Rapamycin as rescue therapy in a patient supported by biventricular assist device to heart transplantation with consecutive ongoing rejection.
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Rapamycin is a new immunosuppressive agent that has been shown to be effective in acute heart allograft rejection. This case documents a patient suffering from cardiac sarcoidosis who was bridged to transplantation for 90 days with ongoing rejection after allograft implantation. Rejection did not abate despite treatment with antithymocyte globulin (ATG), FK506, a mycophenolate switch and courses of multiple apheresis. Initiation of rapamycin treatment resulted in a rapid resolution of cardiac rejection and reduction of concomitant immunosuppressive agents with few side-effects. Most notably was the reduction of panel reactive antibodies within a few weeks after the rapamycin initiation. This case illustrates that the utilization of rapamycin ceased ongoing rejection in a patient with a clear hyperimmune state despite prior extensive utilization of a variety of immunosuppressive strategies after heart transplantation. (+info)
Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation.
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OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans. (+info)
Improving care of chronic heart failure: advances from drugs to devices.
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The right combination of drugs and surgical treatment can improve systolic function and prevent, attenuate, or reverse heart failure. Patient education and disease management programs can reduce hospitalizations. Optimal treatment for each patient is guided by a thorough evaluation and use of functional classification and disease staging systems. (+info)
Support with the BVS 5000 assist device during treatment of acute giant-cell myocarditis.
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Giant-cell myocarditis is a rare and aggressive form of myocarditis with a high mortality rate. Our purpose is to summarize 3 cases of acute giant-cell myocarditis that illustrate possible outcomes with mechanical support. We reviewed the cases of 3 patients, aged 39 to 59 years, who had giant-cell myocarditis (confirmed by myocardial biopsy). The indication for ventricular assist was circulatory failure despite maximal medical treatment with 2 or more inotropic agents and intraaortic balloon pump support. Immunosuppression and a biventricular mechanical assist (BVS 5000) were used to treat all these patients. The mean duration of mechanical support was 15.7 days (range, 10 to 19 days). One patient had recovery of myocardial function and was weaned from mechanical support. This case is, to our knowledge, the first reported of ventricular support leading to cardiac recovery after diagnosis of giant-cell myocarditis. The 2nd patient was not a candidate for further surgery and died of multisystem organ failure. The 3rd patient underwent orthotopic heart transplantation after 18 days of support and was discharged. We conclude that patients with giant-cell myocarditis tend to have biventricular involvement and can recover myocardial function on mechanical support and immunosuppression. If recovery is not observed, transplantation is warranted. By avoiding left ventricular cannulation, the BVS 5000 is well suited for bridging to recovery, transplantation, or long-term support. (+info)
Prolonged QTc interval and high B-type natriuretic peptide levels together predict mortality in patients with advanced heart failure.
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BACKGROUND: The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP. METHODS AND RESULTS: QTc intervals were measured in 241 patients with heart failure who had BNP levels >400 pg/mL. QT interval duration was determined by averaging 3 consecutive beats through leads II and V4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (>440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786+/-321 pg/mL in the prolonged QTc group versus 733+/-274 pg/mL in the normal QTc group, P=0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (n=24, 52%), sudden cardiac death (n=18, 39%), or noncardiac causes (n=4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (P<0.0001). On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (P=0.0001), cardiac death (P=0.0001), sudden cardiac death (P=0.004), and pump failure death (P=0.0006). CONCLUSIONS: Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels >400 pg/mL. (+info)
Mechanical treatment of heart failure: the growing role of LVADs and artificial hearts.
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Left ventricular assist devices (LVADs) and artificial hearts are improving. These devices can prolong a patient's life while on a heart transplant list. More exciting, mechanical assistance may provide an opportunity for a damaged heart to recover some function. Still, despite the promise, the use of these devices raises some difficult cost-benefit and ethical questions. (+info)
Left ventricular support by catheter-mounted axial flow pump reduces infarct size.
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OBJECTIVES: We sought to investigate the effect of a catheter-mounted microaxial blood pump (Impella, Aachen, Germany) on myocardial infarct size. BACKGROUND: The small rotary blood pump Impella provides unloading of the left ventricle and is introducible via the femoral artery. METHODS: Myocardial infarction was induced by occlusion of major branches of the left anterior descending coronary artery for 60 min followed by 120 min of reperfusion in 26 sheep. The animals were allocated to four groups: group 1 had no support; group 2 was fully supported with the pump during ischemia and reperfusion; group 3 was supported during reperfusion only; and group 4 was partially supported during reperfusion. Infarct size, hemodynamics, myocardial oxygen consumption, lactate extraction, and myocardial flow were analyzed. RESULTS: Infarct size was significantly reduced in the pump-supported animals (percent area at risk in group 1: 67.2 +/- 4.6%; group 2: 18.1 +/- 10%; group 3: 41.6 +/- 5.8%; group 4: 54 +/- 8%; p = 0.00001). The pump produced 4.1 +/- 0.1 l/min at full support and 2.4 +/- 0.1 l/min at partial support. The pump significantly increased the diastolic and mean blood pressures (groups 2, 3, and 4) and significantly decreased the left ventricular end-diastolic pressure (groups 2 and 3). During ischemia, myocardial flow was not influenced by pump support. At reperfusion, the fully supported group had significantly higher myocardial flow. Pump support reduced myocardial oxygen consumption significantly, and this reduction correlates strongly with the reduction in infarct size (r = 0.9). CONCLUSIONS: Support by a microaxial blood pump reduces myocardial oxygen consumption during ischemia and reperfusion and leads to a reduction of infarct size. This reduction in infarct size correlates with the degree of unloading during reperfusion. (+info)
Differential gene expression and genomic patient stratification following left ventricular assist device support.
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OBJECTIVES: We sought to determine whether mechanical unloading of the failing human heart with a left ventricular assist device (LVAD) results in significant changes in overall left ventricular gene expression. BACKGROUND: Mechanical circulatory support by LVAD in end-stage human heart failure (HF) can result in beneficial reverse remodeling of myocardial structure and function. The molecular mechanisms behind this salutary process are not well understood. METHODS: Left ventricular samples from six male patients were harvested during LVAD placement and subsequently at the time of explantation. Cardiac gene expression was determined using oligonucleotide microarrays. RESULTS: Paired t test analysis revealed numerous genes that were regulated in a statistically significant fashion, including the downregulation of several previously studied genes. Further statistical analysis revealed that the overall gene expression profiles could significantly distinguish pre- and post-LVAD status. Interestingly, the data also identified two distinct groups among the pre-LVAD failing hearts, in which there was blind segregation of patients based on HF etiology. In addition to the substantial divergence in genomic profiles for these two HF groups, there were significant differences in their corresponding LVAD-mediated regulation of gene expression. CONCLUSIONS: Support with an LVAD in HF induces significant changes in myocardial gene expression, as pre- and post-LVAD hearts demonstrate significantly distinct genomic footprints. Thus, reverse remodeling is associated with a specific pattern of gene expression. Moreover, we found that deoxyribonucleic acid microarray technology could distinguish, in a blind manner, patients with different HF etiologies. Expansion of this study and further development of these statistical methods may facilitate prognostic prediction of the individual patient response to LVAD support. (+info)