N-terminal pro–brain natriuretic peptide (NT–pro-BNP) levels have been shown to be increased at baseline in patients undergoing surgical ventricular restoration (SVR) of the left ventricle. However, changes in the values of this marker in the early postoperative period and its prognostic significance remain less known in these patients. We evaluated 31 consecutive patients undergoing SVR who had NT–pro-BNP determined a day before SVR and from postoperative days 0 to 4. Major morbidity was defined as ≥1 of the following: ventilation >48 hours, stroke, acute renal failure, low cardiac output, reoperation, or mediastinitis. The association of preoperative NT–pro-BNP with perioperative outcomes was assessed using multivariable logistic regression analysis. Receiver operating characteristic curve was used to test its discrimination power. Major morbidity occurred in 16 patients (52%) with only 1 death within 30 days of SVR. Mean preoperative NT–pro-BNP was 4.5-fold higher in patients with postoperative major morbidity than in those without it (3,022 ± 2,981 vs 676 ± 533 pg/ml, p = 0.007). On multivariate analysis, preoperative NT–pro-BNP was independently associated with major morbidity after adjusting for baseline confounding, particularly age, ejection fraction, and European System for Cardiac Operative Risk Evaluation (odds ratio 1.002, 95% confidence interval 1.001 to 1.003, p = 0.032). Preoperative NT–pro-BNP had a high discrimination power on receiver operating characteristic analysis for major morbidity (area under the curve 0.84, sensitivity 68%, and specificity 88% for 1,304 pg/ml). Although NT–pro-BNP levels decreased after SVR in patients without major morbidity, their levels remained persistently increased in those with it. In conclusion, preoperative NT–pro-BNP determination may be of value in stratifying the risk for major morbidity after SVR.
In small cohort of patients undergoing surgical ventricular restoration (SVR), plasma N-terminal pro–brain natriuretic peptide (NT–pro-BNP) and/or BNP have been shown to be increased at baseline. Furthermore, after SVR these levels decreased and this decrease paralleled improvement in left ventricular function and symptoms. However, these studies did not evaluate the prognostic significance of baseline NT–pro-BNP on immediate or long-term outcomes. Furthermore, BNP levels were collected at baseline and then 3 to 6 months after surgery, precluding insight into what happens to BNP levels during index hospitalization and the implication of change in these levels on in-hospital outcomes. As such, the immediate postoperative course of NT–pro-BNP and the association of preoperative NT–pro-BNP with perioperative outcomes in patients undergoing SVR are not known. Accordingly, the goal of the present study was to evaluate changes in perioperative NT–pro-BNP in patients undergoing SVR over time during their index hospitalization and to assess the association of preoperative NT–pro-BNP with in-hospital outcomes in patients undergoing this procedure. We hypothesized that SVR results in significant immediate decrease in postoperative NT–pro-BNP over time and that preoperative NT–pro-BNP and changes in its value postoperatively are associated with morbidity and mortality in patients undergoing SVR.
Methods
We evaluated retrospectively consecutive patients who underwent elective SVR with coronary artery bypass graft (CABG) at our institution from January 2007 to December 2008. Of 45 patients undergoing SVR during this period, preoperative value of NT–pro-BNP was not available in 14 patients, excluding them from analysis. The remaining 31 patients formed the basis of the study. These patients had a complete NT–pro-BNP assessment including the preoperative value and values at arrival in the intensive care unit (ICU; day 0) and daily measurements until postoperative day 4. The local ethics committee waived the need for approval of the study. All patients in the study gave informed consent for the scientific analysis of their clinical data in an anonymous form.
Clinical information was obtained from our institutional database that routinely collects clinical information on all patients undergoing cardiac surgery at our institution. Preoperative data collection included demographics and co-morbidities, operative details, and perioperative outcomes. For each co-morbid condition, definitions of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) were followed. Risk stratification was performed using the additive EuroSCORE. Intraoperative data included type of operation performed (SVR + CABG or SVR + CABG + valvular procedure). Postoperative outcome data included major morbidity according to the Society of Thoracic Surgeons definition (any of the following: need for reoperation, sternal wound infection, permanent stroke, renal failure, mechanical ventilation for >48 hours), plus the occurrence of postoperative low cardiac output (need for major inotropic support and/or use of intra-aortic balloon pump). Other outcome data included time on mechanical ventilation (hours), length of stay in the ICU (days), blood loss (milliliters in the first 12 postoperative hours), number of packed red blood cells transfused, peak postoperative serum creatinine value (milligrams per deciliter), postoperative creatinine clearance (milligrams per milliliter), acute renal failure (peak postoperative serum creatinine value 2 times the preoperative value and >2.0 mg/dl), low cardiac output (need for major inotropic support), intra-aortic balloon pump use, respiratory failure (prolonged mechanical ventilation due to poor gas exchange), ventricular arrhythmias, surgical re-exploration, sepsis, and mortality.
Details of the surgical technique have been previously reported. Briefly, the procedure was conducted on an arrested heart with anterograde crystalloid or cold blood cardioplegia. Patients received crystalloid cardioplegia if the preoperative ejection fraction was >0.40 (n = 4, 13%). Therefore, the great majority of the patients received cold blood cardioplegia. Complete coronary revascularization was first performed, almost always with the left internal mammary artery on the left anterior descending coronary artery and sequential venous grafts on the right and circumflex coronary arteries, when needed. Since July 2001, we systematically introduced the use of a preshaped mannequin (TRISVR, Chase Medical, Richardson, Texas) filled at 50 to 60 ml/m 2 to optimize the size and shape of the new ventricle. The technique was a refinement of the Dor technique and allows for standardization of the procedure. Mitral valve repair, if needed, was performed using a previously described endoventricular technique.
Data in tables and figures are presented as median and interquartile range or as number and percentage in the overall population and in patients with preoperative NT–pro-BNP ≤1,304 or >1,304 pg/ml, a cutoff based on the highest sensitivity and specificity determined as discussed below. Differences between the 2 groups were investigated using Student’s t test for independent variables or Mann-Whitney test when appropriate, and a Pearson chi-square test. Logistic regression analysis and a receiver operating characteristics curve were used to evaluate factors significantly associated with a major morbidity. Accuracy of the model was tested by evaluating the area under the curve and calibration with a Hosmer-Lemeshow test. Adequate cut-off points were identified from the coordinates of the receiver operating characteristics curves; the cut-off values were settled at the point where the sum of sensitivity and specificity was the highest, according to the Youden index: (sensitivity + specificity) − 1. All analyses were performed using a computerized statistical package (SPSS 13.0, SPSS, Inc., Chicago, Illinois).
Results
NT–pro-BNP was higher than the normal upper limit (100 pg/ml) in 30 of the 31 patients with SVR at baseline. Particularly high values (>1,360 pg/ml) were observed in 42% of these patients ( Table 1 ). The prevalence of many baseline patient characteristics that portend worse outcomes was greater in patients with higher NT–pro-BNP compared to those with lower values. Thus, these patients had higher EuroSCORE and lower ejection fraction.
| Variable | Overall (n = 31) | Preoperative NT–pro-BNP | p Value | |
|---|---|---|---|---|
| >1,304 pg/ml (n = 13) | ≤1,304 pg/ml (n = 18) | |||
| Age (years) | 62 (56–71) | 67 (56–75) | 60 (56–67) | 0.096 |
| Ejection fraction | 0.35 (0.29–0.39) | 0.33 (0.26–0.36) | 0.37 (0.33–0.42) | 0.044 |
| Body surface area (m 2 ) | 1.90 (1.81–2.0) | 1.81 (1.7–2.0) | 2.0 (1.8–2.1) | 0.065 |
| Hemoglobin (mg/dl) | 14 (13–15) | 13 (12–14) | 14 (13–15) | 0.051 |
| Serum creatinine (mg/dl) | 1.1 (0.98–1.3) | 1.1 (0.99–1.7) | 1.1 (0.92–1.25) | 0.559 |
| Creatinine clearance (ml/min) | 73 (48–95) | 67 (41–81) | 81 (56–99) | 0.316 |
| Women | 2 (6.5%) | 2 (15%) | 0 (0%) | 0.085 |
| New York Heart Association class III–IV | 18 (58%) | 9 (69%) | 9 (50%) | 0.282 |
| Previous myocardial infarction | 30 (97%) | 13 (100%) | 17 (94%) | 0.989 |
| Family history of cardiovascular disease | 14 (45%) | 5 (38%) | 9 (50%) | 0.431 |
| Hypertension | 16 (52%) | 7 (54%) | 9 (50%) | 0.961 |
| Hypercholesterolemia | 15 (48%) | 6 (46%) | 9 (50%) | 0.713 |
| Diabetes | 7 (23%) | 2 (15%) | 5 (28%) | 0.368 |
| Previous cerebrovascular accident | 6 (19%) | 3 (23%) | 3 (17%) | 0.713 |
| Atrial arrhythmias | 5 (16%) | 3 (23%) | 2 (11%) | 0.410 |
| Ventricular arrhythmias | 2 (6.5%) | 0 (0%) | 2 (11%) | 0.085 |
| European System for Cardiac Operative Risk Evaluation | 6 (5–10) | 8 (7–10) | 5 (4–6) | 0.005 |
| Associated valve procedure | 9 (29%) | 6 (46%) | 3 (17%) | 0.074 |
Many in-hospital outcomes were significantly higher in patients with preoperative NT–pro-BNP >1,304 pg/ml compared to those with lower values ( Table 2 ). Thus, these patients were more likely to manifest higher peak creatinine and lower creatinine clearance after surgery and had a longer length of mechanical ventilation and ICU stay. Low cardiac output state, renal failure, and need for intra-aortic balloon pump were threefold higher in this cohort. All patients but 2 with preoperative NT–pro-BNP >1,304 pg/ml had major morbidity in the postoperative period. The only death occurred in the group of patients with higher values. Length of stay in the ICU was on an average 3 days longer in these patients (7.2 ± 6.4 vs 4.1 ± 2.7).
| Variable | Overall (n = 31) | Preoperative NT–pro-BNP | p Value | |
|---|---|---|---|---|
| >1,304 pg/ml (n = 13) | ≤1,304 pg/ml (n = 18) | |||
| Mechanical ventilation (hours) | 19.5 (13.5–35) | 18 (12–21) | 18 (12–22) | 0.013 |
| Intensive care unit stay (days) | 4.5 (3–6) | 4 (3–4) | 4 (2.5–4.5) | 0.003 |
| Blood loss (ml/12 hours) | 532 (387–831) | 500 (400–675) | 500 (375–687) | 0.367 |
| Packed red blood cell transfusions (units) | 4 (2–5) | 3 (2–4) | 3 (2–4) | 0.272 |
| Peak creatinine (mg/dl) | 1.65 (1.2–2.5) | 1.5 (1.2–1.7) | 1.5 (1.1–1.8) | 0.019 |
| Creatinine clearance (ml/min) | 60 (28–70) | 28 (22–60) | 68 (50–72) | 0.005 |
| Low cardiac output | 12 (39%) | 8 (62%) | 4 (22%) | 0.027 |
| Intra-aortic balloon pump | 7 (23%) | 5 (38%) | 2 (11%) | 0.072 |
| Ventricular arrhythmias | 1 (3%) | 1 (8%) | 0 (0%) | 0.232 |
| Respiratory failure | 3 (10%) | 2 (15%) | 1 (6%) | 0.361 |
| Stroke/coma | 1 (3%) | 0 (0%) | 1 (6%) | 0.388 |
| Acute renal failure | 7 (23%) | 5 (38%) | 2 (11%) | 0.072 |
| Sepsis | 1 (3%) | 1 (8%) | 0 (0%) | 0.232 |
| Surgical reexploration | 1 (3%) | 1 (8%) | 0 (0%) | 0.232 |
| Major morbidity | 15 (48%) | 11 (85%) | 4 (22%) | 0.001 |
| Mortality | 1 (3%) | 1 (8%) | 0 (0%) | 0.232 |
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