Lactate Dehydrogenase and Outcomes in Patients With HF and Reduced Ejection Fraction

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 with 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 Hazard ratio does not have unit]; 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).