Risk assessment for continuous flow left ventricular assist devices: does the destination therapy risk score work? An analysis of over 1,000 patients.

Objectives: This study sought to assess the utility of the Destination Therapy Risk Score (DTRS) in patients with continuous flow left ventricular assist devices (LVAD).

Background: The DTRS was developed to predict the risk of 90-day in-hospital mortality with pulsatile flow LVAD as destination therapy (DT). Despite ongoing use in patients with continuous flow devices, its utility has not been studied in such populations.

Pilot investigation of a novel testing strategy for bleeding in ventricular assist device recipients.

Purpose: A universal loss of von Willebrand factor (vWF) high-molecular-weight multimers (HMWM) has been demonstrated in continuous-flow left ventricular assist device (HeartMate II) recipients. However, no reliable clinical or laboratory predictors for an increased bleeding tendency in this patient population have been identified. This study evaluated the ability of a new automated latex particle-enhanced immunoturbidimetric vWF activity assay (ALPEIVA) to predict non-surgical bleeding risk in HeartMate II recipients.

Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee.

Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.

Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature.

Biochemical and neuropathological studies of brains from individuals with Alzheimer disease (AD) provide clear evidence for an activation of inflammatory pathways, and long-term use of anti-inflammatory drugs is linked with reduced risk to develop the disease. As cause and effect relationships between inflammation and AD are being worked out, there is a realization that some components of this complex molecular and cellular machinery are most likely promoting pathological processes leading to AD, whereas other components serve to do the opposite. The challenge will be to find ways of fine tuning inflammation to delay, prevent, or treat AD.

Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee.

Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A).

Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy.

Background: The HeartMate II (HMII) destination therapy (DT) trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes.

Methods And Results: Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group).

Two immunoglobulin tandem proteins with a linking β-strand reveal unexpected differences in cooperativity and folding pathways.

The study of the folding of single domains, in the context of their multidomain environment, is important because more than 70% of eukaryotic proteins are composed of multiple domains. The structures of the tandem immunoglobulin (Ig) domain pairs A164-A165 and A168-A169, from the A-band of the giant muscle protein titin, reveal that they form tightly associated domain arrangements, connected by a continuous β-strand. We investigate the thermodynamic and kinetic properties of these tandem domain pairs.

Responses of mental stress-induced myocardial ischemia to escitalopram treatment: background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial.

Background: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with clinically stable coronary heart disease (CHD) and is associated with poor outcomes. Depression is a risk factor of MSIMI. The REMIT trial investigates whether selective serotonin reuptake inhibitor (SSRI) treatment can improve MSIMI.

Neurocognitive function in destination therapy patients receiving continuous-flow vs pulsatile-flow left ventricular assist device support.

Background: The HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow left ventricular assist device (LVAD) improved survival in destination therapy (DT) patients during a randomized trial compared with pulsatile-flow LVADs. This study documented changes in cognitive performance in DT patients from that trial to determine if there were differences between continuous-flow and pulsatile-flow support.

Methods: Data were collected in a sub-study from 96 HeartMate II continuous-flow and 30 HeartMate XVE pulsatile-flow LVAD patients from 12 of the 35 trial sites that followed the same serial neurocognitive (NC) testing protocol at 1, 3, 6, 12, and 24 months after LVAD implantation.

Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices.

Axial-flow LVADs have become an integral tool in the management of end-stage heart failure. Consequently, nonsurgical bleeding has emerged as a major source of morbidity and mortality in this fragile population. The mechanisms responsible for these adverse events include acquired von Willebrand disease, GI tract angiodysplasia formation, impaired platelet aggregation, and overuse of anticoagulation therapy.

Positron emission tomography and neuropathologic estimates of fibrillar amyloid-β in a patient with Down syndrome and Alzheimer disease.

Background: Down syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined.

Cost-effectiveness analysis of continuous-flow left ventricular assist devices as destination therapy.

Background: Continuous-flow left ventricular assist devices (LVADs) have become the dominant devices for mechanical circulatory support, but their cost-effectiveness is undetermined. This study assessed the cost-effectiveness of continuous-flow devices for destination therapy versus optimal medical management in advanced heart failure and compared the results with previous estimates for pulsatile devices.

Methods And Results: A Markov model was developed to assess cost-effectiveness.

Clinical impact of concomitant tricuspid valve procedures during left ventricular assist device implantation.

Background: Almost 50% of patients referred for implantable left ventricular assist device (LVAD) have significant tricuspid regurgitation (TR). Preoperative TR is associated with negative outcomes but the clinical benefit of concomitant tricuspid valve procedures has not been extensively studied.

Methods: One hundred fifteen patients, undergoing implantable LVADs, were identified as having significant TR by echocardiography prior to their surgical procedure.

Clinical trials in mechanical circulatory support.

Recent advances in mechanically assisted circulation, including refinement of patient selection criteria and enhancements in device design, have been associated with improvements in survival, functionality and quality of life as well as reductions in adverse events. Novel and innovative trial design, methodology and endpoints have been utilized in the development of the cumulative database supporting the role of ventricular assist devices for the management of patients with advanced heart failure. The rapid and significant improvements in patient-centric outcomes support the expansion of this technology into less moribund populations where the potential benefits may be even more robust.

Patient selection for left ventricular assist devices.

Mechanical circulatory support has become an increasingly common method of supporting patients with advanced heart failure. Paramount to the recent progress observed with this therapy has been a greater understanding of patient selection criteria as a primary determinant of early and late patient outcomes. Prior to device implant, patients should undergo a multidisciplinary evaluation of cardiovascular, noncardiovascular, and psychosocial factors that influence postoperative outcomes.

Durable mechanical circulatory support devices.

Individuals afflicted with advanced systolic heart failure who have become unresponsive to standard medical and electrical therapies are categorized as having American Heart Association stage D heart failure. The high mortality rates for medically treated stage D heart failure have not improved in the last 10 years, and patients at this advanced stage require either palliative measures or surgical management of heart failure. In recent years, surgically implanted ventricular assist devices (VADs) have become available for long-term use and are now commonly used as a therapy for advanced heart failure.

Temporal changes in hospital costs for left ventricular assist device implantation.

Background: A recent prospective, randomized controlled trial demonstrated that a continuous-flow (CF) left ventricular assist device (LVAD) resulted in improved survival at 12 and 24 months compared to a pulsatile-flow (PF) device. The current study examines the hospitalization costs associated with treatment of New York Heart Failure Class IV patients when implanted with a CF LVAD and compares them to previously reported costs of a PF LVAD in the same population.

Methods: Hospital billing data were analyzed for CF LVAD patients in the HeartMate II Destination Therapy trial to determine costs associated with the implantation admission.

The epigenetics of Alzheimer's disease--additional considerations.

The critical commentaries following our review of the epigenetics of Alzheimer's disease (AD) amplify a number of key points with respect to the role of 1-carbon metabolism, the phenomenon of allele-specific methylation, the potentially critical explanatory link provided by epigenetic mechanisms for genome-wide association and large-scale gene expression array studies, and new therapeutic approaches afforded by epigenetic manipulation in Alzheimer's disease.

Presentation and management of left ventricular assist device inflow cannula malposition.

An unusual problem associated with the use of left ventricular assist devices (LVADs) relates to malposition of the apical inflow cannula. From 2005 to 2010, we implanted 154 continuous-flow HeartMate II (Thoratec, Pleasanton, CA) LVADs at our institution. In 4 separate instances, patients appeared to have malposition of the inflow cannula that resulted in serious symptoms.

Epigenetic mechanisms in Alzheimer's disease.

Epigenetic modifications help orchestrate sweeping developmental, aging, and disease-causing changes in phenotype by altering transcriptional activity in multiple genes spanning multiple biologic pathways. Although previous epigenetic research has focused primarily on dividing cells, particularly in cancer, recent studies have shown rapid, dynamic, and persistent epigenetic modifications in neurons that have significant neuroendocrine, neurophysiologic, and neurodegenerative consequences. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and Alzheimer's disease (AD).