Ularitide as treatment of refractory ascites in cirrhosis- a study protocol for a randomised trial.

INTRODUCTION Ascites is a frequent complication to cirrhosis. When ascites becomes refractory to standard diuretic pharmacotherapy, patients are facing a median survival of less than one year and most likely a need for frequent hospitalisations due to large-volume paracentesis or complications. An unmet need exists for new and improved treatments of refractory ascites and the present study investigates the potential of the natriuretic peptide ularitide for this indication.

Treatments targeting inotropy.

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+.

Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial.

Background: Longer QRS duration (QRSd) improves, but increased left ventricular (LV) end-diastolic volume (LVEDV) reduces, efficacy of cardiac resynchronization therapy (CRT). QRSd/LVEDV ratios differ between sexes. We hypothesized that in the EchoCRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial enrolling patients with heart failure with QRSd <130 ms, those with larger LVEDV would deteriorate but those with the highest QRSd/LVEDV would with CRT.

Cardiac Resynchronization Therapy in Patients With Heart Failure and Narrow QRS Complexes.

Background: Cross correlation analysis (CCA) using tissue Doppler imaging has been shown to be associated with outcome after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with wide QRS. However, its significance in patients with narrow QRS treated with CRT is unknown.

Objectives: The aim of the current study was to investigate the association of mechanical activation delay by CCA with study outcome in patients with HF enrolled in the EchoCRT trial.

Corrigendum to "Falls and Fractures in the Elderly with Sinus Node Disease: The Impact of Pacemaker Implantation".

[This corrects the article DOI: 10.1155/2012/498102.].

Prognostic implications of left ventricular global longitudinal strain in heart failure patients with narrow QRS complex treated with cardiac resynchronization therapy: a subanalysis of the randomized EchoCRT trial.

Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex.

Methods And Results: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis.

"Real world" experience in Cardiac Resynchronization Therapy at a Swiss Tertiary Care Center.

Background: Based on a reduction in morbidity and mortality, cardiac resynchronisation therapy (CRT) has evolved as a standard therapy for patients with advanced heart failure.

Objective: To provide insight into patient demographics, safety, echocardiographic remodelling and long-term follow-up of patients treated with CRT in a "real-world" setting at a Swiss tertiary care centre.

Methods: Patients implanted with a CRT device at the University Heart Centre Zurich between 2000 and 2015 were consecutively enrolled.

Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure.

Background: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis.

Methods: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation.

Effect of cardiac resynchronization therapy in patients with diabetes randomized in EchoCRT.

Aims: As patients with heart failure (HF) and concomitant diabetes carry a poor prognosis, this post-hoc subgroup analysis aimed to compare the outcomes of patients with and without diabetes randomized in the Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) study.

Methods And Results: EchoCRT randomized patients with a QRS duration <130 ms and echocardiographic evidence of left ventricular dyssynchrony to CRT turned on (CRT=ON) vs. off (CRT=OFF) following device implantation.

Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure.

Unlabelled: The TRUE-AHF is a randomized, double-blind, parallel-group, placebo-controlled trial which is evaluating the effects of a 48-h infusion of ularitide (15 ng/kg/min) on the short- and long-term clinical course of patients with acute heart failure. Noteworthy features of the study include the early enrolment of patients following their initial clinical presentation (within 12 h), and entry blood pressure criteria and thresholds for the adjustment of drug infusion rates, which aim to minimize the risk of hypotension. The trial has two primary endpoints: (i) cardiovascular mortality during long-term follow-up; and (ii) the clinical course of patients during their index hospitalization.

Effect of Gender on Outcomes After Cardiac Resynchronization Therapy in Patients With a Narrow QRS Complex: A Subgroup Analysis of the EchoCRT Trial.

Background: In EchoCRT, a randomized controlled trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome (death from any cause or first hospitalization for worsening heart failure) occurred more frequently in the CRT-ON when compared with the control group. In this prespecified subgroup analysis, we evaluated the effect of sex on clinical outcome in EchoCRT.

Methods And Results: In EchoCRT, 585 (72%) of included patients were men.

Association of persistent or worsened echocardiographic dyssynchrony with unfavourable clinical outcomes in heart failure patients with narrow QRS width: a subgroup analysis of the EchoCRT trial.

Aims: EchoCRT was a randomized trial of cardiac resynchronization therapy (CRT) in severely symptomatic heart failure (HF) patients with narrow QRS width <130 ms, ejection fraction ≤35%, and echocardiographic dyssynchrony. All received CRT implants which were then randomized to CRT-On or CRT-Off. While the trial showed no benefit of CRT to these patients, the aim of this subgroup analysis was to test the hypothesis that persistent or worsening dyssynchrony is associated with unfavourable clinical outcomes.

Ularitide: a natriuretic peptide candidate for the treatment of acutely decompensated heart failure.

Treatment for acutely decompensated heart failure (ADHF) has not changed much in the last two decades. Currently available therapies have variable efficacy and can be associated with adverse outcomes. Natriuretic peptides properties include diuresis, natriuresis, vasorelaxation, inhibition of renin-angiotensin-aldosterone system, and are thus chosen in the treatment of ADHF.

Agents with vasodilator properties in acute heart failure: how to design successful trials.

Agents with vasodilator properties (AVDs) are frequently used in the treatment of acute heart failure (AHF). AVDs rapidly reduce preload and afterload, improve left ventricle to aorta and right ventricle to pulmonary artery coupling, and may improve symptoms. Early biomarker changes after AVD administration have suggested potentially beneficial effects on cardiac stretch, vascular tone, and renal function.

The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT trial.

Aims: In EchoCRT, a randomized trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome occurred more frequently in the CRT when compared with the control group. According to current heart failure guidelines, CRT is recommended in patients with a QRS duration of ≥120 ms. However, there is some ambiguity from clinical trial data regarding the benefit of patients with a QRS duration of 120-130 ms.

Cardiac resynchronization therapy in heart failure patients with less severe left ventricular dysfunction.

Cardiac resynchronization therapy is beneficial in heart failure patients with LVEF ≤35% and electrical dyssynchrony. However, its effects among patients with less severe LV dysfunction have not been established. Recent post-hoc analyses of landmark CRT trials suggest that CRT benefit may be present in patients with LVEF >35% and is associated with improvement in cardiac reverse remodelling, all-cause mortality, and need for heart failure hospitalizations.

Long-term performance of modern coronary sinus leads in cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy (CRT) has become an important pillar of contemporary heart failure therapy. The efficacy of CRT, however, critically relies on proper LV lead placement and performance, which is why data regarding the long-term performance of CS leads are of considerable interest. Available studies are limited by a restricted variety of lead vendors, earlier lead models and / or very short follow-up periods.

Cardiac-resynchronization therapy in heart failure with a narrow QRS complex.

Background: Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients.

Methods: We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony.

Comprehensive cardiac resynchronization therapy optimization in the real world.

Background: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients suffering from chronic heart failure (CHF). Optimal device programming is crucial for maximum patient benefit. The goal of the present study was to assess device settings from CHF patients undergoing CRT optimization in a "real world" setting, and to delineate parameters most frequently requiring adjustment.

Prophylactic implantable cardioverter defibrillator treatment in patients with end-stage heart failure awaiting heart transplantation.

Objectives: This study was designed to delineate the role of implantable cardioverter defibrillator (ICD) therapy for the primary and secondary prevention of sudden cardiac death in patients listed for heart transplantation.

Setting: Retrospective observational multicentre study.

Patients: 1089 consecutive patients listed for heart transplantation in two tertiary heart transplant centres were enrolled.

Falls and fractures in the elderly with sinus node disease: the impact of pacemaker implantation.

Background. Falls and fractures in the elderly are among the leading causes of disability. We investigated whether pacemaker implantation prevents falls in patients with SND in a large cohort of patients.

Statins and the risk of cancer after heart transplantation.

Background: Although newer immunosuppressive agents, such as mTOR (mammalian target of rapamycin) inhibitors, have lowered the occurrence of malignancies after transplantation, cancer is still a leading cause of death late after heart transplantation. Statins may have an impact on clinical outcomes beyond their lipid-lowering effects. The aim of the present study was to delineate whether statin therapy has an impact on cancer risk and total mortality after heart transplantation.