Publications by authors named "Tsushung A Hua"

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.

Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care.

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Purpose: Blood pressure variability is associated with traditional cardiovascular risk factors, but little is known about the association with atrial fibrillation. We compared blood pressure variability in patients with and without atrial fibrillation using data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial.

Materials And Methods: The VALUE trial was a randomised-controlled trial of valsartan versus amlodipine in patients with hypertension and high cardiovascular risk, followed for 4.

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Aims: Blood pressure variability is associated with increased risk of cardiovascular events, particularly in high-risk patients. We assessed if variability was associated with increased risk of cardiovascular events and death in hypertensive patients at different risk levels.

Methods And Results: The Valsartan Antihypertensive Long-term Use Evaluation trial was a randomized controlled trial of valsartan vs.

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Background: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response.

Methods And Results: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included.

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Background: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial.

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Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF.

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Background: Atrial fibrillation (AFib) is a common comorbidity in HF and affects patients' outcome. We sought to assess the effects of serelaxin in patients with and without AFib.

Methods: In a post hoc analysis of the RELAX-AHF trial, we compared the effects of serelaxin on efficacy end points, safety end points and biomarkers in 1161 patients with and without AFib on admission electrocardiogram.

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Aims: Women with heart failure are typically older, and more often have hypertension and a preserved left ventricular ejection fraction as compared with men. We sought to analyze if these sex differences influence the course and outcome of acute heart failure.

Methods And Results: We analyzed sex differences in acute heart failure in 1161 patients enrolled in the RELAX-AHF study.

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Background: Acute heart failure (AHF), a common and growing health concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, but corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, with the use of novel assessments.

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To evaluate the effects of achieved systolic blood pressure (SBP) during treatment on cardiovascular (CV) outcomes, the authors measured event rates of a composite primary endpoint (CV death or nonfatal myocardial infarction or stroke) at on-treatment SBPs of ≥140 mm Hg and the 10 mm Hg intervals of <140 mm Hg, <130 mm Hg, and <120 mm Hg in 6459 patients with diabetes (mean age, 67) and 4246 patients without diabetes (mean age, 69) from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial. In the diabetic cohort, the primary endpoint was 49% lower (P<.001) at <140 mm Hg than at ≥140 mm Hg, and the separate components of this endpoint were also significantly reduced.

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Objectives: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes.

Background: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted.

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Background: Serelaxin showed beneficial effects on clinical outcome and trajectories of renal markers in patients with acute heart failure. We aimed to study the interaction between renal function and the treatment effect of serelaxin.

Methods: In the current post hoc analysis of the RELAX-AHF trial, we included all patients with available estimated glomerular filtration rate (eGFR) at baseline (n = 1132).

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Diabetic and new-onset diabetic patients with hypertension have higher cardiac morbidity than patients without diabetes. We aimed to investigate whether baseline predictors of cardiac morbidity, the major constituent of the primary endpoint in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, were different in patients with diabetes and new-onset diabetes compared to patients without diabetes. In total, 15,245 high-risk hypertensive patients in the VALUE trial were followed for an average of 4.

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Aims: Recent hypertension guidelines recommend that also in high cardiovascular (CV) risk, hypertensive patients blood pressure (BP) is lowered to <140/90 mmHg as no evidence is available supporting the lower target of <130/80 mmHg recommended in previous guidelines. Whether this represents the optimal treatment strategy is debated, however.

Methods And Results: The high CV risk hypertensive patients of the Valsartan Antihypertensive Long-term use Evaluation (VALUE) trial were divided into subgroups according to (i) the percentage of on-treatment visits in which BP was reduced to <140/90 or <130/80 mmHg or (ii) the mean systolic or diastolic BP (SBP/DBP) values achieved during the entire treatment period or up to the occurrence of an event.

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Previous studies have debated the notion that low blood pressure (BP) during treatment, particularly diastolic (DBP), is associated with increased risk of cardiovascular disease. We evaluated the impact of low BP on cardiovascular outcomes in a high-risk population of 15,244 hypertensive patients, almost half of whom had a history of coronary artery disease (CAD). In the prospective Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, patients were randomized to valsartan or amlodipine regimens and followed for 4.

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Aims: Troponin elevation is common in acute heart failure (AHF) and may be useful for prognostication; however, available data are mixed and many previous studies used older, less sensitive assays. We examined the association between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and outcomes in RELAX-AHF.

Methods And Results: Hs-cTnT was measured at baseline and days 2, 5, and 14.

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Background: Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking.

Methods And Results: Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief.

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Aims: The purpose of this study was to determine the prognostic significance and associated clinical profile of early post-discharge N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory among patients hospitalized for worsening chronic heart failure (HHF).

Methods And Results: This post-hoc analysis of the Aliskiren Trial in Acute Heart Failure Outcomes (ASTRONAUT) included 1351 HHF patients with ejection fraction (EF) ≤40%, elevated B-type natriuretic peptide ≥400 pg/mL or NT-proBNP ≥1600 pg/mL at admission, and available NT-proBNP measurements (from a central core laboratory) at baseline (median 5 days after admission) and 1-month follow-up. The co-primary endpoints were all-cause mortality and cardiovascular mortality or HHF within 12 months.

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Background: Risk factors for first stroke are well established, but less is known about risk factors for recurrent stroke. In the present analysis, we aimed to assess the effect of heart rate and other possible predictors of stroke in a hypertensive population with previous stroke or transient ischemic attack (TIA).

Methods: The Valsartan Antihypertensive Long-Term Use Evaluation trial was a multicentre, double-masked, randomized controlled, parallel group trial comparing the effects of an angiotensin receptor blocker (valsartan) and a calcium channel blocker (amlodipine) in patients with hypertension and high cardiovascular risk.

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Background: Little is known about mode of death after acute heart failure (AHF) hospitalization. In the RELAX-AHF (Efficacy and Safety of Relaxin for the Treatment of Acute Heart Failure) study, serelaxin, the recombinant form of human relaxin-2, reduced post-discharge mortality at 180 days in selected patients with AHF.

Objectives: The goal of this study was to assess the effect of serelaxin on specific modes of death in patients with AHF.

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Aims: We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF).

Methods And Results: RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation.

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Aims: The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).

Methods And Results: ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators).

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Aim: Patients hospitalized for acute heart failure (AHF) differ with respect of many clinical characteristics which may influence their prognosis and response to treatment. We have assessed possible differences in the effects of serelaxin on dyspnoea relief, 60 Day outcomes and 180 Day mortality across patient subgroups in the RELAX-AHF trial.

Methods And Results: Subgroups were based on pre-specified covariates (age, sex, race, geographic region, estimated glomerular filtration rate, time from presentation to randomization, baseline systolic blood pressure, history of diabetes, atrial fibrillation, ischaemic heart disease, cardiac devices, i.

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Aims: We evaluated the effect of (dual) renin-angiotensin-aldosterone system (RAAS) blockade with valsartan and an ACE inhibitor [92.7% of patients were treated with an ACE inhibitor in the Valsartan in Heart Failure Trial (Val-HeFT)] in patients with NYHA class II-IV heart failure (HF) and reduced EF on cardiovascular (CV) death and HF hospitalization by subgroups and by presence of early worsening of renal function (EWRF) and according to baseline estimated glomerular filtration rate (eGFR).

Methods And Results: We analysed the data from 5010 patients enrolled in the Val-HeFT study.

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