Blood Pressure Response and Symptoms During Active Standing Test Among Hospitalized and Outpatients With Heart Failure: Results From the GRAVITY-HF Prospective Observational Cohort Study.

BACKGROUND: We conducted a multicenter, prospective, observational study to describe the incidence of orthostatic hypotension (OH) and orthostatic hypertension (OHtn) and its association with symptoms at standing and outcomes in patients with heart failure (HF). METHODS AND RESULTS: 321 active standing tests were performed in 87 inpatients during admission, and 316 tests were performed in 208 outpatients during follow-up. Blood pressure (BP) was measured by an automatic device 4 times in the supine position and at 1, 3 and 5 minutes of standing. Patients were queried about symptoms of orthostatic intolerance. The incidence of OH and OHtn was similar in both groups at baseline (classical OH 11%-22%, OHtn 3%-8%, depending on definition and timing). Reproducibility of BP changes with standing was low. Up to 50% of cases with abnormal responses were asymptomatic. Symptoms were variable and occurred mainly during the first minute of standing and had a U-shaped association with BP changes. OH in outpatients with HF was associated with a higher risks of death or readmission due to HF. CONCLUSIONS: Patients with HF have variable hemodynamic responses and symptoms during repeated active standing tests. OH might identify outpatients with HF who are at risk of long-term negative outcomes.

Relationship of Liver Stiffness With Congestion in Patients Presenting With Acute Decompensated Heart Failure.

OBJECTIVE: The significance of liver stiffness (LS) in the setting of cardiovascular congestion during the course of acute decompensated heart failure (ADHF) is under investigation. The aim of this study was to assess LS with the use of transient elastography (TE) and its associations with volume overload as determined by means of bioimpedance vector analysis (BIVA) in ADHF. METHODS AND RESULTS: TE (Fibroscan 502; Echosens) and BIVA (ABC-01, Medass) were performed in the first 48 hours of admission and on the day of discharge in 149 ADHF patients without known primary chronic liver disease or acute hepatitis. During hospitalization the median value of LS decreased from 12.2 kPa (interquartile range 6.3-23.6) to 8.7 (5.9-14.4) kPa (P < .001). Changes in LS correlated (P < .001) with changes in weight and BIVA parameters. LS was compared with histologic features of livers of ADHF patients who died (n = 7). Liver fibrosis 2B-4 was observed but was not associated with LS. LS at discharge was associated with increased risk of 12-month all-cause death, HF readmission, and the combined end point. CONCLUSIONS: There was a moderate association between LS with clinical congestion and volume overload according to BIVA and no correlation with degree of histologic liver fibrosis. LS may be a marker of negative HF outcomes.

Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study.

AIMS: Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin. METHODS: This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 µg kg(-1) day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls. RESULTS: A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study. CONCLUSIONS: The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment.

Addressing Orthostatic Hypotension in Heart Failure: Pathophysiology, Clinical Implications and Perspectives.

Heart failure (HF)is a condition at high risk for orthostatic hypotension (OH)given the large proportion of patients at an advanced age and high burden of comorbidities contributing to OH, as well as a high prevalence of medications with neurovascular and volume modulating properties. Early identification of OH in HF seems to be crucial as OH can have an impact on patient symptoms, activity level and independence, be a marker of specific pathophysiological changes or be an indicator of need for personalized treatment. OH might contribute significantly to bad enough prognosis in HF, as, besides a risk of falls and cognitive decline, it was found to be associated with cardiovascular morbidity and mortality. In this review, we aimed to incentivize the routine use of orthostatic testing in HF, as well as stimulate future research in this field, which could lead to significant advances in the treatment and outcomes.