Assessing Safety of Anticoagulation for Atrial Fibrillation in Patients with Cirrhosis: A Real-World Outcomes Study.

Aims: In patients with atrial fibrillation (AF) and stroke risk factors, randomized trials have demonstrated that anticoagulation decreases the risk of ischemic stroke. However, all trials to date have excluded patients with significant liver disease, leaving guidelines to extrapolate recommendations. We aim to evaluate the impact of anticoagulation on safety events in patients with AF and cirrhosis.

Early diastolic heart sounds caused by the atrial kick.

An 81-year-old male with a history of coronary artery disease, hypertension, paroxysmal atrial fibrillation and chronic kidney disease presents with asymptomatic bradycardia. Examination was notable for an early diastolic heart sound. 12-lead electrocardiogram revealed sinus bradycardia with a markedly prolonged PR interval and second-degree atrioventricular block, type I Mobitz.

Utility of preoperative troponin I to predict mortality in adult liver transplant recipients: Revisiting pretransplant cardiac risk in the current MELD-allocation era.

Background: Preoperative risk assessment in liver transplant (LT) candidates, particularly related to cardiac risk, is an area of intense interest for transplant clinicians. Various cardiac testing methods are employed by transplant centers to characterize cardiac risk. Serum troponin is an established method for the detection of myocardial injury in a wide variety of clinical settings.

Biomolecules Orchestrating Cardiovascular Calcification.

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli.

Takayasu Arteritis With Extensive Cardiovascular, Neurovascular, and Mesenteric Involvement.

Takayasu arteritis is a rare large vessel vasculitis with an incidence of 1 to 3 per million. This disease typically involves the aorta and its primary branches but has been found to involve the coronary arteries in 7% to 9% of cases. We highlight the need for prompt diagnosis and treatment.

Incidence, Predictors, and Outcomes of New-Onset Left Ventricular Systolic Dysfunction After Orthotopic Liver Transplantation.

Background: Adverse cardiovascular events after liver transplantation (LT) are relatively common and are a significant source of early mortality. Although new-onset systolic dysfunction after LT is a reported phenomenon, there is little data regarding its incidence, risk factors, and outcomes.

Methods And Results: This single-center retrospective study included all adult patients from January 2002 to March 2015 with deceased-donor LT and available preoperative transthoracic echocardiograms (TTEs).

Liver transplantation in highest acuity recipients: identifying factors to avoid futility.

Objective: To identify medical predictors of futility in recipients with laboratory Model of End-Stage Liver Disease (MELD) scores of 40 or more at the time of orthotopic liver transplantation (OLT).

Background: Although the survival benefit for transplant patients with the highest MELD scores is indisputable, the medical and economic effort to bring these highest acuity recipients through OLT presents a major challenge for every transplant center.

Methods: This study was undertaken to analyze outcomes in patients with MELD scores of 40 or more undergoing OLT during the period February 2002 to December 2010.

Accuracy of stress myocardial perfusion imaging to diagnose coronary artery disease in end stage liver disease patients.

Patients with end-stage liver disease (ESLD) who also have underlying coronary artery disease (CAD) may be at increased risk for undergoing hemodynamically challenging orthotopic liver transplantation. Noninvasive single-photon emission computed tomographic (SPECT) imaging is often used to determine whether a patient with ESLD has unsuspected CAD. The objective of this study was to determine the accuracy of SPECT imaging for detection of CAD in patients with ESLD.

Aspergillus fumigatus vegetation of a prosthetic aortic root graft with mycotic aneurysm and subarachnoid hemorrhage.

A 58-year-old woman with a history of Bentall aortic graft and bioprosthetic aortic valve replacement 3 months prior to admission, presented with headache and fever. Imaging yielded a large obstructive filling defect in the ascending aorta, a subarachnoid hemorrhage, and a mycotic aneurysm. Intraoperative specimens grew Aspergillus fumigatus, and despite aggressive measures the patient died.

A role for NADPH oxidase 4 in the activation of vascular endothelial cells by oxidized phospholipids.

Previous studies from our group have demonstrated that oxidized 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine (Ox-PAPC) activates over 1000 genes in human aortic endothelial cells (HAECs). Prominent among these are genes regulating inflammation, cholesterol homeostasis, antioxidant enzymes, and the unfolded protein response. Previous studies from our lab and others suggested that transcriptional regulation by Ox-PAPC may be controlled, at least in part, by reactive oxygen species.

Ox-PAPC activation of PMET system increases expression of heme oxygenase-1 in human aortic endothelial cell.

Oxidized-1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine (Ox-PAPC) has been demonstrated to accumulate in atherosclerotic lesions and regulates expression of more than 1,000 genes in human aortic endothelial cell (HAEC). Among the most highly induced is heme oxygenase-1 (HO-1), a cell-protective antioxidant enzyme, which is sensitively induced by oxidative stress. To identify the pathway by which Ox-PAPC induces HO-1, we focused on the plasma membrane electron transport (PMET) complex, which contains ecto-NADH oxidase 1 (eNOX1) and NADPH:quinone oxidoreductase 1 (NQO1) and affects cellular redox status by regulating levels of NAD(P)H.

Altered proteome biology of cardiac mitochondria under stress conditions.

Myocardial ischemia-reperfusion induces mitochondrial dysfunction and, depending upon the degree of injury, may lead to cardiac cell death. However, our ability to understand mitochondrial dysfunction has been hindered by an absence of molecular markers defining the various degrees of injury. To address this paucity of knowledge, we sought to characterize the impact of ischemic damage on mitochondrial proteome biology.

Systematic characterization of the murine mitochondrial proteome using functionally validated cardiac mitochondria.

Mitochondria play essential roles in cardiac pathophysiology and the murine model has been extensively used to investigate cardiovascular diseases. In the present study, we characterized murine cardiac mitochondria using an LC/MS/MS approach. We extracted and purified cardiac mitochondria; validated their functionality to ensure the final preparation contains necessary components to sustain their normal function; and subjected these validated organelles to LC/MS/MS-based protein identification.

Past and present course of cardioprotection against ischemia-reperfusion injury.

Despite tremendous advances in cardiovascular research and clinical therapy, ischemic heart disease remains the leading cause of serious morbidity and mortality in western society and is growing in developing countries. For the past 5 decades, many scientists have studied the pathophysiology of myocardial ischemia-reperfusion (I/R) injury leading to infarction. With the exception of reperfusion therapy, attempts to salvage the myocardium during an acute myocardial infarction showed disappointing results in directly decreasing infarct size.

Role of endothelial nitric oxide synthase in the regulation of SREBP activation by oxidized phospholipids.

Oxidized-1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (Ox-PAPC), found in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to synthesize chemotactic factors, such as interleukin (IL)-8. Previously, we demonstrated that the sustained induction of IL-8 transcription by Ox-PAPC was mediated through the activation of sterol regulatory element-binding protein (SREBP). We now present evidence for the role of endothelial nitric oxide synthase (eNOS) in the activation of SREBP by Ox-PAPC.

Mitochondria and ischemia/reperfusion injury.

Cardiac ischemia/reperfusion injury results in a variable mixture of apoptotic, necrotic, and normal tissue that depends on both the duration and severity of ischemia. Injury can be abrogated by activation of protective pathways via ischemic and pharmacologic preconditioning. Mitochondria serve as final arbiters of life and death of the cell as these organelles not only are required to generate ATP but also can trigger apoptosis or necrosis.

K+-dependent regulation of matrix volume improves mitochondrial function under conditions mimicking ischemia-reperfusion.

To delineate the role of mitochondrial K+ fluxes in cardioprotection, we investigated the effect of extramitochondrial K+ on the ability of mitochondria to support membrane potential (DeltaPsi), regulate matrix volume, consume oxygen, and phosphorylate ADP under conditions mimicking key elements of ischemia-reperfusion. Isolated energized mitochondria responded to ADP addition with depolarization, increased O2 consumption, and matrix shrinkage. The time required for full recovery of DeltaPsi, signaling the completion of ADP phosphorylation, was used to evaluate the rate of ATP synthesis during repeated ADP pulses.

Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition.

Mitochondrial permeability transition (MPT) pores have recently been implicated as a potential mediator of myocardial ischemic injury. Nitric oxide (NO) donors induce a powerful late phase of cardioprotection against ischemia-reperfusion injury; however, the cellular mechanisms involved are poorly understood. The role of MPT pores as a target of cardioprotective signaling pathways activated by NO has never been explored in detail.