The ASIS-TC (Use of Short-term Mechanical Circulatory Support Devices as a Bridge to Urgent Heart Transplant in Spain) study is a retrospective multicenter registry which collected data on all patients over age 18 years listed for a highly urgent first HT who were receiving support with MCS devices from 2010 to 2015 in Spain. The study did not include patients with a previous HT or listed for multiorgan transplant. The registry included all 16 Spanish hospitals with an adult HT program.

The ASIS-TC study recorded information on patients listed with the National Transplant Organization for HT as “grade 0 urgency” (assisted with venoarterial extracorporeal membrane oxygenation [ECMO] or short-term ventricular assist devices) or “grade 1 urgency” (assisted with intra-aortic balloon pump counterpulsation). For the purpose of the study, short-term ventricular assist devices were considered to include the Impella Recover (percutaneous insertion, continuous flow), Levitronix Centrimag (surgical insertion, continuous flow), Abiomed BVS5000 (surgical insertion, pulsing flow), and similar devices. The overall results of the series have been previously published.7

The registry information was obtained by an individualized, case-by-case review of all medical records for included patients. Individuals were identified for the study by approved queries of the National Transplant Organization database, with cooperation by local and autonomous community transplant coordination offices for participating hospitals.

For each patient, more than 500 variables were collected on clinical characteristics during circulatory assist and at the time of HT, as well as on the type of device implanted, complications associated with circulatory assist, waiting list times, and posttransplant complications. Several additional variables related to donor characteristics, HT surgical procedure, and long-term posttransplant survival were obtained by targeted queries of the National Heart Transplant Registry.

The study protocol was approved by the Clinical Research Ethics Committee of Galicia and was ratified by the ethics committees at each participating site.

We describe the results of a subanalysis of the ASIS–TC registry database focused on the prognostic value of serum lactate in patients receiving an urgent HT. The individuals selected for these analyses were patients from the “grade 0 urgency” cohort who underwent HT with registry database information on pretransplant serum lactate. Patients were not included in the analyses if they died before HT or had been excluded from the urgent waiting list.

A descriptive and comparative analysis was performed of study patients’ baseline (at HT) clinical characteristics according to the presence or absence of preoperative hyperlactatemia, defined as serum lactate ≥ 2 mmol/L at the last determination during the pretransplant waiting period. This is the most commonly accepted cutoff point in the medical literature to define abnormal serum lactate levels.4

Quantitative variables are expressed as mean ± standard deviation, and the proportion of affected participants was used for qualitative variables. Study group distributions for qualitative variables were compared by the chi-square test or by the Student t test for continuous quantitative variables.

The primary endpoint was 1-year survival after HT. The Kaplan-Meier method was used to construct survival curves over the entire period, and survival probability between study groups was compared by the log-rank test.

To identify 1-year posttransplant mortality predictors, a Cox multivariate regression was run backwards stepwise with “P out” < .05. The first step of this analysis included clinical variables for the donor and recipient with a proven univariate association with posttransplant risk of death with P < .20 (recipient age, diabetes mellitus, mechanical ventilation, renal replacement therapy, ECMO-type MCS, serum creatinine, hemoglobin, vasoactive-inotropic score, serum lactate, ischemia time). The multivariate model obtained by the backwards stepwise analysis was subsequently used to estimate the hazard ratio (HR) for 1-year posttransplant mortality in patients with preoperative hyperlactatemia (≥ 2 mmol/L) compared with patients without hyperlactatemia (< 2 mmol/L). A P value < .05 was considered significant for all hypothesis contrasts. The statistical analysis was performed using SPSS 20.

From January 2010 to December 2015, 291 patients were listed with the National Transplant Organization for HT with a “grade 0 urgency” priority and on a temporary MCS device at 16 Spanish sites; 230 of these patients received HT. The ASIS–TC registry database contained information on preoperative serum lactate levels for 177 (77%) of these urgent HT recipients, who comprised our study population.

At the time of HT, 90 patients were on venoarterial ECMO, 64 with Levitronix Centrimag (26 biventricular and 38 left ventricular), 13 with Abiomed BVS5000 (9 biventricular and 4 left ventricular), 9 with Impella Recover (left ventricular), and 1 with biventricular Abiomed AB5000.

Serum lactate levels before urgent HT in the study population are shown in Figure 1. The mean ± standard deviation was 1.8 ± 1.7 mmol/L; 44 recipients (25%) of had pretransplant hyperlactatemia, defined as ≥ 2 mmol/L.

Figure 1.

Distribution of pretransplant serum lactate levels in the study population.

(0.06MB).

Table 1 compares the baseline clinical characteristics of all patients included in the subanalysis, based on the presence or absence of preoperative hyperlactatemia. Baseline clinical characteristics of the 177 urgent HT recipients in the cohort analyzed were similar to those of the 230 urgent HT recipients in the overall ASIS–TC cohort.

There was a higher proportion of women among patients with hyperlactatemia, and the latter were more likely to be on invasive mechanical ventilation and to have higher serum creatinine and higher vasoactive-inotropic score before HT. Mean pretransplant serum lactate was 1.1 ± 0.4 mmol/L in patients without hyperlactatemia and 3.9 ± 3.4 mmol/L in patients with hyperlactatemia.

A total of 52 (29.4%) patients died during the first year after HT; 48 of these deaths occurred during the immediate postoperative hospitalization.

The Cox univariate analysis showed a statistically significant association between preoperative serum lactate and 1-year posttransplant risk of death (per 0.1 mmol/L, crude HR = 1.01; 95% confidence interval [95%CI], 1.00-1.02; P = .040). Figure 2 shows the Kaplan-Meier survival curves during this period, with stratification of the study population by preoperative serum lactate tertiles. The log-rank test showed a statistically significant linear trend for 1-year posttransplant mortality in the higher preoperative lactate tertiles (P = .01).

Figure 2.

One-year posttransplant survival curves, stratified by preoperative serum lactate tertiles. Tertile 1: preoperative serum lactate < 1 mmol/L; tertile 2: 1.00-1.69 mmol/L; tertile 3: ≥ 1.7 mmol/L.

(0.1MB).

In the Cox multivariate analysis, preoperative serum lactate was an independent predictor of higher 1-year posttransplant risk of death (per 0.1 mmol/L, adjusted HR = 1.02; 95%CI, 1.01-1.03; P = .007). Other independent predictors of mortality were recipient age, ischemia time, vasoactive-inotropic score, and pretransplant venoarterial ECMO, as shown in Table 2.

According to the Kaplan-Meier estimate, the probability of 1-year posttransplant survival was 53.1% (95%CI, 45.3-60.9) for patients with preoperative hyperlactatemia (≥ 2 mmol/L) and 75.6% (95%CI, 71.8-79.4) for patients without hyperlactatemia (P = .011). The adjusted HR for 1-year posttransplant mortality in patients with preoperative hyperlactatemia (≥ 2 mmol/L) compared with patients without hyperlactatemia was 1.94 (95%CI, 1.04-3.63; P = .039).

Table 3 lists the causes of posttransplant death based on the presence or absence of preoperative hyperlactatemia (≥ 2 mmol/L). In patients with hyperlactatemia, bacterial infections (n = 7 [35%]), primary graft failure (n = 5 [25%]), and postoperative multiorgan failure (n = 4 [20%]) were the most common causes of mortality, accounting for 80% of all deaths. Patients without hyperlactatemia showed more variety in the causes of mortality, with the most frequent being primary graft failure (n = 10 [31%]).

Figure 3 contains the 1-year posttransplant Kaplan-Meier survival curves for patients with and without preoperative hyperlactatemia, according to the type of MCS used at the time of HT.

Figure 3.

One-year posttransplant survival curves according to the presence or absence of hyperlactatemia (serum lactate ≥ 2 mmol/L) prior to surgery. A, patients with venoarterial extracorporeal membrane oxygenation. B, patients with temporary ventricular assist devices.

(0.16MB).

In the subgroup of patients supported with venoarterial ECMO, preoperative hyperlactatemia was associated with a statistically significant increase in 1-year posttransplant mortality (P = .024); however, no significant differences were observed in posttransplant mortality between patients with and without preoperative hyperlactatemia in the subgroup of recipients on short-term ventricular assist devices (P = .301).

This study has several limitations. The first is related to the observational and retrospective nature of the registry, which may have led to the selection, information, or confusion biases inherent to this type of study. As stated in the Methods section, 53 recipients of urgent HT were excluded from this subanalysis due to a lack of information on their preoperative lactate levels; however, the clinical characteristics and posttransplant mortality of patients included in the subanalysis were generally consistent with those of the registry as a whole.

In view of the retrospective nature of the registry, it was not possible to define a priori the same specific time point for serum lactate determinations in all patients; moreover, because this was a multicenter study without a single core laboratory, the test results may be subject to local variations. There was also no information on postoperative serum lactate trends after HT. Last, serum lactate ≥ 2 mmol/L was arbitrarily selected as a cutoff to define hyperlactatemia due to widespread acceptance in the medical literature. However, the use of alternative cutoff points was not explored in this analysis to avoid problems of multiple comparisons, which might have led to different conclusions from those obtained.