Jeremiah G. Allen

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.

Quality of life and functional status in patients surviving 12 months after left ventricular assist device implantation.

BACKGROUND As left ventricular assist device (LVAD) support duration increases, quality of life (QoL) becomes a concern. We reviewed the QoL in patients on LVAD support for >or=1 year. METHODS We retrospectively reviewed our prospective database for patients supported >or=1 year by HeartMate pulsatile- (HM1) or continuous-flow (HM2) LVADs from 2000 to 2009. Transplant or death before 1 year merited exclusion. Metabolic equivalents of tasks (METs), the Minnesota Living with Heart Failure Questionnaire (MLHFQ), the 6-minute walk distance (6MWD), and New York Heart Association (NYHA) class were reviewed. Complications and re-admissions were assessed. RESULTS Thirty patients were supported for >or=1 year (7 HM1s, 23 HM2s). Mean support duration was 594 +/- 173 days. Mean QoL metrics/functional status indicators at 12 months were: 6MWD, 393 +/- 290 m; MET tolerance, 3.3 +/- 1; MLHFQ, 35 +/- 31; and NYHA, 1.4 +/- 0.6. Mean re-admissions/year was 2.9 +/- 2, with a duration of 13.8 +/- 21 days. Three patients were never re-admitted. Mean out-of-hospital time was 471 +/- 172 days (87.3% of days). Infectious complications led to 43% of re-admissions and occurred in the: drive-line (47%) at 442 +/- 236 days; blood (37%) at 472 +/- 257 days; and LVAD pocket (20%) at 550 +/- 202 days. Twenty-three patients (77%) required additional operations (1.7 +/- 1.8/year). The most common indication was drive-line infection, but ranged from ischemic bowel to defibrillator exchange. Eight required LVAD exchanges for mechanical (n = 4), electrical (n = 3), and thrombotic (n = 1) issues. CONCLUSIONS Although LVAD support is not without complications, patients spend the majority of time outside the hospital enjoying a good quality of life.

Infectious complications after pulsatile-flow and continuous-flow left ventricular assist device implantation.

BACKGROUND Infection is a significant source of morbidity and mortality after left ventricular assist device (LVAD) implantation. Newer generation continuous-flow (CF) LVADs are smaller, requiring smaller pump pockets and drive-line exit sites as compared with pulsatile-flow (PF) devices. With their recent adoption, CF device patients benefit from improved provider experience in the detection and treatment of infectious complications. Given these advances in design and experience, we examined the incidence of infectious complications in patients receiving CF and PF devices. METHODS We reviewed patients who received CF or PF LVADs (June 2000 to May 2009) at our institution. Incidences and timing of systemic infections (bacteremia, sepsis, severe sepsis, septic shock), device-associated infections (drive-line, LVAD pocket, sternal wound) and non-device-associated infections (catheter-related bloodstream, pneumonia, urinary tract) were compared between devices. Primary outcomes were sepsis, severe sepsis, a composite of drive-line and LVAD pocket infection, and catheter-related bloodstream infection. RESULTS Of 133 LVADs, 86 were CF. CF patients had lower pre-operative risk, more recent device implantation, and longer LVAD support time. Device type was highly correlated with reduced infections; however, on multivariate analysis, implantation date appeared to drive this association. Kaplan-Meier estimates of freedom from all primary outcomes were improved with more recent implantation (p < 0.05). On multivariate analysis, implantation date was predictive of all primary outcomes except severe sepsis, for which advanced age and worse Seattle Heart Failure Model score were predictive. CONCLUSION In this institutional review of post-LVAD infections, a decrease in infectious complications in CF patients was likely related to increased provider experience associated with a more recent date of implantation.

Heart Transplantation for Adults With Congenital Heart Disease: Analysis of the United Network for Organ Sharing Database

BACKGROUND Congenital heart disease (CHD) in the adult is an uncommon indication for heart transplantation but has been increasing. We assessed survival and predictors of death after heart transplantation for adults with CHD. METHODS Adult primary heart transplant recipients (aged > 17 years) reported to the United Network for Organ Sharing (1987 to 2006) were reviewed and categorized by diagnosis of CHD vs other diagnoses. Kaplan-Meier survival analysis and Cox regression modeling were performed. RESULTS During the study period, 35,334 adults underwent primary heart transplantation, and 689 (2%) had CHD. Adult CHD recipients had longer mean waiting list time (218 vs 195 days; p = 0.004), longer ischemic time (3.5 vs 2.9 hours, p < 0.0001), and were more likely to have pretransplant pulmonary vascular resistance exceeding 4 Woods Units (62% vs 51%, p < 0.0001) vs other recipients. Thirty-day mortality was 16% vs 6% (p < 0.0001), although Kaplan-Meier survival did not differ between groups (p = 0.92) out to 10 years. Ischemic time (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.02 to 1.35; p = 0.02), African American race (HR, 1.9; 95% CI, 1.04 to 3.58; p = 0.03), and pulmonary vascular resistance exceeding 4 Woods Units (HR, 1.5; 95% CI, 1.01 to 2.19; p = 0.04) were predictors of death for adult CHD recipients. CONCLUSIONS Heart transplantation for adults with CHD is effective and has good long-term prognosis. The 30-day mortality rate is high, but 5- and 10-year survival is not statistically different from patients without CHD.

Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation

BACKGROUND No standard index based on donor factors exists for predicting mortality after orthotopic heart transplantation (OHT). We utilized United Network for Organ Sharing (UNOS) data to develop a quantitative donor risk score for OHT. METHODS We examined a prospectively collected open cohort of 22,252 patients who underwent primary OHT (1996 to 2007). Of the 284 donor-specific variables, those associated with 1-year (year) mortality (exploratory p-value < 0.2) were incorporated into a multivariate (MV) logistic regression model. The final model contained donor factors that improved the explanatory power (by pseudo-R2, area under the curve and likelihood ratio test). A quantitative donor risk score was created using odds ratios (ORs) from the final model. For external validity, a cross-validation strategy was employed whereby the score was generated using a randomly generated subset of cases (n = 17,788) and then independently validated on the remaining patients (n = 4,464). RESULTS A 15-point scoring system incorporated 4 variables: ischemic time; donor age; race mismatching; and blood urea nitrogen (BUN)/creatinine ratio. Derivation and validation cohort scores ranged from 1 to 15 and 1 to 12, respectively (mean 4.0 ± 2.1 for each). Each increase of 1 point increased the risk of 1-year death by 9% (OR = 0.09 [1.07 to 0.12]) in the derivation cohort and 13% (OR = 0.13 [1.08 to 0.18]) in the validation cohort (each p < 0.001). The odds of 1-year mortality by increments of 3 points were: 0 to 2 points (reference); 3 to 5 points (OR = 0.25 [1.12 to 0.40], p < 0.001); 6 to 8 pts (OR = 0.77 [1.56 to 2.02], p < 0.001); and 9 to 15 points (OR = 1.92 [1.54 to 2.39], p < 0.001). Donor risk score was predictive for 30-day mortality (OR = 0.11 [1.08 to 0.14], p < 0.001) and 5-year cumulative mortality (OR = 0.11 [1.09 to 0.13], p < 0.001). CONCLUSIONS We present a novel donor risk index for OHT predicting short- and long-term mortality. This donor risk score may prove valuable for donor heart allocation and prognosis after OHT.

Bleeding complications and blood product utilization with left ventricular assist device implantation

BACKGROUND Bleeding complications are a major source of morbidity and reoperation after left ventricular assist device (LVAD) implantation, yet remain poorly characterized in patients receiving LVADs. We assessed bleeding complications in an institutional cohort of LVAD patients. METHODS We reviewed patients who received continuous-flow (CF) LVADs at our institution (October 2004 to May 2009). Intraoperative and postoperative transfusion requirements (packed red blood cells, fresh frozen plasma, and platelets), chest tube output, and reoperation for bleeding complications were assessed. Univariate and multivariable Cox proportional hazard analysis assessed the impact of intraoperative bleeding on mortality. A subset of our patient population underwent delayed sternal closure as opposed to primary closure and an analysis of reoperation for bleeding was undertaken stratifying patients by approach to closure. RESULTS Eighty-six CF LVADs were implanted over our study period. Patients had poor preoperative cardiac function and high preoperative risk indices. Patients receiving LVADs had high intraoperative (11.6 ± 7.5 units) and postoperative (15.6 [±12.6] units in the first week) blood product requirements, as well as significant chest tube output (5,880 [±4,480] milliliters in the first week). On multivariable analysis, intraoperative packed red blood cell transfusions were a significant predictor of mortality. Eleven (28%) patients undergoing primary sternal closure required reoperation for bleeding, while delayed sternal closure patients generally had resolution of bleeding prior to sternal closure. The incidence of gastrointestinal bleeding was 28% at one year. CONCLUSIONS On multivariable analysis, intraoperative packed red blood cell transfusions were a significant predictor of 30-day and one-year mortality, while chest tube output during the first postoperative 48 hours predicted 30-day but not one-year mortality.

The impact of recipient body mass index on survival after lung transplantation

BACKGROUND Lung transplant (LTx) candidates are frequently over or underweight. Few studies have examined recipient weight and outcomes after LTx. The United Network for Organ Sharing (UNOS) database provides an opportunity to examine outcomes related to body mass index (BMI) in a large cohort of LTx patients. METHODS The UNOS data set was retrospectively reviewed for 11,411 adult primary LTx patients (1998 to 2008). Patients were stratified by recipient BMI (kg/m(2)): less than 18.5 (underweight), 18.5 to 24.9 (normal), 25.0 to 29.9 (overweight), more than 30 (obese). All-cause mortality was examined with Cox proportional hazard regression incorporating 15 variables. Survival was modeled using the Kaplan-Meier method. RESULTS Of 11,411 recipients, 1,355 (11.9%) were underweight, 4,998 (43.8%) were normal weight, 3,662 (62.1%) were overweight, and 1,396 (12.2%) were obese. During the study, 4,959 patients (43.5%) died. Mortality was significantly different between the strata, with incremental increases in death for each BMI category above or below normal. On multivariable analysis, BMI strata predicted death compared with normal weight. Risk of death was increased in recipients who were underweight (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.03-1.26; p = 0.01), overweight (HR, 1.06; 95% CI, 0.99-1.14; p = 0.1), and obese (HR, 1.16; 95% CI, 1.04-1.28; p = 0.005). Kaplan-Meier modeling showed a significant effect of BMI on survival; however, this effect was no longer significant when first-year deaths were excluded. CONCLUSIONS Mortality is higher in underweight, overweight, and obese LTx patients than in normal-weight controls. However, this effect appears to be governed by survival in the first year after LTx.

The impact of center volume on survival in lung transplantation: an analysis of more than 10,000 cases.

BACKGROUND Whether center volume influences outcomes in lung transplantation is unknown. We reviewed United Network for Organ Sharing data to examine the effect of center volume on short-term mortality. METHODS We reviewed United Network for Organ Sharing data (1998 through 2007) to identify 10,496 first-time adult lung transplantation recipients at 79 centers. Centers were stratified by quartiles of mean annual volume. Risk of 30-day mortality and 1- and 5-year mortality (censored for 30-day death) were assessed by multivariable Cox proportional hazards regression. RESULTS Mean center volume ranged from less than 1 to 58.2 (median, 9.4 cases/year; volume quartiles: 0 to 2.1, 2.2 to 9.4, 9.5 to 19.9, and 20 to 58.2 cases). Each 1 case/year decrease led to a 2% increase in 30-day mortality (hazard ratio, 1.02; 95% confidence interval, 1.01 to 1.02; p < 0.001). Centers of lowest quartile (performing <or=2.1 lung transplantations/year) had a 30-day cumulative mortality of 9.6% or 89% increase in the risk of death (hazard ratio, 1.89; 95% confidence interval, 1.01 to 3.44; p = 0.05) compared with the highest quartile centers despite fewer idiopathic pulmonary fibrosis patients (15.6% versus 25.8%; p < 0.001) and younger age (40.9 versus 51.5 years; p < 0.001). Low-volume centers had double the risk of 30-day censored 1-year mortality (hazard ratio, 1.95; 95% confidence interval, 1.30 to 2.92; p = 0.001). High-volume centers (>or=20 lung transplantations/year) had the lowest 30-day mortality (4.1%). CONCLUSIONS We provide an initial examination of the relationship of volume and lung allocation score to outcomes for lung transplantation. Low center volume is associated with increased short-term and cumulative mortality despite fewer idiopathic pulmonary fibrosis patients and younger patients.

Evaluation of Risk Indices in Continuous-Flow Left Ventricular Assist Device Patients

BACKGROUND The Leitz-Miller (LM), Columbia (COL), Acute Physiology and Chronic Health Evaluation II (APACHE II), Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), and Seattle Heart Failure Model (SHFM) risk scores have been used to risk stratify patients with pulsatile-flow left ventricular assist devices (LVAD). We assessed the predictive ability of these scores in a cohort of continuous-flow LVAD patients. METHODS Preoperative scores were calculated from prospective data of patients who received continuous-flow LVADs between June 2000 and May 2009. Cox proportional hazard analysis assessed the effect of preoperative variables and scores on 30-day, 90-day, and 1-year mortality. Patients were stratified by score into low- and high-risk groups. Survival was modeled using the Kaplan-Meier method. RESULTS During the study period, 86 continuous-flow LVADs were implanted. The mean (+/- standard deviation) preoperative scores were: COL, 1.05 +/- 1.59; LM, 11.9 +/- 5.4; APACHE II, 15.6 +/- 4.3; INTERMACS, 2.64 +/- 1.01; and SHFM, 2.97 +/- 1 .42. On univariate analysis, the SHFM score best differentiated low- and high-risk patients at all mortality end points; the INTERMACS and APACHE II scores were predictive for 90-day and 1-year mortality. On multivariable analysis, SHFM (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.02 to 2.21; p = 0.04) and APACHE II (HR, 1.10; 95% CI, 1.01 to 1.21; p = 0.04) predicted 1-year mortality. CONCLUSIONS Among the LM, COL, APACHE II, INTERMACS, and SHFM scores, the best predictor of mortality in a single institutional cohort of continuous-flow LVAD patients was the SHFM score.

The Impact of Donor-Recipient Sex Matching on Survival After Orthotopic Heart Transplantation Analysis of 18 000 Transplants in the Modern Era

Introduction—Single-institution series have suggested that men receiving orthotopic heart transplantation from female donors have decreased survival. No multi-institutional series has comprehensively addressed the issue of donor and recipient sex matching for both male and female orthotopic heart transplantation recipients. Methods and Results—We used data from the multi-institutional prospectively collected United Network for Organ Sharing open transplantation cohort to review 18 240 adult patients who received orthotopic heart transplantation from 1999 to 2007. Four donor recipient strata were identified (male donor/male recipient, N=10 750; female donor/female recipient, N=2201; male donor/female recipient, N=2121; and female donor/male recipient, N=3168). The primary end point of all cause posttransplant mortality was compared among groups using a Cox proportional hazard regression model with additional propensity adjustment. Female recipients, irrespective of donor sex, had 3.6% lower overall survival at 5 years posttransplant (P=0.003). Men who received organs from male donors had the highest cumulative survival at 5 years (74.5%). Men receiving female hearts had a 15% increase in the risk of adjusted cumulative mortality (hazard ratio, 1.15; 95% CI, 1.02 to 1.30; P=0.02). No significant increase in the relative hazard for death occurred for women receiving opposite sex donor organs (1.24; 0.92 to 1.35; P=0.31). Conclusions—The United Network for Organ Sharing data set has provided a large sample examining donor recipient sex pairing in orthotopic heart transplantation. Men receiving organs for same sex donors have significantly improved short- and long-term survival. No survival advantage was seen for women with same sex donors.