Prevalence of lactic acidaemia in patients with advanced heart failure and depressed cardiac output

Abstract

Aims: Heart failure (HF) has been defined classically as a condition in which the heart is unable to deliver sufficient oxygen to match the needs of the metabolizing tissues. Surprisingly, this definition has never been validated. The goal of this study was to determine the prevalence of elevated lactate levels in a cohort of patients with advanced heart failure.

Methods and results: We retrospectively analysed the arterio-venous oxygen difference (A-V O₂ ), haemodynamics, and plasma lactate levels in stage D heart failure patients who were being evaluated for a left ventricular assist device (LVAD). We identified 359 patients with a right heart catheterization (RHC) performed prior to LVAD implantation. Plasma lactate was available for 96 patients. RHC showed that 93% of the patients had an A-V O₂ above the upper limit of normal (>5 mL/100 mL). Among patients with measured lactate levels, the prevalence of elevated lactate (>2.1 mmol/L) was 25% (95% confidence interval 16.7-34.9). The A-V O₂ was widened in all patients with elevated lactate, but plasma lactate did not correlate with A-V O₂ (r = 0.02) and only 27% of patients with increased A-V O₂ had elevated plasma lactate.

Conclusions: Lactate levels were normal in ∼75% of the patients with advanced heart failure and a widened A-V O₂ , suggesting that the cardiac output was sufficient to meet the metabolic needs of the peripheral metabolizing tissues. Given that ∼4% of heart failure patients are in NYHA class IV, these findings suggest that the classic definition of heart failure pertains to ∼1% of patients with HF.

Keywords: Cardiac output; Heart failure with reduced ejection fraction; Lactic acid; Left ventricular assist device.

Figure 1. A-V O₂ and plasma lactate in the study cohort

A) A-V O₂ values from the 359 stage D heart failure patients in the study cohort. The upper limit of normal (A-V O₂ = 5 mmol/100ml) is marked by an horizontal black line. 93% of patients (n=334) had an elevated AV O₂; B) Plasma lactate levels measured within the study cohort. The upper limit of the reference range for the essay used (2.1 mmol/l) is marked by an horizontal black line. Only 25% of patients were found to have elevated plasma lactate.

Figure 2. Distribution of A-V O₂ relative to plasma lactate

The value of A-V O₂ and the value of plasma lactate for each patient is represented on a scatter plot. The upper limit of normal A-V O₂ (5 ml/100ml) is marked by an horizontal black line and the upper limit of normal plasma lactate (2.1 mmol/L) is marked by a vertical black line identifying 4 quadrants: normal lactate/normal A-V O₂ (lower left, n=7), normal lactate and elevated A-V O₂ (upper left, n=65), elevated A-V O₂ and elevated lactate (upper right, n=24), elevated lactate and normal A-V O₂ (lower right, n=0).

Figure 3. Correlation between plasma lactate and A-V O₂ or Cardiac Index

The values of plasma lactate were plotted as a function of A-V O₂ (panel A) or Cardiac index (panel B). Spearman correlations were created to evaluate the linear relationship between the variables. As indicated by the linear trendline and the calculated r factor, plasma lactate had no correlation with A-V O₂ or cardiac index.

Figure 4. Prevalence of elevated lactate by INTERMACS class

The prevalence of patients with elevated plasma lactate is indicated among patients in INTERMACS class 3 or higher (IM 3+), patients in INTERMACS class 2 (IM 2) and patients in INTERMACS class 1 (IM 1). The prevalence of patients with elevated plasma lactate increases with worsening clinical status as indicated by lower INTERMACS class (p-value for trend based on Cochran-Armitage test 0.006).

Figure 5. Distribution of AST and MELD score relative to plasma lactate

The value of plasma lactate weas plotted against Aspartate Amino Transferase in U/l and MELD score for each patient on a scatter plot. The relationship between AST and lactate is represented in panel A. The upper limit of normal AST (47 U/l) is marked by a horizontal black line and the upper limit of normal plasma lactate (2.1 mmol/L) is marked by a vertical black line identifying 4 quadrants: normal lactate/normal AST (lower left, n=40), normal lactate and elevated AST (upper left, n=32), elevated AST and elevated lactate (upper right, n=15), elevated lactate and normal AST (lower right, n=9). The values of AST are plotted on a log scale. There is a weak linear correlation between AST and plasma lactate as shown by a Spearman correlation coefficient r=0.33 (p<0.001). In panel B plasma lactate levels are plotted against MELD score. There is a weak linear correlation also between MELD score and plasma lactate as shown sy a Spearman correlation coefficient r=0.37 (p<0.001).

Figure 6. Prevalence of HF patients meeting the classic definition of Heart Failure

It has been estimated that only 4% of all heart failure patients are in NYHA class IV (15)(gray slices). Since only ~ 25% of the patients in the present study of Stage D patients had elevated lactate levels, it is estimated that only 1% of HF patients fail to support the metabolic demands of their tissues at rest (shaded grey slice)