Showing papers by "Guillermo Torre-Amione published in 2007"
TL;DR: Although cellular recovery and improvement in ventricular function are observed, the degree of clinical recovery is insufficient for device explantation in most patients with chronic heart failure.
Abstract: Background— Myocardial recovery after left ventricular assist device (LVAD) support has been reported. The LVAD Working Group Recovery Study was a prospective multicenter trial to assess the incidence of myocardial recovery in patients bridged to cardiac transplantation. Methods and Results— After LVAD implantation, patients were evaluated with the use of rest echocardiograms with partial LVAD support and cardiopulmonary exercise testing. Dobutamine echocardiography with hemodynamic measurements was performed in those patients with left ventricular ejection fraction >40% during resting studies. Histological analysis was performed on myocardial samples taken at LVAD implantation and explantation. Sixty-seven LVAD patients with heart failure participated in the study. After 30 days, significant improvement occurred in left ventricular ejection fraction (17±7% versus 34±12%; P<0.001) and reductions in left ventricular end-diastolic diameter (7.1±1.2 versus 5.1±1.1 cm; P<0.001) and left ventricular mass (320±...
381 citations
TL;DR: The endothelin receptor antagonist tezosentan did not improve symptoms or clinical outcomes in patients with acute heart failure and was not associated with worse outcomes.
Abstract: ContextPlasma concentrations of the vasoconstrictor peptide endothelin-1 are increased in patients with heart failure, and higher concentrations are associated with worse outcomes. Tezosentan is an intravenous short-acting endothelin receptor antagonist that has favorable hemodynamic actions in heart failure.ObjectiveTo determine if tezosentan improves outcomes in patients with acute heart failure.Design, Setting, and ParticipantsThe Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies, 2 independent, identical, and concurrent randomized, double-blind, placebo-controlled, parallel-group trials conducted from April 2003 through January 2005 at sites in Australia, Europe, Israel, and North America. Patients admitted within the previous 24 hours with persisting dyspnea and a respiratory rate of 24/min or greater were eligible provided they fulfilled 2 of 4 criteria: (1) elevated plasma concentrations of B-type or N-terminal pro–B-type natriuretic peptide, (2) clinical pulmonary edema, (3) radiologic pulmonary congestion or edema, or (4) left ventricular systolic dysfunction.InterventionInfusion of tezosentan (5 mg/h for 30 minutes, followed by 1 mg/h for 24 to 72 hours [n = 730]) or placebo (n = 718).Main Outcome MeasuresThe coprimary end points were change in dyspnea (measured at 3, 6, and 24 hours using a visual analog scale from 0-100) over 24 hours (as area under the curve) in the individual trials and incidence of death or worsening heart failure at 7 days in both trials combined.ResultsOf the 1435 patients who received treatment as assigned, 855 (60%) were men; mean age was 70 years. Mean left ventricular ejection fraction (measured in 779 patients [54%]) was 29% (SD, 11%). Baseline dyspnea scores were similar in the 2 treatment groups. Tezosentan did not improve dyspnea more than placebo in either trial, with a mean treatment difference of −12 (95% confidence interval [CI], −105 to 81) mm · h (P = .80) in the first trial and −25 (95% CI, −119 to 69) mm · h (P = .60) in the second. The incidence of death or worsening heart failure at 7 days in the combined trials was 26% in each treatment group (odds ratio, 0.99; 95% confidence interval, 0.82-1.21; P = .95).ConclusionThe endothelin receptor antagonist tezosentan did not improve symptoms or clinical outcomes in patients with acute heart failure.Trial Registrationclinicaltrials.gov Identifiers: NCT00525707 (VERITAS-1) and NCT00524433 (VERITAS-2).
368 citations
TL;DR: Global SRIVR by 2-dimensional speckle tracking is strongly dependent on LV relaxation, and E/SRIVR can predict LV filling pressures with reasonable accuracy, particularly in patients with normal ejection fraction and in those with regional dysfunction.
Abstract: Background— Diastolic strain rate (SR) measurements that comprise all left ventricular (LV) segments are advantageous over myocardial velocity for assessment of diastolic function. Mitral early diastolic velocity (E)/SR ratio during the isovolumetric relaxation (IVR) period can be used to estimate LV filling pressures. Methods and Results— Simultaneous echocardiographic imaging and LV pressure measurements (7F catheters) were performed in 7 adult dogs. Loading conditions were altered by saline infusion and caval occlusion, and lusitropic state was changed by dobutamine and esmolol infusion. A curve depicting global SR was derived from each of the 3 apical views, and SR was measured during IVR (SRIVR) and early LV filling (SRE). SRIVR had a strong correlation with time constant of LV pressure decay during the IVR period (τ) (r=−0.83, P<0.001), whereas SRE was significantly related to LV end-diastolic pressure (r=0.52, P=0.005) in the experimental stages where τ was <40 ms. In 50 patients with simultaneous ...
339 citations
TL;DR: LV UR is reduced in patients with depressed EF, but not in those with diastolic dysfunction and normal EF, and is primarily determined by twist and ESV.
Abstract: Background— Recent studies validated the measurement of left ventricular (LV) untwisting rate (UR) by speckle tracking echocardiography. A few reports suggest that it may provide additional noninvasive insight into LV diastolic function. Methods and Results— Simultaneous echocardiographic imaging and LV pressure measurements (7F Millar catheters) were performed in 8 adult dogs. Loading conditions were altered by caval occlusion, whereas lusitropic state was changed by dobutamine and esmolol infusion. Inferior vena cava occlusion at all experimental stages (baseline, dobutamine, esmolol) led to a significant decrease (P≤0.01) in LV end-systolic volume (ESV) and a significant increase in UR (P=0.03). The best relation was observed between LV UR and ESV (r=−0.8, P<0.001). The clinical study was conducted in 67 patients (age 57±17 years, 19 women) undergoing simultaneous right heart catheterization and echocardiographic imaging, with 20 healthy subjects as a control group. There were 34 patients with ejection...
180 citations
TL;DR: In this article, it was reported that HSP60 doubled in end-stage heart failure, even though levels of the protective HSP72 were unchangeable, and showed that the level of heat shock protein (HSP72 was unchanged.
Abstract: Heat shock protein (HSP) 60 is a mitochondrial and cytosolic protein. Previously, we reported that HSP60 doubled in end-stage heart failure, even though levels of the protective HSP72 were unchange...
141 citations
TL;DR: Survival and freedom from cardiac allograft vasculopathy in patients who receive a transplant for PPCM are no worse than in women who require a transplants for other indications, regardless of parity.
Abstract: Background Outcomes of patients with a prior diagnosis of peri-partum cardiomyopathy (PPCM) undergoing heart transplantation are not well described but may be worse than for women who undergo transplantation for other etiologies. Methods Between 1999 and 2005, 69 women aged younger than 40 underwent transplantation for PPCM in 29 institutions participating in the Cardiac Transplant Research Database. Patients with PPCM were compared with 90 female recipients of similar age with idiopathic dilated cardiomyopathy (IDC) and history of pregnancy (P+), 53 with no prior pregnancy (P−), and with 459 men of a similar age with IDC. Rejection, infection, cardiac allograft vasculopathy, and survival were compared. Results Recipients with PPCM accounted for 1% of all transplants and 5% of transplants in women. Comparisons of the 4 patient groups were made. The risk of cumulative rejection was higher in the PPCM Group compared with the P− Group ( p p p = 0.9), and there was a trend toward improved survival compared with the P + Group ( p = 0.07) and improved survival compared with the P− Group ( p = 0.05). Conclusions Heart transplantation for PPCM remains relatively infrequent. Survival and freedom from cardiac allograft vasculopathy in patients who receive a transplant for PPCM are no worse than in women who require a transplant for other indications, regardless of parity.
47 citations
TL;DR: This study suggests that istaroxime is potentially useful in the treatment of HF and may offer a unique treatment for systolic and/or diastolic dysfunction.
Abstract: Istaroxime (PST2744) is a luso-inotrope that stimulates the sarcoplasmic reticulum calcium adenosine triphosphatase isoform 2a without chronotropic effects. Additionally, it has beneficial effects on myocardial energetics. This phase 1–2 clinical trial in patients with chronic stable heart failure (HF) is the first evaluation of istaroxime in humans. Three cohorts of 6 patients each were exposed to 4 sequentially increasing 1-hour infusions with a random placebo. Doses were 0.005–5.0 μ/kg per min. Safety and hemodynamics were evaluated by impedance cardiography, digital Holter recorder, and electrocardiography. Pharmacokinetic data were obtained for 1 hour during treatment and for 6 hours after dosing. The mean age was 53 ± 7 years, and the mean left ventricular ejection fraction was 0.27 ± 0.08. Impedance cardiography demonstrated enhanced contractility as measured by the acceleration index, left cardiac work index, cardiac index, and pulse pressure at doses ≥1 μ/kg per min, with evidence of activity at doses of 0.5 μ/kg per min. Istaroxime shortened QT c . After infusion, the hemodynamic effect rapidly dissipated over 1–2 hours. Istaroxime was pharmacologically active and well tolerated at doses up to 3.33 μ/kg per min. Side effects were related to gastrointestinal symptoms and injection site pain at higher doses, which dissipated within minutes after the infusion ended. Ventricular ectopy was not altered. This study suggests that istaroxime is potentially useful in the treatment of HF and may offer a unique treatment for systolic and/or diastolic dysfunction. Additional studies are under way to further define its utility in acute HF.
45 citations
TL;DR: Etanercept appeared to decrease LV hypertrophy by decreasing extracellular matrix deposition as well as degree of collagen deposition at 6 months and incidence of adverse events.
Abstract: Cardiac allograft hypertrophy is associated with persistent expression of cardiac tumor necrosis factor (TNF)-alpha. We investigated whether TNFalpha antagonism would impact allograft hypertrophy. EFECT (EFfect of Etanercept on Cardiac Transplantation) was a randomized, controlled, double-blind trial evaluating the effect of etanercept versus placebo treatment immediately posttransplant. The primary end-point was change in left ventricular (LV) mass after 6 months. Secondary endpoints included degree of collagen deposition at 6 months and incidence of adverse events. Forty-nine patients were randomized to either etanercept or placebo. LV mass increased significantly in both arms at 6 months, with a smaller increase in the etanercept group (19% vs. 33%, P=ns). Myocardial collagen content increased in the placebo, but not the etanercept, group (+39.8%, P<0.08 vs. -7.0%, P=NS). Allograft hypertrophy develops posttransplant with a corresponding increase in extracellular matrix. Etanercept appeared to decrease LV hypertrophy by decreasing extracellular matrix deposition.
18 citations