Showing papers by "Guillermo Torre-Amione published in 2005"

Immune activation in chronic heart failure.

Abstract: In chronic heart failure (CHF), activation of the immune system occurs, which results in the production and release of proinflammatory cytokines, activation of the complement system, and production of autoantibodies. Thus, it is important to consider CHF as a systemic illness, not just a disease of the "pump." Immune activation in CHF can be divided into 2 broad categories: (1) immune activation by direct antigenic stimulation, or (2) immune activation secondary to cardiac injury that exposes "new antigens" capable of triggering an immune response against the heart. Cytokines are essential for the propagation and magnification of the immune response. They are involved in recruiting cells to the area of inflammation, stimulating cell division, proliferation, and differentiation. Circulating levels of the cytokine tumor necrosis factor-alpha (TNF-alpha) are increased in patients with CHF. Thus, cytokines are key elements of immune activation. Studies to investigate the role of increased TNF-alpha levels have failed to show a correlation with worsening CHF, most likely because the immune system is redundant, and other proinflammatory cytokines (interleukin [IL]-1 and IL-6) are known to be elevated in CHF. Approaches showing promise are those that enhance the natural anti-inflammatory response (eg, intravenous immunoglobulin (IVIG), immunoadsorption, immune-modulation therapy [IMT]), rather than those that specifically target a single type of cytokine. The mechanism by which IVIG modulates the immune system is unknown. Immunoadsorption involves the removal of specific antibodies from circulation. IMT works by inducing apoptosis in a sample of blood, which is then administered back to the patient. The immune system reacts by removing the apoptotic cells, thus inducing a systemic anti-inflammatory response.

Cellular and hemodynamics responses of failing myocardium to continuous flow mechanical circulatory support using the DeBakey-Noon left ventricular assist device: a comparative analysis with pulsatile-type devices.

Abstract: Background An increasing number of continuous flow pumps are currently under clinical studies, however very little data exist on the hemodynamic and cellular responses of the failing heart to continuous flow support. The purpose of this investigation was to characterize the response of the failing myocardium to continuous flow support. Methods We compared echocardiographic and cellular markers of failing myocardium at the time of left ventricular assist device (LVAD) implantation and explantation in 20 consecutive patients (12 pulsatile flow [Novacor] and 8 continuous flow [DeBakey-Noon]). Results The use of mechanical support with both continuous- or pulsatile-type LVADs resulted in a reduction of left ventricular end-diastolic dimension (LVEDD), end-diastolic volume (EDV), end-systolic volume (ESV) and left atrial volume (LAV), as well as a decrease in mitral E/A ratio, tricuspid regurgitation velocity (TRV) and pulmonary valve acceleration time (PVAT). Comparative analyses for patients treated with a continuous- vs pulsatile-type LVAD support showed a greater degree of unloading with the latter type, as shown by the effect on LVEDD (−13.7% vs −33.7%, p = 0.0.004), EDV (−23.5% vs −41.2%, p = 0.015), ESV (−25.6% vs −57.6%, p = 0.001) and LAV (−25.2% vs −40.4%, p = 0.071). The hemodynamic effects of continuous vs pulsatile LVAD support were similar, as shown by their effect on mitral E/A ratio (−23.9% vs −39.9%, p = NS), TRV (−26.4% vs −23.8%, p = NS) and PVAT (28.5% vs 38.5%, p = NS). Only pulsatile support demonstrated a statistically significant percent change in mass (−6.3% vs −20.6%, p = 0.038). Continuous and pulsatile forms of mechanical support demonstrated equivalent reductions in myocardial tumor necrosis factor-α (TNF-α), total collagen and mycocyte size. Conclusions Our findings show that, although there are differences between these 2 devices in magnitude of unloading, both forms of support effectively normalize cellular markers of the failing phenotype.

Impact of left venticular assist device (LVAD)-mediated humoral sensitization on post-transplant outcomes

Abstract: Background Humoral sensitization, defined as a panel-reactive antibody (PRA) screen of >10%, places heart transplant recipients at a greater risk of acute rejection and mortality. Previous studies have suggested an increased sensitization in left ventricular assist device (LVAD) recipients, although neither the impact of device selection nor the clinical importance of elevated PRA in these patients has been completely described. Methods Using the registry of the International Society for Heart and Lung Transplantation (ISHLT), we compared PRA levels in 7,686 heart transplant recipients to determine the impact of LVAD therapy on humoral sensitization, acute rejection and mortality. To determine the impact of device selection on sensitization, we compared data from the ISHLT registry as well as from our own institution. Results Elevated PRA levels were found in 16.6% of LVAD recipients, compared with 7.6% of non-LVAD controls ( p p = 0.01). Despite these findings, LVAD use had no impact on rejection rates. LVAD use was associated with a small increase (4.4% and 4.3%, respectively) in 1- and 2-year mortality. Conclusions These findings support the concept that mechanical circulatory support increases the rate of humoral sensitization. However, these differences in sensitization do not translate to substantial differences in the clinical outcomes of rejection and mortality.

Statin use and risks of death or fatal rejection in the Heart Transplant Lipid Registry

Abstract: Although small, randomized trials have shown that statin use is associated with decreased risks of mortality and severe rejection, no study has examined statin therapy as used in actual practice in large numbers of heart transplant recipients. We analyzed data from the Heart Transplant Lipid Registry (n = 12 centers). Patients were included if they underwent transplantation between 1995 and 1999, survived ≥30 days after transplantation, and had ≥30 days of Registry follow-up. Multivariable Cox regression models, with propensity scoring performed to adjust for nonrandom allocation of statin therapy, were performed to determine the association of statin therapy with death and fatal rejection. The study included 1,186 patients, with a mean follow-up of 580 ± 469 days; 937 patients (79%) received statin therapy. Overall, 71 patients (6%) died and 40 (3.4%) had fatal rejection. The statin group had a lower frequency of death (4% vs 13.7%, p <0.0001) and fatal rejection (2.4% vs 7.2%, p = 0.0001). Using multivariable Cox regression, with propensity scoring included to adjust for likelihood of receiving statin therapy, statin use was the only factor associated with lower risk of death (hazard ratio 0.29, 95% confidence interval 0.13 to 0.67) and fatal rejection (hazard ratio 0.27, 95% confidence interval 0.09 to 0.78). This study represents the largest population of heart transplant recipients analyzed for the relation between statin therapy and clinical outcomes in actual practice. Statin therapy was significantly associated with lower risk of death and fatal rejection, benefits that were independent of lipid values.

Echocardiographic ejection fraction in patients with acute heart failure : correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome

Abstract: Background Although echocardiographic ejection fraction (EF) is frequently used for the estimation of left ventricular contractility in patients with acute heart failure, its exact role and correlations with clinical, hemodynamic, and neurohormonal variables of cardiac contractility is not known. Methods Patients (343) with acute heart failure, enrolled into two prospective placebo-controlled hemodynamic studies of tezosentan, and in whom EF was available at baseline, were included. Outcome was evaluated in a subset of 94 patients who were enrolled in the placebo arms of the studies. Results Higher echocardiographic EF was correlated with older age, increased incidence of hypertension and atrial fibrillation, and female gender. We observed weak correlation between EF and cardiac output or cardiac power and no correlation with wedge pressure, and the change in hemodynamic variables over time. Higher EF was correlated with more baseline leukocytosis and higher plasma levels of endothelin-1 and blood urea nitrogen, while lower EF was related to higher baseline B-type natriuretic peptide (BNP). We observed no overall correlations between EF and outcome. Conclusions In patients with acute heart failure, echocardiographic EF is weakly correlated with hemodynamic measures of left ventricular contractility and outcome; hence, it should be interpreted cautiously when evaluating patients admitted due to acute heart failure.

Broad Modulation of Tissue Responses (Immune Activation) by Celacade May Favorably Influence Pathologic Processes Associated with Heart Failure Progression

Abstract: Immune activation and inflammation contribute to the progression of chronic heart failure (CHF), but therapeutic approaches directed against these processes have been largely unsuccessful. This clinical study evaluated a novel, nonpharmacologic immune modulation therapy, shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines. A total of 75 patients with New York Heart Association (NYHA) functional class III or IV CHF were randomized to receive either Celacade (immune modulation therapy) or placebo (n = 38 and n = 37, respectively) in a double-blind trial for 6 months, during which standard therapy for CHF was maintained. Patients were evaluated using the 6-minute walk test, changes in NYHA class, cardiac function, and quality-of-life assessments, and were observed for the occurrence of death and hospitalization. There was no between-treatment difference in the 6-minute walk test results, but 15 Celacade-treated patients (compared with 9 placebo-treated patients) improved NYHA classification by ≥1 class (p = 0.140). Kaplan-Meier survival analysis showed that Celacade significantly reduced the risk of death (p = 0.022) and hospitalization (p = 0.008). Analysis of a clinical composite score demonstrated a significant between-group difference (p = 0.006). There was no difference in left ventricular ejection fraction between groups, but there was a trend toward improved quality of life favoring the Celacade-treated group (p = 0.110). These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of CHF, and they establish the basis for a phase 3 trial to define the benefit of Celacade in CHF.

Placement of a left ventricular assist device in a patient with dextrocardia.

Abstract: Dextrocardia most commonly presents in the setting of situs inversus, but it may occur as an isolated anomaly with normal position of the abdominal organs. Herein we present a 54-year-old man with ischemic cardiomyopathy and dextrocardia with normal position of the abdominal organs who presented with an exacerbation of congestive heart failure requiring inotropic support as well as mechanical ventilation. An implantable, wearable left ventricular assist device was placed in this patient to allow for ambulation and eventual discharge home. The patient survived 4 months before he developed pneumonia and expired.

Mechanical Circulatory Support: Response of the Failing Heart to a New Generation of Pumps

Abstract: Since the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) clinical trial demonstrated the superiority of long-term mechanical support for end-stage heart failure2 patients have been offered ventricular assist devices (VAD) as a standard therapeutic bridge to cardiac transplantation.1.4 However, expanding indications and greater utilization of mechanical circulatory support has led to the development of smaller and technically varied VADs. As opposed to the currently approved VADs, newer systems provide continuous non-pulsatile circulatory support using impellers in an axial flow system (Figure 1). The purpose of this review is to present the current status and applications of axial flow pumps, as well as to discuss the response of the failing myocardium to continuous flow support.

Traitement de la myocardite

Abstract: Selon l'invention, une inflammation cardiaque, illustree par la myocardite chez un patient mammifere, est attenuee par un procede qui consiste a: extraire une aliquote de sang du patient; effectuer un traitement extracorporel de l'aliquote par exposition a une contrainte oxydative et a une emission electromagnetique; et readministrer l'aliquote traitee au patient, selon une quantite et d'une maniere ayant comme resultat la prophylaxie ou l'attenuation des symptomes de la myocardite chez le patient.