Worsening Heart Failure and Poor Long-Term Prognosis in Reduced Ejection Fraction

In patients with heart failure with reduced ejection fraction, worsening heart failure increases risk for poor clinical outcomes.

A poor long-term prognosis in heart failure with reduced ejection fraction (HFrEF) is independently associated with worsening HF, according to study findings published in The American Journal of Cardiology.

Researchers sought to explore the association between worsening HF and HFrEF among patients treated with guideline-directed medical therapy. The primary endpoint was all-cause mortality. They defined worsening HF as the urgent need for intravenous diuretics or hospitalization for HF.

They conducted a single-center (Leiden University Medical Center, Leiden, The Netherlands) retrospective study that included 1801 adult patients (mean age 64 [SD, 12] years; 26% women) identified with a first echocardiographic diagnosis of left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) ≤45%). All patients were at least 18 years of age and identified from an ongoing patient registry (November 1993 to June 2020). Exclusions included patients who died within the first 30 days of follow-up and those diagnosed with cancer at baseline.

Some of the characteristics with significant differences between those with worsening HF vs those with nonworsening HF included higher prevalence of family history of coronary artery disease (27% vs 18%), myocardial infarction (49% vs 39%), percutaneous coronary intervention (35% vs 27%), and cardioverter-defibrillator implantation (51% vs 31%). The researchers found that patients with worsening HF vs patients with nonworsening HF also experienced higher use of antiarrhythmic drugs, diuretics, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.

…worsening HF, defined by HF hospitalization or urgent need for intravenous diuretics, in patients with HFrEF is independently associated with poor long-term prognosis.

They noted that 15% of patients experienced worsening HF during the median 20-month follow-up, and, overall, 24% of patients died during a median 60-month (IQR, 28-60 months) follow-up.

Analysis disclosed a significantly lower 5-year survival rate in the cohort with worsening HF vs the cohort with nonworsening HF (log-rank P <.0001). A comparison of the worsening HF cohort vs the nonworsening HF cohort showed researchers a significant difference in a lower 5-year survival rate for LVEF equal to or less than 25% (log-rank P <.0001) and LVEF of 26% to 34% (log-rank P =.038), but not for LVEF of 35% to 45% (log-rank P =.14).

The researchers observed worsening HF was associated independently with a higher risk of all-cause mortality following adjustment for echocardiographic and clinical predictors (hazard ratio, 1.46; 95% CI, 1.09-1.96; P =.011).

Study limitations include the single-center design and retrospective nature, as well as missing data for exact cause of death (data only were available for all-cause mortality).

“…worsening HF, defined by HF hospitalization or urgent need for intravenous diuretics, in patients with HFrEF is independently associated with poor long-term prognosis,” the researchers wrote. “Patients who develop worsening HF during follow-up should be considered very high-risk patients, regardless of baseline LV systolic function.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Chimed S, Stassen J, Galloo X, et al. Impact of worsening heart failure on long-term prognosis in patients with heart failure with reduced ejection fraction. Am J Cardiol. Published online September 23, 2022. doi:10.1016/j.amjcard.2022.08.035