In‐hospital worsening heart failure

Acute worsening heart failure (WHF) is seen in a sizable portion of patients hospitalized for heart failure, and is increasingly being recognized as an entity that is associated with an adverse in‐hospital course. WHF is generally defined as worsening heart failure symptoms and signs requiring an intensification of therapy, and is reported to be seen in anywhere from 5% to 42% of heart failure admissions. It is difficult to ascertain the exact epidemiology of WHF due to varying definitions used in the literature. Studies indicate that WHF cannot be precisely predicted on the basis of baseline variables assessed at the time of admission. Recent data suggest that some experimental therapies may reduce the risk of development of WHF among hospitalized heart failure patients, and this is associated with a reduction in risk of subsequent post‐discharge cardiovascular mortality. In this respect, WHF holds promise as a endpoint for acute heart failure clinical trials to better elucidate the benefit of targeted novel therapies. Better understanding of the pathophysiology and a consensus on the definition of WHF will further improve our epidemiological and clinical understanding of this entity.     

Lessons learned in acute heart failure

Acute heart failure (HF) is a global pandemic with more than one million admissions to hospital annually in the US and millions more worldwide. Post‐discharge mortality and readmission rates remain unchanged and unacceptably high. Although recent drug development programmes have failed to deliver novel therapies capable of reducing cardiovascular morbidity and mortality in patients hospitalized for worsening chronic HF, hospitalized HF registries and clinical trial databases have generated a wealth of information improving our collective understanding of the HF syndrome. This review will summarize key insights from clinical trials in acute HF and hospitalized HF registries over the last several decades, focusing on improving the management of patients with HF and reduced ejection fraction.     

Serelaxin in acute heart failure: Most recent update on clinical and preclinical evidence

Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising healthcare costs and is one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long‐term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin‐2 hormone. Relaxin was discovered in pregnancy, but eventually found to have a number of other physiological actions, not only in pregnancy, but also in nonpregnant women and men. The actions of serelaxin are primarily via nitric oxide, leading to the observed vasodilatory effects, and increase in renal plasma flow. It has also been found to increase expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)‐2 and MMP‐9. The antifibrotic and antiinflammatory effects of the drug also play a role in heart failure. In Phase II studies, serelaxin has shown reduction in pulmonary arterial pressure, pulmonary capillary wedge pressure, and NT‐proBNP. The recently published results of the RELAX‐AHF, a phase III clinical trial on serelaxin, has opened new avenues into our understanding of its effects in heart failure. The trial showed improvement in short‐term dyspnea scores and 180‐day mortality, but, interestingly, failed to show any improvement of the secondary endpoints of death or readmission at 60 days. Ongoing Phase III trials like RELAX‐AHF‐2 and RELAX‐AHF‐ASIA would explain these data better and improve understanding of the use of serelaxin in clinical practice. This article summarizes the most updated published preclinical and clinical study data on serelaxin, including pharmacokinetic, pharmacodynamic, safety studies in hepatic, renal impaired patients, Phase II and Phase III trials.