Related Experiment Video
Updated: Jan 14, 2026
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Lactate Dehydrogenase and Outcomes in Patients With HF and Reduced Ejection Fraction: Insights From GALACTIC-HF
Ryohei Ono1, Misato Chimura2, Kieran F Docherty1
1British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Insights
Higher lactate dehydrogenase (LDH) levels indicate increased risk for adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF). This finding was confirmed in the GALACTIC-HF trial, highlighting LDH as a significant prognostic marker.
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure Research
Background:
- Lactate dehydrogenase (LDH) is a cytoplasmic enzyme elevated in cases of cellular injury.
- Elevated LDH levels are recognized as a potential prognostic indicator in heart failure (HF).
- This study investigates the prognostic value of LDH in patients with heart failure with reduced ejection fraction (HFrEF).
Purpose of the Study:
- To evaluate the association between baseline lactate dehydrogenase (LDH) levels and clinical characteristics in patients with HFrEF.
- To determine the relationship between LDH levels and adverse clinical outcomes in HFrEF patients.
- To assess the incremental predictive value of LDH when added to existing risk models for HFrEF.
Main Methods:
- Analysis of data from the GALACTIC-HF trial, a phase 3 randomized, placebo-controlled study.
- Examined the correlation between baseline LDH levels and patient demographics, HF status, and other biomarkers.
- Assessed the association of LDH with the primary outcome (HF event or cardiovascular death) using Cox proportional hazards models and evaluated its predictive performance using Harrell's C statistic, IDI, and NRI.
Main Results:
- Higher baseline LDH levels were observed in patients with worse HF status, female sex, and elevated levels of creatinine, liver enzymes, creatine kinase, NT-proBNP, and troponin I.
- Patients in higher LDH quartiles (Q2, Q3, Q4) had significantly increased hazard ratios for the primary outcome compared to the lowest quartile (Q1).
- Elevated LDH independently predicted higher risk for adverse outcomes, and its inclusion improved the predictive accuracy of the PREDICT-HF risk model.
Conclusions:
- Higher lactate dehydrogenase (LDH) levels are independently associated with an increased risk of adverse clinical outcomes in patients with HFrEF.
- LDH serves as a valuable prognostic biomarker in HFrEF, enhancing risk stratification beyond established models.
- The findings from the GALACTIC-HF trial underscore the importance of LDH in managing patients with heart failure.
Background:
Lactate dehydrogenase (LDH) is a cytoplasmic enzyme found in most cells. Increased LDH levels are a nonspecific measure of cellular injury and may be prognostically important in heart failure (HF).
Objectives:
This study aims to assess the relationship between LDH and clinical characteristics and outcomes in heart failure and reduced ejection fraction (HFrEF).
Methods:
Using data from GALACTIC-HF, a phase 3, randomized, placebo-controlled trial evaluating the efficacy and safety of omecamtiv mecarbil (OM) in patients with HFrEF, the relationship between LDH and clinical outcomes was analyzed. The incremental value of LDH added to a validated prognostic model (PREDICT-HF) was also calculated using Harrell's C statistic, integrated discrimination index (IDI), and net reclassification index (NRI).
Results:
In GALACTIC-HF, baseline LDH data were available for 8,179 patients, including 6,138 outpatients. Patients with higher LDH were more frequently female and had worse HF status. They were also more likely to have elevated serum creatinine, liver enzymes, creatine kinase, NT-proBNP, and high-sensitivity troponin I. Compared with patients in the lowest LDH (Q1: 155 U/L [25th-75th percentile: 144-163 U/L]), the HRs for the primary outcome (first HF event or cardiovascular death) were Q2: 183 U/L (25th-75th percentile: 177-188 U/L); HR: 1.15 [95% CI: 1.02-1.31]; Q3: 207 U/L (25th-75th percentile: 201-215 U/L); HR: 1.39 [95% CI: 1.23-1.58]; and Q4: 253 U/L (25th-75th percentile: 236-280 U/L); HR: 1.84 [95% CI: 1.62-2.08], respectively. Even after adjustment, elevated LDH remained independently associated with higher HR. When added to the PREDICT-HF risk model, baseline LDH improved Harrell's C statistic, IDI, and NRI for the primary outcome.
Conclusions:
In GALACTIC-HF, higher LDH levels were independently associated with a higher risk of clinical outcomes in HFrEF. (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure [GALACTIC-HF]; NCT02929329; EudraCT number: 2016-002299-28).
Related Concept Videos
01:17Pathophysiology of Heart Failure
01:29Heart Failure II: Pathophysiology
01:30Heart Failure V: Medical Management
01:27Heart Failure I: Introduction
01:26Heart Failure III: Clinical Manifestations
01:30Heart Failure IV: Classification and Diagnostic Evaluation