Sirolimus Adverse Event Profile in a Non-Clinical Trial Cohort of Heart Transplantation Patients.

BACKGROUND Sirolimus has been used increasingly in heart transplantation for its ability to reduce acute rejection, prevent the progression of cardiac allograft vasculopathy (CAV), and preserve renal function. We sought to assess the adverse reactions associated with the use of sirolimus compared to mycophenolate mofetil (MMF). MATERIAL AND METHODS We retrospectively reviewed the charts of 221 adult heart transplant patients who received either sirolimus or MMF as part of their immunosuppression from June 1, 2001 to April 1, 2005.

Gene expression profiling to study racial differences after heart transplantation.

Background: The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.

The liver in heart failure: a biopsy and explant series of the histopathologic and laboratory findings with a particular focus on pre-cardiac transplant evaluation.

The pathologic liver changes in chronic heart failure have been characterized mostly based on autopsy series and include sinusoidal dilation and congestion progressing to pericellular fibrosis, bridging fibrosis, and ultimately to cardiac cirrhosis or sclerosis. Liver biopsies are commonly obtained as part of the work up before heart transplantation in patients with longstanding right heart failure, particularly if ascites, abnormal liver function tests or abnormal abdominal imaging are noted as part of the pre-transplant evaluation. In these cases, the liver biopsy findings may be used to further risk stratify patients for isolated heart or combined heart and liver transplantation.

Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients.

Background: Gene expression profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of gene expression profiling test scores within a patient may predict risk of future events of allograft dysfunction or death.

Method: Patients from the IMAGE study with rejection surveillance gene expression profiling tests performed at 1- to 6-month intervals were selected for this cohort study.

Divergent trends in survival and readmission following a hospitalization for heart failure in the Veterans Affairs health care system 2002 to 2006.

Objectives: This study sought to determine recent trends over time in heart failure hospitalization, patient characteristics, treatment, rehospitalization, and mortality within the Veterans Affairs health care system.

Background: Use of recommended therapies for heart failure has increased in the U.S.

Gene-expression profiling for rejection surveillance after cardiac transplantation.

Background: Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy.

Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation.

Background: Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.

Methods: Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).

Molecular testing for long-term rejection surveillance in heart transplant recipients: design of the Invasive Monitoring Attenuation Through Gene Expression (IMAGE) trial.

Background: Acute rejection continues to occur beyond the first year after cardiac transplantation, but the optimal strategy for detecting rejection during this late period is still controversial. Gene expression profiling (GEP), with its high negative predictive value for acute cellular rejection (ACR), appears to be well suited to identify low-risk patients who can be safely managed without routine invasive endomyocardial biopsy (EMB).

Methods: The Invasive Monitoring Attenuation Through Gene Expression (IMAGE) study is a prospective, multicenter, non-blinded, randomized clinical trial designed to test the hypothesis that a primarily non-invasive rejection surveillance strategy utilizing GEP testing is not inferior to an invasive EMB-based strategy with respect to cardiac allograft dysfunction, rejection with hemodynamic compromise (HDC) and all-cause mortality.

Prognostic value of electrocardiographic criteria for left ventricular hypertrophy.

Background: Many electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) exist, but few studies have compared their relative prognostic value for predicting cardiovascular (CV) mortality.

Methods: We analyzed the first ECG on 46950 consecutive veterans. We targeted male outpatients with a body mass index > 20 to avoid confounding by complicating catabolic illnesses and further excluded those with conduction abnormalities.

Prognostic value of low-level cardiac troponin-I elevations in patients without definite acute coronary syndromes.

Background: Low-level cardiac troponin-I (cTn-I) elevations predict adverse cardiovascular outcomes in patients with definite acute coronary syndromes (ACS), as defined by the presence of chest pain accompanied by ischemic electrocardiographic changes. However, their prognostic value in other clinical situations remains unclear.

Methods: We studied 366 patients with suspected myocardial infarction (MI) but without definite ACS, including 57 patients with low-level cTn-I elevations (1.