TOPLINE:

Higher levels of lactate dehydrogenase (LDH) at baseline were independently linked to an increased risk for heart failure (HF) events or cardiovascular death in patients with HF with reduced ejection fraction (HFrEF). Adding baseline LDH to an established model also modestly improved prediction of 1-year risk.

METHODOLOGY:

• Researchers analyzed data from a phase 3, randomized, international trial (GALACTIC-HF) to evaluate whether baseline LDH levels were associated with clinical outcomes in patients with HFrEF.
• The post hoc analysis included 8179 patients with HFrEF (6138 outpatients) who were on guideline-directed medical therapy and had elevated levels of natriuretic peptide. The mean age of the patients ranged from 63.3 to 65.1 years, and 73.6%-83.6% were male.
• Levels of serum LDH were measured at baseline, at 48 weeks, and then every 48 weeks. Outpatients were categorized into four quartiles (Q1-Q4), with median LDH values of 155 U/L for Q1, 183 U/L for Q2, 207 U/L for Q3, and 253 U/L for Q4.
• LDH levels up to 250 U/L were considered normal, and levels above 250 U/L were considered high. Changes by 48 weeks were grouped as remaining normal, becoming high, becoming normal, or remaining high.
• The primary outcome was a composite of time to first HF event or cardiovascular death. Secondary outcomes included the first HF event, cardiovascular death, and all-cause death.

TAKEAWAY:

• Patients in the higher quartiles of LDH levels at baseline had 18%-48% higher risk for the primary outcome than those in Q1 (adjusted hazard ratios, 1.18; 95% CI, 1.03-1.35, 1.24; 95% CI, 1.09-1.42, and 1.48; 95% CI, 1.29-1.69 for Q2, Q3, and Q4, respectively).
• Patients with LDH levels above 250 U/L had 45% higher odds of experiencing hypoperfusion or preshock than those with normal LDH levels (adjusted odds ratio, 1.45; 95% CI, 1.17-1.79).
• Elevated LDH levels remained independently associated with worse outcomes after adjusting for other prognostic variables and biomarkers. Adding baseline LDH level to the PREDICT-HF model modestly improved the 1-year risk prediction for the composite outcome across three performance metrics (P < .001 for all).
• Patients with higher LDH levels were more often female and had worse HF status, with elevated levels of serum creatinine, liver enzymes, creatine kinase, and high-sensitivity troponin I.

IN PRACTICE:

“[The study] findings suggest that [lactate dehydrogenase] may serve as a practical biomarker for low-output states in patients with HFrEF, particularly in situations where clinicians may have become accustomed to chronically elevated creatinine, hepatic enzymes, or natriuretic peptides,” the researchers of the study wrote.

SOURCE:

The study was led by Ryohei Ono, MD, PhD, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland. It was published online on January 15, 2026, in JACC: Heart Failure.

LIMITATIONS:

This was a post hoc analysis of a selected trial group; thus, the results may not apply to all patients with HFrEF. Residual confounding may have remained because LDH level could be elevated in a range of other conditions. Laboratory errors from hemolysis could not be ruled out, and the findings were not validated in another cohort.

DISCLOSURES:

The GALACTIC-HF trial received funding from Amgen, Cytokinetics, and Servier. One author reported receiving support from a British Heart Foundation Centre of Research Excellence Grant and the Vera Melrose Heart Failure Research Fund. Several other authors reported receiving research grants and personal and/or speaker fees, serving on advisory boards, and having other financial ties with several organizations including the funding agencies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.