borderzone stretching was reduced and contractile function improved by reperfusion. Contractile function of remote regions was also improved with reperfusion. Ventricular dilatation after ischemia was reversed within 180 minutes of reperfusion. Chronically, reperfusion significantly improved global remodeling when compared with nonreperfused controls. Reperfused animals had thicker infarcts and akinetic rather than dyskinetic apical segments. CONCLUSIONS: Reperfusion acutely increases area at risk wall thickness, reduces area at risk and borderzone stretching, and improves borderzone and remote function. Reperfusion increases mature scar thickness and improves chronic global remodeling. These beneficial effects of reperfusion result primarily from reduced infarct expansion (stretching).