A low voltage activated Ca current found in a subset of human ventricular myocytes.

Low voltage activated (I) calcium currents including Cav1.3 and T-type calcium current (I) have not been reported in adult human left ventricular myocytes (HLVMs). We tried to examine their existence and possible correlation with etiology and patient characteristics in a big number of human LVMs isolated from explanted terminally failing (F) hearts, failing hearts with left ventricular assist device (F-LVAD) and nonfailing (NF) human hearts.

Sarcoidosis presenting as massive splenomegaly and severe epistaxis, case report.

Sarcoidosis is a multisystem disorder of unknown etiology. Extrapulmonary sarcoidosis can involve any organ, but isolated spleen involvement is rare. Diagnosis can be challenging as other etiologies may have similar presentations.

Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared.

Utility of concomitant tricuspid valve procedures for patients undergoing implantation of a continuous-flow left ventricular device.

Objective: Patients referred for implantable continuous-flow left ventricular assist devices (cfLVAD) frequently have preoperative right heart failure and tricuspid regurgitation (TR). The objective of this report is to examine early clinical benefits of concomitant tricuspid surgery for these patients.

Methods: Sixty-one of 200 consecutive cfLVAD patients at our institution displayed preimplant right heart dysfunction and significant TR.

X-linked inhibitor of apoptosis protein-mediated attenuation of apoptosis, using a novel cardiac-enhanced adeno-associated viral vector.

Successful amelioration of cardiac dysfunction and heart failure through gene therapy approaches will require a transgene effective at attenuating myocardial injury, and subsequent remodeling, using an efficient and safe delivery vehicle. Our laboratory has established a well-curated, high-quality repository of human myocardial tissues that we use as a discovery engine to identify putative therapeutic transgene targets, as well as to better understand the molecular basis of human heart failure. By using this rare resource we were able to examine age- and sex-matched left ventricular samples from (1) end-stage failing human hearts and (2) nonfailing human hearts and were able to identify the X-linked inhibitor of apoptosis protein (XIAP) as a novel target for treating cardiac dysfunction.

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.

Impact of tricuspid valve regurgitation in patients treated with implantable left ventricular assist devices.

Background: The progression of tricuspid valve regurgitation (TR) and the impact of preoperative TR on postoperative outcomes in patients having left ventricular assist device (LVAD) implantation has not been studied.

Methods: One hundred seventy-six consecutive implantable LVAD procedures were retrospectively reviewed. A total of 137 patients comprised the final study group with complete preimplant characteristics, before and after echocardiogram assessment of TR, and outcomes data.

Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model.

Objective: Achieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model.

Methods: Nine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device.

Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients.

Background: Bleeding is a major cause of morbidity in recipients of continuous-flow left ventricular assist devices (CF-LVAD). A better understanding of the impact of CF-LVAD support on the hemostatic profile is necessary to establish better strategies for anticoagulation therapy and risk assessment for bleeding complications. A prospective multicenter study was conducted to characterize von Willebrand factor (vWF) profiles in patients undergoing CF-LVAD implantation.

Impact of left ventricular assist device bridging on posttransplant outcomes.

Background: Bridge to heart transplantation with a left ventricular assist device (LVAD) can be a promising therapy for patients who are not effectively stabilized with conservative measures. However, referral for LVAD therapy may be limited secondary to reports of poor outcomes when mechanical circulatory support is required before transplantation.

Methods: A retrospective review was undertaken to evaluate outcomes in United Network of Organ Sharing (UNOS) status 1 heart transplant recipients who were bridged to transplant with an implantable LVAD or with intravenous inotropes only from 1994 to 2007.

Two-photon laser scanning microscopy of the transverse-axial tubule system in ventricular cardiomyocytes from failing and non-failing human hearts.

Objective. The transverse-axial tubule system (TATS) of cardiomyocytes allows a spatially coordinated conversion of electrical excitation into an intracellular Ca(2+) signal and consequently contraction. Previous reports have indicated alterations of structure and/or volume of the TATS in cardiac hypertrophy and failure, suggesting a contribution to the impairment of excitation contraction coupling.

Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation.

Abnormal L-type Ca(2+) channel (LTCC, also named Cav1.2) density and regulation are important contributors to depressed contractility in failing hearts. The LTCC agonist BAY K 8644 (BAY K) has reduced inotropic effects on failing myocardium.

The inotropic effect of cardioactive glycosides in ventricular myocytes requires Na+-Ca2+ exchanger function.

Glycoside-induced cardiac inotropy has traditionally been attributed to direct Na(+)-K(+)-ATPase inhibition, causing increased intracellular [Na(+)] and consequent Ca(2+) gain via the Na(+)-Ca(2+) exchanger (NCX). However, recent studies suggested alternative mechanisms of glycoside-induced inotropy: (1) direct activation of sarcoplasmic reticulum Ca(2+) release channels (ryanodine receptors; RyRs); (2) increased Ca(2+) selectivity of Na(+) channels (slip-mode conductance); and (3) other signal transduction pathways. None of these proposed mechanisms requires NCX or an altered [Na(+)] gradient.

Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy.

Physiological hemodynamic stress, such as aerobic exercise, is intermittent and requires an increase in Ca2+ -dependent contractility through sympathetic nervous system activation. Pathological hemodynamic stress, such as hypertension, is persistent and requires sustained increases in cardiac function. Over time, this causes left ventricular hypertrophy (LVH)-reduced responsiveness to sympathetic stimulation.

Effect of acute unloading via head-up tilt on QTc prolongation in patients with ischemic or non-ischemic cardiomyopathy.

Patients with advanced cardiomyopathy develop prolongations in ventricular myocyte action potential duration that are reflected by prolongations of QT intervals on surface electrocardiograms. Recent studies demonstrate that the placement of a left ventricular (LV) assist device, which induces profound cardiac decompression, acutely increases QT intervals within hours. The goal of this study was to use head-up tilt (HUT) to examine electrocardiographic responses to cardiac unloading in patients with cardiomyopathy.

Prolonged repolarization after ventricular assist device support is associated with arrhythmias in humans with congestive heart failure.

Background: Recent observations indicate that the QTc interval often increases in the early postoperative period (<1 week) after mechanical unloading of severely failing hearts with a left ventricular assist device (LVAD). The present study examined whether early changes in ventricular repolarization after LVAD placement are associated with ventricular arrhythmias.

Methods And Results: An electrocardiogram was obtained within 4 days before LVAD placement, <12 hours after LVAD placement, and weekly thereafter.

Effect of older donor age on risk for mortality after heart transplantation.

Background: Despite the increasingly common use of donor hearts at least 50 years of age, controversy still remains regarding long-term outcome. Our goal was to determine if older donor age is associated with an increased risk of mortality and specifically if the use of donor hearts at least 50 years of age reduces survival.

Methods: We retrospectively studied records of all primary heart transplants performed between January 1990 and July 2002.

Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart.

Objectives: The objective of the present study was to determine whether improved contractility after left ventricular assist device (LVAD) support reflects altered myocyte calcium cycling and changes in calcium-handling proteins.

Background: Previous reports demonstrate that LVAD support induces sustained unloading of the heart with regression of pathologic hypertrophy and improvements in contractile performance.

Methods: In the human myocardium of subjects with heart failure (HF), with non-failing hearts (NF), and with LVAD-supported failing hearts (HF-LVAD), intracellular calcium ([Ca(2+)](i)) transients were measured in isolated myocytes at 0.

Successful treatment of esophageal cancer with transhiatal esophagectomy after heart transplantation.

A 55-year-old heart transplant recipient with reflux esophagitis presented for routine endoscopic surveillance of an area of Barrett's metaplasia initially seen 3 years previously. Esophagogastroduodenoscopy revealed adenocarcinoma at 33 cm from the incisors. The preoperative clinical stage was T1N0M0 by endoscopic ultrasound.

Use of LeVeen pleuroperitoneal shunt for refractory high-volume chylothorax.

We present a case of intractable high-volume (> 2L/d) chylothorax after transhiatal esophagectomy treated successfully with the simultaneous insertion of both Denver (Denver Biomedical, Golden, CO) and LeVeen (Becton-Dickinson, Rutherford, NJ) pleuroperitoneal shunts. The patient initially had chemoradiotherapy for a T4N1 squamous cell carcinoma of the thoracic esophagus. Re-staging showed a dramatic shrinkage of tumor, and a transhiatal esophagectomy was performed.

Myocyte nitric oxide synthase 2 contributes to blunted beta-adrenergic response in failing human hearts by decreasing Ca2+ transients.

Background: Human heart failure (HF) usually exhibits blunted response to beta-adrenergic receptor (AR) stimulation. Here, we examined whether expression of nitric oxide synthase-2 (NOS2, or inducible NOS) contributes to this loss of inotropic reserve in human HF.

Methods And Results: Failing human hearts were obtained at transplantation.

Abnormal frequency-dependent responses represent the pathophysiologic signature of contractile failure in human myocardium.

Background: - The normal increase in isometric developed force (DF) with faster pacing rates, known as the positive force-frequency response/relationship (FFR), is altered in failing myocardium, as shown by its negative response to increased pacing. The objective of this study was to determine if increasing Ca2+ influx with L-type Ca2+ channel (L-CaCh) agonists: BayK 8644 (BayK) and FPL 64176 (FPL) or increased extracellular Ca2+ could increase contractility and normalize the FFR in failing myocardium.

Methods: - Isometric DF was measured in right ventricular trabeculae from failing (n = 28) and non-failing (n = 12) human hearts at various stimulation frequencies (0.

Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts.

Background: Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals.

Methods: Hearts from Yorkshire pigs (100 kg) were studied in 3 groups.

Dynamic regulation of sodium/calcium exchange function in human heart failure.

Background: Sarcolemmal Na/Ca exchange (NCX) regulates cardiac Ca and contractility. NCX function during the cardiac cycle is determined by intracellular [Ca] and [Na] ([Ca]i, and [Na]i) and membrane potential (Em), which all change in human heart failure (HF). Therefore, changes in NCX function may contribute to abnormal Ca regulation in human HF.