Christopher Edwards

Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) Development Program Correlation With Outcomes

OBJECTIVESnThe aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure.nnnBACKGROUNDnHospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage.nnnMETHODSnThe Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies.nnnRESULTSnSerelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro-brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion.nnnCONCLUSIONSnEarly administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission.

Worsening Heart Failure Following Admission for Acute Heart Failure : A Pooled Analysis of the PROTECT and RELAX-AHF Studies

OBJECTIVESnThese studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF).nnnBACKGROUNDnWHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF.nnnMETHODSnIndividual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heartxa0Failure) phase II and III studies were pooled for analysis.nnnRESULTSnOf 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from 9.5% to 14.5% among studies. A multivariable model provided modest discrimination between patients who did or did not develop WHF (C-indexxa0= 0.68). After multivariable adjustment, WHF was associated with a mean increase in length of stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased risks of 60-day HF or renal failure readmission or cardiovascular death (hazard ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI: 1.55 to 2.41) (all pxa0< 0.001). The risk of mortality was higher in patients whose WHF required intravenous inotropes or mechanical therapy (HR: 3.03, 95% CI: 2.11 to 4.36) compared with patients whose WHF was treated with intravenous loop diuretic alone (HR: 1.80, 95% CI: 1.36 to 2.36) (both pxa0< 0.001). WHF was associated with larger increases in markers of renal and hepatic dysfunction during the first days of admission, but remained significantly associated with adverse outcomes after adjustment for these changes.nnnCONCLUSIONSnWHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death.

Patient journey after admission for acute heart failure: length of stay, 30-day readmission and 90-day mortality.

The course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30‐day post‐discharge readmission and 90‐day post‐discharge mortality in 1990 patients enrolled in the PROTECT study.

Patterns of leukocyte counts on admissions for acute heart failure — presentation and outcome — results from a community based registry

OBJECTIVEnTo determine the correlation between differential white blood cell (WBC) count and characteristics and outcome of acute heart failure (AHF) syndromes.nnnBACKGROUNDnPrevious studies suggested that different white blood cell count patterns are related to outcome in patients with heart failure (HF) and other cardiovascular disorders.nnnMETHODSnData from all qualifying AHF admissions to a city hospital (n=340) was prospectively collected. Patients were followed from admission up to 6 months post-discharge. The relationship between patients demographics, clinical and laboratory characteristics and outcome were assessed in relation to WBC count and lymphocyte to WBC ratio (LWR).nnnRESULTSnWBC count >10,100×10 (9)/L (upper tertile) on admission was associated with higher admission blood pressure, lower oxygen saturation, higher heart rate and increased troponin, with no impact on either short-term worsening HF or long-term adverse outcome. Lower LWR was associated with higher BUN and troponin and lower hemoglobin, but not with a distinct clinical presentation. The lower LWR tertile (≤13%) was associated with a 60% increase in worsening HF risk and a substantially higher 1 month (15% versus 2%) and 6 months mortality (23% vs. 3%) for lowest versus highest quartile (p<0.0001).nnnCONCLUSIONSnWhile increased WBC count is associated with a more vascular presentation and certain severity markers, it is not related to worse patient outcome. Low LWR (≤13%) is predictive of worse outcome and higher mortality. It is also associated with certain laboratory abnormalities, but not related to a specific clinical profile.

Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) study

Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone‐marrow‐derived, lineage‐directed, autologous cardiopoietic mesenchymal stem cells (C3BS‐CQR‐1) on LV remodelling in patients with advanced HF enrolled in the CHART‐1 study.

Liver Function, In-Hospital, and Post-Discharge Clinical Outcome in Patients With Acute Heart Failure—Results From the Relaxin for the Treatment of Patients With Acute Heart Failure Study

BACKGROUNDnElevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF.nnnMETHODSnWe investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality.nnnRESULTSnMean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [Pxa0= .030] and 1.97 [Pxa0= .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [Pxa0= .005] and 1.95 [Pxa0= .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; Pxa0= .001) but not with worsening HF (HR 0.95; Pxa0= .248). Total protein was associated with only worsening HF (HR 0.91; Pxa0= .004).nnnCONCLUSIONSnAbnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.

Low lymphocyte ratio as a novel prognostic factor in acute heart failure: results from the Pre-RELAX-AHF study.

Background: Previous studies have suggested that a lower lymphocyte ratio (Ly%) in the white blood cell (WBC) differential count is related to worse outcomes in patients with acute heart failure (AHF) and other cardiovascular disorders. Methods: In the Pre-RELAX-AHF study, 234 patients with AHF, systolic blood pressure >125 mm Hg and brain natriuretic peptide ≧350 pg/ml or equivalent were randomized to 1 of 4 intravenous doses of relaxin or placebo and followed up for 6 months following randomization. Complete blood count and differential were performed by a central laboratory at baseline and then daily to day 5 and on day 14. Results: The WBC count by itself was not associated with measures of disease severity or outcome, and patients with Ly% <13% had similar baseline characteristics to patients with Ly% >13%, except for a higher baseline WBC count, elevated baseline glucose, older age and higher rates of peripheral vascular disease. However, patients with Ly% <13% had less improvement of dyspnea, greater worsening of heart failure, longer length of initial hospital stay and fewer days alive and out of hospital. Statistical significance was reached for all-cause death by days 60 and 180 (hazard ratio = 1.11 per percent decrease, 95% confidence interval 1.03–1.19; p = 0.0048). Conclusions: Despite no association with any baseline characteristic known to strongly predict outcome in AHF, low Ly% is associated with less symptom relief and worse in-hospital and postdischarge clinical outcomes.

Locus of control, depression and quality of life among persons with sickle cell disease in Jamaica

This study explored how locus of control (LOC), depression and quality of life (QOL) interplay in patients with sickle cell disease. One hundred and forty-three sickle cell clinic patients with consecutive clinic consultations completed the Multidimensional Health Locus of Control and Short Factor 36 (SF-36) scales as well as the Beck Depression Inventory. Participants in this study had higher scores on the “chance”, “other people” and “internal” domains of LOC than persons with a number of other chronic illnesses in a previous study. Hierarchical regression analyses showed that high scores on the “internal” domain of LOC were associated with better QOL and fewer symptoms of depression. Depressive symptoms were greater in persons with high scores on the “other people” LOC domain and in younger persons. These findings would suggest that it is possible that interventions which enhance internal LOC and discourage “other people” orientations might improve QOL and ameliorate depression among persons with sickle cell disease.

Predictors and Associations With Outcomes of Length of Hospital Stay in Patients With Acute Heart Failure: Results From VERITAS

BACKGROUNDnThe length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs.nnnMETHODS AND RESULTSnWe examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01-1.16; Pu2009=u2009.019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02-1.07; Pu2009<u2009.001), although these associations are partially explained by concurrent end-organ damage and worsening heart failure during the first days of admission.nnnCONCLUSIONSnIn patients who have been admitted for AHF, longer length of hospital stay is associated with a higher rate of short-term mortality.nnnCLINICAL TRIAL REGISTRATIONnVERITAS-1 and -2: Clinicaltrials.gov identifiers NCT00525707 and NCT00524433.

Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF).

Patients with acute heart failure (HF) in Africa are rarely being treated with a hydralazine/nitrates combination. Therefore the effect of this treatment was studied here.