Acute HF in the Emergency Department: Door-to-Furosemide Time Matters

Megan Brooks

July 07, 2017

CIBA, JAPAN — For acute heart failure (HF) patients arriving in the emergency department (ED), administration of intravenous (IV) furosemide within 1 hour is independently associated with lower in-hospital mortality, according to results of the observational REALITY-AHF study[1].

Yet only about a third of these patients are treated within the first hour, the study found. "That was the most surprising finding for us, because we assumed that we are doing much better," Dr Yuya Matsue (Kameda Medical Center, Ciba, Japan) told|Medscape Cardiology.

"We don't know exactly what causes this delay, but our results are suggesting that we are treating very obvious AHF quickly, but when the diagnosis is not clear from their symptoms, we are taking our time even though such patients could be at high risk," added Matsue.

The emergency department is a "major stage" for hospitalized patients with acute HF, Matsue and colleagues point out in their report, published June 27, 2017 in the Journal of the American College of Cardiology. More than one million ED visits annually in the US involve acute HF, and most result in hospital admission.

"The importance of the emergency-department phase in managing AHF has become increasingly apparent as recent post hoc studies have highlighted that although patient characteristics are important, the efficacy of any intervention/treatment may be time dependent," they write. Recent HF guidelines and recommendations also emphasize the importance of immediate diagnosis and treatment of patients presenting with acute HF.

The prospective REALITY-AHF study assessed the association between time to loop-diuretic treatment and clinical outcome in patients with acute HF admitted through the emergency department at 20 Japanese centers.

Door-to-furosemide (D2F) time was defined as the time from patient arrival at the emergency department to the first IV furosemide injection. Early treatment was defined as a D2F time of <60 minutes and nonearly treatment as D2F time of >60 minutes. The primary outcome was all-cause in-hospital mortality.

Among 1291 acute-HF patients treated with IV furosemide within 24 hours of emergency-department arrival, the median D2F time was 90 minutes (interquartile range 36–186 min), with 481 patients (37.3%) in the early-treatment group and 810 (62.7%) in the nonearly group.

Patients who received IV furosemide early were more likely to arrive by ambulance and had more signs of congestion compared with those treated later.

In-hospital mortality was significantly lower in patients in the early group than in the nonearly group (2.3% vs. 6.0%; P=0.002).

Although the mortality rate increased as the Get With the Guidelines-Heart Failure (GWTG-HF) risk score increased in both groups (P for trend <0.05 for both groups), a lower mortality rate in the early-treatment group compared with that for the nonearly treatment group was "consistently observed across all quartiles," with the absolute risk difference increasing as GWTG-HF risk score quartile rose (P for trend=0.027), the study team reports.

In multivariate analysis, early treatment remained significantly associated with lower in-hospital mortality (odds ratio 0.39; 95% CI 0.20–0.76; P=0.006).

A "novel and interesting" finding, say the authors, is the observation that the association between D2F time and mortality might not be linear. "In the first few hours after emergency-department arrival, mortality steeply increased as D2F time was delayed, but this effect leveled off after approximately 100 min. These findings might support the currently recommended time window of 30 to 60 min after emergency-department arrival for the initiation of management for patients with AHF," they note.

"We need to be as quick as possible when we evaluate and start treating AHF patients in the emergency department," Matsue said.

"I do believe early treatment can improve outcome of AHF patients," added Matsue. "However, I think we need more data that replicate our results before we can recommend early treatment for all AHF patients. Also, we don't know which is more important; early diagnosis or early treatment."

The authors of an accompanying editorial say the investigators are to be "congratulated in providing prospective data on an important issue in acute cardiovascular care" and demonstrating that more rapid decongestion therapy may improve outcomes, perhaps by limiting ongoing myocardial and end-organ injury present in those with acute HF[2].  

"Although optimal management of acute HF may begin with the faster prescription of intravenous furosemide, diagnostic and therapeutic follow-up in acute HF is far more complex, and gaps in HF care following admission and initial therapy may be associated with major risk regardless of whether the first dose of furosemide was delivered rapidly," write Dr James L Januzzi Jr (Massachusetts General Hospital, Boston) and Dr G Michael Felker (Duke University, Durham, NC).

They conclude, "although it is probably important to rapidly introduce effective decongestion therapy . . . optimal acute HF care remains a far more complicated process."

The study was funded by the Cardiovascular Research Fund, Tokyo, Japan. Matsue is supported by the Japan Society for the Promotion of Science Overseas Research Fellowships and received an honorarium from Otsuka Pharmaceutical. Disclosures for the coauthors are listed in the paper. Januzzi has received research grants from Roche Diagnostics, Siemens, Prevencio, Novartis, and Singulex; and served as a consultant for Roche Diagnostics, Siemens, Critical Diagnostics, Philips, Myokardia, Novartis, Boehringer Ingelheim, Amgen, Pfizer, and Abbvie. Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Novartis, Amgen, Roche Diagnostics, and Merck; and served as a consultant for Novartis, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Myokardia, Medtronic, and Cardionomics.

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