Worsened Heart Failure Mortality Seen in Presence of Hyperlactatemia

A new investigation of clinical outcomes among patients with a primary diagnosis of and hospitalization for acute heart failure (AHF)—either new-onset or worsening HF—notes there are greater mortality risks in the presence of hyperlactatemia and certain disturbances in the blood’s acid-base balance, particularly respiratory acidosis.

All of the patients (N = 4012 with normal blood pressure [≥90 mm Hg]; arterial blood gas measured upon hospital admission) received care in the Department of Cardiology of Rambam Health Care Campus in Haifa, Israel, between January 2005 and December 2016, with the primary study outcome being in-hospital mortality. Secondary end points were in-hospital mortality or need for inotrope/vasopressor therapy (eg, dopamine, dobutamine, epinephrine, milrinone, norepinephrine, neosynephrin, or vasopressin).

Study findings on appeared last month in European Heart Journal: Acute Cardiovascular Care.

“In AHF, multiple mechanisms can affect the production or clearance of lactate. Severe HF is considered one of the most common causes of lactic acidosis,” the study authors wrote. “However, few data are available on the clinical significance of elevated lactate levels and acid-base abnormalitiesin the setting of AHF.”

Thirty-eight percent of the overall patient cohort (mean [SD] age, 75 [13] years) had hyperlactatemia, a condition characterized by mild/moderately increased blood lactate levels absent metabolic acidosis, which itself had a strong positive correlation with hyperglycemia. In addition, patients classified as having acidosis had the greatest prevalence of hyperlactatemia (43.7%), followed by patients with alkalosis (42.0%) or a normal blood pH (31.0%).

For their study, the authors used these definitions:

• Elevated blood lactate: ≥ 2 mmol/L
• Acidosis: pH < 7.36
• Alkalosis: pH > 7.44
• Hypoxaemia: PaO₂ < 60 mm Hg
• Hypercapnia: PaCO₂ > 44 mm Hg
• Low bicarbonate: HCO₃ < 22 mg/dL

They also used multivariable logistic regression to determine the relationships between lactate levels and acid-base status with in-hospital mortality, and from this they show a 49% greater risk of in-hospital mortality among the 16.4% and 11.1% of their cohort who did and did not have hyperlactatemia (adjusted odds ratio [aOR], 1.49; 95% CI, 1.22-1.82; P < .0001), respectively.

Further, the hospitalization risk jumped even higher in the presence of acidosis and alkalosis, respectively, vs having a normal blood pH: 148% (aOR, 2.48; 95% CI, 1.95-3.16; P < .0001) and 77% (aOR, 1.77; 95% CI, 1.32-2.26; P < .0001).

When comparing in-hospital mortality risk for those with a normal lactate level vs acidosis or alkalosis, the numbers still showed elevated risks, but lower: 18.1% and 10.4%, respectively.

Overall, the authors determined that patients with lactate measurements vs those without such measurement on record were considered high risk because of their typical older age (P < .001), higher levels of serum creatinine and blood urea nitrogen (P < .0001), and lower levels of hemoglobin (P < .0001).

In addition, the group with lactate data on file had an in-hospital mortality rate that was almost 5 times that of patients without such measurements (P < .0001); was more likely to have comorbid diabetes, elevated glucose, elevated troponin, lower systolic blood pressure, higher heart rate, and higher white blood cell count; and had greater evidence of fever and positive blood and urine cultures.

“Increased lactate levels [are] predominantly due to increased production or decreased removal of lactic acid,” the authors wrote. “In HF, the dominant paradigm suggests that rising lactate concentrations indicate anaerobic glycolysis conditions at the cellular level and a marker of end organ hypoperfusion and/or hypoxia.”

However, accelerated aerobic glycolysis can also lead to hyperlactatemia independent of tissue oxygen availability, they added, and they believe their findings support the hypothesis that hyperlactatemia may be a sign of increased metabolic rate and sympathetic activation.

“Abnormal lactate levels seem to be generated by impaired oxygen transport and tissue ischemia in a subset of cases, whereas in others, high lactate more likely results from other mechanisms, including sympathetic stimulation,” the authors concluded. “Lactate is a marker of illness severity and an independently associated with in-hospital mortality in AHF.”

Reference

Bar O, Aronson D. Hyperlactataemia and acid–base disturbances in normotensive patients with acute heart failure. Eur Heart J Acute Cardiovasc Care. Published online February 16, 2022. doi:10.1093/ehjacc/zuac005