Daniel K. Bogen

Large animal model of ischemic mitral regurgitation

A large animal model of ischemic mitral regurgitation (MR) that resembles the multiple presentations of the human disease was developed in sheep. In 76 sheep hearts, the anatomy of the coronary arterial circulation was determined by observation and polymer casts. Two variations, types A and B, which differed by the vessel that supplied the left ventricular apex, were found. In all hearts, the circumflex coronary artery has three marginal branches and terminates in the posterior descending coronary artery. The amount and location of left ventricular (LV) mass supplied by each marginal circumflex branch was determined by dye injection and planimetry. In type A hearts, ligation of the first and second marginal branches infarcts 23% +/- 3.0% of the LV mass, does not infarct either papillary muscle, significantly (p < 0.001) increases LV cavity size 48% at the high papillary muscle level by 8 weeks, and does not cause MR. Ligation of the second and third marginal branches infarcts 21.4% +/- 4.0% of the LV mass, includes the posterior papillary muscle, significantly increases (p < 0.001) LV cavity size 75%, and causes severe MR by 8 weeks. Ligation of the second and third marginal branches and the posterior descending coronary artery infarcts 35% to 40% of the LV mass, increases LV cavity size 39% within 1 hour, and causes massive MR. After moderate (21% to 23%) LV infarction, development of ischemic MR requires both LV dilatation and posterior papillary muscle infarction; neither condition alone produces MR. Large posterior wall infarctions (35% to 40%) that include the posterior papillary muscle produce immediate, severe MR.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic three-dimensional imaging of the mitral valve and left ventricle by rapid sonomicrometry array localization

OBJECTIVES The first objective was to develop a quantitative method for tracking the three-dimensional geometry of the mitral valve. The second was to determine the complex interrelationships of various components of the mitral valve in vivo. METHODS AND RESULTS Sixteen sonomicrometry transducers were placed around the mitral vale anulus, at the tips and bases of both papillary muscles, at the ventricular apex, across the ventricular epicardial short axis, and on the anterior chest wall before and during cardiopulmonary bypass in eight anesthetized sheep. Animals were studied later on 17 occasions. Reproducibility of derived chord lengths and three-dimensional coordinates from sonomicrometry array localization, longevity of transducer signals, and the dynamics of the mitral valve and left ventricle were studied. Reproducibility of distance measurements averages 1.6%; Procrustes analysis of three-dimensional arrays of coordinate locations predicts an average error of 2.2 mm. Duration of serial sonomicrometry array localization signals ranges between 60 and 151 days (mean 114 days). Sonomicrometry array localization demonstrates the saddle-shaped mitral anulus, its minimal orifice area immediately before end-diastole, and uneven, apical descent during systole. Papillary muscles shorten only 3.0 to 3.5 mm. Sonomicrometry array localization demonstrates nonuniform torsion of papillary muscle transducers around a longitudinal axis and shows rotation of papillary muscular bases toward each other during systole. CONCLUSION Tagging of ventricular structures in experimental animals by sonomicrometry array localization images is highly reproducible and suitable for serial observations. In sheep the method provides unique, quantitative information regarding the interrelationship of mitral valvular and left ventricular structures throughout the cardiac cycle.

Large animal model of left ventricular aneurysm

In 28 Dorsett sheep, ligation of the distal homonymous (equivalent to human left anterior descending) and second diagonal coronary arteries produced a constant transmural infarct of 22.9% +/- 2.5% (mean +/- standard deviation) of the left ventricular mass. Serial left ventriculograms showed that within four hours the infarct segment expands, wall thickness decreases, and aneurysmal dilatation occurs and progresses over the next 60 days in all sheep. Epicardial ventricular point references indicated that adjacent noninfarcted myocardium participates in the formation of the aneurysm. Anatomy of the coronary vasculature was studied in 22 excised sheep hearts. In sheep, coronary arterial anatomy is remarkably constant. The left coronary artery provides all of the blood supply to the left ventricle and septum and only a small rim of both the anterior and posterior right ventricles. Cardiac veins from the left ventricle drain into the coronary sinus, which also receives the left azygos vein. Right ventricular veins drain separately. The essentially separate coronary circulations to the two ventricles, the paucity of coronary collateral circulation, and the consistent evolution of left ventricular infarcts into aneurysms are important advantages of the ovine model for both metabolic and ventricular mechanical studies of acute myocardial infarction and left ventricular aneurysm.

Pathogenesis of acute ischemic mitral regurgitation in three dimensions

Changes in the geometric and intravalvular relationships between subunits of the ovine mitral valve were measured before and after acute posterior wall myocardial infarction in three dimensions by means of sonomicrometry array localization. In 13 sheep, nine sonomicrometer transducers were attached around the mitral anulus and to the tip and base of each papillary muscle. Five additional transducers were placed on the epicardium. Snares were placed around three branches of the circumflex coronary artery. One to 2 weeks later, echocardiograms, dimension measurements, and left ventricular pressures were obtained before and after the coronary arteries were occluded. Data were obtained from seven sheep. Coronary occlusion infarcted 32% of the posterior left ventricle and produced 2 to 3+ mitral regurgitation by Doppler color flow mapping. Multidimensional scaling of dimension measurements obtained from sonomicrometry transducers produced three-dimensional spatial coordinates of each transducer location throughout the cardiac cycle before and after infarction and onset of mitral regurgitation. After posterior infarction, the mitral anulus enlarges asymmetrically along the posterior anulus, and the tip of the posterior papillary muscle moves 1.5 +/- 0.3 mm closer to the posterior commissure at end-systole. The posterior papillary muscle also elongates 1.9 +/- 0.3 mm at end-systole. The left ventricle enlarges asymmetrically and ventricular torsion along the long axis changes. The development of postinfarction mitral regurgitation appears to be the consequence of multiple small changes in ventricular shape and contractile deformation and in the spatial relationship of mitral valvular subunits.

Myocardial electrical impedance mapping of ischemic sheep hearts and healing aneurysms.

BackgroundThis study was designed to examine the bulk electrical properties of myocardium and their variation with the evolution of infarction after coronary occlusion. These properties may be useful in distinguishing between normal, ischemic, and infarcted tissue on the basis of electrophysiological parameters. Methods and ResultsThe electrical impedance of myocardial tissue was studied in a sheep model of infarction. The animal model involved a one-stage ligation of the left anterior descending and second diagonal arteries at a point 40% of the distance from the apex to the base. By use of a four-electrode probe, an epicardial mapping system was developed that allowed for cardiac cycle gated and signal-averaged measurements. Subthreshold current (15 μA) was injected through two of the electrodes at frequencies of 1, 5, and 15 kHz and the induced potential measured with the other two electrodes. Epicardial maps of the left ventricle were obtained during acute infarction and at 1-, 2-, and 6-week intervals after occlusion. Results showed the average specific impedance of the myocardium before infarction to be 158±26 Ω-cm independent of location on the epicardium. By 60 minutes after coronary occlusion, the specific impedance had increased by 199% (p<0.005, n=9); it remained elevated for up to 4 hours. One week after infarction, the specific impedance decreased to 59% of the control value (p<0.025, n=8). Six weeks after occlusion, the specific impedance remained low at 57% of that of the noninfarcted tissue (p<0.005, n=9). The phase angle of the complex impedance was also measured and revealed similar changes. The hydroxyproline content of the tissue was assayed to assess infarct healing. ConclusionsIn this animal model, impedance is a bulk electrical property of tissue that varies with the evolution of myocardial infarction. Impedance mapping revealed significantly different values for normal, ischemic, and infarcted tissue and may prove useful in better defining the electrophysiological characteristics of such tissue.

Changes in left ventricular systolic wall stress during biventricular circulatory assistance

Extracorporeal membrane oxygenation (ECMO) reduces the systolic stress integral (SSI) in the normal left ventricle. We tested the hypothesis that the SSI does not decrease in poorly contracting, dilated, ejecting hearts during ECMO. In 14 sheep, four pairs of ultrasonic crystals measured changes in left ventricular (LV) wall thickness and three LV diameters. Volume calculations were validated by balloon distention of the ventricles after death (slope = 0.85; r = 0.85). SSI was measured during ECMO flows of 20 to 100 ml/kg/min in both normal and dilated, poorly contracting hearts produced by 30 minutes of warm ischemia. After warm ischemia, end-systolic elastance, an index of contractility, decreased from 8.3 +/- 0.6 mm Hg/ml to 2.9 +/- 0.4 mm Hg/ml (p = 0.001) and peak systolic pressure decreased from 47.4 +/- 0.7 mm Hg to 37.5 +/- 0.08 mm Hg (p = 0.01). In normal hearts, as ECMO flow increased, SSI decreased from 10.5 +/- 2.2 mm Hg.sec to 7.7 +/- 0.8 mm Hg.sec at 60 ml/kg/min (p = 0.001). However, in postischemic hearts, SSI progressively increased from 6.6 +/- 0.3 mm Hg.sec before ECMO to 12.4 +/- 1.8 mm Hg.sec at ECMO = 100 ml/kg/min. These studies indicate that the initial effect of ECMO on the poorly contracting, dilated heart increases LV wall stress and that the increase in stress is proportional to ECMO flow. The increase in stress is primarily due to an increase in afterload, which more than offsets decreases in systolic and diastolic volumes.

The association of health literacy with adherence and outcomes in moderate-severe asthma

BACKGROUND Low health literacy is associated with poor outcomes in asthma and other diseases, but the mechanisms governing this relationship are not well defined. OBJECTIVE We sought to assess whether literacy is related to subsequent asthma self-management, measured as adherence to inhaled steroids, and asthma outcomes. METHODS In a prospective longitudinal cohort study, numeric (Asthma Numeracy Questionnaire) and print literacy (Short Test of Functional Health Literacy in Adults) were assessed at baseline in adults with moderate or severe asthma for their impact on subsequent electronically monitored adherence and asthma outcomes (asthma control, asthma-related quality of life, and FEV1) over 26 weeks, using mixed-effects linear regression models. RESULTS A total of 284 adults participated: age, 48 ± 14 years, 71% females, 70% African American, 6% Latino, mean FEV1 66% ± 19%, 86 (30%) with hospitalizations, and 148 (52%) with emergency department visits for asthma in the prior year. Mean Asthma Numeracy Questionnaire score was 2.3 ± 1.2 (range, 0-4); mean Short Test of Functional Health Literacy in Adults score was 31 ± 8 (range, 0-36). In unadjusted analyses, numeric and print literacy were associated with better adherence (P = .01 and P = .08, respectively), asthma control (P = .005 and P < .001, respectively), and quality of life (P < .001 and P < .001, respectively). After controlling for age, sex, and race/ethnicity, the associations diminished and only quality of life (numeric P = .03, print P = .006) and asthma control (print P = .005) remained significantly associated with literacy. Race/ethnicity, income, and educational attainment were correlated (P < .001). CONCLUSION While the relationship between literacy and health is complex, interventions that account for and address the literacy needs of patients may improve asthma outcomes.

Use of sonomicrometry and multidimensional scaling to determine the three-dimensional coordinates of multiple cardiac locations: feasibility and initial implementation

The authors describe a new method which uses sonomicrometry and the statistical technique of multidimensional scaling (MDS) to measure the three-dimensional (3D) coordinates of multiple cardiac locations. The authors refer to this new method as sonomicrometry array localization (SAL). The new method differs from standard sonomicrometry in that each piezoelectric transducer element is used as both transmitter and receiver and the set of intertransducer element distances is measured. MDS calculates the 3D coordinates of each sonomicrometry transducer element from the set of intertransducer element distances. The feasibility of this new method was tested with mathematical simulations which demonstrated the ability of MDS to compensate for signal error and missing intertransducer element distances. The authors describe the design elements of a modified digitally controlled sonomicrometer in which a single transducer element can sequentially broadcast to as many as 8 receiver elements. That design is used to validate SAL in a water bath and in ex vivo and living hearts. Correlation with caliper measurement in the water bath (y int.=3.91/spl plusmn/3.36 min, slope=1.04/spl plusmn/0.05, r/sup 2/=0.969/spl plusmn/0.027) and with radiography in ex vivo (y int.=-0.87/spl plusmn/0.92 mm, slope=0.97/spl plusmn/0.02, r/sup 2/=0.960/spl plusmn/0.023) and in vivo hearts (y int.=2.98/spl plusmn/2.59 mm, slope=1.01/spl plusmn/0.06, r/sup 2/=0.953/spl plusmn/0.031) was excellent. Sonomicrometry array localization is able to accurately measure the 3D coordinates of multiple cardiac locations. It can potentially measure myocardial deformation and remodeling after ischemic or valvular injury.<<ETX>>

Problem solving to improve adherence and asthma outcomes in urban adults with moderate or severe asthma: A randomized controlled trial

BACKGROUND Improving inhaled corticosteroid (ICS) adherence should improve asthma outcomes. OBJECTIVE In a randomized controlled trial we tested whether an individualized problem-solving (PS) intervention improves ICS adherence and asthma outcomes. METHODS Adults with moderate or severe asthma from clinics serving urban neighborhoods were randomized to PS (ie, defining specific barriers to adherence, proposing/weighing solutions, trying the best, assessing, and revising) or standard asthma education (AE) for 3 months and then observed for 3 months. Adherence was monitored electronically. Outcomes included the following: asthma control, FEV(1), asthma-related quality of life, emergency department (ED) visits, and hospitalizations. In an intention-to-treat-analysis longitudinal models using random effects and regression were used. RESULTS Three hundred thirty-three adults were randomized: 49 ± 14 years of age, 72% female, 68% African American, 7% Latino, mean FEV(1) of 66% ± 19%, and 103 (31%) with hospitalizations and 172 (52%) with ED visits for asthma in the prior year. There was no difference between groups in overall change in any outcome (P > .20). Mean adherence (61% ± 27%) decreased significantly (P = .0004) over time by 14% and 10% in the AE and PS groups, respectively. Asthma control improved overall by 15% (P = .002). In both groups FEV(1) and quality of life improved by 6% (P = .01) and 18% (P < .0001), respectively. However, the improvement in FEV(1) only occurred during monitoring but not subsequently after randomization. Rates of ED visits and hospitalizations did not significantly decrease over the study period. CONCLUSION PS was not better than AE in improving adherence or asthma outcomes. However, monitoring ICS use with provision of medications and attention, which was imposed on both groups, was associated with improvement in FEV(1) and asthma control.

Exposure to community violence is associated with asthma hospitalizations and emergency department visits.

BACKGROUND Exposure to community violence (ECV) has been associated with asthma morbidity of children living in inner-city neighborhoods. OBJECTIVE To examine with prospective longitudinal data whether ECV is independently associated with asthma-related health outcomes in adults. METHODS Adults with moderate-severe asthma, recruited from clinics serving inner-city neighborhoods, completed questionnaires covering sociodemographics, asthma severity, and ECV and were followed for 26 weeks. Longitudinal models were used to assess unadjusted and adjusted associations of subsequent asthma outcomes (emergency department [ED] visits, hospitalizations, FEV(1), quality of life). RESULTS A total of 397 adults, 47 +/- 14 years old, 73% women, 70% African American, 7% Latino, mean FEV(1) 66% +/- 19%, 133 with hospitalizations and 222 with ED visits for asthma in the year before entry, were evaluated. Ninety-one reported ECV. Controlling for age, sex, race/ethnicity, and household income, those exposed to violence had 2.27 (95% CI, 1.32-3.90) times more asthma-related ED visits per month and 2.49 (95% CI, 1.11-5.60) times more asthma-related hospitalizations per month over the 26-week study period compared with those unexposed. Violence-exposed participants also had 1.71 (95% CI, 1.14-2.56) times more overall ED visits per month and 1.72 (95% CI, 0.95-3.11) times more overall hospitalizations per month from any cause. Asthma-related quality of life was lower in the violence-exposed participants (-0.40; 95% CI, -0.77 to -0.025; P = .04). Effect modification by depressive symptoms was only statistically significant for the ECV association with overall ED visits and quality-of-life outcomes (P < .01). CONCLUSION In adults, ECV is associated with increased asthma hospitalizations and emergency care for asthma or any condition and with asthma-related quality of life.