This was a retrospective cohort study of patients older than 18 years who had received an orthotopic HT in our center from April 1991, when the program started, until December 2014. The study data were taken from a local database and supplemented with review of clinical records. The A Coruña-Ferrol Clinical Research Ethics Committee approved the study (Consellería de Sanidade, Xunta de Galicia).

The analysis included only patients for whom the pretransplant NRI could be calculated. This parameter was determined using the modified formula where NRI = 1.519 × serum albumin (g/L) + 41.7 × (actual body weight [kg] / ideal body weight [kg]). Ideal body weight was calculated using the Lorenz formulae, ie height (cm) – 100 – ([height (cm) – 150] / 4) for men and height (cm) – 100 – ([height (cm) – 150] / 2.5) for women. As in previous publications,7,9 when the value of (actual body weight [kg] / ideal body weight [kg]) was ≥ 1, NRI was set at 1. The serum albumin levels and actual body weight used for the preoperative NRI calculation were the closest available to the date of HT in each patient's medical records.

The study patients were classified into 4 nutritional risk categories according to their preoperative NRI, as defined in previous studies7,9: severe nutritional risk (NRI < 83.5), moderate nutritional risk (83.5 ≤ NRI < 97.5), mild nutritional risk (95.7 ≤ NRI < 100) and no nutritional risk (NRI ≥ 100). We compared the baseline clinical characteristics, incidence of adverse clinical events, and post-HT survival of these 4 patient categories.

Primary graft dysfunction was defined as isolated right ventricular failure or moderate or severe left ventricular failure of the cardiac graft during the first 24hours post-HT, in line with the consensus criteria of the International Society for Heart and Lung Transplantation.14 Cardiac surgical reintervention was defined as any cardiac surgical intervention requiring a repeat sternotomy during the post-HT hospital stay. Postoperative infection was defined as any infection proven by a microbiological isolate and requiring intravenous antibiotic treatment during the post-HT hospital stay. Prolonged mechanical ventilation was defined as invasive mechanical ventilatory support lasting longer than 36hours after HT. Acute rejection was defined as any episode of biopsy-proven grade 2R or above acute cellular rejection,15 any episode of biopsy-proven grade 1 or above antibody-mediated rejection with associated cardiac graft dysfunction,16 or any episode of clinically suspected acute rejection not proven on biopsy that was treated with intravenous bolus steroids, anti-thymocyte globulin, or polyclonal gamma globulin during the post-HT hospital stay.

Information was available on the vital status of all patients at 1 year post-HT. All-cause mortality during this period was the primary event in this study.

In this article, continuous variables are presented as–mean ± standard deviation or median [interquartile range], depending on the normality of their distribution, while categorical variables are presented as percentages. The baseline characteristics of the different NRI categories were compared using the chi-square test for linear trend for categorical variables and ANOVA with a first-order polynomial contrast for continuous variables.

The Cox proportional hazards model was used to identify independent predictors of mortality during the first year post-HT. First, the preoperative variables that showed a statistically significant association with mortality (P < .05) were selected. These variables were included in a backward stepwise analysis (exit criterion, P > .05) such that the remaining variables (among which was NRI) formed the final multivariable model. To control for potential confounders, the statistical effect of preoperative NRI on post-HT mortality was adjusted using a second extended multivariable model. We forced into this model those variables that showed a significantly asymmetrical distribution over the 4 nutritional risk categories (body mass index, bilirubin, mechanical ventilation, inotropic support, and ischemia time) and the demographic variables (age and sex of recipient), as well as the independent predictors of mortality previously identified from the backward stepwise analysis. The final multivariable model was also used to estimate the adjusted hazard ratio (aHR) for mortality during the first year post-HT for recipients with moderate or severe nutritional risk (NRI < 97.5) compared with recipients with mild or absent nutritional risk (NRI ≥ 97.5).

Using a method similar to that described for the mortality analysis, we employed multivariable logistic regression to identify the predictors of postoperative adverse events for which the univariable analysis showed a statistically significant association (P < .05) with the preoperative NRI values (postoperative infection and prolonged mechanical ventilatory support). Although the univariable analysis also showed a statistically significant association between preoperative NRI and incidence of postoperative stroke, we decided not to perform a multivariable analysis due to the low number of strokes recorded in the study population.

Lastly, the Kaplan-Meier method was used to construct survival curves for the first year post-HT for patients with moderate or severe nutritional risk (NRI < 97.5) and patients with mild or absent nutritional risk (NRI ≥ 97.5). The 2 survival curves were compared using the log-rank test. For all comparisons, a P-value < .05 was considered statistically significant. The statistical analysis was performed with SPSS 20.0.

From April 1991 to December 2014, 633 patients > 18 years old received an orthotopic HT in our center. The preoperative NRI could not be calculated in 89 (13%) of them, because information on the pretransplant albumin levels was unavailable. Therefore, the sample analyzed consisted of 574 patients.

Figure 1 shows the preoperative NRI distribution in the study population. Prior to HT, 33 patients (5%) were at severe nutritional risk (NRI < 83.5); 146 (22%) were at moderate nutritional risk (83.5 ≤ NRI < 97.5), and 63 (10%) were at mild nutritional risk (97.5 ≤ NRI < 100). The mean preoperative NRI was 100.9 ± 9.9.

Figure 1.

Distribution of preoperative nutritional risk index values in the study population.

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Table 1 shows the baseline clinical characteristics of the study patients by the 4 nutritional risk categories described above. Life support measures, such as inotropes, mechanical ventilation, and mechanical circulatory support were used more frequently before HT in patients with a lower preoperative NRI and in cases of emergency HT (P < .001 for all linear contrasts of these variables). Patients with lower preoperative NRI were also younger (P = .021) and had shorter waiting list times (P < .001), lower body mass index (P = .001), lower serum albumin levels (P = .004) and longer organ ischemia times (P = .001).

Table 2 summarizes the adverse clinical events that occurred during the in-hospital post-transplant period in the 4 patient subgroups defined by pretransplant NRI. Pretransplant NRI values had an inverse correlation with duration of postoperative vasoactive drug support (P = .008), mechanical ventilation (P < .001), and postoperative intensive care unit stay (P < .001). Total postoperative hospital stay did not have a statistically significant association with preoperative NRI (P = .332).

Univariable linear trend analysis revealed a statistically significant increased cumulative incidence in patients with lower preoperative NRI values of postoperative stroke (NRI < 83.5, 6.1%; 83.5 ≤ NRI < 97.5, 2.7%; 97.5 ≤ NRI < 100, 0%; NRI ≥ 100, 0.9%; P = .022), prolonged mechanical ventilatory support (NRI < 83.5, 72.7%; 83.5 ≤ NRI < 97.5, 43.1%; 97.5 ≤ NRI < 100, 33.1%; NRI ≥ 100, 24.5%; P < .001), and postoperative infection (NRI < 83.5, 39.4%; 83.5 ≤ NRI < 97.5, 27.4%; 97.5 ≤ NRI < 100, 25.4%; NRI ≥ 100, 17.8%; P = .022). However, no statistically significant association was observed between preoperative NRI and the cumulative risk of other adverse events, such as primary graft dysfunction, cardiac surgical reintervention, or acute rejection during the post-HT hospital stay.

Multivariable logistic regression analysis identified preoperative NRI as a statistically significant independent predictor of prolonged need for postoperative mechanical ventilatory support (adjusted odds ratio [aOR] per unit = 0.96; 95% confidence interval [95%CI], 0.94-0.98; P = .001) and postoperative infection (aOR per unit = 0.97; 95%CI, 0.95-1.00; P = .027), as shown in Table 3. The statistical association between NRI and prolonged mechanical ventilatory support (aOR per unit = 0.96; 95%CI, 0.93-0.98; P < .001) and postoperative infection (aOR per unit = 0.98; 95%CI, 0.95-1; P = .038) did not change substantially when the demographic variables (age and sex) and other clinical variables with asymmetrical distribution in the 4 nutritional risk categories (body mass index, bilirubin, mechanical ventilation, mechanical circulatory support, inotropes, and ischemia time) were forced into the regression model.

In the first year of follow-up post-HT, 102 patients (17.8%) died. The in-hospital post-HT mortality rates were 18.2%, 25.3%, 7.9%, and 10.2% (P < .001) for recipients with severe, moderate, mild, and absent preoperative nutritional risk, respectively. In the same categories, the overall mortality rates in the first year after HT were 18.2%, 28.8%, 11.1%, and 14.2% (P < .002).

In the Cox multivariable regression analysis, preoperative NRI was identified as an independent predictor of lower risk of death from any cause in the first year post-HT (aHR per unit = 0.95; 95%CI, 0.93-0.98; P < .001) (Table 4). The statistical effect of preoperative NRI on mortality in the first year post-HT did not change substantially with the extended adjustment model that included demographic variables and baseline clinical variables with an asymmetrical distribution over the different nutritional risk groups (aHR per unit = 0.95; 95%CI, 0.93-0.98; P = .001).

Patients with moderate or severe preoperative nutritional risk, defined as a preoperative NRI < 97.5, had a significantly higher all-cause mortality in the first year post-HT than patients with mild or absent preoperative nutritional risk (aHR = 1.55; 95%CI, 1.22-1.97; P < .001). The Kapan-Meier survival curves for both groups are shown in Figure 2.

Figure 2.

Survival curves for the first year post-transplant in patients with moderate or severe preoperative nutritional risk (NRI < 97.5) and low or absent preoperative nutritional risk (NRI ≥ 97.5). NRI, nutritional risk index.

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Our study has some methodological limitations. Given its retrospective design, it is subject to the potential selection bias and information bias inherent to this type of study. To control any potential confounding bias, rigorous multivariable adjustment was performed. Nonetheless, we cannot entirely rule out that another untested variable could have interfered with the observed statistical associations. The single-center setting of the study meant that the external validity of the results could not be guaranteed, therefore we may not be able to extrapolate our conclusions to other patient populations. The selection of a historic cohort spanning a long time period is in itself a limitation when interpreting the study results, which could have been affected by historic changes and improvements in the perioperative treatment protocol for HT patients.

The lack of information on preoperative albumin levels led to the exclusion of 89 HT recipients from the study, but it seems unlikely that the inclusion of these patients in the analysis would have led to a significant change in the observed results. Lastly, as we retrospectively used previously-collected data, it is highly likely that the time elapsed from the preoperative determination of albumin level and body weight to HT varied between study patients.