Timothy J. George

Creation of a Quantitative Recipient Risk Index for Mortality Prediction After Cardiac Transplantation (IMPACT)

BACKGROUND No recipient risk index exists predicting short-term mortality after orthotopic heart transplantation (OHT). We utilized United Network for Organ Sharing (UNOS) data to develop a novel quantitative recipient risk score for use in OHT. METHODS A prospectively collected open cohort of 21,378 primary OHT patients (1997 to 2008) was randomly divided into subgroups. The training cohort (n=17,079) was used for score derivation and the test cohort (n=4,299) was used for independent validation. Recipient specific variables associated with 1-year mortality (exploratory p value<0.2) were incorporated stepwise into a multivariable logistic regression model. The final model contained variables which maximized explanatory power (assessed by pseudo R2, area under the curve, and likelihood-ratio test). A risk index was created by apportioning points approximating the relative impact of variables on 1-year mortality. The Kaplan-Meier method was used to assess impact of risk score on short-term survival. RESULTS The 50-point scoring system incorporated 12 recipient specific variables. Derivation and validation cohort scores ranged from 0 to 33 and 0 to 27, respectively (mean 6.1±3.7 and 6.1±3.7). Each point increased the odds of 1-year death by 14% in the derivation cohort (odds ratio 1.14 [1.13 to 1.15], p<0.001) and 15% in the validation cohort (odds ratio 1.15 [1.12 to 1.17], p<0001). One-year survivals in the validation cohort (by increments of 3 points) were the following: 0 to 2 (92.5%); 3 to 5 (89.9%); 7 to 9 (86.3%); and 10 or greater (74.9%); p<0.001. Patients transplanted with risk scores of 20 or higher had 1-year mortality rates greater than 50%. CONCLUSIONS We present a novel internally validated OHT recipient risk score, which is highly predictive of 1-year mortality. This risk index may prove valuable for patient prognosis, organ allocation, and research stratification in OHT.

Surgical Repair of Ventricular Septal Defect After Myocardial Infarction: Outcomes From The Society of Thoracic Surgeons National Database

BACKGROUND The development of a ventricular septal defect (VSD) after myocardial infarction (MI) is an uncommon but highly lethal complication. We examined The Society of Thoracic Surgeons database to characterize patients undergoing surgical repair of post-MI VSD and to identify risk factors for poor outcomes. METHODS This was a retrospective review of The Society of Thoracic Surgeons database to identify adults (aged≥18 years) who underwent post-MI VSD repair between 1999 and 2010. Patients with congenital heart disease were excluded. The primary outcome was operative death. The covariates in the current The Society of Thoracic Surgeons model for predicted coronary artery bypass grafting operative death were incorporated in a logistic regression model in this cohort. RESULTS The study included 2,876 patients (1,624 men [56.5%]), who were a mean age of 68±11 years. Of these, 215 (7.5%) had prior coronary artery bypass grafting operations, 950 (33%) had prior percutaneous intervention, and 1,869 (65.0%) were supported preoperatively with an intraaortic balloon pump. Surgical status was urgent in 1,007 (35.0%) and emergencies in 1,430 (49.7%). Concomitant coronary artery bypass grafting was performed in 1,837 (63.9%). Operative mortality was 54.1% (1,077 of 1,990) if repair was within 7 days from MI and 18.4% (158 of 856) if more than 7 days from MI. Multivariable analysis identified several factors associated with increased odds of operative death. CONCLUSIONS In the largest study to date to examine post-MI VSD repair, ventricular septal rupture remains a devastating complication. As alternative therapies emerge to treat this condition, these results will serve as a benchmark for future comparisons.

What Predicts Long-Term Survival After Heart Transplantation? An Analysis of 9,400 Ten-Year Survivors

BACKGROUND This case-control study was conducted to identify factors predictive of 10-year survival after orthotopic heart transplantation (OHT). METHODS Prospectively collected data from the United Network for Organ Sharing registry were reviewed to identify adult patients undergoing OHT between 1987 and 1999 (N=22,385) who had survived 10 years. Controls were those who had died within 10 years of OHT. Factors associated with 10-year survival were identified with multivariate logistic regression analysis. Lowess smoothing plots were used to identify linear breakpoints in continuous variables, and splines were incorporated when appropriate. RESULTS There were 9,404 ten-year survivors (42%; mean follow-up, 14.0±3.0 years) and 10,373 controls (46%) with a mean survival of 3.7±3.3 years post-OHT. Predictors of 10-year survival in the optimal multivariate model were age younger than 55 (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.10 to 1.38; p<0.001), white race (OR, 1.35; 95% CI, 1.17 to 1.56; p<0.001), shorter ischemic time (OR, 1.11; 95% CI, 1.05 to 1.18; p<0.001), younger donor age (OR, 1.01; 95% CI, 1.01 to 1.02; p<0.001), annual center volume of 9 or more (OR, 1.31; 95% CI, 1.17 to 1.47; p<0.001), mechanical ventilation (OR, 0.53; 95% CI, 0.36 to 0.78; p=0.001), and diabetes (OR, 0.67; 95% CI, 0.57 to 0.78; p<0.001). CONCLUSIONS Age younger than 55 years, annual center volume of 9 or more, white race, shorter ischemic time, and younger donor age improved the likelihood of 10-year survival after OHT. Mechanical ventilation and diabetes reduced this likelihood. These data should serve as a useful guide to long-term prognostication in adult OHT.

Contemporary Etiologies, Risk Factors, and Outcomes After Pericardiectomy

BACKGROUND The leading causes of constrictive pericarditis have changed over time leading to a commensurate change in the indications and complexity of surgical pericardiectomy. We evaluated our single-center experience to define the etiologies, risk factors, and outcomes of pericardiectomy in a modern cohort. METHODS We retrospectively reviewed our institutional database for all patients who underwent total or partial pericardiectomy. Demographic, comorbid, operative, and outcome data were evaluated. Survival was assessed by the Kaplan-Meier method. Multivariable Cox proportional hazards regression models examined risk factors for mortality. RESULTS From 1995 to 2010, 98 adults underwent pericardiectomy for constrictive disease. The most common etiologies were idiopathic (n=44), postoperative (n=30), and post radiation (n=17). Total pericardiectomy was performed in 94 cases, most commonly through a sternotomy (n=93). Thirty-three cases were redo sternotomies, 34 underwent a concomitant procedure, and 34 required cardiopulmonary bypass. Overall in-hospital, 1-year, 5-year, and 10-year survival rates were 92.9%, 82.5%, 64.3%, and 49.2%, respectively. Survival differed sharply by etiology with idiopathic, postoperative, and post-radiation 5-year survivals of 79.8%, 55.9%, and 11.0%, respectively (p<0.001). On multivariable analysis, only the need for cardiopulmonary bypass (hazard ratio [HR]: 21.2, p=0.02) was predictive of 30-day mortality while post-radiation etiology (HR: 3.19, p=0.02) and hypoalbuminemia (HR: 0.57, p=0.03) were associated with increased 10-year mortality. CONCLUSIONS Although survival varies significantly by etiology, pericardiectomy continues to be a safe operation for constrictive pericarditis. Post-radiation pericarditis and hypoalbuminemia are significant risk factors for decreased long-term survival.

Effect of sensitization in US heart transplant recipients bridged with a ventricular assist device: Update in a modern cohort

OBJECTIVE Preformed anti-human leukocyte antigen antibodies have been associated with prolonged wait times and increased mortality in orthotopic heart transplantation. We used United Network for Organ Sharing data to examine panel reactive antibody titers in patients bridged to transplant with left ventricular assist devices. METHODS This was a retrospective review of the United Network for Organ Sharing dataset for all patients bridged to orthotopic heart transplantation with a HeartMate II or HeartMate XVE (Thoratec Corp, Pleasanton, Calif) from January 2004 to December 2009. Patients were primarily stratified by device type and secondarily grouped for comparisons by high (>25%) versus low (0%) panel reactive antibody activity (class I and II). Outcomes included survival (30-day and 1-year), treated rejection in the year after orthotopic heart transplantation, and primary graft dysfunction. Cox proportional hazards regression examined 30-day and 1-year survival. RESULTS A total of 871 patients (56.1%) received the HeartMate II device, and 673 patients (43.9%) received the HeartMate XVE device. Patients with high panel reactive antibody had longer duration on the wait list (205 days [interquartile range, 81-344] vs 124 days [interquartile range, 51-270], P = .01). High panel reactive antibody class II was more common in patients with the HeartMate XVE device (51/547 [9.3%] vs 42/777 [5.4%], P < .001). When the entire cohort was examined together, there was no 30-day or 1-year survival difference based on panel reactive antibody activity. Device type did not affect post-orthotopic heart transplantation survival, and panel reactive antibody activity was not associated with worse mortality in Cox regression. Although panel reactive antibody activity did not affect rejection in the year after orthotopic heart transplantation for either device type, high panel reactive antibody class II was associated with higher rates of primary graft dysfunction for both devices (P < .05). CONCLUSIONS This is the largest modern study to examine the impact of detailed panel reactive antibody information in patients bridged to transplant. High panel reactive antibody levels do not affect drug-treated rejection episodes in the first year post-orthotopic heart transplantation; however, there is an associated higher rate of primary graft dysfunction, regardless of device type. Highly sensitized patients bridged to transplant experience excellent survival outcomes after orthotopic heart transplantation.

Outcomes and temporal trends among high-risk patients after lung transplantation in the United States

INTRODUCTION Although several studies have evaluated risk factors for death after lung transplantation (LTx), few studies have focused on the highest-risk recipients. We undertook this study to evaluate the effect of high lung allocation scores (LAS), ventilator support, and extracorporeal membrane oxygenation (ECMO) support on outcomes after LTx. METHODS We retrospectively reviewed all LTx recipients in the United Network for Organ Sharing database. Primary stratification was by recipient acuity at the time of LTx. The 3 strata consisted of (1) recipients in the highest LAS quartile (LAS ≥ 48.4), (2) those requiring ventilator support, and (3) those requiring ECMO support. The primary outcome was 1-year mortality. Sub-group analysis focused on temporal trends. RESULTS From May 2005 to June 2011, 9,267 adults underwent LTx. Before LTx, 1,874 (20.2%) were in the highest LAS quartile, 526 (5.7%) required ventilator support, and 122 (1.3%) required ECMO support. Unadjusted analysis showed decreased 1-year survival associated with ventilator (67.7%) and ECMO support (57.6%) compared with the highest LAS quartile (81.0%; p < 0.001 for each comparison). These differences persisted on adjusted analysis for ventilator support (hazard ratio, 1.99, p < 0.001) and ECMO support (hazard ratio, 3.03; p < 0.001). Increasing annual center volume was associated with decreased mortality. In patients bridged to LTx with ECMO support, 1-year survival improved over time (coefficient, 8.03% per year; p = 0.06). CONCLUSIONS High-acuity LTx recipients, particularly those bridged with ventilator or ECMO support, have increased short-term mortality after LTx. However, since the introduction of the LAS, high-risk patients have demonstrated improving outcomes, particularly at high-volume centers.

Lung Transplant in Idiopathic Pulmonary Fibrosis

OBJECTIVE To review the present status of lung transplant (LTx) in patients with idiopathic pulmonary fibrosis (IPF). DATA SOURCES Current English-language literature review using MEDLINE. STUDY SELECTION Prospective and retrospective trials, series, reviews, databases, and editorials regarding the clinical and basic science aspects of LTx in patients with IPF. DATA EXTRACTION We analyzed results from trials and series. DATA SYNTHESIS Idiopathic pulmonary fibrosis is an incurable disease with a dismal prognosis. The only treatment of proven benefit is LTx. Since the introduction of the Lung Allocation Score, IPF has become the most common indication for LTx in the United States. These patients have a limited life expectancy and benefit from early referral for transplant. Although controversial, the most recent data suggest that bilateral LTx is superior to single LTx in the population of patients with IPF. For this population, LTx increases the length and quality of their lives. CONCLUSION Although patients with IPF have a dismal prognosis, LTx is a safe and effective treatment to improve their survival and functional status.

Valve-sparing aortic root replacement in Loeys-Dietz syndrome

BACKGROUND Loeys-Dietz syndrome (LDS) is a recently recognized aggressive aortic disorder characterized by root aneurysm, arterial tortuosity, hypertelorism, and bifid uvula or cleft palate. The results of prophylactic root replacement using valve-sparing procedures (valve-sparing root replacement [VSRR]) in patients with LDS is not known. METHODS We reviewed all patients with clinical and genetic (transforming growth factor-β receptor mutations) evidence of LDS who underwent VSRR at our institution. Echocardiographic and clinical data were obtained from hospital and follow-up clinic records. RESULTS From 2002 to 2009, 31 patients with a firm diagnosis of LDS underwent VSRR for aortic root aneurysm. Mean age was 15 years, and 24 (77%) were children. One (3%) patient had a bicuspid aortic valve. Preoperative sinus diameter was 3.9±0.8 cm (z score 7.0±2.9) and 2 (6%) had greater than 2+ aortic insufficiency. Thirty patients (97%) underwent reimplantation procedures using a Valsalva graft. There were no operative deaths. Mean follow-up was 3.6 years (range, 0 to 7 years). One patient required late repair of a pseudoaneurysm at the distal aortic anastomosis, and 1 had a conversion to a David reimplantation procedure after a Florida sleeve operation. No patient suffered thromboembolism or endocarditis, and 1 (3%) patient experienced greater than 2+ late aortic insufficiency. No patient required late aortic valve repair or replacement. CONCLUSIONS Loeys-Dietz syndrome is an aggressive aortic aneurysm syndrome that can be addressed by prophylactic aortic root replacement with low operative risk. Valve-sparing procedures have encouraging early and midterm results, similar to those in Marfan syndrome, and are an attractive option for young patients.

Acute Kidney Injury Increases Mortality After Lung Transplantation

BACKGROUND Acute kidney injury requiring renal replacement therapy (RRT) is associated with increased mortality after cardiac surgery. Studies examining the impact of RRT after lung transplantation (LTx) are limited. We evaluated risk factors and outcomes associated with RRT after LTx. METHODS We retrospectively reviewed all LTx recipients in the United Network for Organ Sharing database. Preoperative renal function was stratified by glomerular filtration rate (GFR) as determined by the Modification of Diet in Renal Disease formula (strata: ≥90, 60 to 90, and <60 mL · min(-1) · 1.73 m(-2)). Primary outcomes were 30-day, 1-year, and 5-year survival and need for post-LTx RRT. Risk adjusted multivariable Cox proportional hazards regression examined mortality. A multivariable logistic regression model evaluated risk factors for RRT. RESULTS From 2001 to 2011, 12,108 patients underwent LTx. After LTx, 655 patients (5.51%) required RRT. Patients requiring post-LTx RRT had decreased survival at 30 days (96.7% versus 76.0%, p < 0.001), 1 year (85.5% versus 35.8%, p < 0.001), and 5 years (56.4% versus 20.0%, p < 0.001). These differences persisted on multivariable analysis at 30 days (hazard ratio [HR] 7.98 [6.16 to 10.33], p < 0.001), 1 year (HR 7.93 [6.84 to 9.19], p < 0.001), and 5 years (HR 5.39 [4.75 to 6.11], p < 0.001). Preoperative kidney function was an important predictor of post-LTx RRT for a GFR of 60 to 90 (odds ratio 1.42 [1.16 to 1.75], p = 0.001) and a GFR less than 60 (odds ratio 2.68 [2.07 to 3.46], p < 0.001]. High center volume was protective. CONCLUSIONS In the largest study to evaluate acute kidney injury after LTx, the incidence of RRT is 5.51%. The need for post-LTx RRT dramatically increases both short- and long-term mortality. Several variables, including preoperative renal function, are predictors of post-LTx RRT and could be used to identify transplant candidates at risk for acute kidney injury.

Association of operative time of day with outcomes after thoracic organ transplant

CONTEXT Recent emphasis on systems-based approaches to patient safety has led to several studies demonstrating worse outcomes associated with surgery at night. OBJECTIVE To evaluate whether operative time of day was associated with thoracic organ transplant outcomes, hypothesizing that it would not be associated with increased morbidity or mortality. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study of adult heart and lung transplant recipients in the United Network for Organ Sharing database from January 2000 through June 2010. Primary stratification was by operative time of day (night, 7 PM-7 AM; day, 7 AM-7 PM). MAIN OUTCOME MEASURES Primary end points were short-term survival, assessed by the Kaplan-Meier method at 30, 90, and 365 days. Secondary end points encompassed common postoperative complications. Risk-adjusted multivariable Cox proportional hazards regression examined mortality. RESULTS A total of 27,118 patients were included in the study population. Of the 16,573 who underwent a heart transplant, 8346 (50.36%) did so during the day and 8227 (49.64%) during the night. Of the 10,545 who underwent a lung transplant, 5179 (49.11%) did so during the day and 5366 (50.89%) during the night. During a median follow-up of 32.2 months (interquartile range, 11.2-61.1 months), 8061 patients (28.99%) died. Survival was similar for organ transplants performed during the day and night. Survival rates at 30 days for heart transplants during the day were 95.0% vs 95.2% during the night (hazard ratio [HR], 1.05; 95% confidence interval, 0.83-1.32; P = .67) and for lung transplants during the day were 96.0% vs 95.5% during the night (HR, 1.22; 95% CI, 0.97-1.55; P = .09). At 90 days, survival rates for heart transplants were 92.6% during the day vs 92.7% during the night (HR, 1.05; 95% CI, 0.88-1.26; P = .59) and for lung transplants during the day were 92.7% vs 91.7% during the night (HR, 1.23; 95% CI, 1.04-1.47; P = .02). At 1 year, survival rates for heart transplants during the day were 88.0% vs 87.7% during the night (HR, 1.05; 95% CI, 0.91-1.21; P = .47) and for lung transplants during the day were 83.8% vs 82.6% during the night (HR, 1.08; 95% CI, 0.96-1.22; P = .19). Among lung transplant recipients, there was a slightly higher rate of airway dehiscence associated with nighttime transplants (57 of 5022 [1.1%] vs 87 of 5224 [1.7%], P = .02). CONCLUSION Among patients who underwent thoracic organ transplants, there was no significant association between operative time of day and survival up to 1 year after organ transplant.