Randomized controlled trial comparing simultaneous versus optimized sequential interventricular stimulation during cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality and improves symptoms in patients with systolic heart failure (HF) and ventricular dyssynchrony. This randomized, double-blind, controlled study evaluated whether optimizing the interventricular stimulating interval (V-V) to sequentially activate the ventricles is clinically better than simultaneous V-V stimulation during CRT. METHODS: Patients with New York Heart Association (NYHA) III or IV HF, meeting both CRT and implantable cardioverter-defibrillator indications, randomly received either simultaneous CRT or CRT with optimized V-V settings for 6 months. Patients also underwent echocardiography-guided atrioventricular delay optimization to maximize left ventricular filling. The V-V optimization involved minimizing the left ventricular septal to posterior wall motion delay during CRT. The primary objective was to demonstrate noninferiority using a clinical composite end point that included mortality, HF hospitalization, NYHA functional class, and patient global assessment. Secondary end points included changes in NYHA classification, 6-minute hall walk distance, quality of life, peak VO(2), and event-free survival. RESULTS: The composite score improved in 75 (64.7%) of 116 simultaneous patients and in 92 (75.4%) of 122 optimized patients (P < .001, for noninferiority). A prespecified test of superiority showed that more optimized patients improved (P = .03). New York Heart Association functional class improved in 58.0% of simultaneous patients versus 75.0% of optimized patients (P = .01). No significant differences in exercise capacity, quality of life, peak VO(2), or HF-related event rate between the 2 groups were observed. CONCLUSIONS: These findings demonstrate modest clinical benefit with optimized sequential V-V stimulation during CRT in patients with NYHA class III and IV HF. Optimizing V-V timing may provide an additional tool for increasing the proportion of patients who respond to CRT.

Conjoined hearts in thoracopagus twins.

This study aimed to identify the anatomic and pathologic structural cardiac abnormalities in conjoined twins and to focus on those that have prevented the successful separation of conjoined hearts. A retrospective review was undertaken to examine consecutive cases of thoracopagus conjoined twins with conjoined hearts evaluated at The Children's Hospital of Philadelphia from 1 January 1980 through 6 October 2008. The records included autopsy and surgical findings as well as clinical reports. The study group included nine sets of conjoined twins with a mean gestational age at birth of 33.8 ± 5.5 weeks. Three twin pairs were stillborn. Five twin pairs died afterward. One pair died of cardiopulmonary failure. The median age at death was 22 days (range, 0-345 days). Major congenital heart disease was present in 94.4% (17/18) of the hearts, and 72.2% (13/18) of the hearts had single-ventricle physiology. Total anomalous pulmonary venous return occurred in 39% (7/18) of the cases. The clinical outcome for thoracopagus twins with conjoined hearts remains poor because of inability to separate conjoined and single ventricles. Surgical nonintervention and palliative care should be strongly considered for these patients.

Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction.

BACKGROUND: Targeted delivery of mesenchymal precursor cells (MPCs) can modify left ventricular (LV) cellular and extracellular remodeling after myocardial infarction (MI). However, whether and to what degree LV remodeling may be affected by MPC injection post-MI, and whether these effects are concentration-dependent, remain unknown. METHODS AND RESULTS: Allogeneic MPCs were expanded from sheep bone marrow, and direct intramyocardial injection was performed within the borderzone region 1 hour after MI induction (coronary ligation) in sheep at the following concentrations: 25x10(6) (25 M, n=7), 75x10(6) (75 M, n=7), 225x10(6) (225 M, n=10), 450x10(6) (450 M, n=8), and MPC free media only (MI Only, n=14). LV end diastolic volume increased in all groups but was attenuated in the 25 and 75 M groups. Collagen content within the borderzone region was increased in the MI Only, 225, and 450 M groups, whereas plasma ICTP, an index of collagen degradation, was highest in the 25 M group. Within the borderzone region matrix metalloproteinases (MMPs) and MMP tissue inhibitors (TIMPs) also changed in a MPC concentration-dependent manner. For example, borderzone levels of MMP-9 were highest in the 25 M group when compared to the MI Only and other MPC treatment group values. CONCLUSIONS: MPC injection altered collagen dynamics, MMP, and TIMP levels in a concentration-dependent manner, and thereby influenced indices of post-MI LV remodeling. However, the greatest effects with respect to post-MI remodeling were identified at lower MPC concentrations, thus suggesting a therapeutic threshold exists for this particular cell therapy.

Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension.

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.

Assessment of left ventricular systolic function by echocardiography.

Echocardiography serves an extremely important role in the diagnosis and management of patients with heart failure. The various stages of structural and functional changes that constitute progressive left ventricle remodeling have all been characterized by two-dimensional echocardiography. In addition, echocardiography has defined the transition from compensated hypertrophy to left ventricle dilatation and progression to end-stage heart failure. Echocardiography has also played an important role in clinical heart failure trials of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and demonstrated their efficacy in heart failure.

Economic value and cost-effectiveness of biventricular versus right ventricular pacing: results from the BLOCK-HF study.

Aims: The Biventricular vs Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) demonstrated that biventricular (BiV) pacing resulted in better clinical and structural outcomes compared to right ventricular (RV) pacing in patients with atrioventricular (AV) block and reduced left ventricular ejection fraction (LVEF; ≤50%). This study investigated the cost-effectiveness of BiV vs RV pacing in the patient population enrolled in the BLOCK-HF trial. Methods: All-cause mortality, New York Heart Association (NYHA) Class distribution over time, and NYHA-specific heart failure (HF)-related healthcare utilization rates were predicted using statistical models based on BLOCK-HF patient data. A proportion-in-state model calculated cost-effectiveness from the Medicare payer perspective. Results: The predicted patient survival was 6.78 years with RV and 7.52 years with BiV pacing, a 10.9% increase over lifetime. BiV pacing resulted in 0.41 more quality-adjusted life years (QALYs) compared to RV pacing, at an additional cost of $12,537. The "base-case" incremental cost-effectiveness ratio (ICER) was $30,860/QALY gained. Within the clinical sub-groups, the highest observed ICER was $43,687 (NYHA Class I). Patients receiving combined BiV pacing and defibrillation (BiV-D) devices were projected to benefit more (0.84 years gained) than BiV pacemaker (BiV-P) recipients (0.49 years gained), compared to dual-chamber pacemakers. Conclusions: BiV pacing in AV block patients improves survival and attenuates HF progression compared to RV pacing. ICERs were consistently below the US acceptability threshold ($50,000/QALY). From a US Medicare perspective, the additional up-front cost associated with offering BiV pacing to the BLOCK-HF patient population appears justified.

Failure of digital echocardiography to accurately diagnose intracardiac shunts.

BACKGROUND: Intravenous agitated saline injection during transthoracic echocardiography assists in the detection of right to left intracardiac and intrapulmonary shunts. Whether digital echocardiography offers comparable sensitivity and specificity to analog tape recording to assess shunts is unknown. Technical differences between methods could lead to significant differences in shunt detection. METHODS: Agitated saline was injected intravenously at rest and with Valsalva in 189 consecutive patient studies (406 injections). Echocardiographers assessed presence and degree of left ventricle contrast on simultaneously recorded analog tape and digital echocardiography images in blinded fashion. RESULTS: Digital echocardiography had low overall sensitivity (rest 0.50, valsalva 0.63, late 0.39) compared to analog tape. Longer clip lengths improved sensitivity for detection of late contrast passage (rest 0.50, valsalva 0.67, late 0.46). CONCLUSION: Digital echocardiography saline contrast studies have poor sensitivity for assessment of intracardiac shunts versus analog tape, and increasing clip length only modestly increases sensitivity. Joint Photographic Experts Group digital compression losses may be an important cause of failure to detect intracardiac shunts, including patent foramen ovale.

Patterns of structural and functional remodeling of the left ventricle in chronic heart failure.

Patients with heart failure show a wide variety of alterations in left ventricular (LV) volume, mass, and function. The purpose of this study was to define the common patterns of LV structural and functional remodeling and consider their clinical implications in patients with chronic heart failure. Two-dimensional echocardiograms obtained during the screening phase of a study involving patients (n = 315) with chronic heart failure were used to calculate LV volume, mass, geometry, and ejection fraction (EF). Inclusion required the diagnosis of heart failure in symptomatic patients on medical therapy. Measures of LV size or function were not used as inclusion or exclusion criteria. Plots of EF against LV end-diastolic volume (EDV) showing an inverse curvilinear relation allowed a description of 4 remodeling patterns. Pattern A (n = 66) was defined as normal EDV (<91 ml/m(2)) and normal EF (> or =50%); 65% of these patients showed LV hypertrophy or concentric remodeling. Pattern B (n = 65) was defined as normal EDV and depressed EF; hypertrophy or concentric remodeling was present in 63%. Pattern C (n = 175) was defined as increased EDV and depressed EF; eccentric hypertrophy was present in 94%. Pattern D (n = 9) was defined as increased EDV and normal EF; eccentric hypertrophy was present in 88%. In conclusion, these patterns of remodeling encompass a wide spectrum of geometric changes with different clinical and pathophysiologic features and possibly different management strategies.

Effects of cardiac resynchronization therapy on ventricular remodeling.

Remodeling reflects the structural and functional deterioration that occurs in heart failure. Indices of remodeling constitute an important marker of the severity of heart failure, and reverse remodeling is an accepted goal in the treatment of heart failure. Cardiac resynchronization therapy (CRT) has been shown to reverse the remodeling process by improving ventricular size, shape, and mass and reducing mitral regurgitation in the short and long term. Diastolic function, right ventricular size, and atria exhibit reverse remodeling. Trials of medical therapy for heart failure strongly link remodeling indices with outcomes, and emerging data suggest that remodeling indices may be among the most accurate predictors of long-term morbidity and mortality in heart failure patients with CRT devices. This review discusses remodeling and focuses on the evidence for CRT-induced reverse remodeling.

Racial/Ethnic Differences in Left Ventricular Structure and Function in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. METHODS: In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors. RESULTS: We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69). CONCLUSION: In a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients.

Effect of annular shape on leaflet curvature in reducing mitral leaflet stress.

BACKGROUND: Leaflet curvature is known to reduce mechanical stress. There are 2 major components that contribute to this curvature. Leaflet billowing introduces the most obvious form of leaflet curvature. The saddle shape of the mitral annulus imparts a more subtle form of leaflet curvature. This study explores the relative contributions of leaflet billowing and annular shape on leaflet curvature and stress distribution. METHODS AND RESULTS: Both numerical simulation and experimental data were used. The simulation consisted of an array of numerically generated mitral annular phantoms encompassing flat to markedly saddle-shaped annular heights. Highest peak leaflet stresses occurred for the flat annulus. As saddle height increased, peak stresses decreased. The minimum peak leaflet stress occurred at an annular height to commissural width ratio of 15% to 25%. The second phase involved data acquisition for the annulus from 3 humans by 3D echocardiography, 3 sheep by sonomicrometry array localization, 2 sheep by 3D echocardiography, and 2 baboons by 3D echocardiography. All 3 species imaged had annuli of a similar shape, with an annular height to commissural width ratio of 10% to 15%. CONCLUSION: The saddle shape of the mitral annulus confers a mechanical advantage to the leaflets by adding curvature. This may be valuable when leaflet curvature becomes reduced due to diminished leaflet billowing caused by annular dilatation. The fact that the saddle shape is conserved across mammalian species provides indirect evidence of the advantages it confers. This analysis of mitral annular contour may prove applicable in developing the next generation of mitral annular prostheses.

Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT. METHODS AND RESULTS: Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both P<0.001), reduced LV mass (P<0.01), increased ejection fraction (P<0.001), reduced MR (P<0.001), and improved myocardial performance index (P<0.001) compared with control. beta-Blocker treatment status did not influence the effect of CRT. Improvements with CRT were greater in patients with a nonischemic versus ischemic cause of heart failure. CONCLUSIONS: CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling, improved systolic and diastolic function, and decreased MR. LV remodeling likely contributes to the symptomatic benefits of CRT and may herald improved longer-term survival.

Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling.

BACKGROUND: Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region- and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown. METHODS AND RESULTS: Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9+/-5.4%), transition (18.0+/-2.9%), and MI (53.8+/-11.0%) regions at 8 weeks after MI (P<0.05) and was greatest in the MI region (P<0.05). Region- and type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 abundance was unchanged in the remote, fell to 3+/-2% in the transition, and was undetectable in the MI region (P<0.05). MMP-13, MMP-8, and MT1-MMP increased by >300% in the transition and MI regions (P<0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region. CONCLUSIONS: The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.

Prevention of ischemic mitral regurgitation does not influence the outcome of remodeling after posterolateral myocardial infarction.

OBJECTIVES: This study was designed to test the hypothesis that ischemic mitral regurgitation (IMR) results from, but does not influence, the progression of left ventricular (LV) remodeling after posterolateral infarction. BACKGROUND: Surgical correction of chronic IMR is being increasingly recommended. METHODS: Three groups of sheep had coronary snares placed around the second and third obtuse marginal coronary arteries. Occlusion of these vessels in the control group resulted in progressive IMR over eight weeks. In a second group, Merseline mesh was fitted to cover the exposed LV before infarction. In a third group, a ring annuloplasty was placed before infarction to prevent IMR. Remodeling and degree of IMR were assessed with echocardiography at baseline and at 30 min and two, five, and eight weeks after infarction. RESULTS: Eight weeks after infarction, mean IMR grade was significantly higher in control animals than mesh and annuloplasty animals. At eight weeks, LV end-systolic volume and end-systolic muscle-to-cavity-area ratio (ESMCAR) were significantly better in mesh-treated sheep than in control sheep; also, at eight weeks, ESMCAR and akinetic segment length were significantly better in mesh-treated sheep than in annuloplasty sheep. Ejection fraction was significantly higher in the mesh than the annuloplasty group. There was no significant difference in any measure of remodeling between the annuloplasty and control groups. CONCLUSIONS: Prophylactic ventricular restraint reduces infarct expansion, attenuates adverse remodeling, and reduces IMR severity. Prevention of IMR by prophylactic ring annuloplasty does not influence remodeling. Ischemic mitral regurgitation is a consequence, not a cause, of postinfarction remodeling; infarct expansion is the more important therapeutic target.

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.

Ventricular assist devices for treatment of acute heart failure and chronic heart failure.

Despite therapeutic advances that improve longevity and quality of life, heart failure (HF) remains a relentless disease. At the end stage of HF, patients may become eligible for mechanical circulatory support (MCS) for the indications of stabilising acute cardiogenic shock or for chronic HF management. MCS use is growing rapidly in the USA and some countries of the European Union, especially in transplant-ineligible patients. In others, it remains largely a tool to stabilise patients until heart transplant. MCS comprises a heterogeneous group of temporary and durable devices which augment or replace the pumping function of one or both ventricles, with postimplant 2 year survival rivalling that of transplant in selected, lower-risk patients. In transplant-eligible and non-transplant-eligible patients, improvement in end-organ perfusion, functional capacity and quality of life have been noted. Even for optimal candidates, however, there are a host of potential complications that require constant vigilance of a coordinated care team. Recently, there has been official recognition of the importance of palliative care expertise in advance care planning preimplant and management of patients with ventricular assist devices at the end of their lives.

Annuloplasty ring selection for chronic ischemic mitral regurgitation: lessons from the ovine model.

BACKGROUND: Chronic ischemic mitral regurgitation (CIMR) is poorly understood and repair operations are often unsatisfactory. This study elucidates the mechanism of CIMR in an ovine model. METHODS: Sonomicrometry array localization measured the three-dimensional geometry of the mitral annulus and subvalvular apparatus in five sheep before and 8 weeks after a posterior infarction of the left ventricle that produced progressive severe CIMR. RESULTS: End systolic annular area increased from 647 +/- 44 mm(2) to 1,094 +/- 173 mm(2) (p = 0.01). Annular dilatation occurred equally along the anterior (47.0 +/- 5.6 mm to 60.2 +/- 4.9 mm, p = 0.001) and posterior (53.8 +/- 3.1 mm to 68.5 +/- 8.4 mm, p = 0.005) portions of the annulus. The tip of the anterior papillary muscle moved away from both the anterior and posterior commissures by 5.2 +/- 3.2 mm (p = 0.021) and 7.3 +/- 2.2 mm (p = 0.002), respectively. The distance from the tip of the posterior papillary muscle to the anterior commissure increased by 11.0 +/- 5.7 mm (p = 0.032) while the distance from the tip of the posterior papillary muscle to the posterior commissure remained constant. CONCLUSIONS: Progressive dilatation of both the anterior and posterior mitral annuli, increased annular area, and asymmetric ventricular dilatation combine to cause CIMR by distortion of mitral valve geometry and tethering of leaflet coaptation. Therefore complete ring annuloplasty may be superior to partial annuloplasty in the treatment of CIMR.

Infarct restraint attenuates remodeling and reduces chronic ischemic mitral regurgitation after postero-lateral infarction.

BACKGROUND: Chronic ischemic mitral regurgitation (IMR) is produced by adverse postinfarction ventricular remodeling. We hypothesize that restraining infarct expansion reduces left-ventricular (LV) dilatation and the severity of mitral regurgitation. METHODS: Two groups of 6 sheep had coronary snares placed around the second and third obtuse marginal coronary arteries and four piezoelectric transducers sutured within myocardium across the mid short axis of the LV. In one group, a patch of Marlex mesh was precisely fitted and lightly sutured to myocardium destined for infarction (determined by temporary snare occlusion). Two weeks after instrumentation, coronary snares were tied tight to infarct approximately 24% of the posterolateral LV mass. Transdiaphragmatic echocardiograms were obtained in all animals at baseline, and 30 minutes, and 2, 5, and 8 weeks after infarction. RESULTS: Echocardiograms confirmed similar infarct sizes and locations in both groups. Eight weeks after infarction, IMR grade averaged 3.6+ (scale: 0, no MR; 4, severe MR) in control sheep and 1.9+ in mesh-restrained animals (p = 0.0001). LV end-diastolic and end-systolic volumes at the eighth week were less in mesh-treated sheep (87 +/- 11.3 vs 113 +/- 18.3; 61 +/- 10.6 vs 77 +/- 14.1, respectively), but differences were not significant. Data from mid short axis piezoelectric transducers indicated significantly less strain in the infarcted myocardium in mesh-restrained sheep than in control. CONCLUSIONS: Early restraint of postero-lateral infarct expansion attenuates the severity of ischemic mitral regurgitation and slows ventricular dilatation. However, the remodeling process is not arrested 8 weeks after infarction.

An ovine model of postinfarction dilated cardiomyopathy.

BACKGROUND: Coronary arterial disease is the major cause of congestive heart failure, but suitable animal models of postinfarction, dilated cardiomyopathy do not exist. This article describes an ovine model that develops after an anterobasal infarction. METHODS: The distribution of ovine myocardium supplied by the first two diagonal branches of the left homonymous artery were determined in 20 slaughterhouse hearts and eight live sheep using methylene blue and tetrazolium injections, respectively. Seven additional animals had the infarction and underwent serial hemodynamic, microsphere and echocardiographic studies more than 8 weeks and histologic studies at the eighth week. Infarcts represented 24.6% +/- 4.7% and 23.9% +/- 2.2% of the left ventricular mass in slaughterhouse and live hearts, respectively. RESULTS: During remodeling, left ventricular end-systolic and end-diastolic volumes increased 115% and 73%, respectively, ejection fraction decreased from 41.2% +/- 6.7% to 29.1% +/- 5.7%, systolic wall thickening remote from the infarct decreased by 68%, sphericity index increased from 0.465 +/- 0.088 to 0.524 +/- 0.038, and left ventricular end-diastolic pressure increased from 1.7 +/- 1.0 to 8.2 +/- 3.5 mm Hg. Serial microsphere measurements documented normal blood flow (1.34 mL/g per minute) to all uninfarcted myocardium and 22% of normal to the infarct. Viable myocardium showed mild interstitial fibrosis. CONCLUSIONS: This ovine model meets all criteria for postinfarction, dilated cardiomyopathy and has the advantages of controlling for variations in coronary arterial anatomy, collateral vascularity, and differences in the numbers, location, and severity of atherosclerotic lesions that confound human studies of the pathogenesis of this disease. This simple model contains only infarcted and fully perfused, hypocontractile myocardium produced by a moderate-sized, regional infarction.