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Background-We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices. Methods and Results-We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, ␤-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the ␤ 2 -agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2Ϯ12.6 years (16 male patients), patients were on 2.0Ϯ0.9 inotropes, 7 (35%) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39Ϯ0.43 L ⅐ min Ϫ1 ⅐ m Ϫ2 , pulmonary capillary wedge pressure was 31.5Ϯ5.7 mm Hg, and heart failure history was 3.4Ϯ3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2%) were explanted after 286Ϯ97 days. Eight had symptomatic heart failure for Յ6 months and 4 for Ͼ6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70Ϯ7%, left ventricular end-diastolic diameter was 48.6Ϯ5.7 mm, left ventricular end-systolic diameter was 32.3Ϯ5.7 mm, mV O 2 was 21.6Ϯ4 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 , pulmonary capillary wedge pressure was 5.9Ϯ4.6 mm Hg, and cardiac index was 3.6Ϯ0.6 L ⅐ min Ϫ1 ⅐ m Ϫ2 . Estimated survival without heart failure recurrence was 83.3% at 1 and 3 years. After a 430.7Ϯ337.1-day follow-up, surviving explants had an ejection fraction of 58.1Ϯ13.8%, left ventricular end-diastolic diameter of 59.0Ϯ9.3 mm, left ventricular end-systolic diameter of 42.0Ϯ10.7 mm, and mV O 2 of 22.6Ϯ5.3 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 . Conclusions-Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy. (Circulation. 2011;123:381-390.)

for the RIME Investigators Background-The role of mitral valve repair (MVR) during coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation (MR) is uncertain. We conducted a randomized, controlled trial to determine whether repairing the mitral valve during CABG may improve functional capacity and left ventricular reverse remodeling compared with CABG alone. Methods and Results-Seventy-three patients referred for CABG with moderate ischemic MR and an ejection fraction Ͼ30%were randomized to receive CABG plus MVR (34 patients) or CABG only (39 patients). The study was stopped early after review of interim data. At 1 year, there was a greater improvement in the primary end point of peak oxygen consumption in the CABG plus MVR group compared with the CABG group (3.3 mL/kg/min versus 0.8 mL/kg/min; PϽ0.001). There was also a greater improvement in the secondary end points in the CABG plus MVR group compared with the CABG group: left ventricular end-systolic volume index, MR volume, and plasma B-type natriuretic peptide reduction of 22.2 mL/m

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Abstract-Hibernating myocardium refers to chronically dysfunctional myocardium in patients with coronary artery disease in which cardiac viability is maintained and whose function improves after coronary revascularization. It is our hypothesis that long-term adaptive genomic mechanisms subtend the survival capacity of this ischemic myocardium. Therefore, the goal of this study was to determine whether chronic repetitive ischemia elicits a gene program of survival protecting hibernating myocardium against cell death. Accordingly, we measured the expression of survival genes in hibernating myocardium, both in patients surgically treated for hibernation and in a chronic swine model of repetitive ischemia reproducing the features of hibernation. Human hibernating myocardium was characterized by an upregulation of genes and corresponding proteins involved in anti-apoptosis (IAP), growth (VEGF, H11 kinase), and cytoprotection (HSP70, HIF-1␣, GLUT1). In the swine model, the same genes and proteins were upregulated after repetitive ischemia, which was accompanied by a concomitant decrease in myocyte apoptosis. These changes characterize viable tissue, because they were not found in irreversibly injured myocardium. Our report demonstrates a novel mechanism by which the activation of an endogenous gene program of cell survival underlies the sustained viability of the hibernating heart. Potentially, promoting such a program offers a novel opportunity to salvage postmitotic tissues in conditions of ischemia. Key Words: gene expression Ⅲ coronary artery disease Ⅲ ischemia Ⅲ stunning Ⅲ hibernation B ecause the cardiac myocyte has a limited capacity for regeneration, most forms of heart disease, including ischemic heart disease and heart failure, are characterized by a loss of cardiomyocytes. 1-3 Historically, any evidence of prolonged left ventricular dysfunction after myocardial ischemia was thought to be caused by irreversible myocyte damage. This traditional concept was challenged with the discoveries of myocardial stunning (in which ischemia is followed by prolonged but fully reversible dysfunction), 4 ischemic preconditioning (in which a brief ischemic episode protects the myocardium against a subsequent episode of sustained ischemia), 5 and hibernating myocardium (in which chronic dysfunction resulting from repeated ischemia recedes after bypass revascularization). 6,7 Hibernating myocardium is submitted to repetitive bouts of ischemia caused by normally occurring increases in myocardial metabolic demand in the face of significant coronary stenosis and limited coronary reserve, yet it does not develop irreversible damage. 8,9 The diagnosis of this condition is of the highest priority in patients with chronic coronary artery disease, because successful coronary revascularization and restoration of coronary flow reserve in hibernating myocardium are followed by an improvement of contractile performance; 10,11 however, if left untreated, this condition leads to progressive exacerbation of heart failure and death.Despite t...

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