Elevated lactate in acute heart failure patients with intracellular iron deficiency as identifier of poor outcome

Abstract

Background: We believe that there is a physiological link between intracellular iron status (assessed by soluble transferrin receptor [sTfR]) and efficiency of energy production/consumption (assessed by lactate, a product of anaerobic cell metabolism), which may further impact the outcome of patients with acute heart failure (AHF). Aim: To examine if elevated levels of lactate (> 2 mmol/L) accompanied by unmet cellular iron requirements (defined as sTfR > 1.59 mg/L) identify AHF patients with an unfavourable outcome. Methods: The study is a single-centre, retrospective analysis of AHF patients in whom lactate and iron status were assessed on admission. The endpoint of the study was one-year mortality. Results: The study population consisted of 89 patients at a mean age of 65 ± 13 years. Mean systolic blood pressure and creatinine level were 135 ± 36 mmHg and 1.3 ± 0.6 mg/dL, respectively, and median [25 th-75 th quartiles] lactate level on admission was 2.0 [1.6-2.6] mmol/L. In 17 (19%) patients, both lactate and sTfR were below the cutoff values (group 1). In 38 (43%) individuals one of the markers was elevated (group 2) and in the remaining 34 (38%) patients both markers were above the predefined cutoff values (group 3). There was no difference in clinical and laboratory characteristics between the groups. During one-year follow-up 23 (26%) patients died. Mortality risk in group 3 was higher compared to the rest of the population (hazard ratio 5.6, 95% confidence interval 2.2-14, p = 0.0003), even after adjustments for well-defined prognostic factors. Conclusions: Patients with unmet iron cell requirements and hyperlactataemia on admission have significantly higher mortality risk compared to individuals without those pathologies.

Development and Validation of a Simple-to-Use Nomogram for Predicting In-Hospital Mortality in Patients With Acute Heart Failure Undergoing Continuous Renal Replacement Therapy

“…In the setting of AHF, several mechanisms, such as peripheral hypoperfusion, low cardiac output, activation of AHF, hypoxemia, and liver or renal dysfunction (elimination lactate), can alter the lactate homeostasis ( 32 ). It is well-documented that elevated lactate levels and their continued elevation are useful for identifying high-risk patients and for predicting worse outcomes and the high risk of mortality in patients with AHF ( 33 , 34 ). The elevated blood lactate acid, ≥2 mmol/L, predicted nearly 1.8-folds on 1-year mortality than low blood lactate acid (<2.5 mmol/L) ( 33 ).…”

Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology

“…Accordingly, deficiency in iron impairs mitochondrial function at many levels. ID has been linked to morphological changes in the mitochondria, such as an increase in size and a decrease in cristae [ 191 ], as well as functional changes such as reduced production of ATP [ 192 ], mitochondrial DNA damage [ 191 ], increased gluconeogenesis [ 187 , 193 ], increased lactic acid production [ 185 , 186 , 194 ], reduced mitochondrial biogenesis and impaired mitophagy [ 179 , 189 ], increased mitochondrial cytochrome c release (and hence apoptosis) and reactive nitrogen species expression [ 195 , 196 , 197 , 198 , 199 , 200 ]. All of this culminates in mitochondrial damage.…”

Differences in the Biomarker Profile of De Novo Acute Heart Failure versus Decompensation of Chronic Heart Failure

“…A link between lactate and iron levels in HF has also recently been suggested, which is perhaps expected given the well-described role iron plays in cell energy production [35]. Soluble transferrin receptor (sTfR) concentrations are relative to the cellular iron demand, and raised levels are indicative of iron deficiency [36][37][38].…”