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Background: Although implantation of a left ventricular assist device (LVAD) induces reverse remodeling of the left ventricle in end-stage nonischemic dilated cardiomyopathy (DCM), the underlying mechanism is not fully understood. It has been shown that epigenetic modification, such as methylation or acetylation of the histone, is one of the most important upstream signals in cardiac failure. This study hypothesized that histone profiles may be modified by LVAD implantation for end-stage nonischemic DCM, in association with reverse left ventricular remodeling., Methods: Hemodynamic changes associated with histone modification profiles in the left ventricle were comprehensively assessed in 14 patients with a diagnosis of end-stage nonischemic DCM. These patients underwent LVAD implantation and subsequent cardiac transplantation in our institution (Osaka University Hospital, Osaka, Japan). Samples of normal left ventricle from 3 different people were used as a control., Results: After LVAD support for 2.5 ± 1.2 years, the study cohort showed a significant reverse remodeling of left ventricular function associated with histopathologic changes in the left ventricle, such as reduction of myocyte size. Although the left ventricle of the cohort histologically expressed less 3 histone methylation-related molecules (eg, H3 lysine 4 trimethylation [H3K4me3], H3 lysine 9 dimethylation [H3K9me2], and H3 lysine 9 trimethylation [H3K9me3]) compared with normal left ventricle, LVAD support reversed expression of these molecules, associated with up-regulation of H3 lysine 9 [H3K9] methyltransferase and suppressor of variegation 3-9 homologue 1 [SUV39H1] and with down-regulation of H3K9 demethylase and jumonji domains [JMJDs] in the LVAD-supported left ventricle. Moreover, expression of atrial natriuretic peptide and brain natriuretic peptide (ANP and BNP) was negatively correlated with that of H3K9me2 and H3K9me3., Conclusions: The epigenetic state of cardiac myocytes (eg, as histone methylation) was substantially modulated in end-stage nonischemic DCM. LVAD support partially reversed the epigenetic state and its upstream signals, in association with pathologic and functional reverse remodeling., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac valve disease is common in patients with end-stage heart failure undergoing left ventricular assist device implantation (LVAD). The aim of this study was to determine if preoperative mitral regurgitation (MR) affects outcomes and hemodynamics in patients after LVAD implantation., Methods: From March 2006 through May 2015, 238 consecutive patients underwent LVAD implantation. Patient cohorts included less than moderate to severe MR (< moderate-severe, n = 195) and greater than or equal to moderate to severe MR (≥ moderate-severe, n = 43). Demographics, operative characteristics, postoperative outcomes, hemodynamic and echocardiographic data, and resolution of MR were compared at 30 and 180 days post-LVAD., Results: Significant hemodynamic improvements were seen in central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, left ventricular ejection fraction, and left ventricular end-diastolic diameter, irrespective of preoperative MR severity. Significant resolution of MR occurred across both cohorts, with only 4 of 168 (2.4%) patients with ≥ moderate-severe MR at 180 days post-LVAD. There were no differences in complications or survival between MR severity cohorts postoperatively., Conclusions: LVAD implantation unloads the left ventricle to promote left ventricle reverse remodeling and correct functional MR across all severity levels. The resolution of MR is sustained at 180 days post-LVAD. These results coupled with no survival difference with uncorrected MR between < moderate-severe MR and ≥ moderate-severe MR makes concomitant mitral valve repair or replacement at the time of LVAD implantation unnecessary., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The mechanism underlying left ventricular remodeling and reverse remodeling in the setting of mechanical support following acute myocardial infarction (MI) is unclear. We tested the hypothesis that left ventricular assist device (LVAD) unloading can decrease apoptotic signals after MI., Methods: An MI model was created in 16 sheep by coronary artery ligation. Eight were unloaded with a LVAD during the first 2 weeks after MI and observed for 10 more weeks. Myocardial tissue was collected from the nonischemic adjacent zone and the remote zone. Proteins in the apoptotic matrix metalloproteinases (MMPs)-2/c-Jun N-terminal kinase (JNK) and prosurvival β1D-integrin/focal adhesion kinase (FAK) pathway were quantified., Results: Increased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive nuclei were observed in the MI group and to a lesser extent in the LVAD group (6.18 ± 0.26 versus 0.82 ± 0.18; p < 0.05). Pro-MMP-2, MMP-2, JNK, and phosphorylated (p)-JNK were all elevated in the adjacent zone of the MI-only group but not in the adjacent zone of the LVAD-supported group. There were higher levels of prosurvival p-FAK in the LVAD-supported group than in the MI group., Conclusions: MMP-2/JNK apoptotic and β1D-integrin/FAK survival pathways are activated in the nonischemic adjacent zone after MI in adult sheep. LVAD unloading of approximately 50% cardiac output for 2 weeks attenuates remodeling in part by its negative effect on stretch-induced apoptosis and inhibition of MMP-2 activity., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Surgical extended septal myectomy is appropriate treatment for obstructive hypertrophic cardiomyopathy (HCM) with refractory symptoms. Using 3-layer speckle tracking imaging, we aimed to evaluate the effects of myectomy on left ventricular (LV) regions and the potential factors associated with LV reverse remodeling., Methods: In 71 patients (mean age, 41.0 ± 15.0 years) undergoing septal myectomy, 3-layer speckle tracking was performed before myectomy and latest review. We evaluated the myectomy site (target anteroseptum) and LV free wall longitudinal strain (LS) and circumferential strain (CS) in endocardial, midmyocardial, and epicardial layers. The thickness of each free wall segment was calculated and totaled for the free wall thickness score., Results: Compared with before myectomy, LS increased; however, CS decreased at the myectomy site after myectomy. For the free wall, LS and CS improved in all 3 layers after the procedure (all p < 0.05). Factors independently associated with latest-review free wall strain were free wall thickness score (LS, β = -0.150; p < 0.001; CS, β = -0.090; p < 0.001), age (LS, β = 0.118; p < 0.001), and ΔLV outflow tract gradient (CS, β = 0.039; p = 0.002). Factors independently associated with myectomy site strain were resected thickness (LS, β = -0.439; p = 0.001; CS, β = -0.736; p = 0.001), and age (LS, β = 0.178; p < 0.001)., Conclusions: Sufficient relief of obstruction and lower resected thickness in the target anteroseptum lead to more favorable remodeling. Free wall thickness score and age are important factors associated with reverse remodeling., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure., Methods: Previously described finite element models of the LV based on magnetic resonance imaging data obtained in 5 sheep 16 weeks after anteroapical myocardial infarction were used. Simulated polyethylene terephthalate fiber (Dacron) patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated, and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated., Results: VIRTUAL-DOR was associated with significant RS that was tensile (2.89 ± 1.31 kPa) in the remote myocardium and compressive (234.15 ± 65.53 kPa) in the border zone. VIRTUAL-DOR+RS (compared with VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS, with the greatest change in the border zone (43.5-fold and 7.1-fold, respectively; p < 0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%; p = 0.0606, and 10.6%; p = 0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS., Conclusions: Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the border zone and associated with reductions in FS and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In adults, myocardial infarction (MI) results in a brisk inflammatory response, myocardium loss, and scar formation. We have recently reported the first mammalian large-animal model of cardiac regeneration after MI in fetal sheep. We hypothesize that the ability of the fetus to regenerate functional myocardium after MI is owing to differential gene expression regulating the response to MI in the fetus compared with the adult., Methods: Myocardial infarction was created in adult (n=4) or early gestation fetal (n=4) sheep. Tissue was harvested after 3 or 30 days, and RNA was extracted for microarray, followed by principal component analysis and global gene expression analysis for the following gene ontology terms: response to wounding, inflammatory response, extracellular matrix, cell cycle, cell migration, cell proliferation, and apoptosis., Results: Principal component analysis demonstrated that the global gene expression pattern in adult infarcts was distinctly different from the uninfarcted region at 3 days and remained different at 30 days after MI. In contrast, gene expression in the fetal infarct was different from the uninfarcted region at 3 days, but by 30 days it returned to a baseline expression pattern similar to the uninfarcted region. Three days after MI there was an increase in the expression of genes related to all gene ontology terms in fetal and adult infarcts, but this increase was much more pronounced in adults. By 30 days, the fetal gene expression returned to baseline, whereas in the adult it remained significantly elevated., Conclusions: These data demonstrate that the global gene expression pattern is dramatically different in the fetal regenerative response to MI compared with the adult response and may partly be responsible for the regeneration., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Valve-sparing root replacement is controversial in patients with significant aortic insufficiency (AI) because the aortic valve cusps often require repair, which may potentially jeopardize long-term valve function. The purpose of this study was to evaluate valve function and left ventricular reverse remodeling in patients undergoing valve-sparing root replacement in the setting of significant AI., Methods: A review of the Emory Aortic Surgery database between 2004 and 2012 identified 616 aortic root replacements. Of these procedures, 169 were performed for patients with 3+ or greater AI. Fifty-one patients (30%) underwent a David V procedure. Echocardiography was used to evaluate the degree of AI, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter., Results: The mean echocardiographic follow-up was 18 ± 21 months (range, 1 to 89). Patients undergoing valve-sparing root replacement had an increase in ejection fraction (preoperative 51% ± 7% versus postoperative 57% ± 6%, p < 0.01) and a reduction in left ventricular end-diastolic diameter (preoperative 58 ± 8 mm versus postoperative 48 ± 6 mm, p < 0.01) and left ventricular end-systolic diameter (preoperative 40 ± 8 mm versus postoperative 32 ± 6 mm, p < 0.01). During the follow-up period, freedom from greater than 1+ AI was 96%, and freedom from aortic valve replacement was 98%. The addition of cusp repair did not represent a significant risk factor for recurrent postoperative AI (p = 0.21)., Conclusions: The David V technique produces significant left ventricular reverse remodeling and improved ventricular function in patients with chronic severe AI. Long-term data and close follow-up will be paramount in evaluating the durability of valve repair in this patient population., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The Acorn CorCap Cardiac Support Device (CSD; Acorn Cardiovascular Inc, St. Paul, MN) is a woven polyester jacket that is placed around the heart and designed to reverse the progressive remodeling associated with dilated cardiomyopathy. However, the effects of the Acorn CSD on myofiber stress and ventricular function remain unknown. We tested the hypothesis that the Acorn CSD reduces end-diastolic (ED) myofiber stress., Methods: A previously described weakly coupled biventricular finite element (FE) model and circulatory model based on magnetic resonance images of a dog with dilated cardiomyopathy was used. Virtual applications of the CSD alone (Acorn), CSD with rotated fabric fiber orientation (rotated), CSD with 5% prestretch (tight), and CSD wrapped only around the left ventricle (LV; LV-only) were performed, and the effect on myofiber stress at ED and pump function was calculated., Results: The Acorn CSD has a large effect on ED myofiber stress in the LV free wall, with reductions of 55%, 79%, 92%, and 40% in the Acorn, rotated, tight, and LV-only cases, respectively. However, there is a tradeoff in which the Acorn CSD reduces stroke volume at LV end-diastolic pressure of 8 mm Hg by 23%, 25%, 30%, and 7%, respectively, in the Acorn, rotated, tight, and LV-only cases., Conclusions: The Acorn CSD significantly reduces ED myofiber stress. However, CSD wrapped only around the LV was the only case with minimal negative effect on pump function. Findings suggest that LV-only CSD and Acorn fabric orientation should be optimized to allow maximal myofiber stress reduction with minimal reduction in pump function., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Traditional pulmonary artery banding (PAB) is not always suitable for mature subpulmonary ventricle retraining. We sought to assess in detail the myocardial morphologic adaptations of two different protocols for inducing right ventricular (RV) hypertrophy in an adult animal model., Methods: Eighteen adult goats were distributed into three groups: sham (no systolic overload), traditional (continuous systolic overload), and intermittent (daily 12-hour systolic overload). Systolic overload was adjusted to achieve a 0.7 RV-to-aortic pressure ratio. All animals underwent weekly echocardiographic studies, and hemodynamic evaluations were performed 3 times a week. After 4 weeks, the animals were humanely killed for morphologic assessment., Results: A 37.2% increase was observed in the RV wall thickness of the intermittent group (p<0.05), but no significant echocardiographic changes were observed in the other two groups. The intermittent and traditional groups had a 55.7% and 36.7% increase in RV mass, respectively, compared with the sham group (p<0.05). No differences were observed in myocardial water content of the three groups (p=0.27). RV myocardial fiber and nuclei diameters were increased in the intermittent group compared with the sham group (p<0.05). The area of collagen deposition in the RV interstitium was increased 98% in traditional group compared with the sham group (p<0.05). No significant cellular proliferation occurred in any group., Conclusions: This study suggests that a more effective and harmless hypertrophy can be achieved in adult animals using intermittent PAB compared with the traditional approach., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Preventing expansion and dyskinetic movement of a myocardial infarction (MI) can limit left ventricular (LV) remodeling. Using a device designed to produce variable alteration of infarct stiffness and geometry, we sought to understand how these parameters affect LV function and remodeling early after MI., Methods: Ten pigs had posterolateral infarctions. An unexpanded device was placed in 5 animals at the time of infarction and 5 animals served as untreated controls. One week after MI animals underwent magnetic resonance imaging to assess LV size and regional function. In the treatment group, after initial imaging, the device was expanded with 2, 4, 6, 8, and 10 mL of saline. The optimal degree of inflation was defined as that which maximized stroke volume (SV). The device was left optimally inflated in the treatment animals for 3 additional weeks., Results: One week after MI, device inflation to 6 mL or greater significantly (p < 0.05) decreased end-systolic volume (0 mL, 59.9 mL ± 3.8; 6 mL, 54.0 mL ± 3.1; 8 mL, 50.5 mL ± 4.8; and 10 mL, 46.1 mL ± 2.2) and increased ejection fraction (EF) (0 mL, 0.346 ± 0.016; 6 mL, 0.0397 ± 0.009; 8 mL, 0.431 ± 0.027; and 10 mL, 0.441 ± 0.009). Systolic volume significantly (p < 0.05) improved for the 6 mL and 8 mL volumes (0 mL, 31.2 mL ± 2.6; 6 mL, 35.7 mL ± 2.0; and 8 mL, 37.5 mL ± 1.9) but trended downward for 10 mL (36.6 mL ± 2.8). At 4 weeks after MI, end-diastolic volume and end-systolic volume were unchanged from 1-week values in the treatment group while the control group continued to dilate. Systolic volume (38.2 ± 4.4 mL vs 34.0.1 ± 4.8 mL, p = 0.08) and EF (0.360 ± 0.026 vs 0.276 ± 0.014, p = 0.04) were also better in the treatment animals., Conclusions: Optimized isolated infarct restraint can limit adverse LV remodeling after MI. The tested device affords the potential for a patient-specific therapy to preserve cardiac function after MI., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Stentless porcine bioroots and pericardial composite roots were developed as prostheses that avoid the anticoagulation necessary for mechanical composite roots. Data on the hemodynamics of all root replacements are lacking and questions remain regarding comparative performance., Methods: This study evaluated patients receiving a stentless porcine bioroot, a pericardial, or a mechanical composite root at a single institution from January 2000 to December 2008. All patients underwent preoperative, postoperative and greater than 1-year echocardiograms. All root replacements were performed for aortic insufficiency or aneurysm. Median follow-up was 3.3 years (1 to 8 years)., Results: There were no significant differences in preoperative left ventricular ejection fraction, aortic valve peak gradient, mean gradient, left ventricular end diastolic diameter, and left ventricular end systolic diameter. Postoperative peak and mean gradients in mechanical composite roots were significantly higher than stentless porcine bioroots. At greater than 1 year, stentless porcine bioroots had significantly lower peak and mean gradients than both mechanical composite roots and pericardial composite roots. The end diastolic diameter was also significantly smaller in stentless porcine bioroots at greater than 1 year than mechanical composite roots., Conclusions: All prostheses resulted in favorable hemodynamic and ventricular remodeling. Stentless porcine bioroots had the lowest gradients at greater than 1 year of all root replacements, with significantly better ventricular remodeling when compared with mechanical composite roots. Pericardial roots also had favorable hemodynamics and ventricular remodeling, suggesting that they are a viable alternative., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Tricuspid valve surgery in the presence of severe right ventricular dysfunction and pulmonary hypertension secondary to mitral valve stenosis is associated with poor early outcomes. We report the case of a young patient, presenting with severe chronic mitral-tricuspid disease responsible for long-lasting pulmonary hypertension and altered right ventricular function, who initially underwent mitral valve replacement and 7 days later the correction of her tricuspid insufficiency. This 2-staged approach permitted progressive reduction of pulmonary pressure and partial right ventricular remodeling before closing the systolic release valve of the right ventricle represented by tricuspid regurgitation., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc, Maple Grove, MN) implantation using a finite element model of the left ventricle (LV). Chronic ischemic mitral regurgitation is caused by LV remodeling after posterolateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases chronic ischemic mitral regurgitation., Methods: Finite element models of the LV were based on magnetic resonance images obtained before (preoperatively) and after (postoperatively) coronary artery bypass grafting with Coapsys implantation in a single patient. To determine the effect of Coapsys and LV before stress, virtual Coapsys was performed on the preoperative model. Diastolic and systolic material variables in the preoperative, postoperative, and virtual Coapsys models were adjusted so that model LV volume agreed with magnetic resonance imaging data. Chronic ischemic mitral regurgitation was abolished in the postoperative models. In each case, myofiber stress and pump function were calculated., Results: Both postoperative and virtual Coapsys models shifted end-systolic and end-diastolic pressure-volume relationships to the left. As a consequence and because chronic ischemic mitral regurgitation was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at end-diastole and end-systole in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV prestress was necessary for accurate calculation of LV myofiber stress, especially in the remote zone., Conclusions: Coapsys decreases myofiber stress at end-diastole and end-systole. The improvement in myofiber stress may contribute to the long-term effect of Coapsys on LV remodeling., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

HeartWare continuous flow ventricular assist devices (HVAD) configured as biventricular assist devices maintain diurnal flow variation, lead to end-organ recovery, and provide for a successful bridge-to-heart transplantation in the first successful North American use of continuous flow biventricular assist devices., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Weaning from left ventricular assist devices (LVADs) after myocardial recovery in patients with idiopathic dilated cardiomyopathy is a clinical option. With the broad application of continuous-flow pumps, we observed a decrease in the numbers of possible LVAD explanations due to myocardial recovery in these particular patients. We investigated this phenomenon and its causes., Methods: Between July 1992 and December 2009, 387 patients (age, 0.1 to 82 years) with idiopathic dilated cardiomyopathy underwent LVAD implantation at our institution. Patients were divided into two groups depending on whether they were weaned from the LVAD (group A) or not (group B). Univariate and multivariate analyses were performed on 24 different factors with a possible influence on myocardial recovery., Results: In 34 patients, LVAD removal due to myocardial recovery was performed with long-term stable cardiac function (weaning rate, 8.8%). Patients with a pulsatile-flow LVAD had an almost threefold chance for myocardial recovery (odds ratio, 2.719; 95% confidence interval, 1.182 to 6.254) than patients who received continuous-flow devices. Younger patients had significantly higher recovery rates than older patients (odds ratio, 1.036; 95% confidence interval, 1.016 to 1.057)., Conclusions: Pulsatile-flow LVADs and young age were important factors for myocardial recovery in idiopathic dilated cardiomyopathy patients in our analysis. Further studies should investigate whether pulsatility in itself or the different degrees of left ventricular unloading by the two types of systems play a role in myocardial recovery., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We conducted a prospective study of the clinical outcomes and health-related quality of life after implantation of the CorCap support device (Acorn Cardiovascular Inc, St Paul, MN) for dilated cardiomyopathy., Methods: The criteria adopted for CorCap implantation were dilated cardiomyopathy (left ventricular [LV] end-diastolic diameter≥60 mm, LV ejection fraction≤0.30 and >0.10), and New York Heart Association functional class II or III despite maximal medical therapy. Echocardiographic follow-up and evaluation with the Short Form-36 questionnaire were performed., Results: Included were 39 patients: 5 in New York Heart Association class II and 32 in class III. At 13.3±2.5 months of follow-up, a statistically significant improvement was evident in mean LV volume (LV end-systolic volume from 202±94 to 138±72 ml. p=0.005) and systolic function (LV ejection fraction from 0.26±0.05 to 0.36±0.05, p<0.001). The mean LV sphericity index was significantly increased at the end of the follow-up (p=0.009). Ischemic etiology, diabetes, advanced age, and LV ejection fraction of less than 0.15 predicted lesser reversal of the LV alterations. Operative mortality was 5.1%. Cumulative follow-up mortality was 10.2%. The average Physical Health domain scores (Physical Functioning, Role Physical, General Health) were improved. Average Mental Health domain scores were also increased., Conclusions: The cardiac support device obtains reverse remodelling of the LV and is useful to improve the quality of life of patients with dilated cardiomyopathy and New York Heart Association class III symptoms of heart failure. The integration of different and complementary strategies (cardiac support device and resynchronization therapy) may represent the key to success for more complex patients, although further studies are required., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular assist devices (LVAD)-induced unloading appear to cause reverse cardiac remodeling. However, its effect on arrhythmogenicity is a controversial issue, and prospective data are lacking. We sought to investigate the impact of LVAD-induced unloading on the electrical properties of the failing heart., Methods: We prospectively studied the effects of LVAD therapy on QRS, QT, and QTc durations and ventricular arrhythmias from electrocardiograms and 24-hour ambulatory electrocardiograms recorded before and during 6 months of mechanical support in 12 LVAD patients and 7 other patients with advanced nonischemic cardiomyopathy untreated with LVAD., Results: After 1 week of LVAD support, QTc duration had decreased from 479 ± 79 ms to 411 ± 57 ms (p = 0.037), and QRS duration from 150 ± 46 ms to 134 ± 32 ms (p = 0.029). At 6 months, QTc was found to be 372 ± 56 ms (p = 0.046 versus baseline, 15% shortening) and QRS 118 ± 25 ms (p = 0.028 versus baseline, 11% shortening). A strong correlation was found between QTc shortening and increase in left ventricular ejection fraction and decrease in left ventricular filling pressures. After 2 months of LVAD support, premature ventricular contractions had decreased from 3,507 ± 4,252 to 483 ± 417 in 24 hours (p = 0.043), ventricular couplets from 82 ± 99 to 29 ± 25 in 24 hours (p = 0.05), and ventricular runs from 9 ± 8 to 10 ± 9 (not significant). No patient died suddenly or suffered a symptomatic arrhythmic event during follow-up. No significant electrocardiographic, functional, or hemodynamic change was observed in the 7 patients untreated with LVAD., Conclusions: The LVAD support caused progressive shortening of QTc and QRS intervals, consistent with reverse remodeling of the failing heart's electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) hypertrophy is associated with LV diastolic dysfunction and constitutes a risk factor for cardiac morbidity and mortality. The objective of this study was to investigate the degree of LV mass regression and the changes of LV diastolic function one year after transcatheter aortic valve implantation (TAVI)., Methods: Echocardiography was performed at baseline, before discharge, and at one-year follow-up in 63 consecutive patients with severe aortic stenosis who underwent TAVI with the Medtronic CoreValve System (Medtronic Inc, Minneapolis, MN). The LV mass was calculated using the Devereux formula and indexed to body surface area., Results: One-year all-cause mortality was 29%. The LV mass index decreased from 126 ± 42 g/m(2) at baseline to 110 ± 30 g/m(2) at one-year follow-up (p < 0.001). Left ventricular ejection fraction and LV diastolic function did not change significantly. Mean transaortic gradient decreased from 47 ± 19 mm Hg at baseline to 9 ± 5 mm Hg at discharge and 9 ± 4 mm Hg at one year (p < 0.001), and was accompanied by significant clinical improvement. More than mild paravalvular aortic regurgitation was found in 24% and 15% of patients at discharge and one-year follow-up, respectively., Conclusions: A significant regression in LV mass was found one year after TAVI. However, regression was incomplete and was not accompanied by an improvement in LV diastolic function., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Both the Young-Laplace law and finite element (FE) based methods have been used to calculate left ventricular wall stress. We tested the hypothesis that the Young-Laplace law is able to reproduce results obtained with the FE method., Methods: Magnetic resonance imaging scans with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace)., Results: First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the Young-Laplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress., Conclusions: The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the study was to evaluate the clinical and echocardiographic outcomes, at rest and under exercise testing, of patients with moderate ischemic mitral regurgitation (IMR) undergoing isolated coronary artery bypass graft surgery (CABG)., Methods: Between February 2003 and March 2008, 180 patients with moderate IMR who had isolated CABG were enrolled. Patients were matched 1:2 (n = 360) with patients who underwent isolated CABG without IMR (by propensity score). The study endpoints were freedom from all death, cardiac related-death, late events, and cardiac-related events. Late outcomes and left ventricular remodeling were evaluated according to preoperative percent of ejection fraction. Symptoms and MR grade under exercise test were investigated. Mean follow-up was 30 ± 16 months., Results: The 5-year freedom from all deaths and from cardiac-related deaths among patients without IMR versus with IMR was, respectively, 90.5% ± 1.8% versus 73.7% ± 2.1% (p < 0.001) and 94.2% ± 1.6% versus 79.5% ± 1.5% (p < 0.001). Ischemic mitral regurgitation affects significantly late survival only in patients with ejection fraction 40% or less. The 5-year freedom from cardiac-related events among patients without and with IMR was, respectively, 88.2% ± 2.1% and 62.1% ± 1.2% (p < 0.0001). Patients with IMR experienced more cardiac-related events in comparison with patients without IMR. Ischemic mitral regurgitation promotes left ventricular remodeling in all patients. During exercise testing, the grade of MR moved from mild to moderate in 10 patients (28.5%) and to severe in 5 (14.3%). Among the 42 patients with moderate MR at rest, 32 patients (76%) moved from moderate to severe MR during exercise., Conclusions: Ischemic mitral regurgitation significantly increases the incidence of cardiac-related deaths among patients with ejection fraction 40% or less and the incidence of cardiac-related events, and promotes left ventricular remodeling. Most patients who had at-rest residual mild to moderate MR presented with a worse MR grade under exercise with the appearance of dyspnea., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular remodeling after posterobasal myocardial infarction can lead to ischemic mitral regurgitation. This occurs as a consequence of leaflet tethering due to posterior papillary muscle displacement., Methods: A finite element model of the left ventricle, mitral apparatus, and chordae tendineae was created from magnetic resonance images from a sheep that developed moderate mitral regurgitation after posterobasal myocardial infarction. Each region of the model was characterized by a specific constitutive law that captured the material response when subjected to physiologic pressure loading., Results: The model simulation produced a gap between the posterior and anterior leaflets, just above the infarcted posterior papillary muscle, which is indicative of mitral regurgitation. When the stiffness of the infarct region was reduced, this caused the wall to distend and the gap area between the leaflets to increase by 33%. Additionally, the stress in the leaflets increased around the chordal connection points near the gap., Conclusions: The methodology outlined in this work will allow a finite element model of both the left ventricle and mitral valve to be generated using noninvasive techniques., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Surgical ventricular restoration (SVR) has been introduced to restore the dilated left ventricular (LV) chamber and improve LV systolic function; however, SVR has also been reported to detrimentally affect LV diastolic properties. We sought to investigate the impact of preoperative LV diastolic function on outcomes after SVR in patients with heart failure., Methods: Sixty-seven patients (60 +/- 14 years) with LV systolic dysfunction (LV ejection fraction, 0.27 +/- 0.10) underwent SVR. They were evaluated by echocardiography preoperatively, and early (

Background: Maladaptive left ventricular hypertrophy (LVH) remains a prevalent and highly morbid condition associated with end-stage heart disease. Originally evaluated in the context of bone development, periostin is important in endocardial cushion formation and has recently been implicated in heart failure. Because of its potential role in cardiovascular development, we sought to establish the role of periostin after relief of pressure overload in animal and human models., Methods: Pressure overload induction of LVH was performed by minimally invasive aortic arch banding of C57Bl6 mice. Bands were removed 1 month later to allow regression. Cardiac tissue was procured in paired samples of patients receiving LV assist devices (LVAD), with subsequent reanalysis at the time of explant for transplantation., Results: One week after debanding, heart weight/body weight ratios and echocardiography confirmed decreased LV mass relative to hypertrophied animals. Gene and protein expression of periostin was measured by real-time polymerase chain reaction and Western blot, and was similarly decreased compared with LVH mice. Immunohistochemical localization of periostin showed it was exclusively in the extracellular matrix of the myocardium. The decrease in periostin with pressure relief paralleled changes in interstitial fibrosis observed by picrosirius red staining. Corroborating the murine data, periostin expression was significantly reduced after LVAD-afforded pressure relief in patients., Conclusions: Periostin is closely associated with pressure overload-induced LVH and LVH regression in both animal and human models. The magnitude of expression changes and the consistent nature of these changes indicate that periostin may be a mediator of cardiac remodeling.

Background: The efficacy of surgical ventricular reconstruction (SVR) for ischemic cardiomyopathy has never been truly quantified. Methods to assess ventricular flow have not been applied to these patients. The objective is to develop a volume-independent technique for assessing the effects of ischemic remodeling and SVR on left ventricular blood flow dynamics., Methods: Cardiac magnetic resonance images from a healthy volunteer and from a patient before and after SVR were segmented and transformed to generate a grid model of the heart by generating numeric grids and running third-order approximations to achieve 850 grid images per cardiac cycle. These grids formed the skeletal structure of our patient-specific time-dependent ventricular geometry model, the Karlsruhe Heart Model, used for modeling fluid dynamics. We modeled flow, ejection fraction, and blood washout from the ventricle. The model was validated using a silicone ventricle and mock circulation., Results: In the healthy heart and before SVR, ejection fractions were 0.61 and 0.15 and left ventricular volumes were 166 mL and 175 mL, respectively. Surgical ventricular reconstruction decreased left ventricular volume by one fourth. Postoperative ejection fraction was 0.18 in the patient. Post-SVR shape was more spherical than preoperatively and also more spherical than the healthy heart. Ventricular flow patterns in the patient were significantly altered by SVR. However, fluid washout from the ventricle was similar before and after SVR but worse than in the healthy heart., Conclusions: Fluid dynamic modeling of the heart is possible based on cardiac magnetic resonance imaging data and enables volume-independent quantitative assessment of the surgical procedure. In the future, preoperative modeling for patients with remodeled ventricles may help to achieve optimized post-SVR flow characteristics and potentially outcomes.

Background: Myocardial infarction can result in a spectrum of left ventricular (LV) shape abnormalities. Surgical ventricular restoration (SVR) can be applied to any, but there are no data that relate its effectiveness to LV shape. Moreover, there is no consensus on the benefit of SVR in patients with a markedly dilated ventricle, without clear demarcation between scarred and normal tissue. This study describes postmyocardial infarction shape abnormalities and cardiac function, clinical status, and survival in patients undergoing SVR., Methods: Echo studies of 178 patients were retrospectively reviewed. Three types of LV shape abnormalities were identified: type 1 (true aneurysm), type 2 (nonaneurysmal lesions defined as intermediate cardiomyopathy), and type 3 (ischemic dilated cardiomyopathy)., Results: SVR induced significant improvement in cardiac and clinical status in all patients, regardless LV shape types. Although not significant, mortality was higher in types 2 and 3., Conclusions: Ischemic dilated cardiomyopathy and not just the true aneurysm can be successfully treated with SVR. Shape classification may be useful to improve patient selection and compare results from different institutions that are otherwise impossible to compare.

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.

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.

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.

Background: Limited data are available on left ventricle (LV) diastolic function in patients with ischemic dilated cardiomyopathy submitted to surgical ventricular restoration (SVR). The purpose of this study was to assess postoperative diastolic function changes and identify potential predictors of its worsening., Methods: One hundred and forty-six patients (65 +/- 9 years) with previous anterior myocardial infarction were evaluated before and after SVR. Hemodynamic and geometric parameters including the sphericity index and conicity index were measured. Diastolic function was explored using the transmitral flow velocity pattern, and four classes were defined: normal, abnormal relaxation, pseudonormal, and restrictive pattern. Diastolic function was defined as unchanged (no difference in diastolic pattern), improved (at least one class less), or worsened (at least one class more or, in the case of preoperative restrictive pattern, an early transmitral flow velocity to atrial flow velocity [E/A] ratio increase of at least 20%)., Results: The filling pattern before SVR was normal in 7 patients (4.8%), abnormal relaxation in 99 (68%), pseudonormal in 28 (19%), and restrictive in 12 (8.2%). After SVR, the filling pattern was unchanged in 105 patients (72%), improved in 14 (9.6%), and worsened in 27 (18.4%). Based on the univariate analysis, the preoperative conicity index and the end-diastolic volume difference (the result of surgical volume reduction) were associated with a diastolic pattern worsening., Conclusions: Diastolic function did not change or improve in the majority of patients. In the minority of patients who experienced worsening, this was associated with the preoperative LV shape and residual volume.

Background: We sought to compare host immune cell kinetics, survival profile of donor skeletal myoblasts, and skeletal myoblast graft efficacy after autologous and allogeneic skeletal myoblast transplantation into a rat model of myocardial infarction., Methods: One week after myocardial infarction, 128 animals were divided into four groups: group 1 (n = 24, receiving medium only), group 2 (n = 24, receiving medium and cyclosporine), group 3 (n = 40, autologous skeletal myoblast transplantation), and group 4 (n = 40, allogeneic skeletal myoblast transplantation with cyclosporine treatment). Rats were euthanized 10 minutes, 1 day, and 4, 7, and 28 days later. Host immune cell kinetics were assessed by immunohistochemical studies for macrophages, and CD4+ and CD8+ lymphocytes. Donor skeletal myoblast survival was confirmed by tracking prelabeled signals, and quantified by beta-gal assay. Heart function was evaluated by echocardiography., Results: A transient immune cell infiltration was demonstrated in group 3, with macrophage infiltration on day 1 and day 4, CD8+ cell infiltration on day 4 and day 7, and CD4+ cell infiltration on day 4. In group 4, immunocyte infiltration was slightly more severe than that in group 3. Automyoblasts and allomyoblasts showed no significant difference of survival from day 1 to day 7 (p > 0.10); however, on day 28, automyoblasts showed better survival than allomyoblasts (p < 0.05). Transplantation of allomyoblasts increased systolic heart function and limited heart dilation after myocardial injury to a similar degree as automyoblasts (p > 0.10)., Conclusions: The use of allomyoblasts is feasible and effective for cardiac repair with immunosuppressive treatment as compared with automyoblasts.

Background: Left ventricular aneurysm repair (LVAR) prevents congestive heart failure after myocardial infarction (MI). LV dilation after MI is related to postinfarct myocardial remodeling and leads to CHF. Because changes in matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and the physical properties of collagens are involved in myocardial remodeling, the effect of postinfarct LVAR on these factors was tested., Methods: Rats with surgically induced MI, which did or did not receive postinfarct LVAR, were compared with each other and with controls. TIMP messenger RNA and protein expression, MMP gelatin zymography activity, and collagen fibrosis were measured in heart tissue., Results: A threefold difference in the infarction area ratio was observed between samples of LVAs and of repaired LVAs. Compared with rats without LVAR, rats with repaired LVAs exhibited a higher percentage fractional shortening and significantly lower LV end-systolic and end-diastolic diameters. These salutary effects on LV diameter after LVAR were accompanied by a reversal of myocardial remodeling activity. After MI, TIMP expression decreased, MMP activity increased, and collagen fibrosis increased. After LVAR, TIMP expression increased, and MMP activity and collagen fibrosis decreased. These markers of remodeling activity changed significantly and approached preinfarct levels after LVAR., Conclusions: This study demonstrated that postinfarct LVAR prevents further congestive heart failure by attenuating myocardial remodeling in the LV and is thus indicated both to prevent heart failure and to reduce excessive postinfarct myocardial remodeling.

Background: Left ventricular (LV) remodeling after myocardial infarction (MI) commonly causes infarct expansion (IE). This study sought to interrupt IE through microinjections of a biocompatible composite material into the post-MI myocardium., Methods: MI was created in 21 pigs (coronary ligation). Radiopaque markers (2-mm diameter) were placed for IE (fluoroscopy). Pigs were randomized for microinjections (25 injections; 2- x 2-cm array; 200 microL/injection) at 7 days post-MI of a fibrin-alginate composite (Fib-Alg; fibrinogen, fibronectin, factor XIII, gelatin-grafted alginate, thrombin; n = 11) or saline (n = 10)., Results: At 7 days after injection (14 days post-MI), LV posterior wall thickness was higher in the Fib-Alg group than in the saline group (1.07 +/- 0.11 vs 0.69 +/- 0.07 cm, respectively, p = 0.002). At 28 days post-MI, the area within the markers (IE) increased from baseline (1 cm2) in the saline (1.71 +/- 0.13 cm2, p = 0.010) and Fib-Alg groups (1.44 +/- 0.23 cm2, p < 0.001). However, the change in IE at 21 and 28 days post-MI was reduced in the Fib-Alg group (p=0.043 and p=0.019). Total collagen content within the MI region was similar in the saline and Fib-Alg groups (12.8 +/- 1.7 and 11.6 +/- 1.5 microg/mg, respectively, p = NS). However, extractable collagen, indicative of solubility, was lower in the Fib-Alg group than the saline group (59.1 +/- 3.5 vs 71.0 +/- 6.1 microg/mL, p = 0.020)., Conclusions: Targeted myocardial microinjection of the biocomposite attenuated the post-MI decrease in LV wall thickness and infarct expansion. Thus, intraoperative microinjections of biocompatible material may provide a novel approach for interrupting post-MI LV remodeling.

Purpose: Recent studies have demonstrated that ventricular rate control is a viable treatment strategy for patients in atrial fibrillation (AF). The purpose of this study was to determine whether or not the benefits of coupled pacing (ie, a proposed rate control therapy) could be used during persistent AF., Description: Six mongrel dogs were chronically implanted with endocardial atrial and ventricular pacemaker leads and two standard dual-chamber pacemakers. With the use of two custom "Y"-lead adapters, the pacemakers were used to induce AF and to apply coupled pacing. Left ventricular end-diastolic and systolic volumes were measured by echocardiography to determine ejection fractions., Evaluation: Persistent AF significantly increased both ventricular rate and left ventricular dimensions. After sustained coupled pacing had been applied for 3 to 4 weeks, left ventricular volumes and contractile rate were significantly reduced and returned toward the values measured prior to the induction of persistent AF. Coupled pacing increased the ejection fraction that had been reduced by persistent AF., Conclusions: Coupled pacing reversed the left ventricular remodeling caused by the tachycardia resulting from AF.

Stem cell transplantation is a promising approach for improving cardiac function after severe myocardial damage for which use of autologous donor cells have been preferred to avoid immune rejection. Recently however, rodent, porcine, and even human bone marrow stromal cells have been reported to be uniquely immune tolerant, both in the in vitro mixed lymphocyte co-culture studies and in the in vivo allo-transplant and xeno-transplant models. In this review, we explore the current understanding of the underlying immunologic mechanisms, which can facilitate the use of such cells as "universal donor cells" with fascinating therapeutic implications.

Background: Severe left ventricular (LV) hypertrophy increases risk for adverse outcome after aortic valve replacement. Whether LV geometry influences mortality risk after aortic valve replacement is unclear. And, whether LV mass or relative wall thickness (RWT) better predicts risk for adverse postoperative outcomes is unknown. The purpose of this investigation was to examine the influence of LV geometry and LV hypertrophy on morbidity and in-hospital mortality after aortic valve replacement, and to determine whether LV mass or RWT had better prognostic ability., Methods: Between January 1996 and June 2004, 5,083 patients underwent aortic valve replacement. Preoperative echocardiographic data was used to calculate LV mass and RWT. Left ventricular geometry was classified into one of four categories on the basis of LV mass indexed to body height and RWT: (1) concentric hypertrophy, (2) eccentric hypertrophy, (3) concentric remodeling, and (4) normal. Postoperative mortality and multisystem morbidities of patients with concentric geometries were compared to patients with nonconcentric geometries by propensity and logistic regression modeling. Also, prognostic ability of RWT and LV mass was compared., Results: Nine hundred sixty-four patients with concentric geometry were propensity-matched to 964 patients with nonconcentric geometry. In-hospital mortality (38 [3.9%] versus 18 [1.9%]; p = 0.007), cardiac morbidity (33 [3.4%] versus 17 [1.8%]; p = 0.022), and prolonged intubation (85 [8.8%] versus 58 [6.0%]; p = 0.019) were higher in patients with concentric versus nonconcentric geometry. Increasing RWT, not LV mass, was associated with adverse outcomes., Conclusions: Concentric geometries are associated with increased risk for in-hospital mortality after aortic valve replacement. Increased RWT is associated with adverse outcomes. Preoperative risk stratification should include assessments of LV hypertrophy and LV geometry.

Although numerous surgical techniques have been developed for ischemic/functional mitral regurgitation, none has clearly improved patient outcome. We report the clinical application of a new mitral complex remodeling procedure for ischemic/functional mitral regurgitation that allows comprehensive remodeling of the entire mitral complex. The mitral complex remodeling procedure consists of three major concepts: division and reconstruction of secondary chords, undersized annuloplasty, and bilateral papillary muscle relocation.

Background: The feasibility of left ventricular restoration for patients with ischemic cardiomyopathy complicated with cardiogenic shock remains unclear. We report early and mid-term outcomes of surgical interventions including left ventricular restoration for patients with cardiogenic shock., Methods: From April 2001 to June 2007, 10 patients with ischemic cardiomyopathy who developed cardiogenic shock underwent left ventricular restoration combined with mitral annuloplasty or coronary artery bypass grafting. All had been supported by a maximum dose of inotropic agents, 8 had required an intraaortic balloon pump, and 1 had required extracorporeal life support. Mean left ventricular end-diastolic and end-systolic volume indices were 142 +/- 33 mL/m(2) and 113 +/- 28 mL/m(2), respectively, and ejection fraction was 0.21 +/- 0.059., Results: There was no mortality at 30 days. Five patients demonstrated significant recovery after the operation. Three patients simultaneously underwent left ventricular assist system (LVAS) implantation with left ventricular restoration because of preexisting severe end-organ failure, and 2 of them were subsequently weaned from LVAS, although 1 required reimplantation. The other 2 patients eventually underwent LVAS implantation in the early postoperative period. Two patients who required prolonged LVAS support underwent successful heart transplantation. Seven patients are alive at a mean follow-up of 1.9 years. Patients who required prolonged LVAS support had significantly longer duration of heart failure symptoms (p = 0.04) and higher mean pulmonary artery pressure (p = 0.02) preoperatively., Conclusions: Early combined surgical interventions including left ventricular restoration can be a choice of treatment even in patients with ischemic cardiomyopathy complicated with cardiogenic shock. Additional use of the LVAS followed by bridge to recovery or transplantation should be appropriately applied in these critically ill patients.