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Biomedical subjects

Guillermo Torre-Amione

Publications and source records attributed to Guillermo Torre-Amione.

At least 19 recordsLinked to original sources
PubMed2006

Systolic and diastolic dyssynchrony in patients with diastolic heart failure and the effect of medical therapy.

OBJECTIVES: The purpose of this study was to determine the prevalence of systolic and diastolic dyssynchrony in diastolic heart failure (DHF) patients and identify the effects of medical therapy. BACKGROUND: The prevalence of systolic and diastolic dyssynchrony in DHF patients is unknown with no data on the effects of medical therapy on dyssynchrony. METHODS: Patients presenting with DHF (n = 60; 61 +/- 9 years old, 35 women) underwent echocardiographic imaging simultaneous with invasive measurements. An age-matched control group of 35 subjects and 60 patients with systolic heart failure (SHF) were included for comparison. Systolic and diastolic dyssynchrony were assessed by tissue Doppler and defined using mean and SD values in the control group. RESULTS: Systolic dyssynchrony was present in 20 patients (33%) with DHF and 24 patients (40%) with SHF and was associated in both groups with significantly worse left ventricular (LV) systolic and diastolic properties (p < 0.05 vs. control group and patients without systolic dyssynchrony). Diastolic dyssynchrony was present in 35 patients (58%) with DHF and 36 patients (60%) with SHF and had significant inverse correlations with mean wedge pressure and time constant of LV relaxation. In DHF patients, medical therapy resulted in significant shortening of diastolic time delay (39 +/- 23 ms to 28 +/- 20 ms; p = 0.02) but no significant change in systolic interval (p = 0.15). Shortening of diastolic time delay correlated well with tau shortening after therapy (r = 0.85; p < 0.001). CONCLUSIONS: Systolic dyssynchrony occurs in 33% of DHF patients, and diastolic dyssynchrony occurs in 58%. Medical therapy results in significant shortening of the diastolic intraventricular time delay which is closely related to improvement in LV relaxation.

Aged↗
PubMed2006

Dynamic expression of the membrane attack complex (MAC) of the complement system in failing human myocardium.

Inflammatory cytokine-mediated pathways are activated in heart failure and participate in the pathogenesis and progression of the disease. Another major response to inflammation is mediated through the complement system with the production of the membrane attack complex (MAC), a protein known to cause cell lysis and mediate apoptosis. It was postulated that the complement system is activated in patients with heart failure, and this study investigated whether hemodynamic conditions regulate this pathway. The expression of the MAC was assessed in myocardial biopsy samples of normal and failing hearts by immunohistochemistry and Western blot analysis. Myocardial samples from failing hearts were obtained before and after left ventricular assist device implantation. Immunohistochemical staining and Western blot analysis identified increased MAC expression in failing but not normal myocardium. After hemodynamic unloading with left ventricular assist device support, MAC expression returned to levels found in normal controls. In failing hearts, MAC expression did not differ between ischemic and nonischemic causes of heart failure. In conclusion, increased MAC expression in failing human hearts indicates that the complement system is activated in the heart failure milieu. Its removal after hemodynamic normalization is evidence of dynamic regulation, suggesting a pathogenic role for the MAC. These findings identify the complement system as part of a novel pathophysiologic path in heart failure that can potentially be targeted by future therapy.

Apoptosis↗
PubMed2005

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

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 < 0.0001). Sensitization differed by device type, being present in 21.9% of Thoratec recipients, 14.4% of HeartMate recipients, and 15.5% of Novacor recipients (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.

Antibody Formation↗
PubMed2005

Immune activation in chronic heart failure.

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.

Animals↗
PubMed2005

Broad modulation of tissue responses (immune activation) by celacade may favorably influence pathologic processes associated with heart failure progression.

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 > or = 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.

Aged↗
PubMed2005

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

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.

Chi-Square Distribution↗
PubMed2005

Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS).

BACKGROUND: Endothelin 1 is a potent endogenous vasoconstrictor neurohormone, and endothelin 1 plasma concentrations predict adverse outcomes in patients with acute heart failure (AHF). Tezosentan, an intravenous endothelin receptor antagonist, improved hemodynamics in patients with AHF; however, its effects on morbidity and mortality have not been evaluated. METHODS: The VERITAS program consists of 2 identical, double-blind, randomized, placebo-controlled, concurrently conducted trials (VERITAS-1 and VERITAS-2), performed in 150 centers in Europe, Israel, Australia, and North America. The program is designed to enroll at least 1760 patients hospitalized with dyspnea at rest because of AHF requiring intravenous therapy. In addition to conventional therapy, patients are randomized to receive tezosentan (5 mg/h for 30 minutes, then 1 mg/h for 24-72 hours) or matching placebo. The 2 prespecified primary end points are the incidence of death or worsening heart failure at 7 days in the combined studies and the change from baseline in dyspnea over the first 24 hours of treatment, measured using a visual analog scale in VERITAS-1 and VERITAS-2, individually. RESULTS: Enrollment started in April 2003, and the program was discontinued in November 2005 because of the low probability of achieving a significant treatment effect. CONCLUSIONS: No currently available agents have been shown in a prospective, randomized, clinical trial to improve outcomes in patients with AHF. Thus, the VERITAS program will provide valuable insights into the effect of tezosentan on clinical outcomes in patients with AHF, as well as hemodynamics and clinical symptoms.

Acute Disease↗
PubMed2005

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

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.

Aged↗
PubMed2005

Simvastatin decreases myocardial tumor necrosis factor alpha content in heart transplant recipients.

BACKGROUND: Statins improve patient survival and decrease rejection episodes in heart transplant recipients. We studied the effects of simvastatin treatment on myocardial tumor necrosis factor alpha (TNF-alpha) expression; TNF-alpha is a potent pro-inflammatory cytokine associated with hypertrophy and fibrosis in heart transplant recipients. METHODS: We randomized 10 consecutive heart transplant recipients to receive either 20 mg/day simvastatin (n = 5) or placebo (n = 5) for 6 months after cardiac transplantation. Routine surveillance endomyocardial biopsy specimens were obtained from all patients. We analyzed tissues for myocardial TNF-alpha content, total collagen content, and myocyte size using semiquantitative immunohistochemistry. RESULTS: Myocyte size and total collagen content of placebo and simvastatin groups did not show a statistically significant difference at any biopsy time point. Myocardium TNF-alpha content (% tissue area stained) at 1 week after transplantation was similar in the simvastatin and placebo groups. At the 24(th) week after transplantation, when compared with Week 1 values, we found a significant decrease in myocardium TNF-alpha content in the simvastatin group (15.0% +/- 2.3% vs 5.8% +/- 2.4%, p = 0.02) that was not observed in the placebo group (15.0% +/- 1.5% vs 12.0% +/- 2.6%, p = not significant). CONCLUSION: Simvastatin treatment in heart transplant recipients decreased myocardium TNF-alpha expression. This decrease did not translate into a difference in the markers of hypertrophy. However, decreased myocardial TNF-alpha may be a marker of a general statin-mediated decrease in inflammation in the transplanted heart that leads to improved graft and patient survival.

Aged↗
PubMed2005

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

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.

Comorbidity↗
PubMed2005

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.

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-alpha (TNF-alpha), 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.

Adult↗
PubMed2004

Effects of a novel immune modulation therapy in patients with advanced chronic heart failure: results of a randomized, controlled, phase II trial.

OBJECTIVE: We sought to determine whether a novel, non-pharmacological form of immune modulation therapy (IMT), shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines, improved outcomes in patients with advanced heart failure (HF). BACKGROUND: Immune activation contributes to the progression of HF, but treatments directed against inflammation have been largely unsuccessful. METHODS: Seventy-five HF patients (New York Heart Association [NYHA] functional class III to IV) were randomized to receive either IMT (n = 38) or placebo (n = 37) in a double-blind trial for six months, with continuation of standard HF therapy. Patients were evaluated using the 6-min walk test, changes in NYHA functional class, cardiac function, and quality of life assessments, as well as occurrence of death and hospitalization. RESULTS: There was no between-group difference in 6-min walk test, but 15 IMT patients (compared with 9 placebo) improved NYHA functional classification by at least one class (p = 0.140). The Kaplan-Meier survival analysis showed that IMT 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, but there was a trend toward improved quality of life (p = 0.110). CONCLUSIONS: These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of HF and establish the basis for a phase III trial to define the benefit of IMT in chronic HF.

Aged↗
PubMed2004

Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy.

BACKGROUND: The role of the giant protein titin in patients with heart failure is not well established. We investigated titin expression in patients with end-stage heart failure resulting from nonischemic dilated cardiomyopathy, in particular as it relates to left ventricular (LV) myocardial stiffness and LV function. METHODS AND RESULTS: SDS-agarose gels revealed small N2B (stiff) and large N2BA (compliant) cardiac titin isoforms with a mean N2BA:N2B expression ratio that was significantly (P<0.003) increased in 20 heart failure patients versus 6 controls. However, total titin was unchanged. The coexpression ratio was highest in a subsample of patients with an impaired LV relaxation pattern (n=7), intermediate in those with pseudonormal filling (n=6), and lowest in the group with restrictive filling (n=7). Mechanical measurements on LV muscle strips dissected from these hearts (n=8) revealed that passive muscle stiffness was significantly reduced in patients with a high N2BA:N2B expression ratio. Clinical correlations support the relevance of these changes for LV function (assessed by invasive hemodynamics and Doppler echocardiography). A positive correlation between the N2BA:N2B titin isoform ratio and deceleration time of mitral E velocity, A wave transit time, and end diastolic volume/pressure ratio was found. These changes affect exercise tolerance, as indicated by the positive correlation between the N2BA:N2B isoform ratio and peak O2 consumption (n=10). Upregulated N2BA expression was accompanied by increased expression levels of titin-binding proteins (cardiac ankyrin repeat protein, ankrd2, and diabetes ankyrin repeat protein) that bind to the N2A element of N2BA titin (studied in 13 patients). CONCLUSIONS: Total titin content was unchanged in end-stage failing hearts and the more compliant N2BA isoform comprised a greater percentage of titin in these hearts. Changes in titin isoform expression in heart failure patients with dilated cardiomyopathy significantly impact diastolic filling by lowering myocardial stiffness. Upregulation of titin-binding proteins indicates that the importance of altered titin expression might extend to cell signaling and regulation of gene expression.

Adult↗
PubMed2004

Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices.

OBJECTIVES: We investigated the integrity of dystrophin in left ventricle (LV) and right ventricle (RV) of patients with end-stage heart failure due to ischemic cardiomyopathy (IHD) or dilated cardiomyopathy (DCM), and compared the efficacy of pulsatile or continuous flow assist devices on dystrophin reverse remodeling. BACKGROUND: Recently we demonstrated that the amino (N)-terminus of dystrophin is preferentially disrupted in failing LV myocardium irrespective the underlying etiology, and that this defect is reversed by mechanical unloading using left ventricular assist device (LVAD) therapy. METHODS: Myocardial samples were obtained from seven normal controls, seven failing hearts (either DCM or IHD), and 14 failing-heart patients who underwent placement of either pulsatile (7 patients) or continuous flow (7 patients) LVADs for progressive refractory HF. The expression and integrity of dystrophin in these samples were determined by immunohistochemistry using antibodies against the N-terminal and carboxyl (C)-terminal domains. RESULTS: Immunohistochemical staining identified disruption of the N-terminal dystrophin in both LVs and RVs of all seven failing-heart patients, whereas the C-terminus was normal. Furthermore, this disruption was reversed in 12 of the 14 patients after LVAD therapy using either pulsatile or continuous devices; the degree of the reverse remodeling was similar in both ventricles, although greater recovery was noted in patients treated with pulsatile flow devices. CONCLUSIONS: Integrity of the N-terminus of dystrophin is a useful indicator of both LV and RV function. In addition to improving LV hemodynamics, LVAD therapy results in amelioration of the myocardial structure of the right cardiac chamber.

Adult↗
PubMed2004

The hemodynamic and neurohormonal effects of low doses of tezosentan (an endothelin A/B receptor antagonist) in patients with acute heart failure.

BACKGROUND: In previous studies (the RITZ project), tezosentan, an intravenous (i.v.)-balanced dual endothelin (ET-A/B) antagonist, in doses of 50 and 100 mg/h, improved the hemodynamics but not the clinical outcome of patients with acute heart failure (AHF). OBJECTIVE: To evaluate the effect of lower doses of tezosentan in patients with AHF. SUBJECTS AND METHODS: Included were 130 patients hospitalized due to AHF with dyspnea at rest, despite initial treatment, and were in need of hemodynamic monitoring with cardiac index (CI)<2.5 l/min/m(2) and wedge pressure > or = 20 mm Hg. Patients were randomized in a double-blind fashion to receive placebo or tezosentan: 0.2, 1, 5, or 25 mg/h for 24 h. RESULTS: The primary endpoint of the study, CI increase at 6 h of treatment, was significant in the 5 and 25 mg/h groups. Tezosentan induced a dose-dependent increase in CI and a decrease in wedge pressure, peaking after 3 h in the 5 and 25 mg/h groups. In the 1 mg/h group, this effect was smaller during the first 6 h and increased gradually, becoming significant at 24 h and beyond treatment discontinuation. There was no hemodynamic effect in the 0.2 mg/h arm. Type-B natriuretic peptide (BNP) decreased in the 1, 5, and 25 mg/h groups but not on placebo. Endothelin levels were significantly increased by the 5 and 25 mg/h groups but not in the lower (< or = 1 mg/h) tezosentan doses. Urine output decreased on the 25 mg/h dose. There was a trend towards improvement in patients' subjective dyspnea score and worsening heart failure events, mainly in the 1 mg/h group. CONCLUSIONS: In patients admitted with AHF, tezosentan doses of 1-25 mg/h are efficacious in improving the hemodynamics and reducing BNP. Tezosentan doses beyond 1 mg/h increased plasma endothelin levels and reduced urine output, probably limiting their clinical efficacy, as compared to tezosentan 1 mg/h.

Aged↗
PubMed2004

Evidence of improved right ventricular structure after LVAD support in patients with end-stage cardiomyopathy.

BACKGROUND: Although many reports demonstrate the hemodynamic benefits of left ventricular assist devices (LVAD) in right-sided circulation, it is not known whether the right ventricular myocardium goes through reverse remodeling after left ventricular mechanical circulatory support. Accordingly, the purposes of our studies were 1). to investigate the right ventricular changes that occur in fibrosis, in cellular hypertrophy, and in intra-myocardial tumor necrosis factor alpha (TNF-alpha) levels in patients receiving LVAD support; and 2). to determine whether the type of LVAD used influences right ventricular myocardial changes. METHODS AND RESULTS: We measured myocyte size, total collagen content, and TNF-alpha levels using semi-quantitative immunohistochemical analysis of myocardial samples from the right and left ventricles of control and failing myocardia, either supported by 1 of 2 distinct forms of LVADs or without support. We found that when compared with control, although myocyte size was not increased in the right ventricle of failing myocardia (p = not significant), total collagen content and myocardial TNF-alpha levels were decreased in the right ventricle compared with controls (p < 0.01 and p < 0.001, respectively). CONCLUSION: These data demonstrate that chronic left ventricular unloading with either pulsatile or continuous-flow devices decreases right ventricular total collagen and myocardial TNF-alpha content. We suggest that the decreased fibrosis and normalization of cytokine milieu observed may in part contribute to the recovery of right-sided cardiac function associated with chronic mechanical circulatory support.

Cardiomyopathy, Dilated↗
PubMed2004

The response of the failing heart to chronic mechanical unloading.

PURPOSE OF REVIEW: The authors present a comprehensive analysis of the evidence in support of improvements at the cellular, structural, and hemodynamic levels after left ventricular assist device support. RECENT FINDINGS: The use of left ventricular assist devices as a strategy to bridge patients to cardiac transplantation and, more recently, as a form of destination therapy has provided a great opportunity to study failing myocardium at various time points. Specifically, myocardial samples can be obtained from patients at the time of left ventricular assist device implantation and again at explant, thereby allowing comparisons between paired samples of failing myocardium obtained before and after mechanical unloading. SUMMARY: A body of knowledge has been generated that illustrates the ability of the myocardium to "heal." This information may give us better insight into cellular and molecular mechanisms of heart failure and potential new therapies for patients with end-stage heart failure.

Dystrophin↗