Biomarkers Help Shape Diuretic use in Treating Acute Heart Failure Patients

According to a presentation at Heart Failure 2019, a scientific congress of the European Society of Cardiology (ESC), Adrenomedullin activity predicts which acute heart failure patients (AHFP) are at the greatest risk of death without diuretic treatment post-discharge.

“Therapy at discharge often remains unchanged for several weeks and even months in acute heart failure patients,” said first author Dr. Nikola Kozhuharov, of the University Hospital Basel, Switzerland, in a May 25 statement detailing the study’s findings. “Our study shows that not re-evaluating the need for diuretics in this critical time period has detrimental consequences for patients.” he says.

Heart Failure Photo Credit: U.S. National Library of Medicine, MedlinePlus

According to the researchers, acute heart failure is the most common cause of hospitalization in people over age 50 and over.  Up to 30 percent die in the year after discharge. “This is in part due to the challenge of predicting which patients are at the greatest risk of death and the subsequent uncertainty in defining the appropriate intensity of in-hospital and immediate post-discharge management,” said Dr Kozhuharov.

Predicting Risk Levels in Acute Heart Failure Patients

The study sought to find biomarkers that predict risk levels in AHFP discharged from hospital and who would benefit from heart failure drugs, specifically diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, and aldosterone antagonists.

For the biomarkers, Dr. Kozhuharov’s study used two components of adrenomedullin, a peptide hormone that is a vasodilator, meaning it dilates (opens) blood vessels. Adrenomedullin was selected after pilot studies suggested it can quantify dysfunction of small blood vessels and the associated mortality risk. In addition, activity of adrenomedullin reflects residual congestion in acute heart failure patients and the researchers hypothesised that this could be used to guide diuretic therapy at discharge.

The researchers noted that two components used to quantify the activity of adrenomedullin were midregional proadrenomedullin (MR-proADM), a stable precursor, and the biologically active form of adrenomedullin (bio-ADM).

The study enrolled 1,886 acute heart failure patients presenting with acute breathlessness to emergency departments of university hospitals in the UK, France, and Switzerland. Plasma concentrations of MR-proADM and bio-ADM were assessed within 12 hours of presentation and at discharge from an acute ward.

Twenty seven percent (514 patients) died during the 365-day follow-up. Patients with bio-ADM levels above the median had significantly lower survival if they were not receiving diuretics at discharge. A similar result was found for MR-proADM. Both associations remained significant after adjusting for age and plasma creatinine concentration at discharge. Associations with the other drugs were not significant after correction for multiple testing.

Patients with bio-ADM plasma concentrations above the median had an 87 percent increased risk of death during follow-up compared to those with levels below the median. MR-proADM was even more accurate than bio-ADM for predicting death and the combined risk of death and/or acute heart failure rehospitalization.

“The observation that patients with high bio-ADM have much higher mortality rates if not treated with diuretics at discharge has immediate clinical consequences. Reasons for stopping diuretics during hospitalization included worsening renal function and low blood pressure. Our study shows that patients should be reassessed for contraindications before discharge so that diuretics can be restarted if appropriate, particularly if they have elevated bio-ADM.” says Dr Kozhuharov