Preoperative B-type Natriuretic Peptide Research Articles

The Proportion of BNP Decline after Left Ventricular Assist Device Implantation Predicts Length of Survival after Surgery

Objective: Differences in B-type natriuretic peptide (BNP) values before and after left ventricular assist device (LVAD) surgery were evaluated as a predictor of survival after the surgery. Background: The impact of reduction of pre-operative BNP values, following LVAD surgery, on post-operative survival in heart failure (HF) patients is not known. Methods: Among a total of 287 patients who underwent LVAD surgery at Columbia University Medical Center between 2000 and 2010, 72 patients who had plasma BNP measurements at both 1 week before and 1 month after surgery were enrolled. Patients were divided into 2 groups according to % change of BNP value through surgery (% BNP change): greater (group A) or less than (group B) the median % BNP change. Result: Neither pre-operative nor post-operative BNP values were significantly correlated with post-surgical survival. The % BNP change was significantly correlated with post-surgical survival. Clinical characteristics, laboratory examination, and hemodynamics before and after surgery were not different between the two groups. Group A patients showed significantly better survival at 100 and 200 post-surgical days compared to group B (86.1 % vs. 74.6 %, 80.6 % vs. 54.5%, p=0.0399, respectively). Conclusion: The % BNP change could predict survival after LVAD surgery.

Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Does B-type Natriuretic Peptide or Its Gene Polymorphism Predict Patient Outcome after Coronary Artery Bypass Graft Surgery?

We read with great interest the research article by Fox et al. 1on genetic variation within defined regions of the NPPA /NPPB and NPR3 natriuretic peptide system genes as predictors for ventricular dysfunction after coronary artery bypass graft surgery. What concerns us as clinicians is the relation between those biomarkers and postoperative outcome, which can facilitate the preoperative risk evaluation. This article raised a good question: whether B-type natriuretic peptide (BNP) or its gene polymorphism predicts the prognosis in patients undergoing coronary artery bypass graft surgery.It is well known that a gene's function is mediated by expression of a specific protein. BNP has been established as a prognostic indicator in adults with congestive heart failure2and coronary artery disease,3whereas single nucleotide polymorphisms (SNPs) in the NPPB gene significantly impact BNP levels.4In the article by Dr. Fox et al. , there was mention that genetic variation within NPPA /NPPB and NPR3 genes was associated with risk of ventricular dysfunction after adjustment for preoperative BNP level and clinical factors. However, the authors did not directly analyze the relation between SNPs of these BNP genes with BNP level, especially postoperative BNP, whose level was not provided. Previous study has shown that early postoperative BNP levels correlate significantly with the ensuing duration of inotropic support and duration of hospitalization.5Therefore, we considered that SNPs of BNP genes could affect postoperative BNP rather than preoperative BNP and then predicted the prognosis, because expression of those genetic loci could be up- or down-regulated by mechanical stretch, ischemic injury, hypoxia, or even inflammatory mediators during surgery.6And the analysis should include both preoperative and postoperative BNP levels in this study.We think that the predictive pathway should be: SNPs of BNP–BNP level–clinical prognosis. If this hypothesis is established, it is postoperative BNP rather than SNPs of BNP that directly predicts ventricular dysfunction. Further investigations are still required to elucidate how BNP and its SNPs relate to development of postoperative ventricular dysfunction.*West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. benbinliu@hotmail.com

Natriuretic Peptide System Gene Variants Are Associated with Ventricular Dysfunction after Coronary Artery Bypass Grafting

Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting. A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations. After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034). Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD.

Natriuretic peptides in the management of aortic stenosis

B-type natriuretic peptide (BNP) and its prohormone NT-proBNP are released in response to myocardial wall stress and are established predictors of outcome in heart failure. This article discusses the prognostic value of BNP in aortic stenosis (AS). In recent studies, BNP and NT-proBNP were consistently related to AS severity and symptom status. High or serially rising BNP predicted the short-term need for valve replacement in asymptomatic severe AS. Preoperative BNP or NT-proBNP reflected postoperative outcome. In low-flow low-gradient AS, high BNP greater than 550 pg/mL predicted poor outcome independently of contractile reserve. BNP and NT-proBNP are easy to assess from plasma and improve risk stratification in the whole spectrum of AS.

B‐Type Natriuretic Peptide (BNP) in Patients Undergoing Mitral Valve Surgery

Plasma B-type natriuretic peptide (BNP) level may be increased in patients with valvular disease. Recent studies have suggested that in patients undergoing aortic valve replacement, an increased preoperative BNP is associated with a worse operative outcome. Little is known about the perioperative value of BNP in patients undergoing mitral valve (MV) surgery. We measured the preoperative and postoperative BNP levels in this population and analyzed the impact of the increased BNP level on surgical outcome. From March 2004 to February 2005, 42 patients (mean age 64 +/- 12 years, 18 [42%] male) were enrolled in a prospective study. All patients underwent surgery for severe mitral regurgitation. The mean ejection fraction was 49 +/- 13%, and 26 (62%) patients presented with atrial fibrillation (AF). The median preoperative and postoperative BNP levels were 108 (9.7 to 995) and 357 (143 to 904) pg/mL, respectively (p = 0.002). Heart failure (p = 0.03), atrial fibrillation (AF) (p = 0.01), and ejection fraction (p = 0.01) were associated with an increased preoperative BNP level. In a multivariate analysis, the only independent predictor of the increased BNP level was AF (p = 0.01). In a univariate analysis, the preoperative BNP level was a significant predictor for inotropic support (p < 0.001), ventilation time (p = 0.003), intensive care unit (ICU; p = 0.01), and hospital length of stay (p = 0.02). In the multivariate analysis, BNP was not a predictor of these variables. Preoperative plasma BNP level presents with a high individual variability in patients with MV regurgitation. AF was the only independent predictor of an increased preoperative BNP level. The preoperative BNP level was not a predictor of surgical outcome. Further studies are required to confirm these findings and evaluate the potential role of this marker for patient selection.

A meta‐analysis of the utility of pre‐operative brain natriuretic peptide in predicting early and intermediate‐term mortality and major adverse cardiac events in vascular surgical patients

We conducted a meta-analysis of the utility of pre-operative B-type natriuretic peptide (BNP) and N-terminal-pro B-type natriuretic peptide in predicting early (< 30 days) and intermediate (< 180 days) term mortality and major adverse cardiac events (cardiac death and nonfatal myocardial infarction) in patients following vascular surgery. A Pubmed Central and EMBASE search was conducted up to January 2008. Of 81 studies identified, seven prospective observational studies were included in the meta-analysis representing five patient cohorts: early outcomes (504 patients) and intermediate-term outcomes (623 patients). A B-type natriuretic peptide or N-terminal-pro B-type natriuretic peptide above the optimal discriminatory threshold determined by receiver operating characteristic curve analysis was associated with 30-day cardiac death (OR 7.6, 95% CI 1.33-43.4, p = 0.02), nonfatal myocardial infarction (OR 6.24, 95% CI 1.82-21.4, p = 0.004) and major adverse cardiac events (OR 17.37, 95% CI 3.31-91.15, p = 0.0007), and intermediate-term, all-cause mortality (OR 3.1, 95% CI 1.85-5.2, p < 0.0001), nonfatal myocardial infarction (OR 2.95, 95% CI 1.17-7.46, p = 0.02) and major adverse cardiac events (OR 3.31, 95% CI 2.1-5.24, p < 0.00001). B-type natriuretic peptide and N-terminal-pro B-type natriuretic peptide are potentially useful pre-operative prognostic tests in vascular surgical patients.

Preoperative B-type natriuretic peptide is as independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting

Elevated B-type natriuretic peptide is associated with increased morbidity and mortality in ambulatory patients with congestive heart failure or acute coronary syndromes. Its utility in predicting adverse cardiac surgical outcomes is less certain. We hypothesized that preoperative plasma B-type natriuretic peptide would independently predict in-hospital postoperative ventricular dysfunction, hospital stay, and up to 5-year mortality after primary coronary artery bypass grafting. This is a prospective, longitudinal study of 1023 patients at two institutions undergoing primary coronary artery bypass grafting with cardiopulmonary bypass. Ventricular dysfunction was defined as requirement for at least two inotropes or new intra-aortic balloon pump or ventricular assist device support after coronary artery bypass grafting. Multivariable analyses assessed independent roles of preoperative B-type natriuretic peptide in predicting postoperative ventricular dysfunction, hospital stay, and 5-year all-cause mortality. Preoperative plasma B-type natriuretic peptide concentration predicted ventricular dysfunction, hospital stay, and mortality in univariate and multivariable analyses. Logistic regression demonstrated preoperative B-type natriuretic peptide to independently predict ventricular dysfunction (odds ratio 1.92, 95% confidence interval 1.12-3.29, P = .018), after adjustment for preoperative left ventricular ejection fraction, congestive heart failure severity, and other clinical predictors. Multivariable Cox proportional hazards models showed preoperative B-type natriuretic peptide to independently predict hospital stay (hazard ratio 1.42, 95% confidence interval 1.18-1.72, P = .0002) and mortality (hazard ratio 1.89, 95% confidence interval 1.08-3.33, P = .026). Preoperative plasma B-type natriuretic peptide independently predicted in-hospital ventricular dysfunction, hospital stay, and up to 5-year all-cause mortality after primary coronary artery bypass grafting.

Perioperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis and total cavopulmonary connection

The objective of the study was to determine perioperative B-type natriuretic peptide levels in infants and children undergoing bidirectional cavopulmonary anastomosis or total cavopulmonary connection, and the predictive value of B-type natriuretic peptide levels for outcome. Plasma B-type natriuretic peptide levels were measured before and 2, 12, and 24 hours after surgery in 36 consecutive patients undergoing bidirectional cavopulmonary anastomosis (n = 25) or total cavopulmonary connection (n = 11). B-type natriuretic peptide levels were evaluated as predictors of outcome. B-type natriuretic peptide levels increased after surgery, peaking at 12 hours in most patients. In the bidirectional cavopulmonary anastomosis group, patients with 12-hour B-type natriuretic peptide > or = 500 pg/mL had a longer duration of mechanical ventilation (165 +/- 149 hours vs 20 +/- 9 hours, P = .004), longer intensive care unit stay (11 +/- 7 days vs 4 +/- 2 days, P = .001), and longer hospital stay (20 days +/- 12 vs 9 days +/- 5, P = .003). A 12-hour B-type natriuretic peptide > or = 500 pg/mL had a sensitivity of 80% and a specificity of 80% for predicting an unplanned surgical or transcatheter cardiac intervention, including transplantation (P = .03). In the total cavopulmonary connection group, preoperative B-type natriuretic peptide levels were highest in patients with total cavopulmonary connection failure compared with patients with a good outcome (88 +/- 46 pg/mL vs 15 +/- 6 pg/mL, P = .03). Postoperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis, and preoperative levels are greater in patients with both early and late total cavopulmonary connection failure compared with patients with a good outcome.

Relationship between Plasma B-type Natriuretic Peptide and Ventricular Function in Adult Cardiac Surgery Patients

Plasma concentrations of B-type natriuretic peptide (BNP) were analysed during the peri- and post-operative periods in cardiac surgery patients, and the relationship between plasma BNP concentrations and various clinical parameters was explored. Thirty patients (17 women, 13 men) of age 54.5 +/- 17.1 years undergoing cardiac surgery between June 2004 and March 2005 were enrolled. Plasma BNP concentrations were measured pre-operatively, immediately post-operatively, and on the first, second, fourth and seventh post-operative days. On the first post-operative day, the BNP level was significantly increased but levels returned to baseline values by the seventh post-operative day. The pre-operative BNP level correlated with left ventricular ejection fraction and age, and the level 24 h after surgery correlated with left ventricular end-diastolic dimension and pre-operative BNP levels. These results showed that the plasma BNP concentration becomes markedly and acutely elevated after cardiac surgery, reflecting temporary ventricular dysfunction.

The utility of B‐type natriuretic peptide in predicting postoperative cardiac events and mortality in patients undergoing major emergency non‐cardiac surgery

B-type natriuretic peptide (BNP) levels predict cardiovascular risk in several settings. We hypothesised that they would identify individuals at increased risk of complications and mortality following major emergency non-cardiac surgery. Forty patients were studied with a primary end-point of a new postoperative cardiac event, and/or development of significant ECG changes, and/or cardiac death. The main secondary outcome was all-cause mortality at 6 months. Pre-operative BNP levels were higher in 11 patients who suffered a new postoperative cardiac event (p = 0.001) and predicted this outcome with an area under the receiver operating characteristic curve of 0.85 (CI = 0.72-0.98, p = 0.001). A pre-operative BNP value > 170 pg x ml(-1) has a sensitivity of 82% and a specificity of 79% for the primary end-point. In this small study, pre-operative BNP levels identify patients undergoing major emergency non-cardiac surgery who are at increased risk of early postoperative cardiac events. Larger studies are required to confirm these data.

Utility of B-type natriuretic peptide in predicting perioperative cardiac events in patients undergoing major non-cardiac surgery

B-type natriuretic peptide (BNP) levels predict cardiovascular risk in several settings. We hypothesized that they would identify individuals at increased risk of early cardiac complications after major non-cardiac surgery. The current study tests this hypothesis. Two hundred and four patients undergoing major non-cardiac surgery were studied. The primary end-point was the development of acute myocardial injury [defined as cardiac troponin I (cTnI) level > 0.32 ng ml(-1)] or death in the 3 days after surgery. Preoperative BNP levels were raised in patients who died or suffered perioperative myocardial injury (median 52.2 vs 22.2 pg ml(-1), P = 0.01) and BNP predicted this outcome with an area under the receiver operating characteristic curve of 0.72 [95% confidence interval (CI) 0.59-0.86, P = 0.01]. A preoperative BNP value > 40 pg ml(-1) was associated with an increased risk of death or perioperative myocardial injury [odds ratio (OR) 6.8, 95% CI 1.8-25.9, P = 0.003], and remained independently predictive after correction for the Revised Cardiac Risk Index. Preoperative BNP levels were higher in patients who exhibited new onset atrial fibrillation or ST/T-wave changes on their postoperative ECG (median 50.5 vs 22.5 pg litre(-1), P = 0.01). They were also higher in patients who had either elevation of cTnI > 0.32 ng ml(-1) or postoperative ECG abnormalities (median 50.4 vs 21.5 pg ml(-1), P < 0.001). In the setting of major non-cardiac surgery, preoperative BNP levels are higher in patients who experience perioperative death and myocardial injury. Larger studies are required to confirm these data and to clarify what BNP levels may add to existing methods of risk stratification.

Utility of B-Type Natriuretic Peptide in Predicting Medium-Term Mortality in Patients Undergoing Major Non-Cardiac Surgery

This study was conducted to assess the ability of preoperative B-type natriuretic peptide levels to predict medium-term mortality in patients who undergo major noncardiac surgery. During a median of 654 days of follow-up, 33 patients from a total cohort of 204 patients (16%) died, 17 from cardiovascular causes. The optimal cutoff in this cohort, determined using a receiver-operating characteristic curve, was >35 pg . ml(-1). This was associated with a 3.5-fold increase in the hazard of death (p = 0.001) and a 6.9-fold increase in the hazard of cardiovascular mortality (p = 0.003). In conclusion, these findings extend recent work demonstrating that B-type natriuretic peptide levels obtained before major noncardiac surgery can be used to predict perioperative morbidity and indicate that they also forecast medium-term mortality, particularly cardiovascular death.

Plasma brain natriuretic peptide and cardiac troponin I concentrations after adult cardiac surgery: Association with postoperative cardiac dysfunction and 1-year mortality*

The purpose of the present study was to evaluate the prognostic implications of perioperative B-type natriuretic peptide (BNP) and cardiac troponin I concentrations in patients undergoing cardiopulmonary bypass for cardiac surgery. Prospective observational study. Biochemistry laboratory and surgical care unit in a university hospital. A total of 92 consecutive patients undergoing elective coronary artery (43 patients) or valve surgery (49 patients). None. BNP and cardiac troponin I concentrations were measured before surgery (day 0), and at day 1 after surgery. Postoperative cardiac dysfunction was defined as low cardiac output or hemodynamic instability requiring inotropic support for >24 hrs or congestive heart failure until day 5. One-year survival was also evaluated. Univariate and multivariate analyses were performed. An important BNP secretion was systematically observed after cardiac surgery. Independent predictors of cardiac dysfunction were preoperative New York Health Association class and BNP and cardiac troponin I concentrations measured at day 1. Patients with an elevation of both markers have a 12-fold increased risk of postoperative heart failure. The use of both markers in combination predicted better postoperative heart failure than each one separately. Age, low preoperative left ventricular ejection fraction, and elevated BNP at day 1 (>352 pg/mL) were associated with an increased mortality rate at 1 yr. In multivariate analysis, only left ventricular ejection fraction was significantly associated with 1-yr survival. Postoperative plasma BNP and cardiac troponin I levels are independent predictors of postoperative cardiac dysfunction after cardiac surgery. Simultaneous measurement of BNP and cardiac troponin I improve the risk assessment of postoperative cardiac dysfunction. However, the association between BNP levels and 1-yr outcome was no longer significant after adjustment on left ventricular ejection fraction.

Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy

We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure. In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial. In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California). A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011). In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.

Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery

ObjectivesThe purpose of the present study was to assess whether preoperative and postoperative B-type natriuretic peptide (BNP) levels could be used as predictors of postoperative complications and outcomes in patients after open-heart surgery. BackgroundA variety of multifactor indexes have been proposed for preoperative risk assessment of patients undergoing cardiac surgery, but they have shown limited ability and utility in accurately predicting postoperative complications, hospital stay, and mortality. MethodsSubjects consisted of 98 male patients (63 ± 9.1 years) undergoing open-heart surgery at the San Diego Veterans Administration Health System during a 19-month period. B-type natriuretic peptide levels were analyzed, and postoperative data recorded. ResultsThere was a higher preoperative BNP level in patients requiring the use of intra-aortic balloon pumps (IABPs) (mean BNP = 387 ± 112 pg/ml vs. 181 ± 25 pg/ml), in patients who died within one year (357 ± 93 pg/ml vs. 184 ± 26 pg/ml), and in patients with postoperative hospital stays of 10 days or more (307 ± 68 pg/ml vs. 179 ± 27 pg/ml). Receiver operating characteristic curves demonstrated preoperative BNP levels as predictors of postoperative IABP use, hospital stay ≤10 days, and mortality <1 year with areas under the curve of 0.70, 0.64, and 0.70, respectively. A BNP cut-off value above 385 pg/ml demonstrated high specificity (=90% in each) and accuracy (=86%, 79%, 85%, respectively) for predicting each of these end points. ConclusionsPreoperative BNP levels >385 pg/ml predict the postoperative complications and one-year mortality after heart surgery. Postoperatively, elevated peak BNP levels and elevated change to peak BNP levels were associated with prolonged hospital stay and mortality within one year.