A phase II study of everolimus in combination with imatinib for previously treated advanced renal carcinoma.

Purpose: This phase II study evaluated the activity of combined treatment with the mTOR inhibitor everolimus and the PDGFR inhibitor imatinib in patients with previously-treated, advanced renal carcinoma. The primary endpoint was estimation of the 3-month progression-free rate.

Patients And Methods: Eligible patients had metastatic or unresectable clear cell renal carcinoma, at least one prior systemic therapy, no prior mTOR inhibitor therapy, performance status 0-2, and measurable disease.

Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.

Background: More than 20 genes have been reported to cause idiopathic and familial dilated cardiomyopathy (IDC/FDC), but the frequency of genetic causation remains poorly understood.

Methods And Results: Blood samples were collected and DNA prepared from 313 patients, 183 with FDC and 130 with IDC. Genomic DNA underwent bidirectional sequencing of six genes, and mutation carriers were followed up by evaluation of additional family members.

Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular (LV) enlargement with systolic dysfunction, other causes excluded. When inherited, it represents familial dilated cardiomyopathy (FDC). We hypothesized that IDC or FDC would show with cardiac magnetic resonance (CMR) increased myocardial accumulation of gadolinium contrast at steady state and decreased baseline myocardial blood flow (MBF) due to structural alterations of the extracellular matrix compared with normal myocardium.

Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.

Background: Lamin A/C mutations are a well-established cause of dilated cardiomyopathy (DCM), although their frequency has not been examined in a large cohort of patients. We sought to examine the frequency of mutations in LMNA, the gene encoding lamin A/C, in patients with idiopathic (IDC) or familial dilated cardiomyopathy (FDC).

Methods: Clinical cardiovascular data, family histories, and blood samples were collected from 324 unrelated IDC probands, of whom 187 had FDC.

The use of positive inotropes in end-of-life heart failure care.

End-stage heart failure is associated with mortality equivalent to cancer, yet there is little information about palliative therapy for this disease. Chronic outpatient support with inotropes provides symptomatic relief and life extension for those select patients demonstrating dependence on positive inotropic therapy. The purpose of this review is to provide information about process and implementation of chronic outpatient support with inotropes in patients with end-stage heart failure.

Mutations of presenilin genes in dilated cardiomyopathy and heart failure.

Two common disorders of the elderly are heart failure and Alzheimer disease (AD). Heart failure usually results from dilated cardiomyopathy (DCM). DCM of unknown cause in families has recently been shown to result from genetic disease, highlighting newly discovered disease mechanisms.

Clinical characteristics of 304 kindreds evaluated for familial dilated cardiomyopathy.

Background: Familial dilated cardiomyopathy (FDC) is dilated cardiomyopathy of unknown cause occurring in 2 or more closely related family members.

Methods And Results: Members of 304 families suspected to have FDC were evaluated by family history (FH) and medical record review and were categorized as affected with idiopathic dilated cardiomyopathy (IDC), unaffected, unknown, or no data. Pedigrees were categorized with confirmed FDC, probable FDC, possible FDC or IDC based on strength of evidence.

Prospective evaluation of an outpatient heart failure disease management program designed for primary care: the Oregon model.

Background: Most heart failure care is provided by primary care providers. Although heart failure disease management programs improve outcomes, most have been hospital-based with little integration with primary care providers. To address this issue, a heart failure clinic disease management model was adapted for use in the primary care setting.

Care processes and clinical outcomes of continuous outpatient support with inotropes (COSI) in patients with refractory endstage heart failure.

Background: This study describes the process and outcomes of continuous outpatient support with inotropes (COSI) in patients with Stage D heart failure (HF). Although Stage D HF has recently been defined as end-stage disease requiring special interventions for survival such as COSI or ventricular assist devices, concern has been raised regarding the safety, efficacy, mortality outcomes, and ethics of COSI.

Methods And Results: Inotrope dependence was defined as worsening of the patient's clinical status with attempted inotrope withdrawal such that the patient was deemed unlikely to survive to permit hospital discharge.