Browsing by Author "Prescott, Margaret F."

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    Effects of serelaxin in acute heart failure patients with renal impairment: results from RELAX-AHF
    (Springer, 2016-09) Liu, Licette C. Y.; Voors, Adriaan A.; Teerlink, John R.; Cotter, Gad; Davison, Beth A.; Felker, G. Michael; Filippatos, Gerasimos; Chen, Yakuan; Greenberg, Barry H.; Ponikowski, Piotr; Pang, Peter S.; Prescott, Margaret F.; Hua, Tsushung A.; Severin, Thomas M.; Metra, Marco; Department of Emergency Medicine, IU School of Medicine
    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). Renal impairment was defined as an eGFR <60 ml/min/1.73 m2 estimated by creatinine. Results 817 (72.2 %) patients had a baseline eGFR <60 ml/min/1.73 m2. In placebo-treated patients, baseline renal impairment was related to a higher 180 day cardiovascular (HR 3.12, 95 % CI 1.33–7.30) and all-cause mortality (HR 2.81, 95 % CI 1.34–5.89). However, in serelaxin-treated patients, the risk of cardiovascular and all-cause mortality was less pronounced (HR 1.19, 95 % CI 0.54 –2.64; p for interaction = 0.106, and HR 1.15 95 % CI 0.56–2.34 respectively; p for interaction = 0.088). In patients with renal impairment, treatment with serelaxin resulted in a more pronounced all-cause mortality reduction (HR 0.53, 95 % CI 0.34–0.83), compared with patients without renal impairment (HR 1.30, 95 % CI 0.51–3.29). Conclusion Renal dysfunction was associated with higher cardiovascular and all-cause mortality in placebo-treated patients, but not in serelaxin-treated patients. The observed reduction in (cardiovascular) mortality in RELAX-AHF was more pronounced in patients with renal dysfunction. These observations need to be confirmed in the ongoing RELAX-AHF-2 trial.
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    Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study
    (Wiley, 2015-11) Cotter, Gad; Voors, Adriaan A.; Prescott, Margaret F.; Felker, G. Michael; Filippatos, Gerasimos; Greenberg, Barry H.; Pang, Peter S.; Ponikowski, Piotr; Milo, Olga; Hua, Tsushung A.; Qian, Min; Severin, Thomas M.; Teerlink, John R.; Metra, Marco; Davison, Beth A.; Department of Emergency Medicine, IU School of Medicine
    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. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo. Conclusions In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo.
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    Serial high sensitivity cardiac troponin T measurement in acute heart failure: insights from the RELAX-AHF study
    (Wiley, 2015-12) Felker, G. Michael; Mentz, Robert J.; Teerlink, John R.; Voors, Adriaan A.; Pang, Peter S.; Ponikowski, Piotr; Greenberg, Barry H.; Filippatos, Gerasimos; Davison, Beth A.; Cotter, Gad; Prescott, Margaret F.; Hua, Tsushung A.; Lopez-Pintado, Sara; Severin, Thomas; Metra, Marco; Department of Emergency Medicine, IU School of Medicine
    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. We assessed the relationship between baseline, peak and peak change hs-cTnT with dyspnoea relief by visual analogue scale, cardiovascular death, or HF/renal hospitalization to 60 days and cardiovascular mortality to 180 days. Models were adjusted for clinical variables and treatment assignment. Whether baseline troponin status affected the treatment effect of serelaxin was assessed using interactions terms. In 1074 patients, the median baseline troponin was 0.033 µg/L, and 90% of patients were above the 99th upper reference limit (URL). Patients with hs-cTnT >median were more likely to be men with ischaemic heart disease, worse renal function, and higher N-terminal pro-brain natriuretic peptide. Higher baseline or peak hs-cTnT and greater peak change were associated with worse outcomes independent of adjustment for covariates, but relationships were generally strongest for 180-day cardiovascular mortality (hazard ratio per doubling of baseline hs-cTnT = 1.36, 95% confidence interval 1.15–1.60). Troponin was most strongly associated with death from heart failure or from other cardiovascular causes. The treatment effect of serelaxin did not differ by baseline troponin levels. Conclusion Hs-cTnT was elevated above the 99% URL in the majority of AHF patients. Baseline, peak, and peak change hs-cTnT were associated with worse outcomes, with the strongest relationship with 180-day cardiovascular mortality.
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    Use of High-Sensitivity Troponin T to Identify Patients With Acute Heart Failure at Lower Risk for Adverse Outcomes
    (Elsevier, 2016-07) Pang, Peter S.; Teerlink, John R.; Voors, Adriaan A.; Ponikowski, Piotr; Greenberg, Barry H.; Filippatos, Gerasimos; Felker, G. Michael; Davison, Beth A.; Cotter, Gad; Kriger, Joshua; Prescott, Margaret F.; Hua, Tsushung A.; Severin, Thomas; Metra, Marco; Department of Emergency Medicine, IU School of Medicine
    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. Identification of patients at low risk might decrease unnecessary admissions. Methods A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro–brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo. Linear regression models for continuous endpoints and Cox models for time-to-event endpoints were used. Results Of the 1,076 patients with available baseline hsTnT values, 107 (9.9%) had low hsTnT. No cardiovascular (CV) deaths through day 180 were observed in the low-hsTnT group compared with 79 CV deaths (7.3%) in patients with higher hsTnT. By univariate analyses, low hsTnT was associated with lower risk for all 5 primary outcomes: 1) days alive and out of the hospital by day 60; 2) CV death or rehospitalization for heart failure or renal failure by day 60; 3) length of stay; 4) worsening heart failure through day 5; and 5) CV death through day 180. After multivariate adjustment, only 180-day CV mortality remained significant (hazard ratio: 0.0; 95% confidence interval: 0.0 to 0.736; p = 0.0234; C-index = 0.838 [95% confidence interval: 0.798 to 0.878]). Conclusions No CV deaths through day 180 were observed in patients with hsTnT levels ≤0.014 μg/l despite high N-terminal pro–brain natriuretic peptide levels. Low baseline hsTnT may identify patients with acute heart failure at very low risk for CV mortality.