Significance of Postoperative Acute Renal Failure After Continuous-Flow Left Ventricular Assist Device Implantation

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1 Significance of Postoperative Acute Renal Failure After Continuous-Flow Left Ventricular Assist Device Implantation Jamil Borgi, MD, Athanasios Tsiouris, MD, Arielle Hodari, MD, Chad M. Cogan, MS, Gaetano Paone, MD, and Jeffrey A. Morgan, MD Department of Surgery, Division of Cardiothoracic Surgery, Henry Ford Hospital, Heart and Vascular Institute, Detroit, Michigan Background. Deteriorating renal function is common in patients with advanced heart failure and is associated with poor outcomes. The relationship between renal function and left ventricular assist device (LVAD) implantation is complex and has been explored in multiple studies with contradictory results. The aim of our study is to examine the significance of postoperative renal failure after implantation of a continuous-flow LVAD and its relationship to outcomes. Methods. From March 2006 to July 2011, 100 patients underwent implantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) or HeartWare (Heart International, Inc, Framingham, MA) LVAD at our institution. Patients were stratified based on postoperative development of acute renal failure (ARF). Variables were compared using 2-sided t tests, 2 tests, Cox proportional hazards models, and log-rank tests to determine whether there was a difference between the 2 groups and whether postoperative renal failure was a significant independent predictor of outcome. Results. We identified 28 patients (28%) with postoperative ARF and 72 patients (72%) without postoperative ARF. The 2 groups were similar with regard to demographics and comorbidities. The patients with ARF were more likely to be intubated preoperatively (14.3% versus 1.4%; p 0.021) and had higher preoperative central venous pressure (CVP) (14.3 mm Hg versus 10.7 mm Hg; p 0.015). Postoperatively patients with ARF had a longer hospital stay (32.4 versus 18.7; p 0.05), were more likely to experience right ventricular (RV) failure (25% versus 5.6%; p 0.01) and ventilator-dependent respiratory failure (VDRF) (28.6% versus 6.9%; p 0.007). There was a significant difference when comparing the ARF and non-arf groups for 30-day (17.9% versus 0%; p < 0.001), 180-day (28.6% versus 2.8%; p < 0.001), and 360- day mortality (28.6% versus 6.9%; p 0.012). Conclusions. Patients in whom ARF developed after LVAD implantation had a higher rate of VDRF and RV failure and a longer length of stay (LOS). Postoperative ARF was associated with higher mortality at the 30-day, 180-day, and 360-day intervals. ARF after LVAD may be an early marker of poor outcome, particularly RV failure, and may be an opportunity for early intervention and rescue. (Ann Thorac Surg 2013;95:163 9) 2013 by The Society of Thoracic Surgeons Congestive heart failure continues to be a major medical problem reaching epidemic proportions with approximately 400,000 newly diagnosed patients per year in the United States alone and 500,000 patients with end-stage heart failure refractory to medical treatment [1]. Left ventricular assist device (LVAD) implantation has been used as a bridge to transplantation (BTT) in patients with end-stage heart failure, with proven benefit. Its use is also gaining acceptance with growing evidence as destination therapy (DT) for patients who are deemed not eligible for cardiac transplantation. Superiority of mechanical circulatory support versus best medical management is now widely accepted [2]. Improvement in technology, along with expanding experience in implantation and management of VADs, has resulted in improved complication profiles. Applicability and outcomes have been shown to improve Accepted for publication Aug 27, Address correspondence to Dr Borgi, Department of General Surgery, 2799 W Grand Blvd, Detroit, MI 48202; jamil.borgi@gmail.com. with the introduction of new-generation continuousflow LVADs with axial pumps (Heartmate II, Thoratec Corp, Pleasanton, CA; Jarvik 2000, Jarvik Heart Inc, New York, NY; Debakey VAD, MicroMed Cardiovascular, Inc, Houston, TX) and centrifugal pumps (Heart- Ware HVAD, HeartWare International, Inc, Framingham, MA; DuraHeart, Terumo Heart, Inc, Ann Arbor, MI) [3]. Deteriorating renal function is common in patients with advanced heart failure and is associated with poor outcomes [4 6]. The relationship between renal function and LVADs is complex and has been explored in multiple studies with contradictory results [7 15]. Poor renal function was associated with poor outcomes after LVAD implantation [7, 9, 10, 14, 15]. Conversely, renal function may improve with LVAD therapy [7 15]. In this study, we sought to assess the effect of acute renal failure (ARF) after LVAD implantation on postoperative morbidity as well as its effect on short-term and long-term survival by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 164 BORGI ET AL Ann Thorac Surg POSTOPERATIVE ARF AFTER LVAD IMPLANTATION 2013;95:163 9 Patients and Methods Our health system s institutional review board approved this retrospective study. Between March 2006 and July 2011, 100 patients with end-stage heart failure underwent implantation of LVADs at our hospital, a 1,000-bed quaternary care center. The devices were either Heartmate II (Thoratec Corp) or HeartWare (HeartWare International, Inc) LVADs. Procedures were performed by 3 different surgeons. The patient population was divided into 2 cohorts: those in whom ARF developed (n 28) and those in whom ARF did not develop (n 72). We defined patients with acute renal failure (ARF) as those patients who experienced acute renal injury stage II and greater based on the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria [16]: glomerular filtration rate decrease greater than 50% or doubling of the creatinine level. Patient Data Patient demographics included age, sex, race, body surface area (BSA), body mass index (BMI), previous sternotomy, days in hospital before LVAD implantation, preoperative creatinine level, liver function test results, cause (ischemic versus nonischemic cardiomyopathy), and associated comorbidities: hypertension (HTN), diabetes mellitus (DM), chronic renal insufficiency (CRI), dialysis, chronic obstructive pulmonary disease (COPD), and peripheral vascular disease (PVD). CRI was defined as glomerular filtration rate less than 60 ml/min/m 2. Operative characteristics analyzed were type of device (HeartMate II or Heartware), cardiopulmonary bypass (CPB) time, and indication (BTT or DT). Hemodynamic data collected before and after (at 1 and 6 months) LVAD implantation included central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular ejection fraction (LVEF), cardiac index (CI), LV and RV end-diastolic diameter (LVEDD/RVEDD), and mitral and tricuspid regurgitation (MR/TR). Outcome variables were complications, postoperative mortality (within 30 days of operation), survival at 180 and 360 days, intensive care unit (ICU) length of stay (LOS), and overall LOS, transplantation, reoperation for aortic insufficiency Table 1. Patient Demographics and Comorbidities Patient Characteristics No ARF (n 72) ARF (n 28) Age a Male sex 53 (74.6%) 20 (71.4%) b African American race 41 (58.6%) 19 (67.9%) b BSA a BMI a BTT 48 (66.7%) 20 (71.4%) b DT 24 (33.3%) 8 (28.6%) ICM 26 (36.1%) 8 (28.6%) b NIDCM 46 (63.9%) 20 (71.4%) Comorbidities HTN 64 (88.9%) 23 (82.1%) c DM 32 (44.4%) 13 (46.4%) b CRI 19 (26.4%) 11 (39.3%) b Previous history of dialysis 1 (1.4%) 2 (7.1%) c PVD 7 (9.7%) 4 (14.3%) c Preoperative laboratory values Creatinine a Albumin a AST d ALT d Preoperative characteristics Days in hospital preoperatively d Ventilated preoperatively 1 (1.4%) 4 (14.3%) c CPB time d Previous cardiac operation 22 (30%) 6 (21.4%) c a Probabilities based on 2-sided 2-sample t tests. b Probabilities based on 2 tests. c Probabilities based on Fisher s exact tests. d Probabilities based on 2-sided Wilcoxon rank-sum tests. ALT alanine aminotransferase; ARF acute renal failure; AST aspartate transaminase; BMI body mass index; BSA body surface area; BTT bridge to transplantation; CPB cardiopulmonary bypass; CRI chronic renal insufficiency; DM diabetes mellitus; DT destination therapy; HTN hypertension; ICM ischemic cardiomyopathy; NIDCM nonischemic dilatated cardiomyopathy; PVD peripheral vascular disease; SD standard deviation.

3 Ann Thorac Surg BORGI ET AL 2013;95:163 9 POSTOPERATIVE ARF AFTER LVAD IMPLANTATION (AI), noncardiac surgical procedures performed after LVAD implantation, readmission rates, and cause of death. Complications included repeated sternotomy for bleeding, drive line infections, pocket infections, pneumonia, RV failure, postoperative right VAD (RVAD) implantation, dialysis, ventilator-dependent respiratory failure (VDRF), tracheostomy insertion, hemorrhagic or ischemic stroke, and gastrointestinal bleeding. RV failure was defined as the need for inotropic support for more than 1 week or the need for RVAD support. VDRF was defined as the inability to wean the patient from the ventilator for at least 1 week. 165 Statistical Analysis Patient demographics, operative characteristics, postoperative complications, and hemodynamic data were compared in a univariate analysis. Continuous variables were reported as mean, standard deviation, minimum, and maximum and were compared using 2-sided 2-sample t tests. Alternatively, Wilcoxon rank-sum tests were used if normality could not be assumed. Categorical variables were reported as count and percent and were compared using 2 tests. Alternatively, Fisher s exact tests were used if expected cell counts were not sufficiently large. Thirty-day, 180-day, and 360-day survival rates were compared between ARF and non-arf groups using a log-rank test. Finally, preoperative/operative characteristics were individually placed in separate Cox proportional hazards models with 360-day survival as the outcome. Variables that were significant predictors of survival were then entered into a multiple Cox proportional hazards model on predicting 360-day survival. To adjust for confounding differences, the model also included variables that were significantly associated with renal failure. The model was further restricted to only significant predictors after applying a backward elimination method. Adjusted hazard ratios and 95% confidence intervals for hazard ratios were reported. Tests were considered significant at p values less than All analyses were performed using SAS, version 9.2 (SAS Institute, Cary, NC). Results Univariate Analysis A total of 100 patients who underwent LVAD implantation for BTT or DT were included in our study. After stratifying patients according to the development of postoperative ARF, we identified 28 patients (28%) with ARF and 72 patients (72%) without ARF. The 2 groups were similar when comparing age, sex, race, BSA, and BMI. The prevalence of HTN, DM, CRI, dialysis, COPD, and PVD was equal between the 2 groups. BTT constituted 66.7 % of the non-arf group and 71.4% of the ARF group (p 0.647). The cause of heart failure was also found to be similar, with ischemic cardiomyopathy (ICM) constituting 36.1% in the non- Table 2. Postoperative Outcomes Variable No ARF (n 72) ARF (n 28) Transplantation 21 (29.2%) 7 (25.0%) a Postoperative ICU stay b Overall postoperative stay b Reoperation for bleeding 5 (6.9%) 3 (10.7%) c DL infection 6 (8.3%) 0 (0.0%) c Pocket infection 1 (1.4%) 0 (0.0%) c Pneumonia 6 (8.3%) 4 (14.3%) c RV failure after VAD implantation 4 (5.6%) 7 (25.0%) c Postoperative RVAD implantation 0 (0.0%) 5 (17.9%) c Hemodialysis 0 (0.0%) 9 (32.1%) c VDRF 5 (6.9%) 8 (28.6%) c Tracheostomy 1 (1.4%) 2 (7.1%) c Hemorrhagic stroke 7 (9.7%) 2 (7.1%) c Ischemic stroke 7 (9.7%) 2 (7.1%) c Noncardiac operation after VAD 17 (23.6%) 7 (25.0%) a Reoperation for AI 4 (5.6%) 0 (0.0%) c Severe AI 3 (4.2%) 1 (3.6%) c GIB 17 (23.6%) 5 (17.9%) a Readmitted within 30 d after VAD implantation 19 (26.4%) 5 (17.9%) a Postoperative PRBC transfusion b a Probabilities based on 2 tests. b Probabilities based on 2-sided Wilcoxon rank-sum tests. c Probabilities based on Fisher s exact tests. AI aortic insufficiency; ARF acute renal failure; DL drive line; GIB gastrointestinal bleeding; ICU intensive care unit; PRBC packed red blood cells; RV right ventricular; RVAD right ventricular assist device; SD standard deviation; VAD ventricular assist device; VDRF ventilator-dependent respiratory failure.

4 166 BORGI ET AL Ann Thorac Surg POSTOPERATIVE ARF AFTER LVAD IMPLANTATION 2013;95:163 9 Table 3. Preoperative and Postoperative (at 1 and 6 Months) Hemodynamic Data Variable No ARF (n 72) [Min, Med, Max] ARF (n 28) [Min, Med, Max] Preoperative VAD LVEF [5.0, 15.0, 50.0] [5.0, 15.0, 40.0] a Postoperative VAD LVEF (1 mo) [5.0, 15.0, 40.0] [10.0, 20.0, 45.0] a Postoperative VAD LVEF (6 mo) [5.0, 18.0, 75.0] [15.0, 27.5, 70.0] a Preoperative VAD LVEDD [51.0, 74.0, 107.0] [34.0, 65.0, 85.0] a Postoperative VAD LVEDD (1 mo) [20.0, 61.0, 92.0] [34.0, 50.5, 78.0] a Postoperative VAD LVEDD (6 mo) [23.0, 59.0, 109.0] [25.0, 52.0, 87.0] a Preoperative VAD CI [1.0, 1.8, 3.9] [1.3, 1.9, 3.1] a Postoperative VAD CI (1 mo) [1.5, 2.4, 3.8] [1.5, 2.7, 4.9] a Postoperative VAD CI (6 mo) [1.2, 2.3, 3.8] [2.0, 2.4, 3.6] a Preoperative VAD PCWP [6.0, 22.0, 44.0] [12.0, 25.0, 45.0] a Postoperative VAD PCWP (1 mo) [1.0, 10.0, 37.0] [4.0, 8.5, 27.0] a Postoperative VAD PCWP (6 mo) [1.0, 11.0, 21.0] [4.0, 18.0, 26.0] a Preoperative VAD CVP [1.0, 10.0, 27.0] [3.0, 13.5, 27.0] a Postoperative VAD CVP (1 mo) [0, 10.0, 20.0] [3.0, 10.0, 20.0] a Postoperative VAD CVP (6 mo) [0, 6.0, 17.0] [2.0, 9.0, 22.0] a Preoperative VAD PASP [26.0, 50.0, 91.0] [12.0, 56.0, 73.0] a Postoperative VAD PASP (1 mo) [4.0, 33.5, 70.0] [18.0, 40.0, 63.0] a Postoperative VAD PASP (6 mo) [17.0, 36.0, 60.0] [20.0, 36.0, 58.0] a Preoperative VAD RVEDD [8.0, 25.0, 46.0] [12.0, 28.0, 49.0] a Postoperative VAD RVEDD (1 mo) [11.0, 29.0, 49.0] [11.0, 28.0, 49.0] a Postoperative VAD RVEDD (6 mo) [10.0, 29.0, 52.0] [15.0, 23.5, 42.0] a Preoperative VAD MR, moderate/severe 42 (60.9%) 17 (65.4%) b Postoperative VAD MR (1 mo), moderate/severe 14 (21.2%) 2 (8.7%) c Postoperative VAD MR (6 mo), moderate/severe 7 (12.7%) 5 (31.3%) c Preoperative VAD TR, moderate/severe 34 (50.0%) 14 (53.8%) c Postoperative VAD TR (1 mo), moderate/severe 11 (17.5%) 6 (27.3%) c Postoperative VAD TR (6 mo), moderate/severe 9 (16.7%) 5 (33.3%) c a Probabilities based on 2-sided 2-sample t tests. b Probabilities based on 2 tests. c Probabilities based on Fisher s exact tests. ARF acute renal failure; CI cardiac index; CVP central venous pressure; LVEDD left ventricular end-diastolic diameter; LVEF left ventricular ejection fraction; MR mitral regurgitation; PASP pulmonary artery systolic pressure; PCWP pulmonary capillary wedge pressure; RVEDD right ventricular end-diastolic diameter; ST standard deviation; TR tricuspid regurgitation; VAD ventricular assist device. ARF group and 28.6% in the ARF group (p 0.475). Preoperative laboratory values were not found to be statistically different between the 2 groups. Higher preoperative creatinine levels had a larger but nonsignificant trend in the ARF group (1.6 mg/dl versus 1.3 mg/dl; p 0.023). The patients with ARF were more likely to have been ventilated preoperatively (14.3%) compared with the non-arf group (1.4%; p 0.021). Table 1 compares the preoperative demographics and comorbidities between the ARF and non-arf groups. Postoperative outcomes are compared in Table 2. Complications were similar between the non-arf and ARF groups with the exception of ICU stay (9.5 days versus 18.6 days; p 0.005), total LOS (18.7 days versus 32.4 days; p 0.05), need for hemodialysis (0% versus 32.1%; p 0.001), VDRF (6.9% versus 28.6%; p 0.007) and RV failure (5.6% versus 25%; p 0.01). Patients with ARF required more inotropic support, although the difference did not reach statistical significance, with 78% (22/28) requiring inotropic agents after postoperative day 2 compared with 62% (45/72) (p 0.202) of patients in whom renal failure did not develop. Hemodynamic variables are compared in Table 3. Patients with ARF had a higher CVP before VAD implantation (14.3 mm Hg versus 10.7 mm Hg; p 0.015) and a lower LVEDD before VAD implantation (64.6 versus 74.0; p 0.001). All other hemodynamic measurements were comparable between the 2 groups. There was a significant difference when comparing the non-arf and ARF groups for 30-day mortality (0% versus 17.9%; p 0.001), 180-day survival (2.8% versus 28.6%; p 0.001), and 360-day survival (6.9% versus 28.6%; p 0.002) (Fig 1). Of the 28 patients in whom ARF developed, 7% (2/28) died in the early postoperative period before institution of dialysis, 32% (9/28) required hemodialysis, and 68% (17/28) returned to baseline (preoperative level) within 2 weeks of implantation without requiring dialysis. Of the 9 patients who required dialysis, 33% (3/9) died within 1 month of implantation. Four of the remaining 6 patients

5 Ann Thorac Surg BORGI ET AL 2013;95:163 9 POSTOPERATIVE ARF AFTER LVAD IMPLANTATION Table 5. Multivariable Analysis: Adjusted Predictors of 360- Day Survival (N 100) Characteristic Hazards Ratio 95% Confidence Interval for Hazard Ratio 167 Overall ARF , CRI , ARF acute renal failure; CRI chronic renal insufficiency. Fig 1. Kaplan-Meier curve comparing outcomes between acute renal failure (ARF) after left ventricular device (LVAD) implantation and patients without ARF. were free of dialysis within 1 month of implantation. Two patients (7% of patients with ARF and 2% of the total cohort) required permanent renal replacement therapy, with 1 patient dying within 6 months of implantation. For the patients in whom ARF did not develop, causes Table 4. Unadjusted Predictors of 360-day Survival Characteristic Hazards Ratio 95% Confidence Interval for Hazard Ratio Overall ARF Age Race BSA BMI Days in hospital preoperatively CPB time DT versus BTT HTN DM CRI COPD PVD Ventilated Creatinine Albumin AST ALT Cause (NIDCM versus ICM) ARF acute renal failure; ALT alanine aminotransferase; AST aspartate transaminase; BMI body mass index; BSA body surface area; BTT bridge to transplantation; COPD chronic obstructive pulmonary disease; CPB cardiopulmonary bypass; CRI chronic renal insufficiency; DM diabetes mellitus; DT destination therapy; HTN hypertension; ICM ischemic cardiomyopathy; NIDCM nonidiopathic dilatated cardiomyopathy; PVD peripheral vascular disease. of death included septic shock (20% [1/5]), RV failure (40% [2/5]), stroke (20% [1/5]), and disconnection from the power source (20% [1/5]). Causes of death for the patients in whom renal failure developed were septic shock (25% [2/8]), RV heart failure (38% [3/8]), stroke (25% [2/8]), and bowel perforation (12% [1/8]). Multivariate Analysis Accounting for all the variables that were significant predictors of 360-day mortality in the univariate analysis (Table 4), a multivariate analysis was performed. Postoperative ARF and preoperative CRI were the only statistically significant independent predictors of 360-day survival (Table 5). Comment LVADs continue to stand as an excellent therapeutic option for the growing population of patients with endstage heart disease. The role of these devices is well established as BTT therapy as well as DT [2]. LVAD is proving important in the newly explored role of bridge to candidacy, mostly secondary to the stabilizing and sometimes beneficial effect of circulatory support on end-organ function [7, 17, 18]. With the limited number of donor hearts, predicting outcomes of LVAD is of paramount importance for risk stratification and organ allocation, in particular for patients who are marginally eligible for transplantation [19 22]. The relationship between LVAD and renal function is complex and intricate. Renal dysfunction was shown to be a predictor of poor outcome and death in patients receiving LVADs [7] and is sometimes considered a contraindication for device implantation. Conversely, mechanical circulatory support has proved beneficial for end-organ perfusion and has shown improved renal function in multiple studies [7, 23, 24]. Furthermore, another level of complexity is that function before implantation is not necessarily a strong predictor of ARF after LVAD implantation [7, 24, 25]. In our study, 28 of 100 patients experienced ARF as defined by the RIFLE criteria, a rate of 28% that is comparable to the ARF incidence after LAVD implantation in other studies. The ARF and non-arf groups were comparable with regard to demographics and comorbidities. The mean baseline creatinine level was slightly higher in the group that developed ARF (1.6 mg/dl versus 1.3 mg/dl), but this did not translate into a

6 168 BORGI ET AL Ann Thorac Surg POSTOPERATIVE ARF AFTER LVAD IMPLANTATION 2013;95:163 9 statistically significant difference in the rate of CRI. This is in agreement with the previously described notion that renal dysfunction before implantation may not be the best predictor of postoperative ARF [7, 24, 25]. Another difference between the 2 groups is the higher percentage of patients who were ventilated before implantation in the subgroup of patients in whom ARF developed after implantation (14.3% versus 1.4%), which reflects the sicker or crashing nature of that group. This sicker nature extended to the postoperative stage, with longer ICU stays and overall hospital stays in the ARF versus the non-arf group (18.6 versus 9.5 and 32.4 versus 18.7, respectively). Of the patients in whom renal failure developed, 32% (9/28) proceeded to receive renal replacement therapy (RRT), again a rate similar to that published in the LVAD literature [26]. Of those who required dialysis, 44% (4/9) were free of dialysis within 1 month of implantation. Perhaps the most important finding in this study is the relationship between renal failure after transplantation and mortality, which is shown at 30-day (17.9 % versus 0%), 180-day (28.6% versus 2%) and 360-day (28.6% versus 6.9%) intervals. This relationship may seem intuitive and easily predictable at first, but it acquires more significance in the context of the complex interaction between renal dysfunction before implantation and renal function after implantation. Examining the patients who experienced ARF, we noticed that the vast majority exhibited renal dysfunction in the first few days after implantation. With the association shown between ARF and mortality, postoperative ARF may stand to be the first marker of poor outcome after LVAD implantation. Of note, this association between ARF and mortality seems strongest early on, with 17.9 % mortality at 30 days, which rises to 28.6% at 180 days and subsequently plateaus. This again highlights the importance of ARF as an early marker of mortality in patients receiving LVADs. Looking at the multivariable analysis and adjusting for other confounding variables, postoperative ARF continued to be a strong predictor of mortality with a hazard ratio of Another very interesting point is the difference noted in the rate of RV failure between the ARF and non-arf groups (25% versus 5.6%; p 0.01) and the rate of RVAD placement (17.9% versus 0%). This finding again points to ARF development after implantation as an early marker of poor outcomes that may be due to an underlying dysfunctional right ventricle. According to our hemodynamic data, patients with ARF had higher CVP before LVAD implantation and lower LVEDD before LVAD implantation. This may underline worse RV function that was subclinical before the LVAD implantation. Early placement of an RVAD may be a potential rescue mechanism that deserves to be considered in this particularly sick subgroup. Our study has several limitations. First, this was an observational nonrandomized study and is subject to limitations inherent to any retrospective study. Second, statistical tests were insufficiently powered owing to our relatively small sample size and small percentage of patients in the ARF subgroup. Third, the duration of follow-up is short and long-term outcomes are not defined. Finally, this was a single-institution study and selection bias may be present. In conclusion, in this study we show an association between ARF after LVAD implantation and mortality. This effect on outcome appears to be more significant in the early postoperative period. It also appears to be related to RV failure. One mechanism of rescue may be the early implantation of an RVAD. Finally, the relationship between renal function and LVADs is complex and requires extensive attention. Larger studies are needed to assess and validate the predictors of outcomes and identify the areas of possible beneficial interventions. References 1. American Heart Association: Heart disease and stroke statistics 2007 update. American Heart Association, Dallas, TX, Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med 2001;5;345: Caccamo M, Eckman P, John R. Current state of ventricular assist devices. Curr Heart Fail Rep 2011;8: Forman DE, Butler J, Wang Y, et al. Incidence, predictors and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 2004;43: Hillege HL, Girbes AR, de Kam PJ, et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. 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Patient selection for left ventricular assist device therapy. Ann Thorac Surg 2003;75(6 suppl):s Oz MC, Rose EA, Levin HR. Selection criteria for placement of left ventricular assist devices. Am Heart J 1995;129: Reedy JE, Swartz MT, Termuhlen DF, et al. Bridge to heart transplantation: importance of patient selection. J Heart Transplant 1990;9: Farrar DJ. Preoperative predictors of survival in patients with Thoratec ventricular assist devices as a bridge to heart transplantation: Thoratec Ventricular Assist Device Principal Investigators. J Heart Lung Transplant 1994;13: Sandner SE, Zimpfer D, Zrunek P, et al. Renal function and outcome after continuous flow left ventricular assist device implantation. Ann Thorac Surg 2009;87: Bellomo R, Ronco C, Kellum JA, Mehta RL, Paleversusky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure definition, outcome measures, animal models, fluid therapy and information technology needs: the Second In-

7 Ann Thorac Surg BORGI ET AL 2013;95:163 9 POSTOPERATIVE ARF AFTER LVAD IMPLANTATION ternational Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R Young JB, Rogers JG, Portner PM, et al. Bridge to eligibility: LVAS support in patients with relative contraindications to transplantation (abstract). J Heart Lung Transplant 2005; 24:S Kainuma S, Sakaguchi T, Saito S, et al. Implantation of a Jarvik 2000 left ventricular assist device as a bridge to eligibility for refractory heart failure with renal dysfunction. J Artif Organs 2012;15: Costanzo MR, Augustine S, Bourge RC, et al. Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. Circulation 1995;92: O Connell JB, Bourge RC, Costanzo-Nordin MR, et al. Cardiac transplantation: recipient selection, donor procurement, and medical follow-up. A statement for health professionals from the Committee on Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. Circulation 1992;86: Bourge RC, Naftel DC, Costanzo-Nordin MR, et al. Pretransplantation risk factors for death after heart transplantation: a multi institutional study. The Transplant Cardiologists Research Database Group. J Heart Lung Transplant 1993;12: Ostermann ME, Rogers CA, Saeed I, et al. Pre-existing renal failure doubles 30-day mortality after heart transplantation. J Heart Lung Transplant 2004;23: Letsou GV, Myers TJ, Gregoric ID, et al. Continuous axialflow left ventricular assist device (Jarvik 2000) maintains kidney and liver perfusion for up to 6 months. Ann Thorac Surg 2003;76: Sandner SE, Zimpfer D, Zrunek P, et al. Renal function after implantation of continuous versus pulsatile flow left ventricular assist devices. J Heart Lung Transplant 2008;27: Sandner SE, Zimpfer D, Zrunek P, et al. Renal function and outcome after continuous flow left ventricular assist device implantation. Ann Thorac Surg 2009;87: Demirozu ZT, Etheridge WB, Radovancevic R, Frazier OH. Results of HeartMate II left ventricular assist device implantation on renal function in patients requiring post-implant renal replacement therapy. J Heart Lung Transplant 2011;30: INVITED COMMENTARY Acute renal failure (ARF) is a common sequela of left ventricular assist device (LVAD) implantation in patients with end-stage heart failure. The pathophysiologic interaction of cardiac and renal disorders is highly complex. Compromised hemodynamics and deteriorated renal function often create a vicious circle and pose a therapeutic challenge. The mechanical circulatory support of LVAD with pulsatile or nonpulsatile blood flow may render this clinical entity more intricate. Despite important advances in our understanding of this clinical challenge, little is known about the effects of postoperative ARF on the clinical outcome of LVAD implantation. In a retrospective study, Dr Borgi and coworkers [1] analyzed the clinical data for 100 patients undergoing LVAD implantation (HeartMate II or HeartWare) and stratified them based on the postoperative development of ARF defined as decrease in glomerular filtration rate of more than 50% or doubling of serum creatinine level. The results of this study clearly demonstrate the higher mortality rate of patients with postoperative development of ARF not only in the postoperative period, but also at the 180- and 360-day intervals, when comparing to that of patients without postoperative ARF. In the multivariate analysis of various clinical parameters, postoperative ARF and preoperative chronic renal insufficiency were the only statistically significant independent predictors of 360-day survival. Moreover, postoperative ARF was also associated with worse right ventricular function before LVAD implantation and a higher incidence of postoperative right ventricular failure and requirement for implantation of right ventricular assist device. This article elucidates the predictive value of postoperative ARF as an early marker of a poor clinical outcome of LVAD implantation. It also emphasizes the importance of optimal clinical management and early intervention of right ventricular failure in this very sick and desperate patient population. I believe that this article will broaden the discussion and contribute further evidence regarding this highly relevant clinical topic. Ruoyu Zhang, MD Department of Cardiac, Thoracic Transplantation and Vascular Surgery Hannover Medical School Carl-Neuberg Str Hannover, Germany zhang.ruoyu@mh-hannover.de Reference 1. Borgi J, Tsiouris A, Hodari A, Cogan CM, Paone G, Morgan JA. Significance of postoperative acute renal failure after continuous-flow left ventricular assist device implantation. Ann Thorac Surg 2013;95: by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc