Aortic size in acute type A dissection: implications for preventive ascending aortic replacement.

OBJECTIVE: Elective ascending aortic replacement is recommended to prevent acute type A aortic dissection when any segment of the proximal aorta is greater than 5.5 cm. However, little data exist that meticulously describe the size of the ascending aorta at multiple levels in patients who suffer acute type A dissections. We sought to definitively characterize the size distribution of the proximal aorta in this patient population. METHODS: Preoperative transesophageal echocardiography was used to measure the diameter of the proximal aorta at the aortic annulus, in the sinus segment, at the sinotubular junction and in the ascending aorta in 177 non-Marfan patients with tricuspid aortic valves who presented to one institution over a 10-year period with an acute type A dissection. Predicted aortic diameters for each patient based on the individual's age, gender and body size were also calculated at all four aortic positions using previously published regression equations derived from a large cohort of normal patients. RESULTS: Sixty patients were female (33.9%; aged 67+/-12 years) and 117 were male (66.1%; aged 60+/-17 years). Sixty-two percent of all patients had maximum aortic diameters less than 5.5 cm at time of dissection and 42% of patients had maximum aortic diameters less than 5.0 cm. Over 20% of all patients had maximal aortic dimensions of less than 4.5 cm. In women, 12% of the dissected aortas had a maximal dimension less than 4.0 cm. CONCLUSIONS: The majority of patients with acute type A aortic dissection present with aortic diameters <5.5 cm and thus do not fall within current guidelines for elective ascending aortic replacement. Methods other than size measurement of the ascending aorta are needed to identify patients at risk for dissection. Aggressive medical management of patients with ascending aortic diameters over 4 cm is warranted. Preventative replacement of the ascending aorta at 4.5 cm should be considered especially at high volume aortic surgery centers and patients having cardiac surgery for other indications.

Mild hypothermia to limit myocardial ischemia-reperfusion injury: importance of timing.

BACKGROUND: Hypothermia during ischemia has been shown to reduce myocardial reperfusion injury. We sought to establish the cardioprotective effect of very mild total-body hypothermia (

Regional heterogeneity of myocardial reperfusion injury: effect of mild hypothermia.

BACKGROUND: Mild hypothermia confers a myocardial protective effect that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI). The effect of temperature on the extent and distribution of myocardial reperfusion injury in a collateral deficient ovine model was studied. METHODS: Topical cooling maintained left atrial temperature at 39.5 degrees C (n = 8), 38.5 degrees C (n = 5), 37.5 degrees C (n = 6), 36.5 degrees C (n = 6), or 35.5 degrees C (n = 5) in sheep prior to 1 hour of coronary occlusion to produce an anteroapical myocardial risk area (AR) followed by 3 hours of reperfusion. A dual staining and planimetry technique was used to assess infarct size as a percentage of the AR in 3 myocardial short axis slices that included the entire AR (slice 1= most apical; slice 3= most basal). The subendocardial, midmyocardial, and subepicardial extent in short axis of the infarct was also assessed in each slice. Microspheres assessed transmural blood flow. RESULTS: At 39.5 degrees C there was a long-axis gradient in myocardial injury that was most severe at the apex and lessened toward the base. The midmyocardial region was most susceptible to injury at all long axis levels. Temperature reduction (as little as 1 degrees C) was associated with improved salvage that was most pronounced in the apical subendocardium and least in the basilar midmyocardium. Reperfusion at 39.5 degrees C resulted in severe transmural microvascular injury (no-reflow) that was completely obviated at temperatures below 38.5 degrees C. CONCLUSIONS: Myocardial reperfusion injury varies over the long and short LV axes. Mild hypothermia preferentially improves myocardial salvage at the LV apex. Small temperature changes can dramatically affect microvascular integrity.

Very mild hypothermia during ischemia and reperfusion improves postinfarction ventricular remodeling.

BACKGROUND: Mild hypothermia (< 4 degrees C) improves myocardial salvage after infarct reperfusion in animals and in early clinical studies. In this experiment the effect of mild hypothermia during ischemia and early reperfusion on long-term postinfarction left ventricular (LV) remodeling was assessed in an ovine infarct model. METHODS: In the initial phase of the experiment the effect of progressive degrees of hypothermia on infarct size was quantified. Thirty-eight male sheep were subjected to 1 hour of ischemia using a standardized anteroapical infarct followed by 3 hours of reperfusion. Temperature was maintained at either 39.5 degrees C (n = 11), 38.5 degrees C (n = 7), 37.5 degrees C (n = 7), 36.5 degrees C (n = 7), or 35.5 degrees C (n = 6) for the entire period of ischemia and reperfusion. The area at risk (AR) and infarct size as a percentage of AR (I/AR) were determined with a double staining and planimetry technique. In the second phase of the study, chronic post-infarction remodeling was assessed in animals with nonreperfused infarcts (n = 6), 1 hour of ischemia followed by reperfusion at 39.5 degrees C (n = 6) and 1 hour of ischemia followed by reperfusion at 37.5 degrees C (n = 6). Remodeling was determined at 8 weeks after infarction using echocardiography. RESULTS: The I/AR in the 39.5 degrees C, 38.5 degrees C, 37.5 degrees C, 36.5 degrees C, and the 35.5 degrees C groups was 71.8 +/- 3.0%, 63.1 +/- 1.9%, 49.4 +/- 1.4%, 38.7 +/- 1.4%, and 21.7 +/- 2.2%, respectively (p < 0.05 between all groups). In the chronic study LV end systolic volume at 8 weeks after infarction was 81 +/- 8 mL in the nonreperfused group, 57 +/- 4 mL in the 39.5 degrees C reperfusion group, and 41 +/- 3 mL in the 37.5 degrees C reperfusion group (p < 0.05 for between group differences). CONCLUSIONS: Subtle degrees of hypothermia can significantly improve immediate myocardial salvage and long-term LV remodeling after infarct reperfusion.

Endocarditis with massive aortic root abscess and atrioventricular septal destruction.

Endocarditis involving the aortic root and intervalvular fibrous skeleton presents a reconstructive dilemma. We report a case of endocarditis involving the aortic root and tricuspid valve with extensive destruction of the atrioventricular septum. Debridement necessitated resection of the aortic root, aortic valve, tricuspid valve, and a large portion of atrioventricular septum, leaving the right atrium, right ventricle, left ventricle and aorta in open communication. Reconstruction was accomplished by separating the left and right hearts with a Dacron patch, tricuspid valve replacement, and aortic root replacement. Proper planar localization of the aortic root was necessary to avoid left ventricular outflow obstruction and coronary torsion.

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).

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.

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.

Quantification and localization of mitral valve tenting in ischemic mitral regurgitation using real-time three-dimensional echocardiography.

OBJECTIVE: Ischemic mitral regurgitation (IMR) 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 IMR was employed. Real-time three-dimensional echocardiography was performed on each animal at baseline, immediately after infarction and 8 weeks after infarction. Intercommissural width and mitral annular area were calculated for each subject at each time point. Mitral valve tenting area and height were calculated at discrete intervals along the entire intercommissural axis. The location at which maximal tenting area and height occurred was recorded. Mitral valve tenting volume was calculated by summation. RESULTS: Both immediate and long-term increases were observed in mean intercommissural width and mean mitral annular area (from 33.2 to 36.3 to 39.7 mm and from 740 to 810 to 1020 mm(2), respectively). Both immediate and long-term increases were observed in maximum mitral valve tenting area and height (from 38.5 to 50.6 to 112.1mm(2) and from 3.9 to 4.7 to 10.1mm, respectively). Mitral valve tenting area and height at the mid-point of the intercommissural axis did not change significantly during the observation period. The position along the intercommissural axis at which maximal mitral valve tenting area and height occurred shifted progressively toward the anterior commissure (from 51.8% to 45.1% to 38.9% and from 52.9% to 45.1% to 37.8%). Both immediate and long-term increases were observed in mitral valve tenting volume (from 474.0 to 622.1 to 1483.5mm(3)). CONCLUSIONS: We have described a technique that utilizes 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 surrogate measure of subvalvular remodeling.

Effects of hemodynamic alterations on anterior mitral leaflet curvature during systole.

OBJECTIVES: The application of repair techniques to treat mitral valve incompetence has increased progressively during the past 20 years. Unfortunately, recent reports have demonstrated the longevity of these repairs to be less than previously believed. Most repair failures are stress related. Computational models to optimize valve repair are in development, but to be brought to fruition, a better understanding of dynamic leaflet geometry is necessary. In this study, sonomicrometry was used in an ovine model to compute systolic leaflet curvature at varying afterloads and states of contractility. METHODS: The anterior leaflet of 12 sheep was instrumented with 5 piezoelectric transducers in a cruciate array. Systolic blood pressure ranged from 90 to 200 mm Hg with increasing phenylephrine hydrochloride infusion. Epinephrine was used to vary contractile state. Leaflet curvature was calculated continuously (200 Hz) during systole. RESULTS: Anterior leaflet curvature in the septolateral direction was double that in the intercommisural direction. There were also significant changes in leaflet curvature during systole. Curvature in neither direction was affected by afterload. Epinephrine augmented intercommisural curvature in a dose-independent fashion, whereas it had no effect on curvature in the septolateral direction. CONCLUSIONS: Dynamic mitral anterior leaflet geometry was found to be amazingly constant over a wide range of hemodynamic conditions. These data provide information about leaflet geometry that will aid in the construction of realistic computational models. Such models may facilitate the design of annuloplasty rings and surgical techniques that minimize leaflet stress and increase mitral valve repair longevity.

Role of acetaminophen in acute myocardial infarction.

Acetaminophen, the active ingredient in Tylenol, is a widely used drug that is well known for its analgesic and antipyretic properties. Acetaminophen is a commonly used alternative to nonsteroidal anti-inflammatory drugs, which have recently been demonstrated to increase mortality after acute myocardial infarction (AMI). The safety and potential cardioprotective properties of acetaminophen in the setting of AMI have recently been investigated; however, the results from these studies have been inconclusive. Using both large (ovine) and small (rabbit) collateral-deficient animal models, we studied the effects of acetaminophen in the setting of reperfused AMI. In both species we studied the effects of acetaminophen on myocardial salvage and ventricular function. Additionally, we studied the effects of acetaminophen on myocardial perfusion in sheep and on myocyte apoptosis in rabbits. Sixteen sheep and twenty-two rabbits were divided into two groups and administered acetaminophen or a vehicle before undergoing ischemia and reperfusion. The ischemic period was 60 min in sheep and 30 min in rabbits. All animals were reperfused for 3 h. There were no significant differences observed in myocardial perfusion, myocyte apoptosis, or infarct size in acetaminophen-treated animals. Acetaminophen increased cardiac output and mean arterial pressure before ischemia in sheep but had no effect on any other hemodynamic parameter. In rabbits, no effect on cardiac output or blood pressure was detected. These results support the role of acetaminophen as a safe drug in the postmyocardial infarction setting; however, no significant cardioprotective effect of the drug could be demonstrated.

Borderzone geometry after acute myocardial infarction: a three-dimensional contrast enhanced echocardiographic study.

BACKGROUND: Regional myocardial geometry, function, and perfusion status are critical variables for understanding infarction-induced left ventricle (LV) remodeling. Three-dimensional contrast echocardiography (3DCE) is uniquely suited to measure these parameters. We evaluate the ability of 3DCE to assess geometric changes in the normally perfused but hypocontractile borderzone myocardium (BZM) immediately after a myocardial infarction (MI) in an ovine model, and we compare 3DCE with two-dimensional contrast echocardiography (2DCE) in the long and short axis. METHODS: Four sheep were studied with 3DCE and 4 were studied using 2DCE, before and 30 minutes after an anteroapical MI. Each 3DCE data set was acquired over 18 consecutive cardiac cycles. The LV geometry was reconstructed and perfusion data spatially correlated, thereby constituting a 3D model of ventricular geometry and perfusion. The borderzone was defined as the contrast-perfused myocardium adjacent to the infarct. RESULTS: The 2DCE short-axis analysis demonstrated decreased curvature and decreased wall thickness in the borderzone after MI. These findings are consistent with increased BZM wall stress. However, the long-axis 2DCE analysis demonstrated increased BZM wall thickness and a surprising change in BZM concavity acutely after infarction. The 3DCE analysis confirmed these findings and added additional information regarding regional variability in BZM geometry that was not evident in the two orthogonal 2D views. CONCLUSIONS: This study provides evidence that regional changes in BZM geometry are more complex than previously believed and are not necessarily indicative of increased regional stress. The superiority of 3DCE over 2DCE for assessing these changes is strongly supported.

Early postinfarction ventricular restraint improves borderzone wall thickening dynamics during remodeling.

BACKGROUND: Early infarct expansion impairs function of normally perfused borderzone myocardium (BZM), initiates adverse remodeling, and portends a poor long-term outcome. Early ventricular restraint has been demonstrated to improve global remodeling but its effect on BZM function has not been assessed. Using an ovine model of infarct induced remodeling and MRI, we tested the hypothesis that ventricular restraint early after MI preserves BZM function and reduces remodeling. METHODS: Six sheep had a large anterior infarction after ligation of all diagonal branches. One week after infarction 3 sheep had placement of a cardiac support device (CSD) to restrain infarct expansion. Global remodeling and borderzone wall thickening strain were assessed using tagged MRI before and 8 weeks after infarction. RESULTS: Global remodeling was greatly reduced in the CSD group compared with control. The BZM systolic wall thickening was similar in both groups at baseline (13.5% +/- 2.0%, control; 12.8% +/- 2.0%, CSD, p = 0.8). After 8 weeks of infarction-induced remodeling, systolic wall thickening strain decreased significantly to 4.9% +/- 0.7% in the control group (p = 0.03). In contrast, systolic wall thickening was preserved in the CSD group at 8 weeks (11.0% +/- 1.6%, p = 0.3). In the control group all thickening occurred during isovolemic contraction, plateauing during ejection. The CSD improved late systolic borderzone wall thickening, although dynamics remained perturbed. CONCLUSIONS: Ventricular restraint early after MI improves both contractile function of the BZM and global ventricular remodeling. The dynamics of BZM wall thickening are impaired during remodeling. The CSD significantly improves but does not completely maintain baseline BZM wall thickening dynamics.

Surgical treatment of ischemic mitral regurgitation might not influence ventricular remodeling.

OBJECTIVES: Surgical treatment for ischemic mitral regurgitation has become more aggressive. However, no clinical study has demonstrated that surgical correction of chronic ischemic mitral regurgitation improves survival. We used 4 well-developed ovine models of postinfarction left ventricular remodeling to test the hypothesis that ischemic mitral regurgitation does not significantly contribute to postinfarction left ventricular remodeling. METHODS: Infarction of 21% to 24% of the left ventricular mass was induced by means of coronary ligation in 77 sheep. Infarctions varied only by anatomic location in the left ventricle: anteroapical, n = 26; anterobasal, n = 16; laterobasal, n = 9; and posterobasal, n = 20. Six additional sheep had ring annuloplasty before posterobasal infarction. End-systolic and end-diastolic left ventricular volume, end-systolic muscle-to-cavity area ratio, left ventricular sphericity, ejection fraction, and degree of ischemic mitral regurgitation, as determined by means of quantitative echocardiography, were assessed before infarction and at 2, 5, and 8 weeks after infarction. RESULTS: All infarcts resulted in significant postinfarction remodeling and decreased ejection fraction. Anteroapical infarcts lead to left ventricular aneurysms. Only posterobasal infarcts caused severe and progressive ischemic mitral regurgitation. Remodeling because of posterobasal infarcts was not more severe than that caused by infarcts at other locations. Furthermore, prophylactic annuloplasty prevented the development of mitral regurgitation after posterobasal infarction but had no effect on remodeling. CONCLUSION: The extent of postinfarction remodeling is determined on the basis of infarct size and location. The development of ischemic mitral regurgitation might not contribute significantly to adverse remodeling. Ischemic mitral regurgitation is likely a manifestation rather than an important impetus for postinfarction remodeling.

Early ventricular restraint after myocardial infarction: extent of the wrap determines the outcome of remodeling.

BACKGROUND: Early infarct expansion initiates adverse remodeling, leads to left ventricular dilatation and portends a poor long-term outcome. Early mechanical prevention of infarct expansion has been proposed as a method to improve remodeling, but the extent of ventricular restraint necessary to optimize the salutary effect is not known. We tested the hypothesis that left ventricular restraint (wrap) is superior to infarct stiffening (patch). METHODS: Infarction of 20% to 25% of the left ventricle was induced by coronary ligation in 69 sheep. Infarcts were either anteroapical (n = 33) or posterobasal (n = 36). Animals with each infarct received either no treatment (anteroapical, n = 26; posterobasal, n = 17), infarct stiffening with a localized Marlex mesh patch (posterobasal, n = 9) or left ventricular wrapping with Merseline mesh (anteroapical, n = 7; posterobasal, n = 10). End-systolic volume, end-diastolic volume, end-systolic muscle to cavity area ratio, left ventricular sphericity, ejection fraction, and degree of mitral regurgitation as determined by quantitative echocardiography were assessed before infarction and at 2, 5, and 8 weeks after infarction to evaluate the extent of left ventricular remodeling. RESULTS: Control animals in both groups experienced adverse remodeling. Anteroapical infarct animals developed large left ventricular aneurysms and the posterobasal infarct animals developed severe mitral regurgitation. Early infarct stiffening did not significantly improve any aspect of remodeling due to the posterobasal infarct. Early left ventricular wrapping significantly improved remodeling after both types of infarctions. CONCLUSIONS: Early left ventricular wrapping attenuates infarct expansion and has a salutary effect on remodeling. Simple infarct stiffening alone is not effective.

A multi-feature and multi-channel univariate selection process for seizure prediction.

OBJECTIVE: To develop a prospective method for optimizing seizure prediction, given an array of implanted electrodes and a set of candidate quantitative features computed at each contact location. METHODS: The method employs a genetic-based selection process, and then tunes a probabilistic neural network classifier to predict seizures within a 10 min prediction horizon. Initial seizure and interictal data were used for training, and the remaining IEEG data were used for testing. The method continues to train and learn over time. RESULTS: Validation of these results over two workshop patients demonstrated a sensitivity of 100%, and 1.1 false positives per hour for Patient E, using a 2.4s block predictor, and a failure of the method on Patient B. CONCLUSIONS: This study demonstrates a prospective, exploratory implementation of a seizure prediction method designed to adapt to individual patients with a wide variety of pre-ictal patterns, implanted electrodes and seizure types. Its current performance is limited likely by the small number of input channels and quantitative features employed in this study, and segmentation of the data set into training and testing sets rather than using all continuous data available. SIGNIFICANCE: This technique theoretically has the potential to address the challenge presented by the heterogeneity of EEG patterns seen in medication-resistant epilepsy. A more comprehensive implementation utilizing all electrode sites, a broader feature library, and automated multi-feature fusion will be required to fully judge the method's potential for predicting seizures.

The dynamic anterior mitral annulus.

BACKGROUND: The anterior mitral annulus is considered a fixed structure. Recent data suggest otherwise. This study tested the hypothesis that the size of the anterior annulus varies with hemodynamic loading and ventricular contractility. METHODS: Sonomicrometry array localization measured annular area, total annular circumference, anterior circumference, and posterior circumference in 6 sheep before and after neosynephrine increased systolic blood pressure by at least 150% during atrial pacing at 120 beats/min. In 6 additional animals the same dimensions were measured during atrial pacing (at 120 and 150 beats/min) and during isoproteronol infusions to increase heart rate to 120 and 150 beats/min. RESULTS: Neosynephrine increased systolic total annular circumference from 99.7 +/- 5.5 mm to 106.9 +/- 9.6 mm. Anterior circumference increased from 40.8 +/- 4.0 mm to 45.3 +/- 5.7 mm whereas posterior circumference only increased from 59.0 +/- 5.5 mm to 61.6 +/- 7.0 mm. Low isoproteronol infusion decreased systolic total annular circumference from 107.5 +/- 8.3 mm to 101.9 +/- 10.6 mm. Most of this change occurred in the posterior circumference. Higher infusions of isoproteronol decreased total annular circumference from 106.8 +/- 8.3 mm to 98.3 +/- 9.7 mm. At this higher inotropic state the decrease in annular size was similar in the anterior and posterior annulus. CONCLUSIONS: In sheep, the anterior annulus is a dynamic structure that varies in size in response to changes in hemodynamic loading and ventricular contractility.

High-frequency oscillations and seizure generation in neocortical epilepsy.

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60-100 Hz) epileptiform oscillations are highly localized in the seizure onset zone, both before and temporally removed from seizure onset. These findings were observed in all six patients with neocortical epilepsy out of 23 consecutive patients implanted with intracranial electrodes for pre-surgical evaluation during the study period. The majority of seizures (62%) in these patients were anticipated by an increase in high-frequency activity in the 20 min prior to neocortical seizure onset. Contrary to observations in normal brain, high-frequency activity was strongly modulated by behavioural state, and was maximal during slow-wave sleep, which may explain the propensity for neocortical onset seizures to begin during sleep. These findings point to an important role for neuromodulatory circuits, probably involving the thalamus, in mechanisms underlying seizure generation in neocortical epilepsy. These findings demonstrate that high-frequency epileptiform oscillations may prove clinically useful in localizing the seizure onset zone in neocortical epilepsy, for identifying periods of increased probability of seizure onset, and in elucidating mechanisms underlying neocortical ictogenesis. Confirmation that prolonged bursts of high-frequency activity may predict focal onset neocortical seizures will require prospective validation on continuous, prolonged recordings in a larger number of patients. Importantly, the results show that the dynamic range utilized in current clinical practice for localization of epileptogenic brain largely ignores fundamental oscillations that are signatures of an epileptogenic brain. It may prove that many currently available clinical EEG systems and EEG analysis methods utilize a dynamic range that discards clinically important information.